Update on the Beans: How to Keep Them Going - Society ofкод для вставки
Update on the Beans: How to Keep Them Going Duminda N. Wijeysundera, MD PhD FRCPC Department of Anesthesia, University of Toronto Prognostic Importance Acute kidney injury (AKI) is an important postoperative complication of cardiac surgery. Even after accounting for comorbidities and other postoperative complications, AKI following cardiac surgery is associated with increased postoperative mortality, regardless of whether the kidney injury is severe enough to require renal replacement therapy.1-5 Even small postoperative elevations in creatinine concentration following cardiac surgery (e.g., 0.3 to 0.5 mg/dL) are associated with increased 30-day postoperative mortality.3 Mechanisms for Perioperative Acute Kidney Injury Therapies for preventing perioperative AKI should be considered based on the potential underlying mechanisms of AKI after cardiac surgery. There are several mechanisms for perioperative AKI, several of which are responsible in any individual affected patient. 1. Renal ischemia due to reduced perfusion and acute anemia. Acute anemia, even with adequate perfusion pressure, predisposes the kidneys to hypoxic injury.6 2. Ischemia-reperfusion injury 3. Inflammation caused by the surgical stress response and cardiopulmonary bypass (CPB) 4. Emboli вЂ“ both microemboli and macroemboli. Examples include microemboli generated during CPB and atheroemboli generated by manipulation of the ascending aorta. 5. Nephrotoxins вЂ“ both exogeneous and endogeneous (e.g., angiographic contrast administered before surgery,7 free hemoglobin released by intra-operative hemolysis8) Defining Acute Kidney Injury Using Changes in Creatinine The diagnosis of AKI, as well as staging of its severity, is based on either of two consensus-based criteria, namely RIFLE and AKIN. Both criteria involve assessment of changes in creatinine or estimated glomerular filtration rate (eGFR), as well as changes in urine output. Application of the AKIN criteria involves two steps вЂ“ an initial diagnosis of AKI based on changes over 48 hours вЂ“ and a staging of AKI based on changes within a seven day period. 9 Diagnosis An abrupt (within 48 hours) reduction in kidney function currently defined as an absolute increase in serum creatinine of more than or equal to 0.3 mg/dl (в‰Ґ 26.4 Ојmol/l), a percentage increase in serum creatinine of more than or equal to 50% (1.5-fold from baseline), or a reduction in urine output (documented oliguria of less than 0.5 ml/kg per hour for more than six hours). AKIN Stage AKIN Stage 1 Serum Creatinine Criteria (based on changes in a seven day period) Increase in serum creatinine of more than or equal to 0.3 mg/dl (в‰Ґ 26.4 Ојmol/l) or increase to more than or equal to 150% to 200% (1.5- to 2-fold) from baseline 1 AKIN Stage 2 AKIN Stage 3 Increase in serum creatinine to more than 200% to 300% (> 2- to 3-fold) from baseline Increase in serum creatinine to more than 300% (> 3-fold) from baseline OR serum creatinine of more than or equal to 4.0 mg/dL (в‰Ґ 354 Ојmol/L) with an acute increase of at least 0.5 mg/dL (44 Ојmol/L) OR requirement for renal replacement therapy The RIFLE criteria define severity or stage of AKI based on changes in creatinine or eGFR observed within the previous 1 to 7 days.10 RIFLE Stage Creatinine or eGFR Criteria (based on changes in prior one to seven days) Risk Increase in serum creatinine X 1.5 or GFR decrease >25% Injury Serum creatinine X 2 or GFR decreased >50% Failure Serum creatinine X 3, or serum creatinine >4 mg/dl (>354 Ојmol/L) with an acute rise >0.5 mg/dL (>44 Ојmol/L) or GFR decreased >75% Loss Complete loss of kidney function >4 weeks End-stage kidney disease End stage renal disease for >3 months Either criterion can be used to diagnose and classify AKI вЂ“ both approaches have shown validity in that patients with increasing severity of AKI (based on either classification system) also have increasingly worse prognosis.11,12 Nonetheless, the AKIN criteria may lead to some overdiagnosis of AKI, especially when applied to individuals who meet AKIN Stage 1 criteria, but do not meet any RIFLE criteria.11 In addition, both classification systems suffer from the limitations of using creatinine as a marker of acute changes in kidney function вЂ“ including influence by factors aside from kidney function (e.g., age, sex, muscle mass, ethnicity, diet), delayed response following acute changes in kidney function, and lack of guidance on the site of kidney injury (e.g., tubular versus glomerular injury). Despite these limitations, either classification system can be used to identify postoperative AKI in the clinical setting, to define outcomes in research related to AKI, and to compare outcomes or quality of care related to AKI. Alternative Markers of Acute Kidney Injury Given the limitations of using creatinine as a marker of AKI, there is increasing interest in alternative biomarkers, especially one that can provide early indications of AKI.13 Such biomarkers could allow for initiation of early treatment of AKI. This approach has theoretical benefits, especially since early renal recovery after AKI is associated with improved long-term survival after cardiac surgery.14 Early detection of AKI could allow for the appropriate targeted use of novel interventions such as allogeneic bone marrow derived human mesenchymal stem cells to promote early recovery of renal function after AKI. Of potential biomarkers that have been evaluated, the most promising is urinary neutrophil gelatinase-associated lipocalin (NGAL) вЂ“ which is a marker of renal tubular injury. In a meta-analysis of studies performed in cardiac surgery patients, the urinary NGAL had a pooled area under the receiver-operating-characteristic (ROC) curve for predicting AKI (diagnosed 2 based on changes in creatinine) of 0.75 (95% CI, 0.70 to 0.87).15 Despite this promise, the diagnostic performance of NGAL is not consistent, with several studies reporting poor accuracy.16,17 Alternative biomarkers include cystatin C (marker of glomerular filtration) and urinary IL-18 (marker of inflammation). While all individual biomarkers continue to have limitations, the combination of biomarkers, with or without clinical risk factors, may represent the most accurate approach for early identification of patients with AKI.18,19 Interventions for Preventing Perioperative Acute Kidney Injury Overall, there are few proven drug interventions for preventing injury to the kidneys during surgery.20 Some interventions showing potential promise are described below. 1. Interventions for Preventing Renal Ischemia If impaired renal perfusion is an important mechanism for perioperative AKI, optimizing renal oxygen delivery may mitigate the risk of this complication. A systematic review of randomized trials found that вЂњgoal-directed therapyвЂќ based on hemodynamic optimization significantly reduce the risk of perioperative AKI (odds ratio 0.64; 95% CI 0.50 to 0.83; P = 0.0007). 21. Similarly, several cohort studies have found that reduced intra-operative hematocrits, especially levels of 0.20 or lower,22,23 were associated with increased risks of perioperative AKI. Other authors have further suggested that the increased risk depends not on the absolute level to which hemoglobin concentration falls, but rather its relative decline from the baseline concentration.24 Specifically, the risk of adverse perioperative outcomes increases once hemoglobin concentrations drops by 50% or greater.24 Nonetheless, it remains unclear whether some of the potential interventions for treating impaired renal perfusion are themselves safe for the kidneys. For example, the usual treatment for acute anemia, namely red cell transfusion, is itself associated with an increased risk of AKI.2 Notably, a randomized trial of restrictive versus liberal red cell transfusion strategies in cardiac surgery found no difference in rates of perioperative AKI.25 In addition, some authors have raised concerns about using hydroxyethyl starches to optimize hemodynamics because these colloids may themselves also cause AKI.26 An alternative approach to optimizing renal perfusion is to use pharmacologic agents that increase renal perfusion. Although still widely used, low-dose dopamine does not prevent AKI, although it does increase urine output (which may be a clinically useful effect in specific circumstances).27 Conversely, fenoldopam, which is a selective dopamine-1-receptor antagonist, has shown some promise in preventing AKI after cardiac surgery. A systematic review of randomized trials in cardiac surgery found that fenoldopam significantly reduced both renal replacement therapy (odds ratio 0.37; CI, 0.23 to 0.59) and in-hospital death (odds ratio 0.46; CI, 0.29 to 0.75).28 These findings were confirmed in a more recent systematic review focused only on placebo-controlled randomized trials.29 Especially since perioperative AKI has a multifactorial etiology, such large risk reductions from fenoldopam alone are implausible. A large randomized trial is warranted, and is presently being undertaken (NCT00621790). Atrial natriuretic peptide (ANP) has multiple potentially beneficial effects, including increased glomerular filtration, natriuresis, diuresis, and inhibition of the renin-angiotensinaldosterone axis. A systematic review of randomized trials in cardiac surgery has shown reductions in progression to renal replacement therapy with ANP.30 These findings have been supported by three recent trials in cardiac surgery patients with normal preoperative kidney 3 function, preoperative ventricular dysfunction, and preoperative renal impairment. 31-33 These promising results support an evaluation of ANP in a large multicenter randomized trial. 2. Reducing Harmful Effects of CPB Cardiopulmonary bypass may cause perioperative AKI through a range of mechanisms, including generation of microemboli, induction of a systemic inflammatory response, and production of atheroemboli through manipulation of the ascending aorta. Thus, simply avoiding CPB through procedures such as off-pump coronary artery bypass (OPCAB) may theoretically reduce the risk of perioperative AKI. A recent systematic review of relevant randomized trials found that OPCAB significantly reduced AKI (odds ratio 0.27; CI, 0.13 to 0.54) but had no statistically significant effect on the need for renal replacement therapy (odds ratio, 0.31; CI, 0.06 to 1.59). However, this analysis was limited by the very heterogeneous definitions of AKI in the relatively few included trials (5 trials with 438 participants).34 By comparison, a single large randomized trial (2203 participants) of off-pump versus on-pump coronary artery bypass graft surgery found no difference in rates of renal replacement therapy (relative risk 0.90; CI, 0.37 to 2.20).35 Nonetheless, this specific trial recruited participants at very low baseline risk for AKI, thus potentially explaining their negative findings. Conversely, a subsequent multicenter trial of 4752 participants found that OPCAB significantly reduced risks of mild AKI (AKIN Stage 1 or RIFLE-Risk categories), but had no significant effect on risks of renal replacement therapy. 36 3. Avoidance of Nephrotoxins A straightforward approach for preventing AKI may be to avoid or minimize the impact of nephrotoxic agents. Angiographic contrast is one such nephrotoxin to which most cardiac surgery patients are exposed. A cohort study evaluated the relationship between perioperative AKI, time interval between contrast exposure and surgery, dose of contrast, and preoperative renal function.7 The risk of postoperative AKI was increased substantially if surgery was performed within 5 days after administration of high-doses (>1.4 mL/kg) of angiographic contrast. Similarly, as indicated above, it is likely prudent to avoid the use of hydroxyethyl starches in cardiac surgery patients at increased risk of perioperative AKI.37 Free hemoglobin and free iron from the hemolysis of red cells during CPB may be another important nephrotoxin to which cardiac surgery patients are exposed.8,38 A recent pilot randomized trial suggested that preoperative (as opposed to intra-operative) transfusion of red cells to anemic cardiac surgery patients (who were invariably going to require transfusion) may mitigate some these physiologic risk factors, although the impact of such a strategy on risks of AKI itself remains unknown.39 An initial pilot randomized trial (100 participants) also found that sodium bicarbonate administration, which helps to alkalinize the urine and thereby remove free hemoglobin, also prevented AKI after cardiac surgery (odds ratio 0.43; CI, 0.19-0.98), as defined by a 25% increase in creatinine concentrations over baseline levels.40 Despite these initial promising results, two subsequent randomized trials, one with 427 participants and another with 350 participants,41,42 did not replicate these initial positive findings. At present, therefore, there are not compelling data to support using sodium bicarbonate to prevent AKI. 4 References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. Chertow GM, Levy EM, Hammermeister KE, et al. Independent association between acute renal failure and mortality following cardiac surgery. Am J Med. 1998;104(00029343)(4):343-348. Karkouti K, Wijeysundera DN, Yau TM, et al. Acute kidney injury after cardiac surgery: focus on modifiable risk factors. Circulation. 2009;119(4):495-502. Lassnigg A, Schmidlin D, Mouhieddine M, et al. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study. J Am SocNephrol. 2004;15(1046-6673)(6):1597-1605. Ryckwaert F, Boccara G, Frappier JM, et al. Incidence, risk factors, and prognosis of a moderate increase in plasma creatinine early after cardiac surgery. Crit Care Med. 2002;30(7):1495-1498. Thakar CV, Worley S, Arrigain S, et al. Influence of renal dysfunction on mortality after cardiac surgery: modifying effect of preoperative renal function. Kidney Int. 2005;67(3):1112-1119. Ragoonanan TE, Beattie WS, Mazer CD, et al. Metoprolol reduces cerebral tissue oxygen tension after acute hemodilution in rats. Anesthesiology. 2009;111(5):988-1000. Medalion B, Cohen H, Assali A, et al. The effect of cardiac angiography timing, contrast media dose, and preoperative renal function on acute renal failure after coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2010;139(6):1539-1544. Vanek T, Snircova J, Spegar J, et al. Increase in plasma free haemoglobin during cardiopulmonary bypass in heart valve surgery: assessment of renal dysfunction by RIFLE classification. Perfusion. 2009;24(3):179-183. Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31. Bellomo R, Ronco C, Kellum JA, et al. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8(4):R204-R212. Englberger L, Suri RM, Li Z, et al. Clinical accuracy of RIFLE and Acute Kidney Injury Network (AKIN) criteria for acute kidney injury in patients undergoing cardiac surgery. Crit Care. 2011;15(1):R16. Haase M, Bellomo R, Matalanis G, et al. A comparison of the RIFLE and Acute Kidney Injury Network classifications for cardiac surgery-associated acute kidney injury: a prospective cohort study. J Thorac Cardiovasc Surg. 2009;138(6):1370-1376. Vanmassenhove J, Vanholder R, Nagler E, et al. Urinary and serum biomarkers for the diagnosis of acute kidney injury: an in-depth review of the literature. Nephrol Dial Transplant. 2013;28(2):254-273. Swaminathan M, Hudson CC, Phillips-Bute BG, et al. Impact of early renal recovery on survival after cardiac surgery-associated acute kidney injury. Ann Thorac Surg. 2010;89(4):1098-1104. Haase M, Bellomo R, Devarajan P, et al. Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and 5 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. meta-analysis. Am J Kidney Dis. 2009;54(6):1012-1024. Perry TE, Muehlschlegel JD, Liu KY, et al. Plasma neutrophil gelatinase-associated lipocalin and acute postoperative kidney injury in adult cardiac surgical patients. Anesth Analg. 2010;110(6):1541-1547. Wagener G, Gubitosa G, Wang S, et al. Urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery. Am J Kidney Dis. 2008;52(3):425-433. Katagiri D, Doi K, Honda K, et al. Combination of two urinary biomarkers predicts acute kidney injury after adult cardiac surgery. Ann Thorac Surg. 2012;93(2):577-583. Koyner JL, Garg AX, Coca SG, et al. Biomarkers predict progression of acute kidney injury after cardiac surgery. J Am Soc Nephrol. 2012;23(5):905-914. Zacharias M, Gilmore IC, Herbison GP, et al. Interventions for protecting renal function in the perioperative period. Cochrane Database Syst Rev. 2005;(3):CD003590. Brienza N, Giglio MT, Marucci M, et al. Does perioperative hemodynamic optimization protect renal function in surgical patients? A meta-analytic study. Crit Care Med. 2009;37(6):2079-2090. Karkouti K, Beattie WS, Wijeysundera DN, et al. Hemodilution during cardiopulmonary bypass is an independent risk factor for acute renal failure in adult cardiac surgery. J Thorac Cardiovasc Surg. 2005;129(2):391-400. Swaminathan M, Phillips-Bute BG, Conlon PJ, et al. The association of lowest hematocrit during cardiopulmonary bypass with acute renal injury after coronary artery bypass surgery. Ann Thorac Surg. 2003;76(3):784-791. Karkouti K, Wijeysundera DN, Yau TM, et al. The influence of baseline hemoglobin concentration on tolerance of anemia in cardiac surgery. Transfusion. 2008;48(4):666-672. Hajjar LA, Vincent JL, Galas FR, et al. Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA. 2010;304(14):1559-1567. Zarychanski R, Abou-Setta AM, Turgeon AF, et al. Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: a systematic review and meta-analysis. JAMA. 2013;309(7):678-688. Friedrich JO, Adhikari N, Herridge MS, et al. Meta-analysis: low-dose dopamine increases urine output but does not prevent renal dysfunction or death. Ann Intern Med. 2005;142(7):510-524. Landoni G, Biondi-Zoccai GG, Marino G, et al. Fenoldopam reduces the need for renal replacement therapy and in-hospital death in cardiovascular surgery: a meta-analysis. J Cardiothorac Vasc Anesth. 2008;22(1):27-33. Zangrillo A, Biondi-Zoccai GG, Frati E, et al. Fenoldopam and acute renal failure in cardiac surgery: a meta-analysis of randomized placebo-controlled trials. J Cardiothorac Vasc Anesth. 2012;26(3):407-413. Nigwekar SU, Hix JK. The role of natriuretic peptide administration in cardiovascular surgery-associated renal dysfunction: a systematic review and meta-analysis of randomized controlled trials. J Cardiothorac Vasc Anesth. 2009;23(2):151-160. Sezai A, Shiono M, Orime Y, et al. Low-dose continuous infusion of human atrial natriuretic peptide during and after cardiac surgery. Ann Thorac Surg. 2000;69(3):732-738. Sezai A, Hata M, Niino T, et al. Continuous low-dose infusion of human atrial natriuretic peptide in patients with left ventricular dysfunction undergoing coronary artery bypass 6 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. grafting: the NU-HIT (Nihon University working group study of low-dose Human ANP Infusion Therapy during cardiac surgery) for left ventricular dysfunction. J Am Coll Cardiol. 2010;55(17):1844-1851. Sezai A, Hata M, Niino T, et al. Results of low-dose human atrial natriuretic peptide infusion in nondialysis patients with chronic kidney disease undergoing coronary artery bypass grafting: the NU-HIT (Nihon University working group study of low-dose HANP Infusion Therapy during cardiac surgery) trial for CKD. J Am Coll Cardiol. 2011;58(9):897903. Nigwekar SU, Kandula P, Hix JK, et al. Off-pump coronary artery bypass surgery and acute kidney injury: a meta-analysis of randomized and observational studies. Am J Kidney Dis. 2009;54(3):413-423. Shroyer AL, Grover FL, Hattler B, et al. On-pump versus off-pump coronary-artery bypass surgery. N Engl J Med. 2009;361(19):1827-1837. Lamy A, Devereaux PJ, Prabhakaran D, et al. Off-pump or on-pump coronary-artery bypass grafting at 30 days. N Engl J Med. 2012;366(16):1489-1497. Zarychanski R, Turgeon AF, FergussonвЂ¦ DA. Renal outcomes and mortality following hydroxyethyl starch resuscitation of critically ill patients: Systematic review and metaanalysis of randomized trials. Open Med. 2009;3(4):E196-E209. Vermeulen Windsant IC, Snoeijs MG, Hanssen SJ, et al. Hemolysis is associated with acute kidney injury during major aortic surgery. Kidney Int. 2010;77(10):913-920. Karkouti K, Wijeysundera DN, Yau TM, et al. Advance targeted transfusion in anemic cardiac surgical patients for kidney protection: an unblinded randomized pilot clinical trial. Anesthesiology. 2012;116(3):613-621. Haase M, Haase-Fielitz A, Bellomo R, et al. Sodium bicarbonate to prevent increases in serum creatinine after cardiac surgery: a pilot double-blind, randomized controlled trial. Crit Care Med. 2009;37(1):39-47. Haase M, Haase-Fielitz A, Plass M, et al. Prophylactic perioperative sodium bicarbonate to prevent acute kidney injury following open heart surgery: a multicenter double-blinded randomized controlled trial. PLoS Med. 2013;10(4):e1001426. McGuinness SP, Parke RL, Bellomo R, et al. Sodium bicarbonate infusion to reduce cardiac surgery-associated acute kidney injury: a phase II multicenter double-blind randomized controlled trial. Crit Care Med. 2013;41(7):1599-1607. 7 ADULT В CONGENITAL В HEART В DISEASE: В В THE В NEW В REALITY В KATHRYN В ROUINE-ВвЂђRAPP, В MD В PROFESSOR В OF В ANESTHESIA, В UNIVERSITY В OF В CALIFORNIA, В SAN В FRANCISCO В В В OBJECTIVES В After В attending В this В session, В the В participant В will В be В better В able В to В В 1. В В В REVIEW В THE В MOST В COMMON В CONGENITAL В ANOMALIES В BEING В SEEN В IN В THE В ADULT В SURGICAL В POPULATION, В INCLUING В CARDIAC В AND В NON-ВвЂђCARDIAC В SURGERY. В В В 2. В В DISCUSS В THE В ANESTHETIC В IMPLICATIONS В FOR В CYANOTIC В PATIENTS В UNDERGOING В SURGICAL В PROCEDURES, В EITHER В CARDIAC В OR В NON-ВвЂђCARDIAC. В В 3. В В PROVIDE В RECOMMENDATIONS В FOR В DEFINING В PATIENTS В AS В NEEDING В A В вЂњCARDIACвЂќ В ANESTHESIOLGIST В В OVERVIEW В An В estimated В 1-ВвЂђ3 В million В adults В in В the В United В States В and В Canada В have В congenital В heart В disease В (CHD). В В In В Europe, В the В estimated В number В is В 1.8 В million. В В Approximately В 85% В of В infants В with В CHD В survive В into В adulthood. В В For В several В years В advances В in В cardiac В surgery, В cardiology В and В anesthesia В care, В intensive В care В and В diagnosis В lead В to В an В increase В in В the В number В of В adults В with В CHD. В В В Currently В there В are В more В adults В with В CHD В than В children, В the В median В age В of В all В patients В with В CHD В is В 40 В years В and В prevalence В of В adult В CHD В is В estimated В at В 3000 В per В million. В В Even В a В geriatric В population В of В adults В with В CHD В has В been В studied. В В These В data В suggest В that В anesthesiologists В will В care В for В adults В with В CHD В with В increasing В frequency. В В Thus В it В is В important В to В learn В the В anatomy В and В physiology В of В the В more В common В lesions. В В (Marelli В et В al. В В Am В Heart В J В 2009; В Dearani В JA В et В al. В В Cardiol В Young В 2007; В Moons В P В et В al. В В Eur В Heart В J В 2010; В Webb В G В et В al. В В J В Am В Coll В Cardiol В 2001; В В Warnes В CA В et В al. В J В Am В Coll В Cardiol В В 2001; В Marelli В AJ В et В al. В В Circulation В 2007; В van В der В Bom В T В et В al. В В Am В Heart В J, В 2012; В В Afilalo В T В et В al. В В J В Am В Coll В Cardiol В 2011). В В В Several В classification В systems В have В been В used В to В promote В comprehension В of В CHD. В В Lesions В are В classified В by В level В of В complexity, В presence В or В absence В of В cyanosis, В and В physiology-ВвЂђinduced В changes В (вЂњshuntвЂќ В lesions). В Using В complexity В classification, В lesions В may В be В simple, В or В of В moderate В or В severe В complexity. В В Overall, В lesions В of В severe В complexity В are В present В in В approximately В 20-ВвЂђ25% В of В adults В with В CHD. В В About В 40% В have В lesions В that В are В вЂњsimpleвЂќ В or В resolved В following В intervention В (Grown-ВвЂђup В congenital В heart В (GUCH) В disease: В current В needs В and В provision В of В service В for В adolescents В and В adults В with В congenital В heart В disease В in В the В UK. В Report В of В the В British В Cardiac В Society В Working В Party. В Heart В 2002;88(Suppl В I):i1вЂ“i14). В В В Some В adults В with В CHD В are В unoperated, В i.e., В never В underwent В correction В of В the В lesion. В В Others В may В have В undergone В an В intervention В to В palliate В the В physiologic В effects В of В the В lesion В (e.g., В a В shunt В between В systemic В and В pulmonary В arteries В to В increase В pulmonary В blood В flow В in В a В cyanotic В patient). В В Alternatively, В they В may В have В undergone В surgical В or В device В closure В of В the В lesion В and В may В have В an В excellent В uncomplicated В result В or В residual В defect В and В sequelae. В В For В comprehensive В assessment В and В information В for В clinical В care В of В adults В with В CHD В please В refer В to В the В following В most В recent В American, В Canadian В and В European В guidelines В for В the В management В of В adults В with В congenital В heart В disease. В В ACC/AHA В 2008 В guidelines В for В the В management В of В adults В with В congenital В heart В disease В В J В Am В Coll В Cardiol. В 2008 В Dec В 2;52(23):e143-ВвЂђ263. В doi: В 10.1016/j.jacc.2008.10.001. В В В Canadian В Cardiovascular В Society В 2009 В Consensus В Conference В on В the В management В of В adults В with В congenital В heart В disease: В complex В congenital В cardiac В lesions. В Silversides В CK, В Salehian В O, В Oechslin В E, В et В al. В В Can В J В Cardiol. В 2010 В Mar;26(3):e98-ВвЂђ117 В В В Canadian В Cardiovascular В Society В 2009 В Consensus В Conference В on В the В management В of В adults В with В congenital В heart В disease: В outflow В tract В obstruction, В coarctation В of В the В aorta, В tetralogy В of В Fallot, В Ebstein В anomaly В and В Marfan's В syndrome. В Silversides В CK, В Kiess В M, В Beauchesne В L, В et В al. В В Can В J В Cardiol. В 2010 В Mar;26(3):e80-ВвЂђ97 В В В Canadian В Cardiovascular В Society В 2009 В Consensus В Conference В on В the В management В of В adults В with В congenital В heart В disease: В shunt В lesions. В Silversides В CK, В Dore В A, В Poirier В N, В et В al. В В Can J Cardiol. 