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Update on the Beans: How to Keep Them Going - Society of

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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 – both microemboli and macroemboli. Examples include microemboli generated
during CPB and atheroemboli generated by manipulation of the ascending aorta.
5. Nephrotoxins – 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 – an initial diagnosis of AKI based on
changes over 48 hours – 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 (≥
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 (≥ 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 (≥ 354 μmol/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 – 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 – 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) – 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 “goal-directed therapy” 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
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7
ADULT  CONGENITAL  HEART  DISEASE:   THE  NEW  REALITY  KATHRYN  ROUINE-­‐RAPP,  MD  PROFESSOR  OF  ANESTHESIA,  UNIVERSITY  OF  CALIFORNIA,  SAN  FRANCISCO    OBJECTIVES  After  attending  this  session,  the  participant  will  be  better  able  to   1.    REVIEW  THE  MOST  COMMON  CONGENITAL  ANOMALIES  BEING  SEEN  IN  THE  ADULT  SURGICAL  POPULATION,  INCLUING  CARDIAC  AND  NON-­‐CARDIAC  SURGERY.    2.   DISCUSS  THE  ANESTHETIC  IMPLICATIONS  FOR  CYANOTIC  PATIENTS  UNDERGOING  SURGICAL  PROCEDURES,  EITHER  CARDIAC  OR  NON-­‐CARDIAC.   3.   PROVIDE  RECOMMENDATIONS  FOR  DEFINING  PATIENTS  AS  NEEDING  A  “CARDIAC”  ANESTHESIOLGIST   OVERVIEW  An  estimated  1-­‐3  million  adults  in  the  United  States  and  Canada  have  congenital  heart  disease  (CHD).   In  Europe,  the  estimated  number  is  1.8  million.   Approximately  85%  of  infants  with  CHD  survive  into  adulthood.   For  several  years  advances  in  cardiac  surgery,  cardiology  and  anesthesia  care,  intensive  care  and  diagnosis  lead  to  an  increase  in  the  number  of  adults  with  CHD.    Currently  there  are  more  adults  with  CHD  than  children,  the  median  age  of  all  patients  with  CHD  is  40  years  and  prevalence  of  adult  CHD  is  estimated  at  3000  per  million.   Even  a  geriatric  population  of  adults  with  CHD  has  been  studied.   These  data  suggest  that  anesthesiologists  will  care  for  adults  with  CHD  with  increasing  frequency.   Thus  it  is  important  to  learn  the  anatomy  and  physiology  of  the  more  common  lesions.   (Marelli  et  al.   Am  Heart  J  2009;  Dearani  JA  et  al.   Cardiol  Young  2007;  Moons  P  et  al.   Eur  Heart  J  2010;  Webb  G  et  al.   J  Am  Coll  Cardiol  2001;   Warnes  CA  et  al.  J  Am  Coll  Cardiol   2001;  Marelli  AJ  et  al.   Circulation  2007;  van  der  Bom  T  et  al.   Am  Heart  J,  2012;   Afilalo  T  et  al.   J  Am  Coll  Cardiol  2011).    Several  classification  systems  have  been  used  to  promote  comprehension  of  CHD.   Lesions  are  classified  by  level  of  complexity,  presence  or  absence  of  cyanosis,  and  physiology-­‐induced  changes  (“shunt”  lesions).  Using  complexity  classification,  lesions  may  be  simple,  or  of  moderate  or  severe  complexity.   Overall,  lesions  of  severe  complexity  are  present  in  approximately  20-­‐25%  of  adults  with  CHD.   About  40%  have  lesions  that  are  “simple”  or  resolved  following  intervention  (Grown-­‐up  congenital  heart  (GUCH)  disease:  current  needs  and  provision  of  service  for  adolescents  and  adults  with  congenital  heart  disease  in  the  UK.  