2010 Mar;26(3):e70-9. В В ESC В Guidelines В for В the В management В of В grown-ВвЂђup В congenital В heart В disease В (new В version В 2010). В Baumgartner В H, В Bonhoeffer В P, В De В Groot В NM, В et В al. В В ; В Task В Force В on В the В Management В of В Grown-ВвЂђup В Congenital В Heart В Disease В of В the В European В Society В of В Cardiology В (ESC). В Eur В Heart В J. В 2010 В Dec;31(23):2915-ВвЂђ57. В Epub В 2010 В Aug В 27. В No В abstract В available. В В В В В Looking В at В the В world В literature, В the В most В common В lesions В in В unoperated В adults В with В CHD В are В atrial В septal В defects В (ASD) В and В ventricular В septal В defects В (VSD). В (Mello В et В al. В В Rev В Bras В Cir В CV В 2012 В & В Hannoush В H В et В Ial. В В lin В Cardiol В 2004). В В In В some В centers, В approximately В half В of В adult В patients В followed В in В a В specialty В clinic В have В these В defects В (Kolo В et В al. В В Niger В Postgrad В Med В infancy; В Hannoush В et В al. В В Clin В Cardiol В 2004). В В The В most В common В cyanotic В lesion В in В patients В after В infancy В is В tetralogy В of В Fallot В (TOF). В В Therefore В a В detailed В discussion В of В these В lesions В will В be В included В in В this В syllabus. В В В В В DISCUSSION В OF В SPECIFIC В CHD В В Atrial septal defects (ASD) are one of the most common defects in the adult population, accounting for one-fourth to one-third of all lesions, occurring more commonly in women There are four types of atrial septal defects: 1. Ostium secundum defect (70%), which occurs in the central portion of the interatrial septum. Varying degrees of mitral valve (MV) prolapse and mitral regurgitation can occur, but hemodynamically significant lesions are uncommon. 2. 3. 4. Ostium primum defect (15%вЂ“25%) is located in the inferior portion of the interatrial septum, near the atrioventricular (AV) valves. It also is a form of a partial atrioventricular septal defect. Abnormalities of the AV valves can occur with a вЂњcleftвЂќ anterior mitral valve and septal tricuspid valve leaflet with variable degrees of regurgitation. Sinus venosus defect (10%) usually is superior and posterior in relation to the superior vena cava or less frequently, the inferior vena cava. These defects frequently are associated with an anomalous drainage of one or more pulmonary veins (PV) into the right atrium or superior vena cava. Surgical correction includes application of a baffle that redirects blood flow to the left atrium. Obstruction of the superior vena cava or pulmonary vein and sinus node dysfunction can occur following repair. Coronary sinus defects (extremely rare) occur between the left atrium and coronary sinus and can be associated with a persistent left superior vena cava. A defect in the interatrial septum typically allows pulmonary venous return to pass from the left to the right atrium. Because this left-to-right shunt increases the venous return to the right ventricle, the right ventricular stroke volume and pulmonary blood flow are increased compared with the systemic blood flow. Right ventricular volume overload results. Right atrial enlargement may occur. Primary or patch closure of an ASD in childhood provides excellent operative results and nearly normal long-term survival in adults. A recent retrospective study suggested improved 10-year survival in patients over the age of 40 years treated surgically (95%) compared with those treated medically (84%). Patients В в‰Ґ В 40 В yrs В with unrepaired ASD are at increased risk of heart failure, sudden death, severe pulmonary infections, embolisms and stroke (Rosas M et al. Int J Cardiol 2004). A prospective clinical trial randomized adult patients with secundum ASD with shunt ratios >1.7:1 to surgical versus medical management, showing improved survival with surgical closure. However, late repair does not appear to reduce the incidence of arrhythmias, which are generally related to preoperative atrial dilatation or postoperative incisional reentry. Operative patch closure is recommended if the degree of left to right shunting is sufficiently large to cause right atrial and right ventricular enlargement and if the defect cannot be closed percutaneously. Other indications for closure include paradoxical embolism and documented orthodeoxia-platypnea, a syndrome associated with intermittent right to left shunting in the absence of pulmonary hypertension. Percutaneous closure with a variety of devices is now widely available and feasible for most ostium secundum defects. Sinus venosus, coronary sinus and ostium primum ASD still require surgical closure. In patients with ostium primum defects, surgical valve repair with or without annuloplasty may reduce the severity of the mitral and tricuspid regurgitation. If severe mitral regurgitation persists, valve re-repair or replacement is necessary. Following repair patients may have a residual shunt. Closure of an ASD in the presence of pulmonary hypertension requires special consideration. According to the current guidelines, it may be considered when there is net left-to-right shunting and the pulmonary vascular resistance is less than 2/3 systemic or if there has been demonstrated response to pulmonary vasodilator therapy. In these patients, careful monitoring of right ventricular function following ASD closure is required and use of pulmonary vasodilators post-operatively may be required. Ventricular septal defects (VSD) are the most common cardiac abnormality in infants and children. Unoperated patients with VSD are encountered less frequently than those with ASD, because large defects usually are closed surgically in childhood when there is evidence of congestive heart failure or pulmonary hypertension. In infancy and childhood, defects have a high rate of spontaneous closure (90% of those that close do so by the time the child is 10 years of age). VSD can be classified by anatomic location into four types: 1. Perimembranous VSD (70%) are found in the membranous region of the septum and can extend into the muscular, inlet, or outlet regions. Part of the border is formed by fibrous continuity between the tricuspid and aortic valves (TV, AV). 2. Muscular VSD (20%) are surrounded by a muscular rim and located within the trabecular portion of the septum, or in the central or apical areas. Multiple defects can occur, either two or three or multiple small ones in a defect known as вЂњswiss cheese septum.вЂќ 3. Doubly-committed or subarterial VSD (so called вЂњsupracristalвЂќ) (5%) are found just below the aortic and pulmonary valves and may have associated aortic cusp herniation and aortic regurgitation. Part of the border of the defect is formed by fibrous continuity between the aortic and pulmonary valves. 4. Inlet VSD (5%) occur close to the AV valves in the posterior and inlet portions of the septum. If the left-to-right shunt is large, the left atrium and left ventricle are dilated. Right ventricular dimension is normal unless there is pulmonary hypertension. In the presence of a perimembranous VSD, the septal leaflet of the tricuspid valve can become adherent to the defect, thus tricuspid regurgitation may occur and can occasionally be severe. Hemodynamically significant aortic valve regurgiation is most common in the presence of a subarterial VSD with herniation of the right coronary cusp. Preoperatively, transthoracic echocardiography can be used to obtain peak velocity across the VSD then estimate the right ventricular systolic pressure and pulmonary artery systolic pressure . According to current guidelines, closure of a VSD is indicated when the pulmonary-tosystemic flow (Qp/Qs) is greater than or equal to 2.0, if there is evidence of LV volume overload, or if the Qp/Qs > 1.5 in the presence of left-ventricular systolic or diastolic failure (9). Another indication is a history of infective (bacterial) endocarditis (IE). In a patient with pulmonary hypertension, VSD closure should be considered if the net Qp/Qs is > 1.5 and the pulmonary vascular resistance is < 2/3 systemic resistance but should not be performed if there is severe irreversible pulmonary vascular disease. Percutaneous closure is possible for many muscular VSD. However, most perimembranous and inlet VSD require surgical closure. Post-repair residua include aortic or pulmonary insufficiency, residual defects, and right ventricular outflow tract obstruction. The VSD permits a left-to-right shunt to occur at the ventricular level, and the physiologic consequences are determined by the size of the defect and the relative resistance of the systemic and pulmonary vascular beds. If the VSD is small and restrictive, there is a large pressure difference between the left and the right ventricles in systole. If the VSD is large (nonrestrictive), there is no pressure difference between the left and the right ventricles; then, the magnitude of the shunt depends on the ratio of pulmonary vascular resistance to systemic vascular resistance. If the pulmonary vascular resistance is lower than the systemic vascular resistance, the left-to-right shunt can be large. When the increased pulmonary blood flow returns to the left ventricle, left ventricular diastolic volume and stroke volume increase. The VSD is unlikely to close spontaneously after adolescence or early adulthood. If the left to right shunt is large, congestive heart failure can occur. If a large VSD is associated with pulmonary hypertension, the chance of the development of pulmonary vascular disease is high. In adults diagnosed with VSD, the overall 10-year survival after initial presentation is approximately 75%. NYHA functional class greater than 1, cardiomegaly, and elevated pulmonary artery pressure (> 50 mm Hg) are clinical predictors of an adverse prognosis. Tetralogy of Fallot, (TOF) is the most common cyanotic defect after infancy and refers to a combination of four lesions consisting of: 1. An interventricular septal defect 2. Infundibular stenosis with or without valvular pulmonic stenosis 3. An aorta overriding the ventricular septal defect 4. Right ventricular hypertrophy, which is a compensatory response to the other lesions The right ventricular obstruction and large VSD result in a high right ventricular pressure that is similar to left ventricular pressure. When the resistance due to the right ventricular outflow obstruction is greater than systemic vascular resistance, there is a right-to-left shunt, arterial desaturation, and if severe, cyanosis. If the right ventricular outflow obstruction is not severe, there may be little or no right-to-left shunt. The shunt may even be left-to-right, and the pulmonary valve and arteries may be normal or large. This lesion is sometimes referred to as вЂњpinkвЂќ or вЂњacyanoticвЂќ TOF. In TOF, associated abnormalities include a right-sided aortic arch in about 25% of patients. In this anomaly, the aorta arches over the right mainstem bronchus, lies to the right of the trachea and esophagus and descends on the right, and commonly the first branch off the aorta is the left innominate artery. Other associated abnormalities include ASD in 10% and coronary anomalies in 10%. In adult patients with a perimembranous VSD, there can be acquired hypertrophy of right ventricular muscle bundles, resulting in dynamic outflow obstruction with pathophysiology similar to TOF. This entity has been termed вЂњdouble chambered right ventricle.вЂќ Most patients with TOF have had palliative operations or corrective surgery by the time they are teenagers. Occasionally, a patient reaches adulthood without surgery. Sometimes patients present with only palliative systemic to pulmonary arterial shunts such as Blalock-Taussig shunt (subclavian to pulmonary artery), PottsвЂ™ shunt (descending aorta to left pulmonary artery), or WaterstonвЂ™s shunts (ascending aorta to right pulmonary artery). Before surgical correction was possible, most patients died in the 2nd decade of life, although there are reports of rare unoperated and palliated patients who have survived to the 7h decade of life. Total intracardiac repair for TOF usually is successful but has several potential postoperative residua, including residual right ventricular outflow tract (RVOT) obstruction, pulmonary valve regurgitation, peripheral pulmonary artery stenosis of one or both pulmonary arteries, ventricular septal patch leaks and arrhythmias . In the early and intermediate follow-up period, important residual right ventricular outflow tract obstruction appears to be the major source of morbidity and mortality. However, in the late follow-up period, patients in whom a transannular patch was required at the time of initial surgical repair to relieve outflow obstruction are at risk to develop pulmonary insufficiency (PI) with eventual right ventricular failure owing to volume overload and ventricular arrhythmias, disability and even death. Patients in this group who develop moderate to severe pulmonary insufficiency undergo pulmonary valve replacements as adults, but without consistent improvement of RV systolic function postoperatively Overall postoperative survival in patients with TOF is about 90% at about 30 years after surgery. (Excerpts taken from Congenital Heart Disease in the Adult, in International Anesthesiology Clinics, vol 50, number 2, Spring 2012. Rouine-Rapp K, Russell I , and Foster E ) В CARDIAC В AND В NON-ВвЂђCARDIAC В SURGERIES В IN В ADULTS В WITH В CHD В В Most В procedures В performed В in В adults В with В CHD В who В have В not В undergone В previous В surgery В include В ASD В and В VSD, В sinus В venosus В defects В usually В with В partial В anomalous В pulmonary В venous В return, В partial В AV В canal В defects В (cleft В mitral В valve, В primum В ASD), В coarctation В of В the В aorta, В congenitally В corrected В transposition В of В the В great В arteries, В anomalous В coronary В artery В anomalies, В and В aortic В stenosis В (usually В with В bicuspid В aortic В valve) В (Guleserian В KJ В et В al. В В Prog В CV В Dis В 2011). В В В Cardiac В reoperations В are В common В among В adult В patients В with В CHD. В В Valve-ВвЂђrelated В procedures В (surgical/interventional) В are В the В most В frequent В indication В for В intervention В in В adults В with В CHD В (Holst В et В al В Ann В Thorac В Surg В 2013); В in В one В 17-ВвЂђyear В follow-ВвЂђup В study, В valve В operations В increased В 42-ВвЂђ63% В more В than В other В procedures В (Inoseseu В I В et В al, В Ann В Thorac В Surg В 2010). В В Patients В with В cyanosis В (TOF, В transposition В of В the В great В vessels В and В single В ventricle В physiology) В often В have В undergone В several В surgical В or В interventional В procedures В prior В to В adulthood. В В In В patients В with В TOF В who В underwent В placement В of В a В bioprosthetic В valve В in В the В pulmonary В position, В the В 5-ВвЂђyear В freedom В from В (pulmonary) В valve В dysfunction В is В 92% В but В at В 10 В years В decreases В to В 20% В (Wilamarta В et В al, В Cardiol В Young В 2011). В В Up В to В 49% В of В adults В with В CHD В undergo В multiple В sternotomies В (or В thoracotomies), В and В operative В mortality В and В cardiac В injury В during В reoperation В increase В proportionately В with В the В number В of В operative В procedures. В В Mortality В and В morbidity В risk В factors В in В adults В with В CHD В who В undergo В cardiac В surgery В include В presence В of В cardiovascular В disease, В NYHA В functional В class В 3 В or В 4, В and В surgery В on В the В aorta В or В aortic В valve В (Kogon В et В al. В В Ann В Thorc В Surg В 2013). В В Postoperatively, В adults В with В CHD В can В have В short В or В long-ВвЂђterm В sequelae В following В surgery. В В These В include В aortopathy В that В leads В to В dilation, В aneurysm В and В rupture, В ventricular В and В atrial В arrhythmias В following В a В ventriculotomy В or В related В to В CHD, В infective В endocarditis, В residual В shunts, В sudden В cardiac В death, В lung-ВвЂђperfusion В abnormalities, В ventricular В dysfunction, В conduction В defects, В and В pulmonary В hypertension. В В В Non-ВвЂђcardiac В surgery В in В adults В with В CHD В is В increasing В and В includes В cholecystectomy В in В 27% В of В unoperated В cyanotic В patients В (Shlina В Y В et В al. В В Int В J В Cardiol В 2011), В successful В surgical В treatment В for В scoliosis В in В patients В post В surgical В correction В of В CHD В (J В Neuro В urg В Pediatr В 2013), В and В cerebral В abscess В surgery В in В patients В with В cyanotic В lesions. В В In В patients В with В a В single В ventricle В who В have В undergone В total В cavopulmonary В anastomosis, В surgical В repair В of В abdominal В hernias В and В varicose В vein В surgery В is В more В common В (Report В of В the В British В Cardiac В Society В Working В Party. В Heart В 2002;88(Suppl В I):i1вЂ“i14). В В Maternal В death В and В peripartum В mortality В and В morbidity В are В increased В in В women В with В CHD В who В have В a В higher В rate В of В cardiac В complications, В as В well В as В preterm В deliveries В and В cesarean В sections В (Karamlou В et В al. В В Ann В Thorac В Surg В 2011). В В В В ANESTHETIC В IMPLICTIONS В FOR В CYANOTIC В PATIENTS В UNDERGOING В SURGICAL В PROCEDURES В The В anesthetic В implications В for В cyanotic В patients В undergoing В cardiac В and В non-ВвЂђ cardiac В surgical В procedures В are В multiple. В В Antibiotic В prophylaxis В for В infective В endocarditis В (IE) В remains В recommended В in В cyanotic В patients В with В prior В episodes В of В IE, В unrepaired В or В palliated В CHD, В patients В within В 6 В months В of В surgical В repair В of В CHD, В and В patients В who В have В undergone В repair В but В have В residual В defects В at В or В adjacent В to В the В site В of В prosthetic В material. В В (Lytle В W В et В al. В В ACC/AHA В 2008 В guideline В update В on В valvular В heart В disease: В В focused В update В on В infective В endocarditis В В J. Am. Coll. Cardiol. published online Jul 28, 2008) Long-ВвЂђterm В effects В of В cyanosis В include В an В increased В production В of В erythropoietin В that В leads В to В polycythemia В and В associated В morbidities. В The В decrease В in В the В plasma В fraction В of В blood В (~ В HCT В > В 60%), В leads В to В abnormalities В in В coagulation В studies, В such В as В a В pseudoprolongation В of В activated В partial В thromboplastin В time. В Thrombocytopenia В occurs, В platelet В aggregation В is В decreased, В and В reduced В synthesis В of В clotting В factors В all В contribute В to В coagulation В defects В during В cardiac В and В non-ВвЂђ cardiac В surgery В (Cannesson В M В et В al. В В Anesth В 2009, В Hofer В A В et В al. В В Br В J В Anaesth В В 2011). В В Other В factors В that В increase В perioperative В bleeding В include В high В central В venous В pressure В and В development В of В collateral В vessels В between В the В systemic В and В pulmonary В circulation. В В These В collaterals В promote В diastolic В runoff В and В вЂњstealвЂќ В blood В from В the В brain, В kidneys В and В gut. В В In В contrast, В hyperviscosity-ВвЂђrelated В thromboembolic В events В that В lead В to В CNS В abnormalities В can В be В exacerbated В by В perioperative В dehydration. В В Central В and В peripheral В venous В and В peripheral В arterial В access В may В be В limited В such В that В cyanotic В patients В often В require В preoperative В venous В and В arterial В ultrasound В evaluation В of В vessel В patency. В В Ipsilateral В limbs В of В patients В whose В vessels В have В been В used В вЂњupstreamвЂќ В to В create В a В systemic В to В pulmonary В anastomosis В are В not В reliable В sites В to В monitor В blood В pressure В or В oxygen В saturation. В В В Other В comorbidities В in В adults В with В cyanotic В CHD В include В sequelae В mentioned В above, В pulmonary В abnormalities, В and В development В of В Eisenmenger В syndrome В after В long-ВвЂђ standing В exposure В of В the В pulmonary В circulation В to В increased В blood В flow В at В systemic В pressures, В subsequent В irreversible В changes В to В the В pulmonary В vasculature В and В resultant В pulmonary В hypertension. В В As В such, В regulation В of В hemodynamic В changes В during В an В anesthetic В including В maintenance В of В baseline В systemic В and В pulmonary В vascular В resistances, В may В be В crucial В in В some В patients В to В decrease В perioperative В morbidity В and В mortality. В В Interestingly, В coronary В artery В disease В was В not В found В in В cyanotic В patients В with В CHD, В who В have В been В defined В in В one В study В as В вЂњatheroma В freeвЂќ В (Perloff В JK В Curr В Cardiol В Rev В 2012). В В В В RECOMMENDATIONS В FOR В CARE В BY В A В CARDIAC В ANESTHESIOLOGIST В There В are В no В evidence-ВвЂђbased В guidelines В for В this В limited В patient В population В (adults В with В CHD) В but В expert В consensus В is В important В & В includes В the В following. В В В The В consensus В statement В from В the В ACC/AHA В 2008 В Guidelines В for В Management В of В Adults В with В Congenital В Heart В Disease В states В that В surgical В (and В diagnostic В and В interventional) В procedures В that В require В general В anesthesia