Report  of  the  British  Cardiac  Society  Working  Party.  Heart  2002;88(Suppl  I):i1–i14).    Some  adults  with  CHD  are  unoperated,  i.e.,  never  underwent  correction  of  the  lesion.   Others  may  have  undergone  an  intervention  to  palliate  the  physiologic  effects  of  the  lesion  (e.g.,  a  shunt  between  systemic  and  pulmonary  arteries  to  increase  pulmonary  blood  flow  in  a  cyanotic  patient).   Alternatively,  they  may  have  undergone  surgical  or  device  closure  of  the  lesion  and  may  have  an  excellent  uncomplicated  result  or  residual  defect  and  sequelae.   For  comprehensive  assessment  and  information  for  clinical  care  of  adults  with  CHD  please  refer  to  the  following  most  recent  American,  Canadian  and  European  guidelines  for  the  management  of  adults  with  congenital  heart  disease.   ACC/AHA  2008  guidelines  for  the  management  of  adults  with  congenital  heart  disease   J  Am  Coll  Cardiol.  2008  Dec  2;52(23):e143-­‐263.  doi:  10.1016/j.jacc.2008.10.001.    Canadian  Cardiovascular  Society  2009  Consensus  Conference  on  the  management  of  adults  with  congenital  heart  disease:  complex  congenital  cardiac  lesions.  Silversides  CK,  Salehian  O,  Oechslin  E,  et  al.   Can  J  Cardiol.  2010  Mar;26(3):e98-­‐117    Canadian  Cardiovascular  Society  2009  Consensus  Conference  on  the  management  of  adults  with  congenital  heart  disease:  outflow  tract  obstruction,  coarctation  of  the  aorta,  tetralogy  of  Fallot,  Ebstein  anomaly  and  Marfan's  syndrome.  Silversides  CK,  Kiess  M,  Beauchesne  L,  et  al.   Can  J  Cardiol.  2010  Mar;26(3):e80-­‐97    Canadian  Cardiovascular  Society  2009  Consensus  Conference  on  the  management  of  adults  with  congenital  heart  disease:  shunt  lesions.  Silversides  CK,  Dore  A,  Poirier  N,  et  al.   Can J Cardiol. 2010 Mar;26(3):e70-9.
  ESC  Guidelines  for  the  management  of  grown-­‐up  congenital  heart  disease  (new  version  2010).  Baumgartner  H,  Bonhoeffer  P,  De  Groot  NM,  et  al.   ;  Task  Force  on  the  Management  of  Grown-­‐up  Congenital  Heart  Disease  of  the  European  Society  of  Cardiology  (ESC).  Eur  Heart  J.  2010  Dec;31(23):2915-­‐57.  Epub  2010  Aug  27.  No  abstract  available.      Looking  at  the  world  literature,  the  most  common  lesions  in  unoperated  adults  with  CHD  are  atrial  septal  defects  (ASD)  and  ventricular  septal  defects  (VSD).  (Mello  et  al.   Rev  Bras  Cir  CV  2012  &  Hannoush  H  et  Ial.   lin  Cardiol  2004).   In  some  centers,  approximately  half  of  adult  patients  followed  in  a  specialty  clinic  have  these  defects  (Kolo  et  al.   Niger  Postgrad  Med  infancy;  Hannoush  et  al.   Clin  Cardiol  2004).   The  most  common  cyanotic  lesion  in  patients  after  infancy  is  tetralogy  of  Fallot  (TOF).   Therefore  a  detailed  discussion  of  these  lesions  will  be  included  in  this  syllabus.      DISCUSSION  OF  SPECIFIC  CHD   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%–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 “cleft” 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  ≥  40  yrs  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 “swiss
cheese septum.”
3.
Doubly-committed or subarterial VSD (so called “supracristal”) (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 “pink” or “acyanotic” 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 “double chambered
right ventricle.”
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), Potts’ shunt (descending
aorta to left pulmonary artery), or Waterston’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 )
 CARDIAC  AND  NON-­‐CARDIAC  SURGERIES  IN  ADULTS  WITH  CHD   Most  procedures  performed  in  adults  with  CHD  who  have  not  undergone  previous  surgery  include  ASD  and  VSD,  sinus  venosus  defects  usually  with  partial  anomalous  pulmonary  venous  return,  partial  AV  canal  defects  (cleft  mitral  valve,  primum  ASD),  coarctation  of  the  aorta,  congenitally  corrected  transposition  of  the  great  arteries,  anomalous  coronary  artery  anomalies,  and  aortic  stenosis  (usually  with  bicuspid  aortic  valve)  (Guleserian  KJ  et  al.   Prog  CV  Dis  2011).    Cardiac  reoperations  are  common  among  adult  patients  with  CHD.   Valve-­‐related  procedures  (surgical/interventional)  are  the  most  frequent  indication  for  intervention  in  adults  with  CHD  (Holst  et  al  Ann  Thorac  Surg  2013);  in  one  17-­‐year  follow-­‐up  study,  valve  operations  increased  42-­‐63%  more  than  other  procedures  (Inoseseu  I  et  al,  Ann  Thorac  Surg  2010).   Patients  with  cyanosis  (TOF,  transposition  of  the  great  vessels  and  single  ventricle  physiology)  often  have  undergone  several  surgical  or  interventional  procedures  prior  to  adulthood.   In  patients  with  TOF  who  underwent  placement  of  a  bioprosthetic  valve  in  the  pulmonary  position,  the  5-­‐year  freedom  from  (pulmonary)  valve  dysfunction  is  92%  but  at  10  years  decreases  to  20%  (Wilamarta  et  al,  Cardiol  Young  2011).   Up  to  49%  of  adults  with  CHD  undergo  multiple  sternotomies  (or  thoracotomies),  and  operative  mortality  and  cardiac  injury  during  reoperation  increase  proportionately  with  the  number  of  operative  procedures.   Mortality  and  morbidity  risk  factors  in  adults  with  CHD  who  undergo  cardiac  surgery  include  presence  of  cardiovascular  disease,  NYHA  functional  class  3  or  4,  and  surgery  on  the  aorta  or  aortic  valve  (Kogon  et  al.   Ann  Thorc  Surg  2013).   Postoperatively,  adults  with  CHD  can  have  short  or  long-­‐term  sequelae  following  surgery.   These  include  aortopathy  that  leads  to  dilation,  aneurysm  and  rupture,  ventricular  and  atrial  arrhythmias  following  a  ventriculotomy  or  related  to  CHD,  infective  endocarditis,  residual  shunts,  sudden  cardiac  death,  lung-­‐perfusion  abnormalities,  ventricular  dysfunction,  conduction  defects,  and  pulmonary  hypertension.    Non-­‐cardiac  surgery  in  adults  with  CHD  is  increasing  and  includes  cholecystectomy  in  27%  of  unoperated  cyanotic  patients  (Shlina  Y  et  al.   Int  J  Cardiol  2011),  successful  surgical  treatment  for  scoliosis  in  patients  post  surgical  correction  of  CHD  (J  Neuro  urg  Pediatr  2013),  and  cerebral  abscess  surgery  in  patients  with  cyanotic  lesions.   In  patients  with  a  single  ventricle  who  have  undergone  total  cavopulmonary  anastomosis,  surgical  repair  of  abdominal  hernias  and  varicose  vein  surgery  is  more  common  (Report  of  the  British  Cardiac  Society  Working  Party.  Heart  2002;88(Suppl  I):i1–i14).   Maternal  death  and  peripartum  mortality  and  morbidity  are  increased  in  women  with  CHD  who  have  a  higher  rate  of  cardiac  complications,  as  well  as  preterm  deliveries  and  cesarean  sections  (Karamlou  et  al.   Ann  Thorac  Surg  2011).     ANESTHETIC  IMPLICTIONS  FOR  CYANOTIC  PATIENTS  UNDERGOING  SURGICAL  PROCEDURES  The  anesthetic  implications  for  cyanotic  patients  undergoing  cardiac  and  non-­‐