В or В conscious В sedation В in В adults В with В moderate В or В complex В CHD В should В be В performed В in В a В regional В adult В CHD В center В with В an В anesthesiologist В familiar В with В adult В CHD В patients. В Additional В consensus В recommends В that В adult В patients В with В complex В or В high-ВвЂђrisk В CHD В should В be В transferred В to В an В adult В CHD В center В for В urgent В or В acute В problems. В В Guidelines В also В recommend В a В cardiologist В consultation В prior В to В procedures В in В moderate В to В high-ВвЂђrisk В adults В with В CHD. В В В According В to В these В guidelines, В except В for В patients В with В lesions В considered В simple В (See В below В for В a В listing В of В lesions В of В вЂњsimpleвЂќ В complexity), В one В should В refer В patients В to В regional В centers В for В multidisciplinary В care. В В Although В most В cardiac В anesthesia В fellowships В include В education В about В and В involvement В in В care В of В patients В with В CHD, В the В role В of В the В anesthesiologist В in В the В care В of В these В patients В is В evolving. В В Common В practice В among В several В anesthesiologists В queried В is В that В at В minimum В one В consults В a В cardiac В anesthesia В colleague В when В caring В for В any В adult В with В CHD, В and В most В transfer В patients В with В moderate В or В complex В CHD В to В regional В adult В CHD В centers. В В However, В in В a В recent В report В of В > В 10,000 В adults В with В CHD, В adults В with В CHD В represent В an В increasing В fraction В of В all В non-ВвЂђcardiac В surgery В admissions В to В hospitals, В non-ВвЂђcardiac В surgery В accounted В for В an В increasing В % В of В their В admissions, В and В the В majority В of В these В patients В in В the В database В underwent В surgery В in В nonteaching В hospitals В (Maxwell В et В al, В Anesth В 2013). В В В In В summary, В here В is В a В statement В taken В from В a В recent В editorial В (Cannesson В & В Earing В Anesth В 2013 В & В their В reference В Landzberg В MJ В et В al В В Task В force В 4: В Organization В of В delivery В systems В for В adults В with В congenital В heart В disease. В J В Am В Coll В Cardiol В 2001; В 37:1187вЂ“93). В В вЂњIT В IS В NOW В WIDELY В ACCEPTED В THAT В ANESTHESIOLOGISTS В AND В CARDIOLOGISTS В WITH В SIGNIFICANT В EXPERTISE В WITH В ACHD В SHOULD В MANAGE В PATIENTS В WITH В MODERATE В OR В SEVERE В CONGENITAL В HEART В DISEASE В PRESENTING В FOR В NON-ВвЂђCARDIAC В SURGERY В (PARTICULARLY В THOSE В WITH В POOR В FUNCTIONAL В CLASS, В PULMONARY В HYPERTENSION, В CONGESTIVE В HEART В FAILURE, В AND В CYANOSIS). В В В (Based В on В Table В 1 В from В Cannesson В et В al В Anesth В 2009) В В Adult В patients В with В simple В CHD В В В Unoperated В patients В Isolated В [mild] В defect В of В the В aortic В valve, В mitral В valve В Isolated В defect В of В the В interatrial В septum В Small В isolated В ventricular В septal В defect В В Isolated В mild В pulmonary В valve В stenosis В В Operated В patients В Previously В ligated В or В occluded В ductus В arteriosus В В Repaired В secundum В or В sinus В venosus В ASD В without В residua В Repaired В VSD В without В residua В В В В Heparin Resistance (HR) during cardiac surgery is defined as the inability of an adequate heparin dose to increase the activated clotting time (ACT) to the desired level. Alternatively, heparin resistance is defined as a decrease in the heparin dose response (HDR). Unfortunately, the heparin dose and ACT goal used to define HR in the literature varies greatly. The definition of HR can greatly impact anticoagulation management as many clinicians alter anticoagulation management strategies to reach the desired ACT. The chief concern amongst clinicians managing HR is that failure to optimize anticoagulation during cardiopulmonary bypass (CPB) will result in activation of the coagulation system. At best, this will result in consumption of coagulation factors and potentially contributing to a consumptive coagulopathy. At worst, a catastrophic thrombosis will occur in the CPB circuit. Anticoagulation with heparin has long been the anticoagulant of choice for CPB as it is fast in onset and readily reversed. One of the main disadvantages of heparin is that the anticoagulant response varies amongst patients. Because of this, the ACT is routinely performed during cardiac surgery to ensure adequate anticoagulation. The ACT is a crude test that entails adding a contact activator to a sample of the patientвЂ™s blood and measuring the time that is required for the blood to form a fibrin clot. Although administering heparin prolongs the ACT, the ACT is also affected by many other variables routinely seen during CPB. Because the ACT is not specific to heparin, it remains unclear if decreased heparin responsiveness as measured by the ACT is always a reflection of inadequate anticoagulation. Adding to the complexity of HR is that the mechanism is multifactorial. Traditionally the mechanism of HR has been thought to be related to antithrombin (AT) deficiency. As heparinвЂ™s anticoagulant effect is mediated through AT, a deficiency would thus make heparin less effective as an anticoagulant. However, many patients with HR have normal AT levels and/or do not respond with an increase in heparin responsiveness when supplemented with AT. Thus, there must be a non-AT dependent mechanism for HR. Despite the limitations in our understanding of HR, many clinicians choose to intervene when the target ACT is not achieved. Options for treatment include administering additional heparin and supplementation of AT with either AT concentrate or fresh frozen plasma. Another option for management of HR would be to accept the current ACT and commence CPB without additional treatment. Without a full understanding of HR, the intervention that is chosen may not only be harmful side effects and costly, but lack efficacy. Therefore, a clinician should choose a rational approach to management of HR that takes into consideration all factors related its diagnosis and mechanism. Genetic Predictors of Perioperative Cardiac Outcomes C. David Collard, MD Professor & Chief Texas Heart Institute, St. LukeвЂ™s Hospital, Houston, TX Lecture Learning Objectives: Goals of this refresher lecture will include familiarizing the audience with: 1. Functional genomics and the genome wide association study (GWAS) approach. 2. Understand how functional genomics can be applied to the perioperative period for clinical risk profiling. 3. Review known genetic predictors of adverse perioperative cardiac outcomes. Functional genomics is the branch of genomics that determines the biological function of genes and their products. Specifically, functional genomics attempts to answer questions about the function of DNA at the levels of genes, RNA transcripts, and protein products. In recent years, a well-accepted approach to functional genomics studies is to take a genome-wide look at these questions using highthroughput methods, rather than assessing these questions by evaluating a select group of candidate genes. The genome-wide association study (GWAS) thus has revolutionized functional genomics in the past decade, and has furthered our understanding of the genetic basis of disease. GWAS typically focuses on associations between single-nucleotide polymorphisms (SNPs) and copy number variants (CNVs) with traits like major diseases or adverse clinical outcomes. Prior to the introduction of GWAS, the primary method of investigation was inheritance studies of genetic linkage in families. While this approach has usefulness for the identification of single gene or Mendelian disorders, this approach has limited usefulness for complex diseases that are caused by a combination of genetic, environmental, and lifestyle factors. This gave rise to the candidate gene association study that attempted to address the question of whether an allele of a genetic variant is found more often than expected in individuals with a particular phenotype of interest. However, the candidate gene association study has been rapidly replaced by GWAS in recent years due to the revolution in molecular biology, including the advent of bio-banks, the International HapMap Project, and the development of the rapid, high-throughput methods of genotyping and microarrays (Figure 1). Thus, in contrast to previous candidate gene methods, which specifically tested one or two genetic regions, GWAS investigates the entire genome. The net result in recent years has been an explosion in information for the genetic basis for complex diseases such as heart disease, diabetes, autoimmune diseases, and psychiatric disorders. 1 Figure 1. GWAS Discoveries over Time. (http://www.genome.gov/multimedia/illustrations/Published_GWA_Reports_6-2012.pdf) In general terms, GWAS compares the DNA of two groups: people with the disease or outcome of interest (cases) and similar people without the disease outcome (controls). Each person gives a sample of DNA, from which millions of genetic variants are read using SNP arrays. If one type of the variant (one allele) is more frequent in people with the disease, the SNP is said to be "associated" with the disease. The associated SNPs are then considered to mark a region of the human genome, which influences the risk of disease. Thus, GWAS provides an unbiased approach to identifying SNPs within genetic loci that are associated with the outcome phenotype. One of the advantages of the GWAS approach is that it is unbiased with respect to genomic structure and previous knowledge of the trait etiology, in contrast to candidate gene studies, where knowledge of the trait is used to identify candidate loci contributing to the trait of interest. This allows identification of novel loci and potential new understanding of biology related to disease phenotype. While GWAS studies may identify genetic variants that are associated with a disease or clinical outcome of interest, they do not specify which genes are causal. Additional follow-up studies such as high-throughput DNA and RNA sequencing are now providing tools for understanding how disease loci influence gene expression. Indeed, recently a new class of polymorphisms called expression quantitative trait loci (eQTL) were identified. These variants associate with gene expression levels but have been hard to map because they act from unpredictably long distances from causative genes, often from different chromosomes. Nonetheless, 2 DNA and RNA sequencing is becoming a useful tool for helping with mechanistic understanding of GWAS generated data. The number of SNPS interrogated in GWAS is often greater than a million. Additionally, clinical variables that could potentially confound the resultant genetic associations have to be accounted for, including gender, age, ethnicity and pertinent medical history. Whether the allele frequency is significantly altered between the GWAS case and control groups is determined by a statistically derived odds ratio. Needless to say, these computations are derived from very large datasets and generally should be preformed by individuals with expertise in genetic statistics using specialized bioinformatics software. After all of the SNP odds ratios and P-values have been calculated, magnitude of genetic associations for the entire large dataset of SNPs are commonly displayed in a вЂњManhattan plotвЂќ (Figure 2). This plot typically shows the negative logarithm of the P-value as a function of genomic location. Thus, the SNPs with the most significant association stand out. As millions of tests are performed, the results must be adjusted to control for false positives. Thus, for 1 million SNPs tested, a GWAS threshold for significance is frequently thought to be P< 5 Г— 10вЂ“8. Moreover, a well-conducted GWAS typically performs the first analysis in a discovery cohort, followed by validation of the most significant SNPs in independent replication cohort. Figure 2. Manhattan plot of genetic variants associated with ventricular dysfunction after primary coronary artery bypass graft surgery. The вЂ“log P value of the allelic genetic model for each SNP according to location on the 22 autosomal chromosomes. Horizontal line indicates the 5 X10-8 P value threshold for genome-wide significance (PLoS ONE 2011 Sept 6(9): e24593). 3 Using GWAS coupled with DNA and RNA sequencing techniques, an exciting picture is emerging of unanticipated genetic overlap between what had initially been thought to be unrelated diseases and traits. To date, over 1,200 human GWA studies have examined over 200 diseases and traits, and almost 4,000 SNP associations have been found. However, the vast majorities of GWAS studies to date have been conducted in ambulatory patients and have not addressed perioperative outcomes. This session will review what is currently known about genetic predictors of perioperative cardiac outcomes. References Nat Rev Genet. 2012 Jan 18;13(2):135-45. PLoS ONE 2011 Sept 6(9): e24593. Nat Rev Genet. 2013 Jul;14(7):483-95. J Hum Genet. 2013 Nov 7; epub ahead of print. Am J Hum Genet. 2012 Jan 13;90(1):7-24. Genetics 2011 Feb 187: 367вЂ“383. Arterioscler Thromb Vasc Biol. 2012 32:169 4 TOPIC: В В Risk В Factors В and В Outcomes В for В Postoperative В Delirium В in В Post В Cardiac В Surgical В Patients В В AUTHOR: В В Allen В N. В Gustin, В Jr., В M.D., В F.C.C.P. В В Learning В Objectives: В В After В attending В this В session, В each В participant В will В be В better В able В to В do В the В following: В В 1. В В Describe В the В scope В of В delirium В in В the В cardiac В surgery В population В 2. В В Recognize В modifiable В and В non-ВвЂђmodifiable В risk В factors В for В delirium В in В cardiac В surgery В 3. В В List В the В effect В of В benzodiazepines В on В delirium В and В outcomes В in В the В critically В ill В В В Presentation В Outline: В В 1. Introduction В to В Delirium: В В В a. Definition В of В delirium В b. Detection В of В delirium В В В c. Problems В with В the В delirium В evaluation В В В 2. DDSM В IV В and В CAM В ICU В criteria В 3. Adult В and В Pediatric В Studies В 4. Delirium В Outcomes В 5. Delirium В due В to В Cardiac В Surgery В 6. Risk В factors В for В Postop В Post В Cardiac В Surgery В Delirium В a. Cerebral В oximetry В 7. Prediction В of В Delirium В 8. Prevention В of В Delirium В a. Risperidone В 9. Modifiable В Risks В for В Delirium В in В the В ICU В 10. Benzodiazepines В and В Use В in В the В ICU В Patient В Population В В В Introduction В to В Delirium: В В В В Delirium В is В defined В as В an В acute В cognitive В disorder В presenting В in В patient В where В fluctuations В in В cognition, В apathy, В and В non В organized В thinking.(1) В В Delirium В includes В alterations В in В attention, В cognition, В consciousness, В and В perception; В and В is В often В associated В with В changes В in В sleep В patterns.(2) В В The В main В characteristic В of В delirium В is В inattention. В В It В can В also В be В termed В intensive В care В unit В (ICU) В psychosis В or В ICU В delirium. В В Delirium В is В categorized В as В either В hyperactive В or В hypoactive.(1) В В Hyperactive В delirium В puts В the В patient В at В greater В risk В of В self-ВвЂђextubation, В of В accidental В removal В of В life В saving/invasive В catheters, В and В of В worsening В patient В ventilator В synchrony.(1) В В On В the В other В hand, В hypoactive В delirium В can В result В in В a В quiet В but В neglected В patient В given В the В decreased В motion В (hypoactive В delirium В suggests В a В worse В prognosis).(1) В В CAM В ICU В (Confusion В Assessment В Method В of В the В ICU) В is В most В commonly В used В to В evaluate В the В prevalence В of В delirium, В though В many В studies В will В also В use В the В DSM В IV В Criteria В for В Delirium. В В В Problems В with В delirium В research В in В the В perioperative В period В can В be В difficult. В Multifactorial В issues В make В it В difficult В to В distinguish В between В emergence В delirium В from В anesthesia В and В the В other В forms В of В delirium.(2) В В One В paper В considered В delirium В after В cardiac В surgery В to В be В quite В distinct В from В other В forms В of В delirium В for В the В following В reasons: В В 1. В В Different В surgical В populations В have В different В medication В profiles В and В require В different В anesthesia В techniques В (thus В pharmacological В triggers В of В delirium В will В vary В depending В on В the В surgery), В В 2. В В The В use В of В cardiopulmonary В bypass В in В cardiac В surgeries В requires В special В consideration В since В its В use В is В associated В with В postoperative В effects В on В neurotransmitter В function В and В an В increase В in В delirium, В and В 3. В В It В is В unknown В if В the В pathophysiology В of В different В postoperative В deliria В differs В (research В has В shown В that В predictors В of В delirium В appear В to В vary В depending В on В the В surgery В type В and В the В levels В of В various В biomarkers В for В delirium).(2) В В Overall, В postoperative В post В cardiac В surgical В delirium В appears В to В be В the В result В of В a В complex В interplay В of В preexisting В predisposing В risk В factors В and В peri/post В operative В risk В factors.(3) В В Preoperative В cognitive В dysfunction В (reported В to В be В 17.8% В in В cardiac В surgery) В had В been В identified В as В a В major В predisposing В risk В factor В for В delirium В in В some В studies В but В has В not В been В identified В as В a В risk В in В others.(3) В В В Confusion В Assessment В Method В of В the В ICU В (CAM В ICU) В and В DSM В IV В Criteria В for В Delirium: В В Regarding В the В existing В delirium В research, В one В of В the В two В following В methods В is В used В for В the В detection В of В delirium В in В ICU В patients: В В CAM В ICU В method В and В the В DSM В IV В Criteria. В В В В CAM В ICU: В В Presented В as В a В worksheet В for В healthcare В providers В to В fill В out. В В Four В Features В are В included В in В the В assessment.(4) В В Feature В 1: В В Acute В Onset В or В Fluctuating В Course. В В Is В the В patient В different В than В his/her В baseline В mental В status? В В OR В has В the В patient В had В any В fluctuation В in В his/her В mental В status В in В the В past В 24 В hours В as В evidenced В by В fluctuation В on В a В sedation В scale В (RASS=Richmond В Agitation В Sedation В Scale), В GCS В (Glascow В Coma В Scale), В or В previous В delirium В assessment? В В Feature В 2: В В Inattention. В В This В Feature В uses В the В Letters В Attention В Test. В В Directions В for В the В healthcare В provider: В В Say В to В the В patient, В вЂњI В am В going В to В read В you В a В series В of В 10 В letters. В В Whenever В you В hear В the В letter В вЂ�A,вЂ™ В indicate В by В squeezing В my В hand.вЂќ В В Read В the В letters В from В the В following В letter В list В in В a В normal В tome В 3 В seconds В apart: В В SAVEAHAART. В В Errors В are В counted В when В a В patient В fails В to В squeeze В on В a В letter В вЂњAвЂќ В and В when В the В patients В squeezes В on В any В letter В other В than В вЂ�A.вЂќ В В В В В Feature В 3: В В Altered В Level В of В Consciousness. В В Present В if В the В Actual В RASS В (Richmond В Agitation В Sedation В Score) В is В anything В other В than В alert В and В calm В (equates В to В a В RASS В = В 0). В Feature В 4: В В Disorganized В Thinking. В В This В feature В uses В both В a В series В of В yes/no В questions В AND В a В command. В В The В yes/no В questions В include В the В following В four В questions: В В 1. В В Will В a В stone В float В on В water? В В 2. В В Are В there В fish В in В the В sea? В В 3. В В Does В one В pound В weigh В more В than В two В pounds? В В 4. В В Can В you В use В a В hammer В to В pound В a В nail? В В Errors В are В counted В when В the В patient В incorrectly В answers В a В question. В В The В command В includes В the В following: В В Say В to В the В patient, В вЂњhold В up В this В many В fingersвЂќ В (hold В 2 В fingers В in В front В of В the В patient). В В вЂњNow В do В the В same В thing В with В the В other В handвЂќ В В An В error В is В counted В if В patient В is В unable В to В complete В the В entire В command. В В В В Scoring В for В CAM В ICU: В В 1 В plus В 2 В and В either В 3 В or В 4 В present В = В CAM В ICU В positive В В The В American В Psychiatric В AssociationвЂ™s В Diagnostic В and В Statistical В Manual В 4th В Edition В (DSM В IV) В Criteria В for В Delirium В (5): В В A. Disturbance В of В consciousness В (reduced В clarity В of В awareness В of В the В environment) В with В reduced В ability В to В focus, В sustain, В or В shift В attention. В B. A В change В in В cognition В or В the В development В of В a В perceptual В disturbance В that В is В not В better В accounted В for В by В a В pre-ВвЂђexisting, В established, В or В evolving В dementia. В C. The В disturbance В developed В over В a В short В period В of В time В (usually В hours В to В days В and В tends В to В fluctuate В during В the В course В of В the В day. В D. There В is В evidence В from В the В history, В physical В examination В or В laboratory В findings В that В the В disturbance В is В caused В by В the В direct В psychological В consequences В of В a В general В medical В condition. В В В Studies В Focusing В on В Delirium В in В Adults: В В В Predominately В only В adult В research В exists В on В the В topic В of В post В cardiac В surgical В delirium. В В В Studies В Focusing В on В Pediatrics: В В No В prospective, В randomized, В or В cohort В research В studies В looking В at В pediatric В patients В and В postoperative В delirium В were В identified. В В В Delirium В as В it В Applies В to В Patient В Outcomes: В В В В Delirium В in В ICU В patients В in В the В postoperative В period В from В cardiac В surgery В varies В from В 8.4% В to В 41.7%.(1) В Delirium В in В ICU В patients В postoperatively В has В shown В to В increase В ICU В mortality, В increase В length В of В ICU В stay, В and В increase В ICU В costs.(1,2,3) В В In В patients В who В are В post В cardiac В surgery, В delirium В can В increase В postoperative В complications В such В as В respiratory В insufficiency, В sternum В instability, В and В need В for В reoperation В of В the В sternum.(1) В В In В one В study, В delirium В was В present В in В 23.5% В of В postoperative В cardiac В surgical В patients В В and В the В risk В of В delirium В was В higher В in В older В patients, В those В who В had В cardiopulmonary В bypass, В those В with В atrial В fibrillation, В В and В those В with В a В history В of В stroke В (cerebrovascular В accident).(1) В В The В mean В time В on В the В mechanical В ventilator В for В patients В with В delirium В was В more В than В in В patients В without В delirium.(1) В В Increased В length В of В stay В in В both В the В ICU В and В in В the В hospital В has В been В seen В in В patients В with В postoperative В cardiac В surgical В patients В with В delirium.(3) В В Patients В with В delirium В in В the В ICU В had В increased В rates В of В cognitive В defects В after В discharge В from В the В hospital.(3) В В Patients В who В had В delirium В post В cardiac В surgery В had В a В mortality В that В was В higher В (than В those В without В delirium) В for В one В year В after В the В ICU В stay.