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-­‐term  effects  of  cyanosis  include  an  increased  production  of  erythropoietin  that  leads  to  polycythemia  and  associated  morbidities.  The  decrease  in  the  plasma  fraction  of  blood  (~  HCT  >  60%),  leads  to  abnormalities  in  coagulation  studies,  such  as  a  pseudoprolongation  of  activated  partial  thromboplastin  time.  Thrombocytopenia  occurs,  platelet  aggregation  is  decreased,  and  reduced  synthesis  of  clotting  factors  all  contribute  to  coagulation  defects  during  cardiac  and  non-­‐
cardiac  surgery  (Cannesson  M  et  al.   Anesth  2009,  Hofer  A  et  al.   Br  J  Anaesth   2011).   Other  factors  that  increase  perioperative  bleeding  include  high  central  venous  pressure  and  development  of  collateral  vessels  between  the  systemic  and  pulmonary  circulation.   These  collaterals  promote  diastolic  runoff  and  “steal”  blood  from  the  brain,  kidneys  and  gut.   In  contrast,  hyperviscosity-­‐related  thromboembolic  events  that  lead  to  CNS  abnormalities  can  be  exacerbated  by  perioperative  dehydration.   Central  and  peripheral  venous  and  peripheral  arterial  access  may  be  limited  such  that  cyanotic  patients  often  require  preoperative  venous  and  arterial  ultrasound  evaluation  of  vessel  patency.   Ipsilateral  limbs  of  patients  whose  vessels  have  been  used  “upstream”  to  create  a  systemic  to  pulmonary  anastomosis  are  not  reliable  sites  to  monitor  blood  pressure  or  oxygen  saturation.    Other  comorbidities  in  adults  with  cyanotic  CHD  include  sequelae  mentioned  above,  pulmonary  abnormalities,  and  development  of  Eisenmenger  syndrome  after  long-­‐
standing  exposure  of  the  pulmonary  circulation  to  increased  blood  flow  at  systemic  pressures,  subsequent  irreversible  changes  to  the  pulmonary  vasculature  and  resultant  pulmonary  hypertension.   As  such,  regulation  of  hemodynamic  changes  during  an  anesthetic  including  maintenance  of  baseline  systemic  and  pulmonary  vascular  resistances,  may  be  crucial  in  some  patients  to  decrease  perioperative  morbidity  and  mortality.   Interestingly,  coronary  artery  disease  was  not  found  in  cyanotic  patients  with  CHD,  who  have  been  defined  in  one  study  as  “atheroma  free”  (Perloff  JK  Curr  Cardiol  Rev  2012).     RECOMMENDATIONS  FOR  CARE  BY  A  CARDIAC  ANESTHESIOLOGIST  There  are  no  evidence-­‐based  guidelines  for  this  limited  patient  population  (adults  with  CHD)  but  expert  consensus  is  important  &  includes  the  following.    The  consensus  statement  from  the  ACC/AHA  2008  Guidelines  for  Management  of  Adults  with  Congenital  Heart  Disease  states  that  surgical  (and  diagnostic  and  interventional)  procedures  that  require  general  anesthesia  or  conscious  sedation  in  adults  with  moderate  or  complex  CHD  should  be  performed  in  a  regional  adult  CHD  center  with  an  anesthesiologist  familiar  with  adult  CHD  patients.  Additional  consensus  recommends  that  adult  patients  with  complex  or  high-­‐risk  CHD  should  be  transferred  to  an  adult  CHD  center  for  urgent  or  acute  problems.   Guidelines  also  recommend  a  cardiologist  consultation  prior  to  procedures  in  moderate  to  high-­‐risk  adults  with  CHD.    According  to  these  guidelines,  except  for  patients  with  lesions  considered  simple  (See  below  for  a  listing  of  lesions  of  “simple”  complexity),  one  should  refer  patients  to  regional  centers  for  multidisciplinary  care.   Although  most  cardiac  anesthesia  fellowships  include  education  about  and  involvement  in  care  of  patients  with  CHD,  the  role  of  the  anesthesiologist  in  the  care  of  these  patients  is  evolving.   Common  practice  among  several  anesthesiologists  queried  is  that  at  minimum  one  consults  a  cardiac  anesthesia  colleague  when  caring  for  any  adult  with  CHD,  and  most  transfer  patients  with  moderate  or  complex  CHD  to  regional  adult  CHD  centers.   