(3) В В В Risk В Factors В for В Delirium: В В Older В age В (1,3,6,>60 В in В 7,>60 В in В 8,>65 В in В 9,>65 В in В 10) В History В of В CVA В (1,3,7,10,11) В Prolonged В mechanical В ventilation В (1,6,8,>24 В hours В in В 10) В Atrial В fibrillation В (1,6,9,11) В Episodes В of В major В depressive В disorder В (variable В in В 2,6,7) В Cardiopulmonary В bypass В (1,duration В of В CPB В in В 3) В Preoperative В Cognitive В impairment В (6,7) В Diabetes В (not В in В 1,yes В in В 9) В Hypertension В (9,11) В Intraoperative В fentanyl В (2) В Intraoperative В ketamine В (2) В Preoperative В antipsychotics В (2) В Postoperative В inotropes В (2) В Lower В MMSE В (Mini В Mental В Status В Exam) В scores В (3) В Emergency В cardiac В surgery В (9) В Peripheral В vascular В disease В (9) В Abnormal В serum В albumin В (7) В Postop В SIRS В (3) В Use В of В intra В aortic В balloon В pump В (9) В Intraoperative В hemofiltration В (9) В Operation В time В > В 3 В hours В (11) В Alcohol В abuse В (11) В Anemia В (6) В Higher В C В Reactive В Protein В postop В (3) В Infection В after В surgery В (10) В Hematocrit В < В 30 В (10) В Duration В of В cardiopulmonary В bypass В (8) В Preoperative В use В of В an В antipsychotic В for В one В year В (2) В Nicotine В abuse В (3) В В В Cerebral В Oximetry В for В Delirium В Risk В for В On-ВвЂђPump В Cardiac В Surgery: В (12) В В A В total В of В 231 В patients В were В scheduled В for В elective В cardiac В surgery В and В enrolled В into В this В study. В В ICU В delirium В was В assessed В by В the В CAM В ICU В criteria В on В the В first В three В ICU В days В after В cardiac В surgery. В В ScO2 В (cerebral В oximetry) В values В were В obtained В on В the В day В before В surgery, В immediately В before В surgery, В and В throughout В the В surgical В procedure. В В Preoperative В cognitive В function, В demographics, В surgery В related/intraoperative/postoperative В physiological В data В were В all В registered. В В Patients В with В delirium В had В lower В pre В and В intra-ВвЂђoperative В ScO2 В readings, В were В older, В had В lower В mental В status В examination В scores, В and В lower В preoperative В hemoglobin В levels. В В The В binary В regression В identified В older В age, В lower В MMSE, В neurological В or В psychiatric В disease, В and В lower В preoperative В ScO2 В as В independent В predictors В of В postoperative В delirium. В В Thus, В a В low В preoperative В ScO2 В is В associated В with В postoperative В delirium В after В on В pump В cardiac В surgery. В В В В В Prevention В of В Delirium: В В A В great В deal В of В emphasis В has В been В placed В on В trying В to В determine В if В delirium В can В be В prevented. В В Efforts В to В evaluate В the В effects В of В perioperative В medications В on В the В incidence В of В delirium В has В been В receiving В the В greatest В focus.(2) В В Given В the В changes В in/excess В of В neurotransmitters В like В dopamine, В norepinephrine, В and В epinephrine В in В the В perioperative В state, В attention В is В being В focused В on В pharmacology В as В a В means В of В modifying В the В risks В for В postoperative В delirium.(2) В В Attention В has В been В paid В to В drugs В that В have В anticholinergic В properties В (digoxin, В furosemide, В or В nefedipine) В that В might В play В a В role В in В delirium.(2) В В Also, В selective В serotonin В reuptake В inhibitors В (SSRIs), В antipsychotics, В and В benzodiazepines В may В also В play В important В contributors В to В delirium В etiology В though В neurotransmitter В pathways.(2) В В One В drug, В postoperative В risperidone В (taken В upon В awakening)(2) В has В shown В to В help В in В the В prevention В of В postoperative В post В cardiac В surgical В delirium. В В Preoperative В drug В administration. В В В Mixed В results В on В drug В effect В on В postoperative В delirium В were В seen В with В the В following В drugs: В В statins, В anticholinergic В agents, В antidepressants, В selective В serotonin В reuptake В inhibitors В (SSRI), В and В benzodiazepines. В В No В effect В on В postoperative В delirium В was В seen В for В the В use В of В cholinesterase В inhibitors, В opioids, В diuretics, В calcium В channel В blockers, В Beta В blockers, В ACE В inhibitors, В angiotensin В receptor В blockers, В Nitrates, В or В benzodiazepines. В В Increased В risk В of В postoperative В delirium В was В seen В when В antipsychotics В were В used В in В a В patient В in В the В weeks В that В led В up В to В the В date В of В surgery.(2) В В Intraoperative В drug В administration. В В No В effect В on В postoperative В delirium В was В seen В with В intraoperative В diazepam. В В Mixed В results В have В been В seen В with В fentanyl. В В Possible В decreased В incidence В of В postoperative В delirium В has В been В seen В with В ketamine.(2) В В Postoperative В administration В of В these В drugs: В В Mixed В results В were В seen В for В effects В on В postoperative В delirium В with В the В use В of В dexmedetomidine. В В No В effect В on В postoperative В delirium В was В seen В with В the В use В of В morphine В or В opioids. В В Increased В risk В of В postoperative В delirium В was В seen В with В the В use В of В inotropes В postoperatively.(2) В В Prophylactic В regimens: В В Decreased В incidence В of В postoperative В delirium В with В the В immediate В postoperative В use В of В risperidone.(4) В В В Prevention В of В Delirium В postoperatively В with В Risperidone:(4) В В Randomized В double В blind В placebo В controlled В study В of В 126 В patients В after В cardiopulmonary В bypass. В В Patients В were В to В receive В either В 1 В mg В of В risperidone В (sublingual В administration) В or В placebo В when В they В regained В consciousness В in В the В ICU. В В Patients В were В assessed В for В delirium В using В the В CAM В ICU. В В The В incidence В of В postoperative В delirium В was В 11% В percent В in В the В risperidone В group В versus В 31% В in В the В control В group В (P В = В 0.009). В В Many В other В perioperative В factors В were В associated В with В postop В delirium В but В there В was В no В statistical В difference В between В the В two В groups В regarding В these В factors. В В Final В outcome: В В one В dose В of В risperidone В administered В relatively В soon В after В cardiac В surgery В reduced В the В incidence В of В postoperative В delirium. В В В В В В Prediction В of В Delirium: В В One В study В was В able В to В predict В postoperative В post В cardiac В surgical В delirium В using В the В combination В of В age, В Mini В Mental В Status В Exam В score, В and В length В of В cardiopulmonary В bypass В with В a В sensitivity В of В 71.2% В and В a В specificity В of В 26%.(3) В В В Dexmedetomidine В Versus В Midazolam В for В Sedation В in В ICU В Patients: В (13) В В ICU В Study: В В Randomized В prospective В double В blind В trial В in В 5 В countries В for В two В years. В В Sedation В for В ICU В patients. В В RASS В and В CAM В ICU В were В used В for В assessment В of В delirium. В В RASS В was В targeted В to В -ВвЂђ2 В to В 1. В В Primary В outcome В was В the В target В RASS В range. В В Other В outcomes: В В duration В of В mechanical В ventilation, В ICU В length В of В stay, В and В adverse В events. В В В В Results: В В No В difference В between В both В drugs В regarding В the В time В within В the В target В RASS В range. В В The В prevalence В of В delirium В during В treatment В was В 54% В in В the В dexmedetomidine В group В versus В 76.% В in В the В midazolam В treated В patients. В В Time В to В extubation В after В the В procedure В was В 1.9 В days В shorter В in В the В dexmedetomidine В treated В patients В and В the В ICU В stay В was В similar В between В the В two В groups. В В Dexmedetomidine В treated В patients В were В more В likely В to В develop В bradycardia В with В a В non-ВвЂђsignificant В increased В need В to В treat В the В bradycardia. В В Overall, В no В difference В between В dexmedetomidine В and В midazolam В were В found В as В related В to В time В at В targeted В sedation В level В in В mechanically В ventilated В ICU В patients. В В At В comparable В sedation В levels, В dexmedetomidine В treated В patients В spent В less В time В on В the В ventilator, В experienced В less В delirium, В and В developed В less В tachycardia/hypertension. В В В В В Lorazepam В is В an В Independent В Risk В Factor В for В Determining В to В Delirium В in В Intensive В Care В Unit В Patients(14) В В This В was В a В cohort В study В in В order В to В investigate В whether В sedative В and В analgesic В mediations В independently В increased В the В probability В of В daily В transition В to В delirium. В В A В total В of В 198 В mechanically В ventilated В patients В were В enrolled В to В determine В the В probability В of В delirium В as В a В function В of В sedative В and В analgesic В dose В during В a В drugвЂ™s В administration В during В the В previous В 24 В hours. В В В Lorazepam В was В an В independent В risk В factor В for В daily В transition В to В delirium В (OR В 1.2; В P В = В 0.003); В whereas В fentanyl, В morphine, В and В propofol В were В associated В with В higher В but В not В statistically В significant В odds В radios. В В Increasing В age В and В Acute В Physiology В and В Chronic В Health В Evaluation В II В (APACHE В II) В scores В were В also В independent В predictors В of В transitioning В to В delirium. В В Lorazepam В administration В is В an В important В and В potentially В modifiable В risk В factor В for В transitioning В into В delirium В even В after В adjusting В for В relevant В covariates. В В В В В В Modifiable В Risk В Factors В in В the В Cardiac В Surgical В ICU: В (15) В В This В is В a В prospective В observational В study В involving В 200 В patients В in В a В cardiovascular В ICU. В В Patients В include В both В postoperative В cardiac В surgical В and В cardiology В ICU В patients. В В Delirium В occurred В in В 26% В of В the В cardiology В and В cardiac В surgical В patients. В В Almost В 92% В of В the В patients В with В delirium В had В the В hypoactive В form. В В Patients В were В prone В to В delirium В when В exposed В to В benzodiazepines В (OR В 2.6, В p=0.02) В or В when В restraints В were В used В (OR В 2.9, В p<0.01) В during В the В stay В in В the В cardiac В surgical В ICU. В В Hemodynamic В status В was В not В associated В with В delirium В in В this В study. В В Thus, В benzodiazepine В use В and В use В of В restraints В were В the В only В two В modifiable В risk В factors В identified В for В reducing В the В incidence В of В postoperative В post В cardiac В surgical В delirium. В В В В В Conclusions: В В Few В modifiable В risk В factors В have В been В identified В that В could В reduce В the В likelihood В of В postoperative В post В cardiac В surgical В ICU В delirium. В В One В should В consider В the В avoidance В of В benzodiazepines В for В sedation, В the В avoidance В of В restraints В in В the В ICU В after В cardiac В surgery, В the В use В of В risperidone В in В the В postoperative В period, В and В control В of В atrial В fibrillation В as В a В means В of В reducing В the В likelihood В of В delirium В after В cardiac В surgery.(1,4,6,9,11,15) В В No В single В prediction В tool В for В delirium В is В going В to В be В 100%. В В However, В knowledge В of В all В risk В factors В will В be В there В to В help В identify В patients В at В risk.(3) В В В В В References: В В В В 1. Shadvar В K, В Baastani В F, В Mahmoodpoor В A, В Bilehjani В E. В В Evaluation В of В the В prevalence В and В risk В factors В of В delirium В in В cardiac В surgery В ICU, В Journal В of В Cardiovascular В Thoracic В Research, В 2013: В 5(40): В 157 В to В 161. В 2. Lurdes, В TS, В Schwartz В SK, В Bowering В JB, В Moore В RL, В Burns В KD, В Richford В CM, В Osborn В JA, В Barr В AM. В В Pharmacological В Risk В Factors В for В Delirium В after В Cardiac В Surgery: В A В Review. В В Current В Neuropharmacology, В 2012; В 10:181-ВвЂђ196. В 3. Guenthar В U, В Theuerkauf В N, В Frommann В I, В Brimmers В K, В Malik В R, В Stori В S, В Scheidemann В M, В Putensen В C, В Popp В J. В В Predisposing В and В Precipitating В Factors В of В Delirium В after В cardiac В surgery. В В A В Prospective В Observational В Cohort В Study. В В В Annals В of В Surgery, В 2013 В 257(6): В 1160-ВвЂђ В 4. Webpage: В В www.icudelirium.org/docs/CAM_ICU_worksheet.pdf. В В Accessed В on В January В 10, В 2014. В 5. Webpage: В В www.wai.wisc.edu/pdf/phystoolkit/diagnosis/DSM-ВвЂђ IV_Criteria_Delirium.pdf. В В Accessed В on В January В 10, В 2014. В 6. Kazmierski В J, В Knowman В M, В Banch В M, В Fendler В W, В Okonski В P. В В Incidence В and В predictors В of В delirium В after В cardiac В surgery: В В Results В form В the В IPDACS В Studey. В В J В Psychosom В Re В 2010; В 69:179-ВвЂђ185. В 7. Rudolph В YL, В Jones В RN, В Levkoff В SE, В Rockett В C, В Inouye В SK, В Selke В FW. В В Derivation В and В validation В of В a В preoperative В prediction В rule В of В delirium В of В cardiac В surgery. В В Circulation В 2009; В 119:229-ВвЂђ36. В 8. Reissmuller В V, В Aguero В TH, В Vander В LJ. В В Preoperative В mild В cognition В dysfunction В predicts В risk В for В post В operating В delirium В after В elective В cardiac В surgery. В В Aging В Clin В Exp В Res В 2007;19:172-ВвЂђ7. В 9. Norkiene В I, В Misiurience В I, В Bubulis В R. В Incidence В and В precipitating В factors В of В coronary В artery В bypass В grafting. В В Scan В Cardiovasc В J В 2007;74:188-ВвЂђ5. В 10. Chang В YL, В Tsai В YF, В Liuc В Y. В В Prevalence В and В risk В factors В for В postoperative В delirium В in В a В cardiovascular В intensive В care В unit. В Am В J В Crit В Care В 2008:17:31-ВвЂђ 50. В 11. Banach В M, В Kazmierski В J, В Kowman В M, В Okonski В PK, В Sobow В T, В Kloszewska В I, В et В al. В В Atrial В fibrillation В as В a В non-ВвЂђpsychiatric В predictor В of В delirium В after В cardiac В surgery. В В Med В Sci В Monit В 2008;14:CR286-ВвЂђ291. В 12. Schoen В J, В Meyerrose В J, В Paramann В H, В Heringlake В M, В Hueppe В M, В Berger В KU, В Preoperative В regional В cerebral В oxygen В saturation В is В a В predictor В of В postoperative В delirium В in В on-ВвЂђpump В cardiac В surgery В patients: В a В prospective В observational В trial. В В Critical В Care В 2011; В 15:R218. В 13. Riker В RR, В Shehabi В Y, В Bokesch В R, В Cersao В D, В Wismandle В W, В Koura В F, В Fhitten В P, В Marolis В B, В Byrne В D, В Ely В WE, В Rocha В M В (SEDCOM: В Safety В and В Efficacy В of В Dexmedetomidine В Compared В with В Midazolam) В Study В Group. В В Dexmedetomidine В vs В Midazolam В for В sedation В of В critically В ill В patients: В В a В randomized В trial, В JAMA В 2009; В 301(5):489-ВвЂђ499. В 14. Pandharipande В P, В Shintani В A, В Petermson В J В et В al. В В Lorazepam В is В an В independent В risk В factor В for В transitioning В to В delirium В in В intensive В care В unit В patients. В В Anesthesiology. В В 2006; В 104:21-ВвЂђ26. В 15. McPherson В JA, В Wagner В CE, В Boehm В LM, В Hall В JD, В Johnson В DC, В Miller В LR, В Burns, В KM, В Thompson В JL, В Shintani В AK, В Ely В EW, В Pandhvaripande В PP. В В Delirium В in В the В Cardiovascular В ICU: В В Exploring В Modifiable В Risk В Factors. В В Critical В Care В Medicine В 2013; В 41:405-ВвЂђ413. В В В В It is Time to Perform Benzodiazepine-free Cardiac Surgery Pratik P. Pandharipande, M.D., MSCI Professor of Anesthesiology, Critical Care Vanderbilt University Medical Center Email: email@example.com Delirium is an acute disturbance of consciousness accompanied by inattention, disorganized thinking, and perceptual disturbances that fluctuates over a short period of time. The incidence of delirium following coronary artery bypass grafting (CABG) and other cardiac surgeries varies from 20 to 40%, and is associated with longer hospital stays, readmissions, poor cognitive and functional outcomes, and mortality. Delirium is thought to be multifactorial, and contributing sources can be summarized as patient related factors (e.g. age, previous dementia, etc.) or iatrogenic risk factors (e.g. psychoactive medications, hypoxemia, etc.) Of these risk factors, benzodiazepines and opiates are potentially modifiable and have been implicated in the development of delirium in a number of ICU and non-ICU patients. Numerous studies have examined risk factors and predictors of delirium and cognitive dysfunction following cardiac surgery. Increasing age, cerebrovascular disease (e.g. prior stroke), peripheral vascular disease, smoking, atrial fibrillation, renal dysfunction, diabetes mellitus, and heart failure (ejection fraction < 40%) are patient characteristics found to be associated with increased risk of postoperative delirium. Perioperative factors that led to increased likelihood of delirium included preoperative cardiogenic shock, emergent operation, operative time > 3 hours, longer cardiopulmonary 1 bypass (CPB) time, balloon pump support, hypothermia, hypoxemia, and high perioperative transfusion requirements. More recently, in a prospective cohort of patients admitted to the CVICU after cardiac surgery, benzodiazepines received in the immediate perioperative period conferred a 3-fold increase in the risk of developing delirium. Benzodiazepines and other immobilization devices were risk factors for further daily development of delirium. Given emergence of strong data implicating benzodiazepines in delirium in non-cardiac and now cardiac surgical patients, it is imperative for us to consider this risk factor since it may be the one that we can control and can therefore potentially modify. The objectives of presentation will be to inform the audience of the deleterious effects of delirium, to demonstrate that benzodiazepines are modifiable risk factors and to share data where non-benzodiazepine sedation paradigms have been associated with better outcomes in critically ill patients. References 1. Koster S, Oosterveld FG, Hensens AG, Wijma A, van der Palen J. Delirium after cardiac surgery and predictive validity of a risk checklist. Ann Thorac Surg 2008;86:1883-1887. 2. Rolfson DB, McElhaney JE, Rockwood K et al. Incidence and risk factors for delirium and other adverse outcomes in older adults after coronary artery bypass graft surgery. Can J Cardiol 1999;15:771-776. 3. Newman MF, Kirchner JL, Phillips-Bute B et al. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Engl J Med 2001;344:395-402. 4. Marcantonio ER, Juarez G, Goldman L et al. The relationship of postoperative delirium with psychoactive medications. JAMA 1994;272:1518-1522. 5. Dubois MJ, Bergeron N, Dumont M, Dial S, Skrobik Y. Delirium in an intensive care unit: a study of risk factors. Intensive Care Med 2001;27:1297-1304. 6. Pandharipande P, Cotton B, Shintani A et al. Prevalence and Risk Factors for Development of Delirium in Surgical and Trauma Intensive Care Unit Patients. Journal of Trauma 2008;65:34-41. 2 7. Pandharipande P, Shintani A, Peterson J et al. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology 2006;104:21-26. 8. Morrison RS, Magaziner J, Gilbert M et al. Relationship between pain and opioid analgesics on the development of delirium following hip fracture. J Gerontol A Biol Sci Med Sci 2003;58:76-81. 9. Bucerius J, Gummert JF, Borger MA et al. Predictors of delirium after cardiac surgery delirium: effect of beating-heart (off-pump) surgery. J Thorac Cardiovasc Surg 2004;127:57-64. 10. Giltay EJ, Huijskes RV, Kho KH, Blansjaar BA, Rosseel PM. Psychotic symptoms in patients undergoing coronary artery bypass grafting and heart valve operation. Eur J Cardiothorac Surg 2006;30:140-147. 11. Ho PM, Arciniegas DB, Grigsby J et al. Predictors of cognitive decline following coronary artery bypass graft surgery. Ann Thorac Surg 2004;77:597-603. 12. Katznelson R, Djaiani GN, Borger MA et al. Preoperative use of statins is associated with reduced early delirium rates after cardiac surgery. Anesthesiology 2009;110:6773. 3 1 CON: Anesthetic Choice Makes no Difference in Delirium in Cardiac Surgery Hilary P. Grocott, MD, FRCPC, FASE Professor, Departments of Anesthesia & Perioperative Medicine and Surgery University of Manitoba Winnipeg, Manitoba, Canada A spectrum of adverse neurologic outcomes manifest in the early postoperative period in patients having undergone cardiac surgery. Though stroke can present as a dramatic neurologic catastrophe, it thankfully remains an uncommon, though highly relevant, event with an incidence generally under 5%. (1) Other more subtle adverse outcomes, such as postoperative cognitive dysfunction (POCD) have received considerable attention. (2,3) Somewhere between stroke and POCD, lay other encephalopathic states, with delirium being most notable. Delirium is one of the most common acute neurologic consequences of cardiac surgery but has a widely variable incidence. This variability (reported from 5-80%), is in part due to differences in patient risk factors, but is also due to differences in the diagnostic criteria used to define it. (4-8) When it does occur, it has been associated with significant major morbidity as well as mortality. (9,10) Coupled with this, delirium results in a substantive increase in the utilization of healthcare resources. (11) As a result, post-cardiac surgery delirium is a common problem of major significance impacting quality of recovery, morbidity and mortality, as well as healthcare costs. (9,11,12) Best characterized as a neurobehavioral syndrome resulting from an ill-defined but fluctuating disruption of normal neural activity, delirium is further defined by its acute onset, altered level of consciousness, and inattention. (13) The contemporary diagnosis of post-cardiac surgery delirium relies on either objective measures such as the confusion assessment method вЂ“ intensive care unit (CAM-ICU) (11,14), or on ill-defined and arguably non-specific postoperative encephalopathy (with or without the need for treatment), which likely underestimates the incidence considerably. (15) Formal use of the Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-V) criteria have been used (16), but the utility of readily available bedside screening tools, such as CAM-ICU, have substantially enhanced our ability to focus efforts on this distressing clinical entity. The etiology and pathophysiology of delirium is incompletely defined but is undoubtedly both complex and multifactorial. (17) A number of potential contributing pathophysiologic mechanisms may precipitate and cause delirium, including cerebral ischemia (18), physiologic stress (19), altered neurotransmitter (notably the acetylcholine balance with dopamine) levels (20-22), inflammatory cytokines (23), and other interneural signal transduction abnormalities. (24,25) The complexity (and associated uncertainty) of its pathophysiology has made identification of therapeutic options difficult. Though many studies have attempted to reduce the incidence and severity using both pharmacologic and non-pharmacologic approaches (26), few have had any meaningful success. Despite its enormous significance, unfortunately few, if any, preventative or therapeutic strategies are available to meaningfully address it. The choice of anesthetic agent is no different and there is little convincing data to suggest it can make a difference. The premise that anesthetic agents can have an impact on the incidence of delirium after cardiac surgery is predicated on an assumption that events occurring intraoperatively can have direct bearing on the 2 subsequent development of delirium. However, the pathophysiology of delirium is sufficiently complex that it is overly simplistic to think that a single anesthetic drug (or avoidance of any on drug), administered in the intraoperative setting could have a lasting effect for the duration of the patientвЂ™s postoperative course. With the etiology of delirium being multifactorial, no single drug or nondrug therapy is likely to be sufficiently robust to prevent this troublesome illness. This does not mean that studies should not be targeted to address this issue; rather, one must be realistic in their expectations of what these trials might offer. There are some studies, mostly observational in nature, that have attempted to address this issue. If there were to be a drug that had an impact, either positive, but more likely negative, it is likely that it would be one of the fixed agents such as benzodiazepines or opiates that we coadminister that might be contributing. It is unlikely that any volatile anesthetic by itself, despite the mixed data regarding their potential neuroprotective effect (27), or their paradoxical neurotoxic effect (28), play a role. These agents, as quickly as they reach therapeutic levels in the brain, are rapidly washed and likely have little residual effect. However, because cardiac surgery is largely being performed in the increasingly elderly patient, and the pharmacokinetics of various drugs are somewhat unpredictable in this population, it is likely that some of the fixed agents, such as benzodiazepines, may have a prolonged effect within the brain. That said, there have not been any randomized trials to investigate the long lasting cerebral effect of benzodiazepines following cardiac surgery. Interestingly, one could make a cogent argument for the fact that the administration of benzodiazepines may be the cause of delirium, (29) or that the failure to administer benzodiazepines in the chronically benzodiazepine-dependent patient might lead to disorganized brain chemistry with subsequent development of overt delirium. (30) Other anesthetic agents that may have an impact include the use ketamine. Although again, one could easily make an argument that this N-methyl-D aspartate (NMDA) agonist might have some adverse effects on the brain (as it has been shown to be associated with hallucinogenic properties and is neurotoxic in animal models (31,32)), there is also some evidence that it may actually lead to a reduction in delirium. Indeed, Hudetz et al have performed a small, randomized pilot trial (n=58) demonstrating that a single induction i.v. dose of ketamine (0.5 mg/kg) was associated with a reduction in postoperative delirium. (33) However, until this maneuver is investigated in a much larger trial, can one ever confidently say that this may have some benefit? Few investigations directed toward specifically investigating individual anesthetic agents (such as sevoflurane or other fixed agents such as propofol) have been undertaken with respect to their impact on incidence of delirium. What little data exists is quite contentious. Nishikawa et al (34) conducted a small study (n=50) in non-cardiac surgery patients. In this study, they examined the incidence of delirium on the first three postoperative days, as well as looking at the delirium ration score (DRS) as an indicator of delirium severity. Although the incidence of delirium in this group was no different in those managed with propofol versus sevoflurane, the DRS was significantly higher (i.e. worse) in those patients receiving propofol on postoperative days 2 to 3. However, Lurati Buse et al (35) examined the incidence of delirium in those receiving sevoflurane and propofol as well. In their trial (n=385), that was primarily directed to examine myocardial endpoints, delirium was a substudy endpoint. There was no difference in the incidence of delirium, approximately 15% in both groups, although this too was in noncardiac surgery patients. No specific studies of these agents have been undertaken in the cardiac surgery population. Of note, Bilotta et al (36) have published the study protocol for the 3 PINOCCHIO trial, which is designed to examine early postoperative cognitive dysfunction and delirium in a randomized controlled trial. This large trial (n>1000) is hoped to provide some additional insight in this area. Although anesthetic agents themselves may not have a direct impact, other drugs delivered (by anesthesiologists) intraoperatively, such as phosphodiesterase inhibitors and their co-administered anticholinergic drugs used to reverse residual neuromuscular blockade, could have an impact. Overall, pharmacologic approaches have largely focused on treatment of delirium rather than prevention. Indeed, haloperidol has been the most widely used therapy for delirium. However, although it can reduce the severity and is still considered a first line therapy, its prophylactic use has largely failed to meaningfully decrease the overall incidence. (37) Several other pharmacologic therapies, such as the atypical antipsychotic risperidone (38), have been used with variable success. Recently, considerable study has focused on the alpha-2 adrenergic agonist dexmedetomidine. Dexmedetomidine is thought to be unique in its ability to help maintain вЂњrestfulвЂќ sleep in the ICU. (39,40) Whether its main effect on reducing delirium is a unique pharmacologic effect, or secondary to a reduction in sleep deprivation is not known. The unilateral pharmacologic approach that is directed at deliriumвЂ™s multifactorial etiology likely contributes to the relative lack of success with drug therapy is general. Accordingly, it is unlikely that one magic pharmacologic bullet can address all the issues associated with its development. Intraoperative monitoring of the brain might have a role in detecting or mitigating delirium. Processed electroencephalography (EEG) such as the bispectral index (BIS) and near infrared spectroscopy (NIRS) cerebral oximetry have been examined with some interesting and compelling results. Recently, Schoen et al have identified that those patients with a low baseline cerebral saturations are at much higher risk of developing delirium following cardiac surgery. (41,42) Whether this indicates that cerebral desaturation (indicative of cerebral ischemia) is at the root cause of delirium remains unknown. There have been no interventional studies using NIRS-guided strategies to reduce delirium. Importantly, although specific anesthetic agents have yet to be directly implicated, overall depth of anesthesia has. The use of BIS may have some ability to discriminate between those with or without risk of delirium. Most recently, Chan et al (n=921) have reported a relationship between low BIS and delirium in a trial of elderly patients undergoing major non-cardiac surgery randomized to either standard of care or a BIS guided anesthetic (with a target of 40-60). The BIS guided group demonstrated a significant reduction in delirium (15.6% vs. 24.1%, P=0.01). (43) Cerebral monitoring continues to be a promising direction for future research. In summary, delirium after cardiac surgery is a common multifactorial problem with numerous risk factors identified. It is a highly significant postoperative problem that impairs quality of recovery, increases morbidity and mortality, and is associated with a significant increase in healthcare utilization. Although no therapies have definitively demonstrated a reduction in this complication, significant advancements have been made as the problem is being redefined and appropriately targeted with both pharmacologic and nonpharmacologic therapies. However, until the pathophysiology of delirium is better delineated, it is unlikely that the choice of anesthetic, be it a sole agent or a combinations of volatile and fixed agents, are going to have any effect. 4 References 1. Newman MF, Mathew JP, Grocott HP, Mackensen GB, Monk T, Welsh-Bohmer KA, Blumenthal JA, Laskowitz DT, Mark DB. Central nervous system injury associated with cardiac surgery. Lancet 2006;368:694-703. 2. Newman MF, Kirchner JL, Phillips-Bute B, Gaver V, Grocott H, Jones RH, Mark DB, Reves JG, Blumenthal JA. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Engl J Med 2001;344:395-402. 3. Selnes OA, Gottesman RF, Grega MA, Baumgartner WA, Zeger SL, McKhann GM. Cognitive and neurologic outcomes after coronary-artery bypass surgery. N Engl J Med 2012;366:250-7. 4. Maldonado JR, Wysong A, van der Starre PJ, Block T, Miller C, Reitz BA. Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery. Psychosomatics 2009;50:206-17. 5. Sockalingam S, Parekh N, Bogoch, II, Sun J, Mahtani R, Beach C, Bollegalla N, Turzanski S, Seto E, Kim J, Dulay P, Scarrow S, Bhalerao S. Delirium in the postoperative cardiac patient: a review. J Card Surg 2005;20:560-7. 6. Tan MC, Felde A, Kuskowski M, Ward H, Kelly RF, Adabag AS, Dysken M. Incidence and predictors of post-cardiotomy delirium. Am J Geriatr Psychiatry 2008;16:575-83. 7. Santos FS, Velasco IT, Fraguas R, Jr. Risk factors for delirium in the elderly after coronary artery bypass graft surgery. Int Psychogeriatr 2004;16:175-93. 8. van der Mast RC, Roest FH. Delirium after cardiac surgery: a critical review. J Psychosom Res 1996;41:13-30. 9. Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE, Jr., Inouye SK, Bernard GR, Dittus RS. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004;291:1753-62. 10. Gottesman RF, Grega MA, Bailey MM, Pham LD, Zeger SL, Baumgartner WA, Selnes OA, McKhann GM. Delirium after coronary artery bypass graft surgery and late mortality. Ann Neurol 2010;67:338-44. 11. Milbrandt EB, Deppen S, Harrison PL, Shintani AK, Speroff T, Stiles RA, Truman B, Bernard GR, Dittus RS, Ely EW. Costs associated with delirium in mechanically ventilated patients. Crit Care Med 2004;32:955-62. 12. Ely EW, Gautam S, Margolin R, Francis J, May L, Speroff T, Truman B, Dittus R, Bernard R, Inouye SK. The impact of delirium in the intensive care unit on hospital length of stay. Intensive Care Med 2001;27:1892-900. 13. Maldonado JR. Delirium in the acute care setting: characteristics, diagnosis and treatment. Crit Care Clin 2008;24:657-722, vii. 14. Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S, Margolin R, Hart RP, Dittus R. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA 2001;286:2703-10. 15. Martin BJ, Buth KJ, Arora RC, Baskett RJ. Delirium: a cause for concern beyond the immediate postoperative period. Ann Thorac Surg 2012;93:1114-20. 16. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM IV, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association, 2000. 5 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. Chaput AJ, Bryson GL. Postoperative delirium: risk factors and management: continuing professional development. Can J Anaesth 2012;59:304-20. Seaman JS, Schillerstrom J, Carroll D, Brown TM. Impaired oxidative metabolism precipitates delirium: a study of 101 ICU patients. Psychosomatics 2006;47:56-61. Kalman J, Juhasz A, Bogats G, Babik B, Rimanoczy A, Janka Z, Penke B, Palotas A. Elevated levels of inflammatory biomarkers in the cerebrospinal fluid after coronary artery bypass surgery are predictors of cognitive decline. Neurochem Int 2006;48:177-80. Golinger RC, Peet T, Tune LE. Association of elevated plasma anticholinergic activity with delirium in surgical patients. Am J Psychiatry 1987;144:1218-20. Flacker JM, Cummings V, Mach JR, Jr., Bettin K, Kiely DK, Wei J. The association of serum anticholinergic activity with delirium in elderly medical patients. Am J Geriatr Psychiatry 1998;6:31-41. Mach JR, Jr., Dysken MW, Kuskowski M, Richelson E, Holden L, Jilk KM. Serum anticholinergic activity in hospitalized older persons with delirium: a preliminary study. J Am Geriatr Soc 1995;43:491-5. de Rooij SE, van Munster BC, Korevaar JC, Levi M. Cytokines and acute phase response in delirium. J Psychosom Res 2007;62:521-5. van der Mast RC. Pathophysiology of delirium. J Geriatr Psychiatry Neurol 1998;11:13845; discussion 57-8. Inouye SK. Delirium in older persons. N Engl J Med 2006;354:1157-65. Cavaliere F, D'Ambrosio F, Volpe C, Masieri S. Postoperative delirium. Curr Drug Targets 2005;6:807-14. Kitano H, Kirsch JR, Hurn PD, Murphy SJ. Inhalational anesthetics as neuroprotectants or chemical preconditioning agents in ischemic brain. J Cereb Blood Flow Metab 2007;27:1108-28. Culley DJ, Xie Z, Crosby G. General anesthetic-induced neurotoxicity: an emerging problem for the young and old? Curr Opin Anaesthesiol 2007;20:408-13. Pandharipande P, Shintani A, Peterson J, Pun BT, Wilkinson GR, Dittus RS, Bernard GR, Ely EW. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology 2006;104:21-6. Bosshart H. Withdrawal-induced delirium associated with a benzodiazepine switch: a case report. J Med Case Rep 2011;5:207. Jevtovic-Todorovic V, Wozniak DF, Benshoff ND, Olney JW. A comparative evaluation of the neurotoxic properties of ketamine and nitrous oxide. Brain Res 2001;895:264-7. Olney JW, Labruyere J, Wang G, Wozniak DF, Price MT, Sesma MA. NMDA antagonist neurotoxicity: mechanism and prevention. Science 1991;254:1515-8. Hudetz JA, Patterson KM, Iqbal Z, Gandhi SD, Byrne AJ, Hudetz AG, Warltier DC, Pagel PS. Ketamine attenuates delirium after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2009;23:651-7. Nishikawa K, Nakayama M, Omote K, Namiki A. Recovery characteristics and postoperative delirium after long-duration laparoscope-assisted surgery in elderly patients: propofol-based vs. sevoflurane-based anesthesia. Acta Anaesthesiol Scand 2004;48:1628. Lurati Buse GA, Schumacher P, Seeberger E, Studer W, Schuman RM, Fassl J, Kasper J, Filipovic M, Bolliger D, Seeberger MD. Randomized comparison of sevoflurane versus 6 36. 37. 38. 39. 40. 41. 42. 43. propofol to reduce perioperative myocardial ischemia in patients undergoing noncardiac surgery. Circulation 2012;126:2696-704. Bilotta F, Doronzio A, Stazi E, Titi L, Zeppa IO, Cianchi A, Rosa G, Paoloni FP, Bergese S, Asouhidou I, Ioannou P, Abramowicz AE, Spinelli A, Delphin E, Ayrian E, Zelman V, Lumb P. Early postoperative cognitive dysfunction and postoperative delirium after anaesthesia with various hypnotics: study protocol for a randomised controlled trial--the PINOCCHIO trial. Trials 2011;12:170. Kalisvaart KJ, de Jonghe JF, Bogaards MJ, Vreeswijk R, Egberts TC, Burger BJ, Eikelenboom P, van Gool WA. Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study. J Am Geriatr Soc 2005;53:1658-66. Raiten JM, Gutsche JT. Use of risperidone in cardiac surgery patients with subsyndromal delirium. Anesthesiology 2012;117:1141; author reply -3. Ji F, Li Z, Nguyen H, Young N, Shi P, Fleming N, Liu H. Perioperative dexmedetomidine improves outcomes of cardiac surgery. Circulation 2013;127:1576-84. Shehabi Y, Grant P, Wolfenden H, Hammond N, Bass F, Campbell M, Chen J. Prevalence of delirium with dexmedetomidine compared with morphine based therapy after cardiac surgery: a randomized controlled trial (DEXmedetomidine COmpared to Morphine-DEXCOM Study). Anesthesiology 2009;111:1075-84. Schoen J, Meyerrose J, Paarmann H, Heringlake M, Hueppe M, Berger KU. Preoperative regional cerebral oxygen saturation is a predictor of postoperative delirium in on-pump cardiac surgery patients: a prospective observational trial. Crit Care 2011;15:R218. Zheng F, Sheinberg R, Yee MS, Ono M, Zheng Y, Hogue CW. Cerebral near-infrared spectroscopy monitoring and neurologic outcomes in adult cardiac surgery patients: a systematic review. Anesth Analg 2013;116:663-76. Chan MT, Cheng BC, Lee TM, Gin T. BIS-guided anesthesia decreases postoperative delirium and cognitive decline. J Neurosurg Anesthesiol 2013;25:33-42. Does Operative Ventilator Management Impact the Incidence of ARDS? Jacob Gutsche, MD Assistant Professor University of Pennsylvania Philadelphia, Pennsylvania Objectives At the conclusion of this educational activity, the participants should be able to: 1. Understand the normal pulmonary anatomy and physiology 2. Discuss the incidence of acute lung injury and ARDS in cardiac surgery patients 3. Summarize the potential contribution of operative mechanical ventilation to acute lung injury in cardiac surgery patients 4. Describe the optimal mode and settings of operative mechanical ventilation in cardiac surgery patients. Prior to 2000, standard postoperative and intraoperative ventilation used tidal volumes in the 10-15 mL/kg range. Large tidal volume ventilation strategies were considered safe and were thought to prevent atelectasis. In addition, high level peep strategies necessary to prevent atelectasis were thought to be potentially harmful. The publication of the ARDSnet trial revolutionized the care of patients with acute respiratory distress syndrome (ARDS).(1) In this landmark trial, mechanically ventilated patients with a combination of an acute decrease in the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) to 300 or less, bilateral pulmonary infiltrates on a chest radiograph consistent with the presence of edema, and a pulmonary-capillary wedge pressure of 18 mm Hg or less were randomized to a low stretch versus standard ventilation strategy. The low stretch strategy ventilated patients with tidal volumes ranging from 4-6 mL/kg based on ideal body weight while maintaining a plateau pressure less than 30 mL of water. High levels of peep were maintained based on an algorithm based on the FIO2. The standard ventilation group started with tidal volumes of 12 mL/kg based on ideal body weight, and the ventilator settings were titrated to maintain a plateau pressure of at least 45 cm of water or a tidal volume of 12 mL/kg. The trial was terminated after enrollment of 861 patients when interim analysis found that patients randomized to the low stretch group had a significantly lower mortality (31.0 per- cent vs. 39.8 percent, P=0.007). ARDS is a acute disease that is noted for diffuse inflammatory lung injury and loss of aerated tissue. The lung is profoundly edematous and the chest radiograph is classically found to have diffuse infiltrates. Management of patients with ARDS is supportive with a focus on source control. Low stretch tidal volume ventilation has become the standard that all other modes of open lung ventilation should be compared to in patients with lung injury. The goal of low stretch ventilation is to minimize damage to more compliant areas of the lung while the source of ARDS is treated.(2) Other modes that have been proposed to improve outcomes in ARDS include airway pressure release ventilation, hi frequency oscillation, and alternative pressure control modes. At the current time none of these has been shown to be superior to low-stretch ventilation. ARDS is known to be a complication following cardiac surgery occurring in up to 0.4-1% of patients. ARDS following cardiac surgery is associated with a high rate of mortality.(3) The mechanism of ARDS is this patient group is likely multi-factorial and may be related to a combination of inflammation due to the surgery and exposure to the cardiopulmonary bypass circuit, blood product administration. Patients undergoing aortic surgery or having circulatory arrest are at even higher risk of developing ARDS after surgery. Several small studies have analyzed the use of low stretch ventilation strategies in cardiac surgery patients. These trials have attempted to demonstrate that low stretch ventilation may reduce the risk of lung injury by measuring inflammatory markers as a surrogate for lung injury.(4) But none have been powered to demonstrate differences in morbidity or mortality. Recently, Futier and colleagues performed a multicenter, double-blind, parallel group trial randomizing 400 abdominal surgery patients to non-protective (10-12 mL/kg) versus a lung protective ventilation strategy (6-8 mL/kg).(5) These patients were deemed to be at intermediate to high risk for pulmonary complications. The patients randomized to the lung protective strategy had a lower incidence of major pulmonary and extrapulmonary complications (10.5% vs 27.5%, relative risk, 0.40; 95% CI [0.24-0.68]; p=0.001). More study is required to evaluate the overall benefit of lung protective strategies and the potential benefit in the cardiac surgery patient cohort. At this time, lung protective strategy with a tidal volume of 6-8 mL/kg should be utilized with low to moderate levels of peep to prevent atelectasis. References and Suggested Reading 1. 2. 3. 4. 5. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. The New England journal of medicine 2000;342:1301-8. Slutsky AS, Ranieri VM. Ventilator-induced lung injury. The New England journal of medicine 2013;369:2126-36. Stephens RS, Shah AS, Whitman GJ. Lung injury and acute respiratory distress syndrome after cardiac surgery. The Annals of thoracic surgery 2013;95:1122-9. Reis Miranda D, Gommers D, Struijs A, Dekker R, Mekel J, Feelders R, Lachmann B, Bogers AJ. Ventilation according to the open lung concept attenuates pulmonary inflammatory response in cardiac surgery. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 2005;28:889-95. Futier E, Constantin JM, Paugam-Burtz C, Pascal J, Eurin M, Neuschwander A, Marret E, Beaussier M, Gutton C, Lefrant JY, Allaouchiche B, Verzilli D, Leone M, De Jong A, Bazin JE, Pereira B, Jaber S, Group IS. A trial of intraoperative low-tidal-volume ventilation in abdominal surgery. The New England journal of medicine 2013;369:428-37. 1 Incidental PFO: To close or not to close? Joseph P. Mathew, MD A patent foramen ovale (PFO) results from persistence of the interatrial communication at the site of the embryonic ostium secundum. In the fetus, blood from the inferior vena cava is directed toward the foramen ovale by the Eustachian valve, passing ultimately from the right atrium to the left atrium. The right atrial aspect of the foramen ovale is characterized by a muscular rim, whereas the left atrial aspect is flat with a crescent-shaped opening. At birth, as left atrial pressures increase, the overlap of the septum primum against this rim closes the foramen ovale. Over the next year of life, the flap of the septum primum and the rim become more adherent resulting in complete closure. However, autopsy findings have reported that the foramen ovale remains probe-patent in 25-35% of patients.1 Since the flap created by the ostium secundum is larger than the fossa, the length of the overlap can be substantial and result in a tunnel-like opening. In one small study, Ho et al2 demonstrated tunnel lengths of 1вЂ“6 mm and widths of 5вЂ“13 mm along the curve of the rim. Based on their experience with transcatheter closure of a PFO, Rana et al3 have proposed that PFOs can be categorized as either simple or complex. A simple PFO is a standard PFO with tunnel length <8 mm, without an atrial septal aneurysm, without a large Eustachian ridge or valve, without a thickened (< 10 mm) septum secundum, and without other defects of the fossa ovalis. A complex PFO, on the other hand, is one that has any of the following characteristics: 1) PFO with a long tunnel length (>8 mm) 2) Multiple openings of the PFO on the left atrial side 3) Atrial septal aneurysm defined as mobility of the septum > 10 mm in either direction 4) Hybrid defect - the concomitant occurrence of a PFO with additional defects on the fossa ovalis 5) Excessive thickening (> 10 mm) of septum secundum 6) Presence of Eustachian ridge 7) Presence of Eustachian valve (or Chiari network). Detection of an intra-atrial shunt is a prerequisite for the diagnosis of a PFO. While different imaging modalities including transcranial Doppler, intracardiac echocardiography, and transthoracic echocardiography have been used to detect a right-toleft shunt, a transesophageal echo (TEE) bubble study remains the gold standard for diagnosing PFO. In one meta-analysis that included 164 patients, TEE had a sensitivity of 89.2% (95% CI: 81.1-94.7%) and specificity of 91.4% (95% CI: 82.3-96.8%) to detect PFO.4 TEE evaluation of the foramen ovale should include two-dimensional assessment for flap movement and color-flow Doppler assessment, optimized for measurement of lower velocity flow. Injection of agitated saline (a вЂњbubble studyвЂќ) along with a Valsalva maneuver is typically used to provoke right to left shunting. In such a study, the bubbles should be injected after the Valsalva maneuver produces a decrease in right atrial volume, and the Valsalva should be released (so as to transiently increase right trial pressure over left atrial pressure) when the microbubbles are first seen to enter the right atrium. Admixture of agitated saline with small quantities of blood has been reported to improve the acoustic signal of the microbubbles. The bubble study is positive if bubbles appear in the left atrium within five cardiac cycles. Multiple complications have been associated with a PFO.5 Of these, the increased incidence of PFO in younger patients with cryptogenic stroke has garnered the greatest attention. In a meta-analysis of 1024 patients, the odds ratio for the presence of a PFO in cryptogenic stroke in individuals < 55 years of age was 3.1 (95% CI 2.3вЂ“4.2).6 On the 2 basis of multiple reports demonstrating a thrombus in transit between the right and left atrium through a PFO, it is commonly assumed that paradoxical embolization is the cause of the increased incidence of cryptogenic stroke.5 However, other mechanisms of embolic stroke in association with a PFO have been proposed including alterations in atrial function similar to those in patients with chronic atrial fibrillation. 