However,  in  a  recent  report  of  >  10,000  adults  with  CHD,  adults  with  CHD  represent  an  increasing  fraction  of  all  non-­‐cardiac  surgery  admissions  to  hospitals,  non-­‐cardiac  surgery  accounted  for  an  increasing  %  of  their  admissions,  and  the  majority  of  these  patients  in  the  database  underwent  surgery  in  nonteaching  hospitals  (Maxwell  et  al,  Anesth  2013).    In  summary,  here  is  a  statement  taken  from  a  recent  editorial  (Cannesson  &  Earing  Anesth  2013  &  their  reference  Landzberg  MJ  et  al   Task  force  4:  Organization  of  delivery  systems  for  adults  with  congenital  heart  disease.  J  Am  Coll  Cardiol  2001;  37:1187–93).   “IT  IS  NOW  WIDELY  ACCEPTED  THAT  ANESTHESIOLOGISTS  AND  CARDIOLOGISTS  WITH  SIGNIFICANT  EXPERTISE  WITH  ACHD  SHOULD  MANAGE  PATIENTS  WITH  MODERATE  OR  SEVERE  CONGENITAL  HEART  DISEASE  PRESENTING  FOR  NON-­‐CARDIAC  SURGERY  (PARTICULARLY  THOSE  WITH  POOR  FUNCTIONAL  CLASS,  PULMONARY  HYPERTENSION,  CONGESTIVE  HEART  FAILURE,  AND  CYANOSIS).    (Based  on  Table  1  from  Cannesson  et  al  Anesth  2009)   Adult  patients  with  simple  CHD    Unoperated  patients  Isolated  [mild]  defect  of  the  aortic  valve,  mitral  valve  Isolated  defect  of  the  interatrial  septum  Small  isolated  ventricular  septal  defect   Isolated  mild  pulmonary  valve  stenosis   Operated  patients  Previously  ligated  or  occluded  ductus  arteriosus   Repaired  secundum  or  sinus  venosus  ASD  without  residua  Repaired  VSD  without  residua     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 patient’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 heparin’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. Luke’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 “Manhattan plot” (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 × 10–8. 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 –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: 367–383.
Arterioscler Thromb Vasc Biol. 2012 32:169
4
TOPIC:   Risk  Factors  and  Outcomes  for  Postoperative  Delirium  in  Post  Cardiac  Surgical  Patients   AUTHOR:   Allen  N.  Gustin,  Jr.,  M.D.,  F.C.C.P.   Learning  Objectives:   After  attending  this  session,  each  participant  will  be  better  able  to  do  the  following:   1.   Describe  the  scope  of  delirium  in  the  cardiac  surgery  population  2.   Recognize  modifiable  and  non-­‐modifiable  risk  factors  for  delirium  in  cardiac  surgery  3.   List  the  effect  of  benzodiazepines  on  delirium  and  outcomes  in  the  critically  ill    Presentation  Outline:   1. Introduction  to  Delirium:    a. Definition  of  delirium  b. Detection  of  delirium    c. Problems  with  the  delirium  evaluation    2. DDSM  IV  and  CAM  ICU  criteria  3. Adult  and  Pediatric  Studies  4. Delirium  Outcomes  5. Delirium  due  to  Cardiac  Surgery  6. Risk  factors  for  Postop  Post  Cardiac  Surgery  Delirium  a. Cerebral  oximetry  7. Prediction  of  Delirium  8. Prevention  of  Delirium  a. Risperidone  9. Modifiable  Risks  for  Delirium  in  the  ICU  10. Benzodiazepines  and  Use  in  the  ICU  Patient  Population    Introduction  to  Delirium:     Delirium  is  defined  as  an  acute  cognitive  disorder  presenting  in  patient  where  fluctuations  in  cognition,  apathy,  and  non  organized  thinking.(1)   Delirium  includes  alterations  in  attention,  cognition,  consciousness,  and  perception;  and  is  often  associated  with  changes  in  sleep  patterns.(2)   The  main  characteristic  of  delirium  is  inattention.   It  can  also  be  termed  intensive  care  unit  (ICU)  psychosis  or  ICU  delirium.   Delirium  is  categorized  as  either  hyperactive  or  hypoactive.(1)   Hyperactive  delirium  puts  the  patient  at  greater  risk  of  self-­‐extubation,  of  accidental  removal  of  life  saving/invasive  catheters,  and  of  worsening  patient  ventilator  synchrony.(1)   On  the  other  hand,  hypoactive  delirium  can  result  in  a  quiet  but  neglected  patient  given  the  decreased  motion  (hypoactive  delirium  suggests  a  worse  prognosis).