7 These abnormalities were more pronounced in those with moderate to large atrial septal aneurysms who in turn were noted to be more likely to have coagulation abnormalities and spontaneous left atrial contrast. Furthermore in patients with PFO and cryptogenic stroke, the incidence of atrial fibrillation (a risk factor for stroke) ranges from 8вЂ“15%.8 An association between PFO and migraine was highlighted when patients who had a PFO closed for other reasons reported an improvement in the frequency and severity of migraine headaches.9 A meta-analysis of 2636 subjects reported an odds ratio of 5.13 (95% CI 4.7вЂ“5.6) but concluded that there was only low grade evidence to support the association between migraine and PFO.10 The only randomized trial of device closure in patients with migraine failed to demonstrate a clear benefit.11,12 Decompression illness in scuba divers is another arena where a PFO may play a critical role. Torti et al13 investigated 230 scuba divers and reported that PFO was present in 23% and was associated with an increased risk of a significant decompression event. The platypneaвЂ“orthodeoxia syndrome is characterized by dyspnea and hypoxemia upon standing up. The symptoms are thought to occur because standing upright causes inferior vena cava inflow redirection towards the inter-atrial septum and therefore, increased shunting through a PFO. The syndrome is typically seen after a right pneumonectomy where the cardiac position is shifted in a manner that increases flow toward the PFO.14 Redirection of inferior vena caval flow towards the inter-atrial septum has also been reported in patients with an enlarged or вЂњhorizontalizedвЂќ aortic root. In this case, the flow alteration is a consequence of the cardiac rotation that distorts atrial septal position.15 Perioperatively, in addition to the reports of systemic embolism, hypoxemia due to shunting through a PFO has been described,16 particularly in those with elevated right atrial pressures (e.g. pulmonary hypertension, right ventricular failure) and/or reduced left atrial pressures (e.g. left ventricular assist device). The intraoperative detection of a previously undiagnosed PFO creates a quandary for the surgical and anesthesia care teams. Sukernik and Bennett-Guerrero concluded that вЂњthere is general agreement that a PFO should be closed when development of a significant right-toleft shunt after surgery is highly likelyвЂќ.17 Two instances where closure is strongly recommended are with the insertion of a left ventricular assist device (unloaded left ventricle lowers right atrial to left atrial pressure gradient and can increase shunting) and with heart transplantation (elevated pulmonary vascular resistance increases right atrial pressures). Surgical closure was also recommended when atriotomies were planned as part of the scheduled surgical procedure although there is no data to specifically support such a strategy. In all other cases, the authors recommended that closure be considered when the risk was increased as defined by a large PFO, a history of paradoxical embolization, interatrial septal aneurysm, history of professional diving, or a right to left shunt (including from luxation of the heart during off-pump surgery).17,18 The rationale here is that the risk of an altered cannulation scheme and prolonged cardiopulmonary bypass time is minimal.19 On the other hand, the typical cardiac surgery patient is elderly and 3 atherosclerosis and atrial fibrillation are more likely sources of embolism. Thus, an argument can be made that there would be minimal benefit to routinely closing the PFO in older patients without right ventricular overload.18 Furthermore, instituting cardiopulmonary bypass in an off-pump procedure could substantially increase patient risk. In a survey of national surgical practice conducted in 2002, the majority of surgeons decided to close an incidental PFO if the PFO was large, if right atrial pressure was elevated or if there was a history of paradoxical embolism.20 Interestingly, during surgery with cardiopulmonary bypass, 28% always closed the PFO while 10% never chose to close the PFO. In off-pump surgery, 28% never altered the surgical plan while 11% always converted to on-pump surgery in order to repair the PFO. A large majority (73%) reported never experiencing a PFO-related complication in the immediate postoperative period that then required additional intervention. To address the impact on PFO repair upon outcomes, Krasuski et al21 evaluated 13,092 cardiac surgical patients without a history of PFO or atrial septal aneurysm. An incidental PFO was diagnosed intraoperatively in 17% and after propensity matching, postoperative stroke or mortality was not different in patients with and without a PFO. Twenty eight percent of the PFO patients had their PFO closed as part of the surgical procedure with closure more likely in younger patients, those undergoing mitral or tricuspid valve surgery, and those with a history of transient ischemic attack or stroke. PFO repair did not offer a long-term survival advantage but was associated with a 2.5 times greater odds of postoperative stroke. This increased risk of stroke is not readily explained since the cardiopulmonary bypass time increased only by a mean of 6 minutes. In addition to primary surgical closure, medical management with anticoagulation/ antiplatelet medications and percutaneous closure may also be considered. In a recent systematic review, the risk of recurrent transient ischemic attack or stroke with device closure was 1.3% compared to 5.2% with medical treatment.22 Although the rate of major complications with percutaneous closure is low at 1.5-2.3%, death, hemorrhage, emergency surgery, tamponade, and pulmonary embolism are possibilities. Other complications include atrial fibrillation which is higher following device closure and may be related to the size of the device. Incomplete PFO closure has also been reported in 20% undergoing device closure with 14% demonstrating large residual shunts.5 The American Heart Association/American Stroke Association has published guidelines that support the use of antiplatelet or warfarin therapy for high-risk patients with other indications such as hypercoagulable state or venous thrombosis.23 Evidence to recommend device closure for a first stroke is insufficient but PFO closure may be considered for recurrent cryptogenic stroke on optimal medical treatment. Although management strategies for an incidental PFO discovered during surgery are not addressed by these guidelines, closure is recommended during heart transplantation and left ventricular assist device placement. It is also reasonable to consider closure in patients with a large PFO, a history of paradoxical embolization, interatrial septal aneurysm, history of professional diving, or a right to left shunt. However, the increased risk of postoperative stroke with no clear survival advantage of repair should be considered in the risk-benefit analysis. 4 References: 1. Hagen PT, Scholz DG, Edwards WD. Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts. Mayo Clinic proceedings. Jan 1984;59(1):17-20. 2. Ho SY, McCarthy KP, Rigby ML. Morphological features pertinent to interventional closure of patent oval foramen. Journal of interventional cardiology. Feb 2003;16(1):33-38. 3. Rana BS, Shapiro LM, McCarthy KP, Ho SY. Three-dimensional imaging of the atrial septum and patent foramen ovale anatomy: defining the morphological phenotypes of patent foramen ovale. European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology. Dec 2010;11(10):i19-25. 4. Mojadidi MK, Bogush N, Caceres JD, Msaouel P, Tobis J. Diagnostic Accuracy of Transesophageal Echocardiogram for the Detection of Patent Foramen Ovale: A Meta-Analysis. Echocardiography. Dec 23 2013. 5. Irwin B, Ray S. Patent foramen ovale--assessment and treatment. Cardiovascular therapeutics. Jun 2012;30(3):e128-135. 6. Overell JR, Bone I, Lees KR. Interatrial septal abnormalities and stroke: a metaanalysis of case-control studies. Neurology. Oct 24 2000;55(8):1172-1179. 7. Rigatelli G, Aggio S, Cardaioli P, et al. Left atrial dysfunction in patients with patent foramen ovale and atrial septal aneurysm: an alternative concurrent mechanism for arterial embolism? JACC. Cardiovascular interventions. Jul 2009;2(7):655-662. 8. Bonvini RF, Sztajzel R, Dorsaz PA, et al. Incidence of atrial fibrillation after percutaneous closure of patent foramen ovale and small atrial septal defects in patients presenting with cryptogenic stroke. International journal of stroke : official journal of the International Stroke Society. Feb 2010;5(1):4-9. 9. Wilmshurst PT, Nightingale S, Walsh KP, Morrison WL. Effect on migraine of closure of cardiac right-to-left shunts to prevent recurrence of decompression illness or stroke or for haemodynamic reasons. Lancet. Nov 11 2000;356(9242):1648-1651. 10. Schwedt TJ, Demaerschalk BM, Dodick DW. Patent foramen ovale and migraine: a quantitative systematic review. Cephalalgia : an international journal of headache. May 2008;28(5):531-540. 11. Carroll JD. Migraine Intervention With STARFlex Technology trial: a controversial trial of migraine and patent foramen ovale closure. Circulation. Mar 18 2008;117(11):1358-1360. 12. Dowson A, Mullen MJ, Peatfield R, et al. Migraine Intervention With STARFlex Technology (MIST) trial: a prospective, multicenter, double-blind, sham-controlled trial to evaluate the effectiveness of patent foramen ovale closure with STARFlex septal repair implant to resolve refractory migraine headache. Circulation. Mar 18 2008;117(11):1397-1404. 13. Torti SR, Billinger M, Schwerzmann M, et al. Risk of decompression illness among 230 divers in relation to the presence and size of patent foramen ovale. European heart journal. Jun 2004;25(12):1014-1020. 14. Aigner C, Lang G, Taghavi S, et al. Haemodynamic complications after pneumonectomy: atrial inflow obstruction and reopening of the foramen ovale. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. Feb 2008;33(2):268-271. 5 15. 16. 17. 18. 19. 20. 21. 22. 23. Eicher JC, Bonniaud P, Baudouin N, et al. Hypoxaemia associated with an enlarged aortic root: a new syndrome? Heart. Aug 2005;91(8):1030-1035. Tabry I, Villanueva L, Walker E. Patent foramen ovale causing refractory hypoxemia after off-pump coronary artery bypass: a case report. The heart surgery forum. 2003;6(4):E74-76. Sukernik MR, Bennett-Guerrero E. The incidental finding of a patent foramen ovale during cardiac surgery: should it always be repaired? A core review. Anesthesia and analgesia. Sep 2007;105(3):602-610. Flachskampf FA. CON: The incidental finding of a patent foramen ovale during cardiac surgery: should it always be repaired? Anesthesia and analgesia. Sep 2007;105(3):613-614. Argenziano M. PRO: The incidental finding of a patent foramen ovale during cardiac surgery: should it always be repaired? Anesthesia and analgesia. Sep 2007;105(3):611-612. Sukernik MR, Goswami S, Frumento RJ, Oz MC, Bennett-Guerrero E. National survey regarding the management of an intraoperatively diagnosed patent foramen ovale during coronary artery bypass graft surgery. Journal of cardiothoracic and vascular anesthesia. Apr 2005;19(2):150-154. Krasuski RA, Hart SA, Allen D, et al. Prevalence and repair of intraoperatively diagnosed patent foramen ovale and association with perioperative outcomes and long-term survival. JAMA : the journal of the American Medical Association. Jul 15 2009;302(3):290-297. Wohrle J. Closure of patent foramen ovale after cryptogenic stroke. Lancet. Jul 29 2006;368(9533):350-352. O'Gara PT, Messe SR, Tuzcu EM, et al. Percutaneous device closure of patent foramen ovale for secondary stroke prevention: a call for completion of randomized clinical trials. A science advisory from the American Heart Association/American Stroke Association and the American College of Cardiology Foundation. Journal of the American College of Cardiology. May 26 2009;53(21):2014-2018. Cheung AT Page 1 of 6 January 10, 2014 CARDIAC CONTROVERSIES: NEUROMONITORING IN CARDIAC SURGERY OR DURING DHCA (DEEP HYPOTHERMIC CIRCULATORY ARREST): OPTIONAL OR IMPERATIVE? Albert T. Cheung, M.D. Professor, Department of Anesthesiology and Critical Care University of Pennsylvania Philadelphia, PA Learning Objectives: 1. Identify changes in the electroencephalogram (EEG) and somatosensory evoked potentials (SEP) caused by metabolic suppression as a consequence of hypothermia. 2. Describe how intraoperative neuromonitoring can be used to detect cerebral malperfusion or ischemia. Identify changes in the electroencephalogram (EEG) and somatosensory evoked potentials (SEP) caused by metabolic suppression as a consequence of hypothermia. Temporary interruption of blood flow to the brain is often necessary for the surgical repair of aortic dissection, thoracic aortic aneurysms, pulmonary embolism, congenital heart disease, and giant intracranial aneurysms. When blood flow to the brain is interrupted, neurons manifest signs of ischemia within 30 seconds. For this reason, brain protection is critical in cases requiring circulatory arrest. Deep hypothermia remains the most reliable and proven method for brain protection for circulatory arrest. The application of deep hypothermia is based on the principle that decreasing the temperature of the brain decreases cerebral metabolic demand, decreases cerebral blood flow requirements, and increases the duration of time neurons can survive in the absence of blood flow and nutrient delivery. However, there is considerable controversy as to the optimal conditions for deep hypothermic circulatory arrest (DHCA) and the maximum time that DHCA can be tolerated without brain injury. As a result, there is considerable variability in the routine conduct of DHCA. Although an average brain temperature of 18 ЛљC is often recommended for DHCA, the blood, nasopharyngeal, tympanic, or bladder temperature does not always reflect the actual temperature or physiologic condition of the brain. Electroencephalography or EEG provides a direct physiologic indicator of cerebral metabolic suppression as a consequence of deliberate hypothermia. Although the mean nasopharyngeal temperature that is associated with electrocortical silence by EEG was 18 ЛљC in adults, a nasopharyngeal temperature of 12 ЛљC was necessary to ensure that 95% of adult patients had EEG criteria for complete cerebral metabolic suppression. Alternatively, active cooling for 50 minutes on cardiopulmonary bypass produced electrocortical silence by EEG in 95% of patients. Both EEG and SEP demonstrate characteristic temperature-dependent changes in response to deliberate hypothermia in anesthetized patients that correlate with brain metabolic activity. As temperature decreases, EEG amplitude decreases, EEG frequency decreases, burst suppression appears, then electrocortical silence occurs. SEPвЂ™s also display characteristic temperature-dependent effects. SEP latencies increase, then the N20-P22 complex disappears, followed by the disappearance of the N13 wave. For these reasons, intraoperative monitoring with EEG or SEP for thoracic aortic operations can be used to provide a physiologic surrogate of the adequate delivery of hypothermia for DHCA in addition to monitoring temperature alone. Another physiologic consequence of deliberate hypothermia that can be monitored during general anesthesia is that cerebral oxygen saturation increases in response to temperature-induced cerebral metabolic suppression. The increase in cerebral oxygen saturation that occurs in response to deliberate hypothermia can be monitored using an oximetric catheter positioned to measure oxygen saturation in the Cheung AT Page 2 of 6 January 10, 2014 jugular bulb. Alternatively, cerebral oxygen saturation can be monitored noninvasively using cerebral near infrared spectrophotometry or NIRS. Because the oxygen saturation value obtained using NIRS is derived from both venous blood (75%) and arterial blood (25%), cerebral oxygen saturation measured using NIRS increases in response to cerebral metabolic suppression caused by deliberate hypothermia. Describe how intraoperative neuromonitoring can be used to detect cerebral malperfusion or ischemia. The more common clinical application of intraoperative neurologic monitoring is for the detection and prevention of neurologic complications of cardiac and thoracic aortic operations. Neurophysiologic monitoring is required to detect neurologic complications because acute neurologic injury cannot be detected by routine clinical examination in patients during general anesthesia. The most common etiologies for intraoperative neurologic injury that can potentially be detected by neurophysiologic monitoring is cerebral ischemia as a consequence of hypoperfusion, embolic stroke, or malperfusion. Hypoperfusion producing cerebral ischemia can be detected immediately by EEG monitoring. Loss of EEG amplitude and decrease in EEG frequency will occur within 30 seconds when cerebral blood flow is interrupted. Global cerebral anoxic injury may also manifest as a burst suppression pattern on EEG or as seizure activity on reperfusion. Global cerebral hypoperfusion will also manifest as a loss of SEP amplitude or by decreased cerebral oxygen saturation measured by NIRS. Among patients with aortic dissection or patients undergoing major thoracic aortic operations, cerebral hypoperfusion or malperfusion may occur in response to cardiac tamponade, cardiopulmonary bypass, dissection of the aortic arch branch vessels, or cannula malposition during selective antegrade cerebral perfusion. EEG, SEP, and NIRS all provide the capability to detect cerebral hypoperfusion of malperfusion when brain activity is present, but only NIRS can detect cerebral malperfusion during deep hypothermia after the onset of electrocortical silence. Unilateral cerebral malperfusion will also manifest as oxygen desaturation over the ipsilateral hemisphere measured by NIRS or asymmetry in the amplitude of the EEG or SEP signals. Cerebral hypoperfusion caused by cardiac tamponade is associated with venous hypertension, cardiogenic shock, and venous congestion. Cardiac tamponade and other conditions associated with venous hypertension will manifest as a marked global reduction in cerebral oxygen saturation measured by NIRS because 75% of the signal is derived from the oxygen saturation of venous blood. EEG is less sensitive for detecting acute embolic stroke unless the area of infarction is very large. Similarly, stroke as a consequence of thromboembolism is unlikely to manifest as changes in cerebral oxygen saturation measured using NIRS because it is only able to sample a small region of the frontal cortex. SEP monitoring is more sensitive for the detection of acute embolic stroke because it monitors the activity of entire sensory pathways from the periphery to the cerebral cortex and will manifest as an acute loss of SEP amplitude in the affected distribution. Is Intraoperative Neurophysiologic Monitoring Imperative for DHCA or Major Thoracic Aortic Operations? Intraoperative EEG and SEP monitoring requires specialized equipment, technical expertise to perform and interpret, and requires time to set up. For these reasons, intraoperative EEG and SEP monitoring are not available nor practical in many institutions and not always feasible for emergency cases, especially if they occur off hours. In contrast, NIRS cerebral oximetry is widely available, non-invasive, and can be easily performed and interpreted. However, despite many published case reports and case series on the utility of EEG, SEP, and NIRS monitoring, definitive evidence of their effectiveness to decrease the risk of neurologic injury based on randomized controlled trials do not exist. The multidisciplinary 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease that was written and endorsed in Cheung AT Page 3 of 6 January 10, 2014 collaboration with the SCA gave a Class I recommendation (should be done) that a brain protection strategy to prevent stroke and preserve cognitive function should be a key element of the surgical, anesthetic, and perfusion techniques used to accomplish repairs of the ascending aorta and transverse aortic arch (Level of Evidence: B). The guidelines recognized also the limitations of intraoperative monitoring and the limited evidence supporting its efficacy and gave a Class IIa (benefits > risks) recommendation that motor (MEP) or somatosensory evoked potential (SEP) monitoring can be useful when the data will help to guide therapy. It is reasonable to base the decision to use neurophysiologic monitoring on individual patient needs, institutional resources, the urgency of the procedure, and the surgical and perfusion techniques to be employed in the open or endovascular thoracic aortic repair (Level of Evidence: B). The 2010 AHA/ACCF did not comment on the use of NIRS monitoring because they were written before the NIRS monitoring became widely available. However, the 2013 Standards and Guidelines for Perfusion Practice issued by the American Society of ExtraCorporeal Technology (AmSECT) stated that cerebral oximetry should be used during CPB (Guideline 7.5). Other Intraoperative Adjuncts to Detect and Prevent Brain Injury Although not technically considered as neurophysiologic monitors, intraoperative transesophageal echocardiography (TEE), carotid Duplex imaging, transcranial Doppler (TCD), and routine invasive hemodynamic monitoring are important adjuncts that can serve to detect and prevent intraoperative brain injury. TEE is useful for characterizing the extent of aortic dissections, indentifying the true and false lumens within the aorta, and verifying that the true lumen is cannulated and perfused on cardiopulmonary bypass and after placement of the cross clamp on the ascending aorta. Ultrasound Duplex imaging is useful for diagnosing extension of aortic dissection into the carotid arteries and verifying antegrade blood flow with the initiation of cardiopulmonary bypass. Transcranial Doppler can also be used to detect blood flow in the middle or anterior cerebral arteries and to detect and quantify cerebral embolism. Loss of the arterial pressure tracing in an upper extremity arterial line in patients with aortic dissection is also a common sign of malperfusion of the aortic arch branch vessels and should prompt examination for evidence of cerebral malperfusion. Although TEE, carotid Duplex, and TCD are powerful diagnostic tools, they require effort to perform and are difficult to use as continuous monitors. Selected References: 1. Stecker MM, Cheung AT, Pochettino A, Kent G, Patterson T, Weiss SJ, Bavaria JE: Deep hypothermic circulatory arrest: I. Effects of cooling on EEG and evoked potentials. Ann Thorac Surg 71:14-21, 2001 2. Cheung AT, Stecker MM: Neurologic Complications of Cardiac Operations. Progress in Anesthesiology, 12:3-20, 1998 3. Cheung AT, Bavaria JE, Pochettino A, Weiss SJ, Barclay DK, Stecker MM: Oxygen delivery during retrograde cerebral perfusion in humans. Anesth Analg 88:8-15, 1999 4. Grigore AM, Grocott HP, Mathew JP, et al. The rewarming rate and increased peak temperature alter neurocognitive outcome after cardiac surgery. Anesth Analg 2002;94:4-10 5. Pochettino A, and Cheung AT. Pro: Retrograde cerebral perfusion is useful for deep hypothermic circulatory arrest. J Cardiothorac Vasc Anesth 2003;17:764-7 6. Reich DL and Uysal S. Con: Retrograde cerebral perfusion is not an optimal method of Neuroprotection in thoracic aortic surgery. J Cardiothorac Vasc Anesth 2003;17:768-9 Cheung AT Page 4 of 6 January 10, 2014 7. Nolan JP, et al. Therapeutic hypothermia after cardiac arrest. An advisory statement by the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation. Circulation 2003;108:118-21 8. Sundt TM, Orszulak TA, Cook DJ, et al. Improving results of open arch replacement. Ann Thorac Surg 2008;86:787-96 9. Cheung AT, Savino JS, Weiss SJ, Patterson T, Richards RM, Gardner TJ, Stecker MM. Detection of Acute Embolic Stroke during Mitral Valve Replacement Using Somatosensory Evoked Potential Monitoring. Anesthesiol 1995;83:208-210 10. Hiratzka LF, Bakris GL, Beckman JA, Bersin RM, Carr VF, et al. (2010) 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease: executive summary. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Circulation 2010;121;e266-e369. 11. Reich DL, Uysal S, Sliwinski M, Ergin MA, Kahn RA, et al. (1999) Neuropsychologic outcome after deep hypothermic circulatory arrest in adults. J Thorac Cardiovasc Surg 117: 156-163. 12. Tanaka H, Okada K, Yamashita T, Morimoto Y, Kawanishi Y, et al. (2005) Surgical results of acute aortic dissection complicated with cerebral malperfusion. Ann Thorac Surg 80: 72-76. 13. Immer FF, Grobety V, Lauten A, Carrel TP (2006) Does malperfusion syndrome affect early and mid-term outcome in patients suffering from acute type A aortic dissection? Interact Cardiovasc Thorac Surg 5: 187-190. 14. Geirsson A, Szeto WY, Pochettino A, McGarvey ML, Keane MG, et al. (2007) Significance of malperfusion syndromes prior to contemporary surgical repair for acute type A dissection: outcomes and need for additional revascularizations. Eur J Cardiothorac Surg 32: 255-262. 15. Girdauskas E, Kuntze T, Borger MA, Falk V, Mohr FW (2009) Surgical risk of preoperative malperfusion in acute type A aortic dissection. J Thorac Cardiovasc Surg 138: 1363-1369. 16. Fischer GW, Lin HM, Krol M, Galati MF, Di Luozzo G, et al. (2011) Noninvasive cerebral oxygenation may predict outcome in patients undergoing aortic arch surgery. J Thorac Cardiovasc Surg 141: 815-821. 17. McCullough JN, Zhang N, Reich DL, Juvonen TS, Klein JJ, et al. (1999) Cerebral metabolic suppression during hypothermic circulatory arrest in humans. Ann Thorac Surg 67: 1895-1899; discussion 1919-1821. 18. Usui A, Abe T, Murase M (1996) Early clinical results of retrograde cerebral perfusion for aortic arch operations in Japan. Ann Thorac Surg 62: 94-103; discussion 103-104. 19. Krahenbuhl ES, Clement M, Reineke D, Czerny M, Stalder M, et al. (2010) Antegrade cerebral protection in thoracic aortic surgery: lessons from the past decade. Eur J Cardiothorac Surg 38: 46-51. Cheung AT Page 5 of 6 January 10, 2014 20. Owen-Reece H, Smith M, Elwell CE, Goldstone JC (1999) Near infrared spectroscopy. Br J Anaesth 82: 418-426. 21. McCormick PW, Stewart M, Goetting MG, Balakrishnan G (1991) Regional cerebrovascular oxygen saturation measured by optical spectroscopy in humans. Stroke 22: 596-602. 22. Ogino H, Ueda Y, Sugita T, Morioka K, Sakakibara Y, et al. (1998) Monitoring of regional cerebral oxygenation by near-infrared spectroscopy during continuous retrograde cerebral perfusion for aortic arch surgery. Eur J Cardiothorac Surg 14: 415-418. 23. Higami T, Kozawa S, Asada T, Obo H, Gan K, et al. (1999) Retrograde cerebral perfusion versus selective cerebral perfusion as evaluated by cerebral oxygen saturation during aortic arch reconstruction. Ann Thorac Surg 67: 1091-1096. 24. Blas ML, Lobato EB, Martin T (1999) Noninvasive infrared spectroscopy as a monitor of retrograde cerebral perfusion during deep hypothermia. J Cardiothorac Vasc Anesth 13: 244-245. 25. Janelle GM, Mnookin S, Gravenstein N, Martin TD, Urdaneta F (2002) Unilateral cerebral oxygen desaturation during emergent repair of a DeBakey type 1 aortic dissection: potential aversion of a major catastrophe. Anesthesiology 96: 1263-1265. 26. Fukada J, Morishita K, Kawaharada N, Yamauchi A, Hasegawa T, et al. (2003) Isolated cerebral perfusion for intraoperative cerebral malperfusion in type A aortic dissection. Ann Thorac Surg 75: 266-268. 27. Orihashi K, Sueda T, Okada K, Imai K (2004) Near-infrared spectroscopy for monitoring cerebral ischemia during selective cerebral perfusion. Eur J Cardiothorac Surg 26: 907-911. 28. Olsson C, Thelin S (2006) Regional cerebral saturation monitoring with near-infrared spectroscopy during selective antegrade cerebral perfusion: diagnostic performance and relationship to postoperative stroke. J Thorac Cardiovasc Surg 131: 371-379. 29. Baraka AS, Naufal M, El-Khatib M (2008) Cerebral oximetry during deep hypothermic circulatory arrest. J Cardiothorac Vasc Anesth 22: 173-174. 30. Santo KC, Barrios A, Dandekar U, Riley P, Guest P, et al. (2008) Near-infrared spectroscopy: an important monitoring tool during hybrid aortic arch replacement. Anesth Analg 107: 793-796. 31. Cheng HW, Chang HH, Chen YJ, Chang WK, Chan KH, et al. (2008) Clinical value of application of cerebral oximetry in total replacement of the aortic arch and concomitant vessels. Acta Anaesthesiol Taiwan 46: 178-183. 32. Totaro P, Argano V (2008) Innovative technique to treat acute cerebral and peripheral malperfusion during type A aortic dissection repair. Interact Cardiovasc Thorac Surg 7: 133-134. 33. Rubio A, Hakami L, Munch F, Tandler R, Harig F, et al. (2008) Noninvasive control of adequate cerebral oxygenation during low-flow antegrade selective cerebral perfusion on adults and infants in the aortic arch surgery. J Card Surg 23: 474-479. Cheung AT Page 6 of 6 January 10, 2014 34. Harrer M, Waldenberger FR, Weiss G, Folkmann S, Gorlitzer M, et al. (2010) Aortic arch surgery using bilateral antegrade selective cerebral perfusion in combination with near-infrared spectroscopy. Eur J Cardiothorac Surg 38: 561-567. 35. Anastasiadis K, Argiriadou H, Antonitsis P, Chalvatzoulis O, Papakonstantinou C (2011) Cerebral oximetry-guided antegrade cerebral perfusion in aortic arch surgery. J Cardiothorac Vasc Anesth 25: 591-592. 36. Wang SC, Lo PH, Shen JL, Shih CC, Chang WK, et al. (2011) Innominate artery dissection with presentation of sudden right frontal desaturation detected by cerebral oximetry in complicated thoracic aortic aneurysm repair surgery: a case report. J Clin Anesth 23: 137-141. 37. Senanayake E, Komber M, Nassef A, Massey N, Cooper G (2012) Effective cerebral protection using near-infrared spectroscopy monitoring with antegrade cerebral perfusion during aortic surgery. J Card Surg 27: 211-216. 38. Pisklak P, Youngblood S, Tolpin D, Coselli JS, LeMaire SA, et al. (2013) Performance of Near Infrared Spectroscopy During Hypothermic Circulatory Arrest and Correlation with Jugular Venous Saturation. ANESTH ANALG 116(SCA Suppl): 1-182. 39. (2013) Standards and Guidelines For Perfusion Practice. American Society of ExtraCorporeal Technology (AmSECT). 40. Denault A, Deschamps A, Murkin JM (2007) A proposed algorithm for the intraoperative use of cerebral near-infrared spectroscopy. Semin Cardiothorac Vasc Anesth 11: 274-281. Pg 1 Controversies in Guidelines: Where is the evidence that they actually improve outcomes? Martin J. London, M.D. Professor of Clinical Anesthesia University of California, San Francisco SCA Annual Meeting 2014 Clinical Guidelines have become a major industry in the brave new world of вЂњevidence-based medicineвЂќ. Many major subspecialty medical societies and health related governmental agencies (eg. NHLBI) have spent many millions of dollars over the past several decades since the very first one was published by the American College of Cardiology/American Heart Association (on pacemakers) in 1984. 1 Most SCA members are likely to be fairly well acquainted with a few relevant guidelines produced by the ACC/AHA of direct interest to our practices, as well as to management of patients with many forms of CV disease (IHD, CHF, Valvular, HOCM, etc.) that we encounter. 2 As well those produced by ASA in collaboration with the SCA have dealt with key process issues such as PA catheterization, TEE, and most recently Central Venous Access (which caused some degree of controversy in the ASA House of Delegates related to recommended use of surface ultrasound). 3-5 Given the echo focus of the SCA, we have been well represented on a number of guidelines from the American Society of Echocardiography (most notably of course the TEE based ones, but also epicardial/epiaortic imaging and vascular cannulation). As well, SCA has partnered on several occasions with the Society of Thoracic Surgeons, most notably on blood conservation guidelines for cardiac surgery. 6 CV practitioners who also wear a critical care hat at times are likely to be familiar with those from the Society of Critical Care Medicine (on management of sepsis), the American College of Chest Physicians (on management of thrombosis and also atrial fibrillation), those related to postoperative management of cardiac patients (including secondary prevention strategies after CABG popularized by the AHAвЂ™s вЂњGet with the GuidelinesвЂќ program) and the recent ACC/AHA/STS/SCA CABG guidelines and more recently by the AABBвЂ™s Guidelines on Blood Transfusion. 7,8 Pg 2 The current status of the universe of guidelines can probably best appreciated by a quick trip to the well maintained section of Agency for Healthcare Research and QualityвЂ™s website where a large list of guidelines indexed by the responsible society is warehoused (http://www.guideline.gov). This вЂњguideline clearinghouseвЂќ is a great effort to develop new strategies to deal with the proliferation of guidelines that are often produced in a somewhat haphazard manner by вЂњup and comingвЂќ societies with a variety of intentions (primarily good willed but possibly also to make themselves more visible). 9 Although there has been вЂњrumblingвЂќ among various вЂњend usersвЂќ of guidelines, almost from the start of the process several decades ago by front line physicians to academic physicians and health researchers trying to figure out who is doing what and how. 10-13 The prestigious Institute of Medicine has gotten involved in this process in a major way developing вЂњClinical Practice Guidelines We Can TrustвЂќ (Standards March 2011, www.iom.edu) with a very broad focus including controversial recommendations to include the lay public on guideline panels. Recently, the often public squabbles between various factions of the same subspecialty society have spilled over big time into the public media. Two recent and particularly heated topics have been reported very frequently (and to my opinion quite expertly) in the New York Times as well as most of the known вЂњblogosphereвЂќ. The firestorm of criticism over the recent ACC/AHA Guidelines for Cholesterol Management with its focus exclusively on randomized trials and dependence of very controversial cardiac risk calculators made it eminently clear to the public that guidelines are вЂњetched in stoneвЂќ. 14 The very long drawn out and contentious process involved in updating the new JNC 8 guidelines for management of hypertension (perhaps the most important public health issue in the country), involving fumbles and вЂњblown callsвЂќ between the government (NHLBI) and organizations such as ACC/AHA have also emphasized problems with this process. 15 Finally, not an issue that has made the news, but one that many CV anesthesiologists are interested in, is the somewhat embarrassing situation that the European Society of Cardiology has found itself in with Don Poldermans, the lead author of their Perioperative Evaluation Guidelines, who has been sacked by his prior employers (Erasmus University, Netherlands) for suspicion of academic impropriety and despite protesting his innocence, has clearly become a persona non gratis in academia. 16 That organization posted a note Pg 3 that it would review the status of the guidelines but has not taken any official action that I am aware of as of yet (and none of his articles have been retracted from any journals as well despite a strongly worded вЂњletter of concernвЂќ by the Journal of the American College of Cardiology). Thus, guideline controversies come in all shapes and flavors! In this short lecture, I will attempt to highlight a few of the less spectacular guidelines that most of us deal with in SCA (as noted above), highlighting what may or may not be known (or scientifically studied) regarding the evidence that guidelines actually alter outcome. I will also point out some of the potential major differences in methodology that even these few organizations use and speculate whether or not there ever will be real standardization! There are limited data out there on a few issues of interest such as how well various practitioners are of some guidelines (particularly the AHA Perioperative Evaluation Stress Testing and Beta Blocker Recommendations and the STS/SCA Blood Management guidelines). 17-30 Having been involved in the CABG guideline I will also point out what I just recently realized is an obvious flaw in the guideline dissemination process via the a lack of thorough guideline indexing for various process related subcomponents covered in the guideline (there are only five mesh terms for the entire guideline!) as well as how lack of publicity by Executive leadership perhaps has kept some of the issues addressed with formal recommendations permanently вЂњoff the radarвЂќ. I think as most of us would guess that trying to scientifically prove the efficacy of a process which is so вЂњprolificвЂќ and so well ingrained into our often flawed individual, group and national decision health policy making is nearly impossible. Obviously, there is no way to do a simultaneous randomized trial of a guideline versus its вЂњnon-useвЂќ so any designs are inherently flawed anyway. My personal opinion is that guidelines are an absolutely necessary and incredibly valuable service provided to rank and file physicians and other health care providers. Inevitable advances in handling of вЂњbig dataвЂќ and вЂњbibliometryвЂќ (eg. automated data searching of literature citations in databases such as PUBMED) allowing capture of information from a burgeoning number of journals and even major data registries and much more precise grading and synthesis of such data will take much of the controversy out of guidelines in the next decade. They will not only Pg 4 alter outcomes, but also drive our practice patterns unless other compelling information emerges. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. Frye RL, Collins JJ, DeSanctis RW, et al.: Guidelines for permanent cardiac pacemaker implantation, May 1984. A report of the Joint American College of Cardiology/American Heart Association Task Force on Assessment of Cardiovascular Procedures (Subcommittee on Pacemaker Implantation). Circulation 1984; 70: 331A-339A London MJ: The role of the SCA and the cardiovascular anesthesiologist in guideline development: The 2011 AHA/ACCF CABG guidelines as a case in point, Practice Guidelines in Cardiovascular Anesthesia: Updates and Controversies. Edited by London MJ. Baltimore, Lippincott Williams & Wilkins, 2012, pp 17 - 33 American SoAaSoCATFoTE: Practice guidelines for perioperative transesophageal echocardiography. An updated report by the American Society of Anesthesiologists and the Society of Cardiovascular Anesthesiologists Task Force on Transesophageal Echocardiography. Anesthesiology 2010; 112: 1084-96 Anonymous: Practice guidelines for pulmonary artery catheterization: an updated report by the American Society of Anesthesiologists Task Force on Pulmonary Artery Catheterization. Anesthesiology 2003; 99: 988-1014 Rupp SM, Apfelbaum JL, Blitt C, et al.: Practice guidelines for central venous access: a report by the American Society of Anesthesiologists Task Force on Central Venous Access. Anesthesiology 2012; 116: 539-73 Ferraris VA, Brown JR, Despotis GJ, et al.: 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg 2011; 91: 944-82 Denton TA, Fonarow GC, LaBresh KA, Trento A: Secondary prevention after coronary bypass: the American Heart Association "Get with the Guidelines" program. Ann Thorac Surg 2003; 75: 758-60. Carson JL, Grossman BJ, Kleinman S, et al.: Red Blood Cell Transfusion: A Clinical Practice Guideline From the AABB*. Ann Intern Med 2012; 157: 49-58 Kahn R, Gale EA: Gridlocked guidelines for diabetes. Lancet 2010; 375: 2203-4 Cabana MD, Rand CS, Powe NR, et al.: Why don't physicians follow clinical practice guidelines? A framework for improvement. Jama 1999; 282: 1458-65 Shaneyfelt TM, Mayo-Smith MF, Rothwangl J: Are guidelines following guidelines? The methodological quality of clinical practice guidelines in the peer-reviewed medical literature. JAMA 1999; 281: 1900-5 Grilli R, Magrini N, Penna A, et al.: Practice guidelines developed by specialty societies: the need for a critical appraisal. Lancet 2000; 355: 103-6 Choudhry NK, Stelfox HT, Detsky AS: Relationships between authors of clinical practice guidelines and the pharmaceutical industry. JAMA 2002; 287: 612-7 Stone NJ, Robinson J, Lichtenstein AH, et al.: 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Pg 5 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2013 James PA, Oparil S, Carter BL, et al.: 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA 2013 Poldermans D, Bax JJ, Boersma E, et al.: Guidelines for pre-operative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery. Eur Heart J 2009; 30: 2769-812 Stover EP, Siegel LC, Parks R, et al.: Variability in transfusion practice for coronary artery bypass surgery persists despite national consensus guidelines: a 24-institution study. Institutions of the Multicenter Study of Perioperative Ischemia Research Group. Anesthesiology 1998; 88: 327-33 Fyfe D: Transesophageal echocardiography guidelines: return to bypass or to bypass the guidelines? J Am Soc Echocardiogr 1999; 12: 343-4 Farid I, Litaker D, Tetzlaff JE: Implementing ACC/AHA guidelines for the preoperative management of patients with coronary artery disease scheduled for noncardiac surgery: effect on perioperative outcome. J Clin Anesth 2002; 14: 126-8 Cassar K, Belch JJ, Brittenden J: Are national cardiac guidelines being applied by vascular surgeons? Eur J Vasc Endovasc Surg 2003; 26: 623-8 Falcone RA, Nass C, Jermyn R, et al.: The value of preoperative pharmacologic stress testing before vascular surgery using ACC/AHA guidelines: a prospective, randomized trial. J Cardiothorac Vasc Anesth 2003; 17: 694-8 Gordon AJ, Macpherson DS: Guideline chaos: conflicting recommendations for preoperative cardiac assessment. Am J Cardiol 2003; 91: 1299-303 Siddiqui AK, Ahmed S, Delbeau H, et al.: Lack of physician concordance with guidelines on the perioperative use of beta-blockers. Arch Intern Med 2004; 164: 664-7 Almanaseer Y, Mukherjee D, Kline-Rogers EM, et al.: Implementation of the ACC/AHA guidelines for preoperative cardiac risk assessment in a general medicine preoperative clinic: improving efficiency and preserving outcomes. Cardiology 2005; 103: 24-9 Barak M, Ben-Abraham R, Katz Y: ACC/AHA guidelines for preoperative cardiovascular evaluation for noncardiac surgery: a critical point of view. Clin Cardiol 2006; 29: 195-8 Likosky DS, FitzGerald DC, Groom RC, et al.: The effect of the perioperative blood transfusion and blood conservation in cardiac surgery Clinical Practice Guidelines of the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists upon clinical practices. J Extra Corpor Technol 2010; 42: 114-21 Likosky DS, FitzGerald DC, Groom RC, et al.: Effect of the perioperative blood transfusion and blood conservation in cardiac surgery clinical practice guidelines of the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists upon clinical practices. Anesth Analg 2010; 111: 316-23 London MJ: New practice guidelines for perioperative beta blockade from the United States and Europe: incremental progress or a necessary evil? Can J Anaesth 2010; 57: 301-12 Pg 6 29. Sear JW, Foex P: Recommendations on perioperative beta-blockers: differing guidelines: so what should the clinician do? Br J Anaesth 2010; 104: 273-5 30. Vigoda MM, Sweitzer B, Miljkovic N, et al.: 2007 American College of Cardiology/American Heart Association (ACC/AHA) Guidelines on perioperative cardiac evaluation are usually incorrectly applied by anesthesiology residents evaluating simulated patients. Anesth Analg 2011; 112: 940-9 В OPCABВ vsВ CABG:В WhereВ isВ theВ Difference?В В RomanВ M.В Sniecinski,В MD,В FASE AnnualВ 2014В AssociateВ ProfessorВ ofВ Anesthesiology EmoryВ UniversityВ SchoolВ ofВ Medicine В LearningВ ObjectivesВ п‚· п‚· ExplainВ theВ anestheticВ implicationsВ ofВ bothВ techniquesВ DescribeВ resultsВ ofВ majorВ trialsВ andВ potentialВ biasesВ В BackgroundВ AlthoughВ notВ widelyВ known,В theВ firstВ successfulВ coronaryВ arteryВ bypassВ wasВ performedВ inВ 1960В byВ RobertВ H.В GoetzВ atВ theВ AlbertВ EinsteinВ CollegeВ ofВ MedicineВ inВ NewВ York.(1)В В ByВ report,В theВ anastomosis,В usingВ aВ speciallyВ designedВ metalВ ringВ forВ theВ internalВ mammaryВ artery,В tookВ underВ 20В seconds.В В TheВ patient,В whoВ underwentВ theВ operationВ forВ intractableВ angina,В returnedВ toВ workВ asВ aВ taxiВ driverВ followingВ anВ uneventfulВ recoveryВ andВ survivedВ forВ moreВ thanВ aВ yearВ afterwards.В В SeveralВ yearsВ later,В VasiliiВ KolesovВ ofВ RussiaВ reportedВ anВ anastomosisВ usingВ aВ sutureВ techniqueВ moreВ closelyВ resemblingВ thatВ usedВ inВ modernВ cardiacВ surgery,(2)В andВ forВ aВ periodВ ofВ timeВ itВ wasВ theВ onlyВ techniqueВ utilized.(3)В В So,В theВ birthВ ofВ coronaryВ arteryВ bypassВ graftingВ (CABG),В oneВ ofВ theВ mostВ commonlyВ performedВ electiveВ surgicalВ proceduresВ inВ theВ world,В actuallyВ occurredВ withoutВ theВ useВ ofВ extracorporealВ circulation.В В ItВ isВ somewhatВ ironicВ thatВ theВ вЂњgoldВ standardвЂќВ becameВ theВ useВ ofВ cardiopulmonaryВ bypassВ (CPB)В forВ theВ procedureВ andВ offвЂђ pumpВ coronaryВ arteryВ bypassВ (OPCAB)В surgeryВ theВ вЂњnewcomer.вЂќВ В CABGВ surgeryВ usingВ CPBВ TheВ firstВ successfulВ useВ ofВ CPBВ occurredВ inВ 1953В whenВ JohnВ GibbonВ closedВ anВ atrialВ septalВ defectВ inВ anВ 18В yearВ oldВ patient.(4)В В TheВ technologyВ wasВ crudeВ atВ theВ time,В however,В andВ itВ wasВ notВ untilВ muchВ laterВ thatВ CPBВ wouldВ beВ appliedВ towardВ coronaryВ revascularizationВ procedures,В whichВ wereВ alsoВ inВ theirВ infancy.В В TheВ firstВ successfulВ coronaryВ arteryВ bypassВ usingВ aВ pieceВ ofВ saphenousВ veinВ andВ extracorporealВ circulationВ isВ largelyВ creditedВ toВ ReneВ FavaloroВ atВ theВ ClevelandВ ClinicВ inВ 1967.(5)В В EnthusiasmВ forВ theВ procedureВ grewВ andВ byВ 1969В thereВ wereВ aroundВ 500В hospitalsВ inВ theВ UnitedВ StatesВ withВ CPBВ capabilityВ performingВ aroundВ 5,000В revascularizationВ proceduresВ ofВ oneВ typeВ orВ anotherВ annually.(6)В В GivenВ thatВ thereВ areВ moreВ thanВ 13В millionВ AmericansВ withВ CAD,В itВ isВ noВ surpriseВ thatВ thisВ numberВ hasВ balloonedВ toВ 400,000В CABGВ proceduresВ nowВ performedВ annually,(7)В withВ aboutВ 80%В ofВ themВ utilizingВ CPB.В FromВ anВ anestheticВ pointВ ofВ view,В theВ challengesВ ofВ CPBВ comeВ notВ duringВ theВ actualВ CABGВ procedure,В butВ fromВ preparingВ forВ itsВ initiationВ andВ separation.В В FactorsВ contributingВ toВ inflammatoryВ andВ hemostaticВ activationВ duringВ CPBВ haveВ beenВ extensivelyВ reviewedВ andВ theВ anesthesiologistвЂ™sВ goalВ isВ toВ minimizeВ theirВ sequelae.