(1)   CAM  ICU  (Confusion  Assessment  Method  of  the  ICU)  is  most  commonly  used  to  evaluate  the  prevalence  of  delirium,  though  many  studies  will  also  use  the  DSM  IV  Criteria  for  Delirium.    Problems  with  delirium  research  in  the  perioperative  period  can  be  difficult.  Multifactorial  issues  make  it  difficult  to  distinguish  between  emergence  delirium  from  anesthesia  and  the  other  forms  of  delirium.(2)   One  paper  considered  delirium  after  cardiac  surgery  to  be  quite  distinct  from  other  forms  of  delirium  for  the  following  reasons:   1.   Different  surgical  populations  have  different  medication  profiles  and  require  different  anesthesia  techniques  (thus  pharmacological  triggers  of  delirium  will  vary  depending  on  the  surgery),   2.   The  use  of  cardiopulmonary  bypass  in  cardiac  surgeries  requires  special  consideration  since  its  use  is  associated  with  postoperative  effects  on  neurotransmitter  function  and  an  increase  in  delirium,  and  3.   It  is  unknown  if  the  pathophysiology  of  different  postoperative  deliria  differs  (research  has  shown  that  predictors  of  delirium  appear  to  vary  depending  on  the  surgery  type  and  the  levels  of  various  biomarkers  for  delirium).(2)   Overall,  postoperative  post  cardiac  surgical  delirium  appears  to  be  the  result  of  a  complex  interplay  of  preexisting  predisposing  risk  factors  and  peri/post  operative  risk  factors.(3)   Preoperative  cognitive  dysfunction  (reported  to  be  17.8%  in  cardiac  surgery)  had  been  identified  as  a  major  predisposing  risk  factor  for  delirium  in  some  studies  but  has  not  been  identified  as  a  risk  in  others.(3)    Confusion  Assessment  Method  of  the  ICU  (CAM  ICU)  and  DSM  IV  Criteria  for  Delirium:   Regarding  the  existing  delirium  research,  one  of  the  two  following  methods  is  used  for  the  detection  of  delirium  in  ICU  patients:   CAM  ICU  method  and  the  DSM  IV  Criteria.     CAM  ICU:   Presented  as  a  worksheet  for  healthcare  providers  to  fill  out.   Four  Features  are  included  in  the  assessment.(4)   Feature  1:   Acute  Onset  or  Fluctuating  Course.   Is  the  patient  different  than  his/her  baseline  mental  status?   OR  has  the  patient  had  any  fluctuation  in  his/her  mental  status  in  the  past  24  hours  as  evidenced  by  fluctuation  on  a  sedation  scale  (RASS=Richmond  Agitation  Sedation  Scale),  GCS  (Glascow  Coma  Scale),  or  previous  delirium  assessment?   Feature  2:   Inattention.   This  Feature  uses  the  Letters  Attention  Test.   Directions  for  the  healthcare  provider:   Say  to  the  patient,  “I  am  going  to  read  you  a  series  of  10  letters.   Whenever  you  hear  the  letter  �A,’  indicate  by  squeezing  my  hand.”   Read  the  letters  from  the  following  letter  list  in  a  normal  tome  3  seconds  apart:   SAVEAHAART.   Errors  are  counted  when  a  patient  fails  to  squeeze  on  a  letter  “A”  and  when  the  patients  squeezes  on  any  letter  other  than  �A.”      Feature  3:   Altered  Level  of  Consciousness.   Present  if  the  Actual  RASS  (Richmond  Agitation  Sedation  Score)  is  anything  other  than  alert  and  calm  (equates  to  a  RASS  =  0).  Feature  4:   Disorganized  Thinking.   This  feature  uses  both  a  series  of  yes/no  questions  AND  a  command.   The  yes/no  questions  include  the  following  four  questions:   1.   Will  a  stone  float  on  water?   2.   Are  there  fish  in  the  sea?   3.   Does  one  pound  weigh  more  than  two  pounds?   4.   Can  you  use  a  hammer  to  pound  a  nail?   Errors  are  counted  when  the  patient  incorrectly  answers  a  question.   The  command  includes  the  following:   Say  to  the  patient,  “hold  up  this  many  fingers”  (hold  2  fingers  in  front  of  the  patient).   “Now  do  the  same  thing  with  the  other  hand”   An  error  is  counted  if  patient  is  unable  to  complete  the  entire  command.     