(8,9)В В OftenВ whatВ isВ doneВ forВ CABGВ onВ CPBВ isВ directlyВ oppositeВ toВ managementВ forВ OPCAB.В В ForВ example,В fluidВ restrictionВ inВ theВ preвЂђCPBВ periodВ isВ oftenВ employedВ toВ minimizeВ hemodilution.В В ForВ OPCABs,В however,В fluidВ loadingВ isВ oftenВ requiredВ toВ ensureВ adequateВ preвЂђloadВ duringВ cardiacВ manipulations.В В TheВ majorВ managementВ differencesВ areВ summarizedВ inВ theВ tableВ below.В В MajorВ ManagementВ DifferencesВ ofВ CABGВ onВ CPBВ vsВ OPCABВ StageВ ofВ ProcedureВ CABGВ onВ CPBВ ConcernsВ OPCABВ ConcernsВ MinimizeВ myocardialВ MVO2 ConsiderВ needВ forВ loadingВ inotropesВ inВ ConduitВ HarvestВ В RestrictВ IVFВ toВ minimizeВ hemodilutionВ InitiationВ ofВ CPBВ EnsureВ adequateВ anticoagulation В AntifibrinolyticВ useВ commonВ DistalВ AnastomosesВ KeepВ heartВ quiescent В MinimalВ hemodynamicВ disturbancesВ SeparationВ fromВ CPBВ RampВ upВ inotropicВ support ProcedureВ EndВ /В Misc.В RewarmingВ managedВ byВ perfusionist anticipationВ ofВ heartВ manipulationsВ В IVFВ administrationВ toВ ensureВ adequateВ preвЂђloadВ (N/A)В ACTВ targetВ lessВ wellвЂђdefinedВ В AspirinВ oftenВ administeredВ KeepВ heartВ beating;В epicardialВ pacingВ oftenВ employedВ В MajorВ hemodynamicВ disturbancesВ (N/A)В OftenВ ableВ toВ weanВ pressorsВ followingВ distalВ completionВ В HypothermiaВ aВ problemВ вЂ“В needВ activeВ heatingВ measuresВ throughoutВ operationВ В В OPCABВ SurgeryВ FromВ aВ surgicalВ standpoint,В itВ isВ moreВ difficultВ toВ sewВ onВ aВ beatingВ heart.В В ThisВ problemВ hasВ beenВ amelioratedВ byВ specializedВ devicesВ developedВ andВ marketedВ inВ theВ midвЂђ1990вЂ™sВ thatВ helpВ positionВ theВ heartВ andВ stabilizeВ theВ involvedВ sectionВ ofВ myocardium.В В DespiteВ theseВ advances,В communicationВ betweenВ theВ surgeonВ andВ anesthesiologistВ isВ criticalВ toВ determineВ whatВ positionВ theВ patientВ willВ orВ willВ notВ tolerate.В В InВ orderВ toВ alleviateВ someВ ofВ theВ hemodynamicВ consequencesВ ofВ OPCABВ duringВ distalВ anastomoses,В surgicalВ maneuversВ suchВ asВ openingВ theВ pleuralВ spaceВ toВ alleviateВ compressionВ andВ employingВ intracoronaryВ shuntsВ canВ beВ used.В В AВ 3В minuteВ вЂњtrialвЂќВ periodВ priorВ toВ arteriotomyВ isВ helpfulВ toВ avoidВ emergentВ conversionВ toВ CPB,В whichВ isВ associatedВ withВ aВ significantlyВ higherВ mortalityВ rate.(10)В В OutcomesВ ofВ CABGВ withВ CPBВ versusВ OPCABВ ThereВ areВ passionateВ proponentsВ andВ opponentsВ whenВ itВ comesВ toВ thisВ issue.В В TheВ majorВ pointsВ ofВ contentionВ areВ generallyВ summedВ upВ asВ follows:В В ProвЂђOPCABВ ArgumentsВ п‚· п‚· п‚· ReducedВ neurocognitiveВ dysfunctionВ byВ avoidingВ cannulationВ andВ aorticВ crossвЂђclampingВ AvoidanceВ ofВ theВ systemicВ inflammatoryВ responseВ andВ itsВ postвЂђopВ sequelaeВ DecreasedВ bloodВ productВ useВ withВ betterВ postвЂђopВ pulmonaryВ andВ renalВ functionВ ProВ CABGВ withВ CPBВ ArgumentsВ п‚· п‚· п‚· IncompleteВ revascularizationВ withВ OPCABВ /В poorerВ longвЂђtermВ graftВ patencyВ EmergencyВ conversionВ ofВ OPCABВ toВ CPBВ resultsВ inВ higherВ mortalityВ OPCABВ hasВ higherВ degreeВ ofВ technicalВ difficultyВ withВ noВ provenВ advantagesВ MultipleВ randomizedВ controlledВ trialsВ haveВ beenВ performedВ toВ addressВ theseВ arguments,В butВ mostВ haveВ beenВ insufficientlyВ poweredВ toВ detectВ differencesВ inВ aВ procedureВ withВ suchВ aВ lowВ morbidityВ andВ mortalityВ rate.В В SomeВ betterвЂђknownВ RCTsВ directlyВ comparingВ CABGВ withВ (on)В andВ withoutВ (off)В theВ useВ ofВ CPBВ areВ presentedВ belowВ withВ theirВ latestВ followвЂђupВ andВ limitations.В В TrialВ (n=On/n=Off)В BHACASВ IВ &В IIВ (201/200)В OctopusВ StudyВ (139/142)В SMARTВ (99/98)В ROOBYВ StudyВ (1099/1104)В CORONARYВ StudyВ (2377/2375)В FollowвЂђupВ /В MajorВ ConclusionsВ 6вЂђ8В yearВ FU:В NoВ differenceВ inВ graftВ patencyВ orВ perceivedВ QOL(11)В 5В yearВ FU:В NoВ differenceВ inВ cognitiveВ functionВ orВ cardiacВ outcome(12)В 6вЂђ8В yearВ FU:В NoВ differenceВ inВ mortalityВ orВ graftВ patency,В lowerВ costsВ inВ OPCAB(13)В 1В yearВ FU:В LowerВ graftВ patencyВ andВ higherВ mortalityВ inВ OPCAB(14)В 1В yearВ FU:В NoВ significantВ differenceВ inВ mortality,В QOL,В orВ cognitiveВ function(15)В NotesВ SignificantВ improvementВ inВ OPCABВ betweenВ trialsВ IВ andВ IIВ LowвЂђriskВ patientВ populationВ onlyВ SingleВ center;В highlyВ experiencedВ surgeonsВ inВ OPCABВ LowВ riskВ malesВ only;В veryВ highВ OPCABВ toВ CPBВ conversionВ rateВ LargestВ multicenterВ RCTВ toВ date;В plannedВ 5В yearВ FUВ В AВ recentВ CochraneВ metaвЂђanalysisВ ofВ 86В trialsВ includingВ overВ tenВ thousandВ patientsВ concludedВ thatВ OPCABВ providedВ noВ benefitВ withВ regardВ toВ strokeВ orВ MIВ and,В inВ fact,В demonstratedВ lowerВ longвЂђtermВ survival.(16)В В However,В asВ mentionedВ above,В mostВ RCTsВ involveВ onlyВ lowВ riskВ patientsВ withВ anВ expectedВ STSВ mortalityВ ofВ 1вЂђ2%.В В InВ anВ observationalВ analysisВ ofВ theВ STSВ databaseВ (14,766В patients),В PuskasВ andВ colleaguesВ reportedВ lowerВ hospitalВ mortalityВ inВ theВ highestвЂђriskВ groupВ withВ OPCAB.(17)В В ItВ isВ likelyВ thatВ theВ bestВ approachВ toВ CABGВ willВ dependВ uponВ patientВ riskВ factorsВ andВ surgeonВ experience.В В ExactlyВ whatВ factorsВ favorВ OPCABВ andВ whatВ surgeonsВ areВ experiencedВ enoughВ willВ likelyВ remainВ aВ matterВ ofВ debateВ forВ someВ time.В В ReferencesВ 1.В В 2.В В 3.В В 4.В В 5.В В 6.В В 7.В В 8.В В 9.В В 10.В В 11.В GoetzВ RH,В RohmanВ M,В HallerВ JD,В DeeВ R,В RosenakВ SS.В InternalВ mammaryвЂђcoronaryВ arteryВ anastomosis.В AВ nonsutureВ methodВ employingВ tantalumВ rings.В TheВ JournalВ ofВ thoracicВ andВ cardiovascularВ surgeryВ 1961;41:378вЂђ86.В KolesovВ VI,В PotashovВ LV.В [SurgeryВ ofВ coronaryВ arteries].В Eksperimental'naiaВ khirurgiiaВ iВ anesteziologiiaВ 1965;10:3вЂђ8.В KonstantinovВ IE.В VasiliiВ IВ Kolesov:В aВ surgeonВ toВ remember.В TexasВ HeartВ InstituteВ journalВ /В fromВ theВ TexasВ HeartВ InstituteВ ofВ StВ Luke'sВ EpiscopalВ Hospital,В TexasВ Children'sВ HospitalВ 2004;31:349вЂђ 58.В GibbonВ JH,В Jr.В ApplicationВ ofВ aВ mechanicalВ heartВ andВ lungВ apparatusВ toВ cardiacВ surgery.В MinnesotaВ medicineВ 1954;37:171вЂђ85;В passim.В FavaloroВ RG.В LandmarksВ inВ theВ developmentВ ofВ coronaryВ arteryВ bypassВ surgery.В CirculationВ 1998;98:466вЂђ78.В GlennВ WW.В SomeВ reflectionsВ onВ theВ coronaryВ bypassВ operation.В CirculationВ 1972;45:869вЂђ77.В EpsteinВ AJ,В PolskyВ D,В YangВ F,В YangВ L,В GroeneveldВ PW.В CoronaryВ revascularizationВ trendsВ inВ theВ UnitedВ States,В 2001вЂђ2008.В JAMAВ :В theВ journalВ ofВ theВ AmericanВ MedicalВ AssociationВ 2011;305:1769вЂђ76.В LevyВ JH,В TanakaВ KA.В InflammatoryВ responseВ toВ cardiopulmonaryВ bypass.В TheВ AnnalsВ ofВ thoracicВ surgeryВ 2003;75:S715вЂђ20.В SniecinskiВ RM,В ChandlerВ WL.В ActivationВ ofВ theВ hemostaticВ systemВ duringВ cardiopulmonaryВ bypass.В AnesthesiaВ andВ analgesiaВ 2011;113:1319вЂђ33.В ChowdhuryВ R,В WhiteВ D,В KilgoВ P,В PuskasВ JD,В ThouraniВ VH,В ChenВ EP,В LattoufВ OM,В CooperВ WA,В MyungВ RJ,В GuytonВ RA,В HalkosВ ME.В RiskВ factorsВ forВ conversionВ toВ cardiopulmonaryВ bypassВ duringВ offвЂђpumpВ coronaryВ arteryВ bypassВ surgery.В TheВ AnnalsВ ofВ thoracicВ surgeryВ 2012;93:1936вЂђ41;В discussionВ 42.В AngeliniВ GD,В CullifordВ L,В SmithВ DK,В HamiltonВ MC,В MurphyВ GJ,В AscioneВ R,В BaumbachВ A,В ReevesВ BC.В EffectsВ ofВ onвЂђВ andВ offвЂђpumpВ coronaryВ arteryВ surgeryВ onВ graftВ patency,В survival,В andВ healthвЂђ relatedВ qualityВ ofВ life:В longвЂђtermВ followвЂђupВ ofВ 2В randomizedВ controlledВ trials.В TheВ JournalВ ofВ thoracicВ andВ cardiovascularВ surgeryВ 2009;137:295вЂђ303.В В 12.В В 13.В В 14.В В 15.В В 16.В В 17.В В В vanВ DijkВ D,В SpoorВ M,В HijmanВ R,В NathoeВ HM,В BorstВ C,В JansenВ EW,В GrobbeeВ DE,В deВ JaegereВ PP,В KalkmanВ CJ.В CognitiveВ andВ cardiacВ outcomesВ 5В yearsВ afterВ offвЂђpumpВ vsВ onвЂђpumpВ coronaryВ arteryВ bypassВ graftВ surgery.В JAMAВ :В theВ journalВ ofВ theВ AmericanВ MedicalВ AssociationВ 2007;297:701вЂђ8.В PuskasВ JD,В WilliamsВ WH,В O'DonnellВ R,В PattersonВ RE,В SigmanВ SR,В SmithВ AS,В BaioВ KT,В KilgoВ PD,В GuytonВ RA.В OffвЂђpumpВ andВ onвЂђpumpВ coronaryВ arteryВ bypassВ graftingВ areВ associatedВ withВ similarВ graftВ patency,В myocardialВ ischemia,В andВ freedomВ fromВ reintervention:В longвЂђtermВ followвЂђupВ ofВ aВ randomizedВ trial.В TheВ AnnalsВ ofВ thoracicВ surgeryВ 2011;91:1836вЂђ42;В discussionВ 42вЂђ3.В ShroyerВ AL,В GroverВ FL,В HattlerВ B,В CollinsВ JF,В McDonaldВ GO,В KozoraВ E,В LuckeВ JC,В BaltzВ JH,В NovitzkyВ D.В OnвЂђpumpВ versusВ offвЂђpumpВ coronaryвЂђarteryВ bypassВ surgery.В TheВ NewВ EnglandВ journalВ ofВ medicineВ 2009;361:1827вЂђ37.В LamyВ A,В DevereauxВ PJ,В PrabhakaranВ D,В TaggartВ DP,В HuВ S,В PaolassoВ E,В StrakaВ Z,В PiegasВ LS,В AkarВ AR,В JainВ AR,В NoiseuxВ N,В PadmanabhanВ C,В BahamondesВ JC,В NovickВ RJ,В VaijyanathВ P,В ReddyВ SK,В TaoВ L,В OlavegogeascoecheaВ PA,В AiranВ B,В SullingВ TA,В WhitlockВ RP,В OuВ Y,В PogueВ J,В ChrolaviciusВ S,В YusufВ S.В EffectsВ ofВ offвЂђpumpВ andВ onвЂђpumpВ coronaryвЂђarteryВ bypassВ graftingВ atВ 1В year.В TheВ NewВ EnglandВ journalВ ofВ medicineВ 2013;368:1179вЂђ88.В MollerВ CH,В PenningaВ L,В WetterslevВ J,В SteinbruchelВ DA,В GluudВ C.В OffвЂђpumpВ versusВ onвЂђpumpВ coronaryВ arteryВ bypassВ graftingВ forВ ischaemicВ heartВ disease.В TheВ CochraneВ databaseВ ofВ systematicВ reviewsВ 2012;3:CD007224.В PuskasВ JD,В ThouraniВ VH,В KilgoВ P,В CooperВ W,В VassiliadesВ T,В VegaВ JD,В MorrisВ C,В ChenВ E,В SchmotzerВ BJ,В GuytonВ RA,В LattoufВ OM.В OffвЂђpumpВ coronaryВ arteryВ bypassВ disproportionatelyВ benefitsВ highвЂђ riskВ patients.В TheВ AnnalsВ ofВ thoracicВ surgeryВ 2009;88:1142вЂђ7.В Fireside Chat: Getting Promoted Without Original Research or NIH Grants Glenn P. Gravlee, MD; Mark F. Newman, MD Educational Objectives After attending this session, the participant will be better able to 1. Describe the variability in promotion criteria among institutions 2. Explain the concept of a teaching portfolio 3. Explain the importance of networking and reputation building In deference to the reality that the вЂњclinical engineвЂќ is largely what drives medical school finances, medical schools around the U.S. increasingly embrace promotion models that honor clinical activity with promotion from assistant to associate professor or even from associate professor to professor. This transition has been fraught with inter-institutional political strife, and the specifics of its application have been many and varied. The political strife derives from those who cling to the вЂњpublish or perishвЂќ model, i.e., basic science researchers. Having been inculcated with вЂњpublication feverвЂќ while earning their Ph.Ds, undergraduate school faculty often resist this change as well. Clinical department chairs best appreciate the need for alternative promotion models, because they constantly engage in a tug-of-war between academic and clinical productivity. Although the money comes primarily from clinical operations, accolades and departmental bragging rights derive largely from research and publications. One can argue that academic anesthesiology departments are caught in this vice grip more than any other clinical department. Anesthesiologists have negligible control over scheduling the clinical service they provide, and they are expected to deliver вЂњservice on demandвЂќ on days, nights, weekends, and holidays. Over the course of my 40 years since medical school graduation, there has been gradual blurring of the definitions of elective vs emergency procedures. Economics have driven this transition as well, which result from pressure to minimize length of hospital stay and the fact that reimbursement is sometimes available for uninsured patients when they come to surgery directly from the emergency room or from an inpatient hospital bed, but unavailable if they present for elective surgery. Another factor pushing clinical productivity is the relatively high compensation of academic anesthesiologists as compared to our colleagues in primary care. If anesthesiologist annual salary expectations fell into the low $200,000s range, then it would be much easier to carve out time for academic pursuits. Market forces that I believe originated from the 1990s shortage of anesthesiologists drove anesthesiologist pay expectations into the $300,000+ range. Since university payer mixes largely preclude sufficient revenue to compensate anesthesiologists at that level, academic departments have become increasingly dependent on subsidies from hospital administrations, which now average over $100,000 per faculty member per year. Even in a university medical school setting, hospital administrators are much more concerned about clinical service than about academic productivity, and the more they contribute to anesthesiologist salaries, the more concerned they become. All of these factors combine to make academic anesthesiologists especially interested in achieving career advancement through means other than the publication of original scientific peer-reviewed research papers. Fortunately, the avenues for pursuit of this goal have been proliferating in recent years. As an example, at the University of Colorado, promotion to Associate Professor requires excellence in one of the following three endeavors: research, teaching, or clinical service, and meritorious performance in one of the other two areas. Owing to the residual influence of basic scientists (and often to research-driven internal medicine departments), the bar for excellence in research is prohibitively high for most academic anesthesiologists. In essence, the coin of that realm is principal investigator status on at least one NIH grant, with significant peer-reviewed first- or senior-author research publications required even for promotion to associate professor. For practical purposes, this excludes all but a few of our faculty. Because of a 7-year up-or-out time clock for promotion to associate professor, this leaves us with teaching or clinical service as conduits to associate professor rank. At the University of Colorado, excellence in teaching involves proving excellence typically several of the following categories: п‚· Greater than average share of teaching duties п‚· Outstanding teaching evaluations or teaching awards п‚· Innovative teaching methods or curricula п‚· Organization of CME courses at a regional to national level п‚· Participation in national activities such as an RRC or board examinations п‚· Visiting professor and national meeting speaking invitations п‚· Educational leadership through mechanisms such as curriculum development, assistant dean roles, allied health education program directorship, residency program director, textbooks, or media/internet course materials Excellence in clinical service is judged by the following criteria: п‚· Extended time spent in clinical activities judged to be highly effective п‚· Development of new techniques, therapies, or delivery systems п‚· Creative participation in the evaluation of effectiveness/quality of patient care п‚· Clinical practice leadership roles, e.g., head of a division or dept., medical staff leadership roles, operating room/ICU/pain clinic management п‚· Regional/national leadership roles: state medical boards, state medical or specialty society leadership, leadership in clinically oriented national committees or task forces п‚· Chairing national symposia and meetings, journal editorial roles, etc. Even in institutions that have developed so-called clinical tracks, there will be at least moderately rigorous standards for judging clinical excellence for promotion to associate professor. For professor in such tracks, there will seldom be escape from proving a national reputation. One cannot assume that showing up and doing satisfactory work in the operating rooms day-in, day-out will result in promotion. The three benchmarks for judging excellence in these non-research domains are 1. DOCUMENTATION, 2. DOCUMENTATION, and 3. DOCUMENTATION. Clinically oriented doctors often err on the side of presuming that the importance of their activities is self-evident. In thinking about this, consider that you will ultimately be judged at least partially by someone like a Professor of Biochemistry who has only begrudgingly accepted that anything other than NIH grants and top-tier first-author research publications should be viewed as acceptable fodder for promotion, even to Associate Professor. So the keys to the castle reside in the faculty memberвЂ™s ability to provide compelling documentation in areas where such documentation requires considerable creativity. ItвЂ™s easy to document research productivity, but much harder to document educational and clinical service activities. IT BEHOOVES JUNIOR FACULTY TO THINK ABOUT THE NEED FOR THIS DOCUMENTATION EARLY AND OFTEN, rather than waiting until year 6.8 out of 7 (or whatever oneвЂ™s local calendar dictates) to commence this process. At CU, deeply entrenched procrastination has engendered mandatory mid-term reviews for assistant professors. To a significant degree, responsibility for conveying this importance resides in the ChairвЂ™s office. The Chair should organize mentorship within (or at times outside) the department to educate young faculty members about how best to вЂњworkвЂќ this system. Systematic development of advisor or mentoring systems is highly desirable. This system should entail periodic meetings between mentor/advisor and mentee/advisee, ideally with some documentation (however cursory) that such meetings have occurred. A critical task is to study and master the requirements for promotion within your specific institution. Ideally one should arm oneself with substantial knowledge of an institutionвЂ™s options and requirements before accepting a faculty position! In most cases, this will viewed as astute rather than pushy. Topics for group discussion could include: п‚· Teaching portfolios in general and specifically п‚· Clinical portfolios in general and specifically п‚· Dossier preparation п‚· Teaching philosophy statements п‚· Former student testimonials and letters п‚· Networking for the purpose of outside promotion letters п‚· Documentation of teaching expertise using outcomes rather than traditional teaching evaluations п‚· п‚· Pros and cons of dual- or multi-track promotion tiers vs single-track systems Specific local perspectives on academic advancement Fireside Chat - Private Practice: Showing value in an ACO model Christopher A. Troianos, MD Professor and Chief of Anesthesiology Western Pennsylvania Hospital of the Allegheny Health Network Western Campus of Temple University School of Medicine Pittsburgh, Pennsylvania Solomon Aronson, MD, MBA Professor and Executive Vice Chair, Department of Anesthesiology Duke University School of Medicine Durham, North Carolina An Accountable Care Organization (ACO) is a collaboration of health care providers and payers who coordinate patient care within a healthcare community for the purpose of effectively managing and ultimately improving the health of the patients within that community. A key aspect of this arrangement is the development of accountability among its members and to promote objectives through an incentive-based compensation system that transcends treatment across the continuum of patient care settings, including physician offices, hospitals, and longterm care facilities. Reimbursement systems are broadly classified as performance risk and utilization risk. The purpose of this collaboration is to provide the highest quality care at the lowest possible cost; ultimately improving the health of the population of people cared for within the ACO. The ACO concept of delivering healthcare is not new, having taken the form of pay-forperformance, bundled payments, and shared savings. The concept has received renewed interest with the passage of the Affordable Care Act by Congress in 20101. Section 3022 of the Affordable Care Act establishes a Shared Savings Program that rewards ACOs that lower growth in healthcare costs while meeting performance standards on quality care.2 If the provision of high quality efficient healthcare saves money, the ACO can share in a percentage of the savings with the Centers for Medicare and Medicaid Services (CMS). Conversely if an ACO fails to provide efficient and cost-effective care, it may be required to return payments to CMS.3 ACOs include group practices, networks of individual practices, partnerships or joint venture arrangements between hospitals and ACO professionals, hospitals employing ACO professionals, and critical access hospitals using certain CMS billing procedures that provide the data elements necessary for an ACO to operate. Anesthesiologists that embrace this patient-centric patient care approach can be very successful in this ACO model because they will be comfortable navigating through diverse patient care settings and with a variety of medical specialties to improve processes and direct protocols. They are generally comfortable with new technologies, and have traditionally been leaders in improving patient safety and quality care. Anesthesiologists will be sought to lead and coalesce fragmented delivery systems. Those who embrace this new role and lead the integration will be most successful as their contributions become recognized and valued by hospitals and other practitioners who face the same scrutiny for value-based outcomes for the same patient population. Cardiac anesthesiologists are particularly suited to this new role because they have been collaborating with cardiac surgeons and cardiologists for many years in their role as echocardiographers. They discuss diagnostic findings, weigh therapeutic options with their colleagues taking into account risks versus benefits, and often care for patients in critical care settings after surgery. They have traditionally led the develop of criteria and protocols for betablocker and hyperglycemic management, fast-tracking, and early extubation protocols to name a few examples. The challenge for private practice anesthesiologists in particular, will be to embrace their role in supporting these endeavors by providing their colleagues the time and resources to вЂњbe at the tableвЂќ during the development of protocols and strategies. It will be hard for private practice anesthesiologists to give up their independence and commit to becoming interdependent with other physicians. Private practice groups will be challenged to be transparent and open in their discussions and protocol development. Yet the success of the ACO is dependent on the efficient utilization of resources, an area where anesthesiologists may be particularly helpful to promote and lead. Anesthesiologists should be accountable for developing protocols and strategies that include more efficient staffing of both hospital and anesthesia resources. They must be open to discuss and explain operational resources, limitations, and administrative strategies for the benefit of the ACO. The only way for anesthesiologists to survive in the era of the ACO will be as willing participants and champions for efficiency and quality care. There is much to lose by trying to hold on to the old paradigm that our value is limited to the intraoperative setting of patient care. The old adage of вЂњif youвЂ™re not at the table, youвЂ™re on the menuвЂќ certainly applies to the ACO model of health care delivery in private practice. References: 1. The вЂњAffordable Care ActвЂќ refers to the Federal Patient Protection and Affordable Care Act (Pub. L. 111-148), as amended by the Federal Healthcare and Education Reconciliation Act of 2010 (Pub. L. 111-152). 2. CMS Medicare Fact Sheet: Improving Quality of Care for Medicare Patients: Accountable Care Organizations. 3. CMS Medicare Fact Sheet: What Providers Need to Know: Accountable Care Organizations.