Scoring  for  CAM  ICU:   1  plus  2  and  either  3  or  4  present  =  CAM  ICU  positive   The  American  Psychiatric  Association’s  Diagnostic  and  Statistical  Manual  4th  Edition  (DSM  IV)  Criteria  for  Delirium  (5):   A. Disturbance  of  consciousness  (reduced  clarity  of  awareness  of  the  environment)  with  reduced  ability  to  focus,  sustain,  or  shift  attention.  B. A  change  in  cognition  or  the  development  of  a  perceptual  disturbance  that  is  not  better  accounted  for  by  a  pre-­‐existing,  established,  or  evolving  dementia.  C. The  disturbance  developed  over  a  short  period  of  time  (usually  hours  to  days  and  tends  to  fluctuate  during  the  course  of  the  day.  D. There  is  evidence  from  the  history,  physical  examination  or  laboratory  findings  that  the  disturbance  is  caused  by  the  direct  psychological  consequences  of  a  general  medical  condition.    Studies  Focusing  on  Delirium  in  Adults:    Predominately  only  adult  research  exists  on  the  topic  of  post  cardiac  surgical  delirium.    Studies  Focusing  on  Pediatrics:   No  prospective,  randomized,  or  cohort  research  studies  looking  at  pediatric  patients  and  postoperative  delirium  were  identified.    Delirium  as  it  Applies  to  Patient  Outcomes:     Delirium  in  ICU  patients  in  the  postoperative  period  from  cardiac  surgery  varies  from  8.4%  to  41.7%.(1)  Delirium  in  ICU  patients  postoperatively  has  shown  to  increase  ICU  mortality,  increase  length  of  ICU  stay,  and  increase  ICU  costs.(1,2,3)   In  patients  who  are  post  cardiac  surgery,  delirium  can  increase  postoperative  complications  such  as  respiratory  insufficiency,  sternum  instability,  and  need  for  reoperation  of  the  sternum.(1)   In  one  study,  delirium  was  present  in  23.5%  of  postoperative  cardiac  surgical  patients   and  the  risk  of  delirium  was  higher  in  older  patients,  those  who  had  cardiopulmonary  bypass,  those  with  atrial  fibrillation,   and  those  with  a  history  of  stroke  (cerebrovascular  accident).(1)   The  mean  time  on  the  mechanical  ventilator  for  patients  with  delirium  was  more  than  in  patients  without  delirium.(1)   Increased  length  of  stay  in  both  the  ICU  and  in  the  hospital  has  been  seen  in  patients  with  postoperative  cardiac  surgical  patients  with  delirium.(3)   Patients  with  delirium  in  the  ICU  had  increased  rates  of  cognitive  defects  after  discharge  from  the  hospital.(3)   Patients  who  had  delirium  post  cardiac  surgery  had  a  mortality  that  was  higher  (than  those  without  delirium)  for  one  year  after  the  ICU  stay.(3)    Risk  Factors  for  Delirium:   Older  age  (1,3,6,>60  in  7,>60  in  8,>65  in  9,>65  in  10)  History  of  CVA  (1,3,7,10,11)  Prolonged  mechanical  ventilation  (1,6,8,>24  hours  in  10)  Atrial  fibrillation  (1,6,9,11)  Episodes  of  major  depressive  disorder  (variable  in  2,6,7)  Cardiopulmonary  bypass  (1,duration  of  CPB  in  3)  Preoperative  Cognitive  impairment  (6,7)  Diabetes  (not  in  1,yes  in  9)  Hypertension  (9,11)  Intraoperative  fentanyl  (2)  Intraoperative  ketamine  (2)  Preoperative  antipsychotics  (2)  Postoperative  inotropes  (2)  Lower  MMSE  (Mini  Mental  Status  Exam)  scores  (3)  Emergency  cardiac  surgery  (9)  Peripheral  vascular  disease  (9)  Abnormal  serum  albumin  (7)  Postop  SIRS  (3)  Use  of  intra  aortic  balloon  pump  (9)  Intraoperative  hemofiltration  (9)  Operation  time  >  3  hours  (11)  Alcohol  abuse  (11)  Anemia  (6)  Higher  C  Reactive  Protein  postop  (3)  Infection  after  surgery  (10)  Hematocrit  <  30  (10)  Duration  of  cardiopulmonary  bypass  (8)  Preoperative  use  of  an  antipsychotic  for  one  year  (2)  Nicotine  abuse  (3)    Cerebral  Oximetry  for  Delirium  Risk  for  On-­‐Pump  Cardiac  Surgery:  (12)   A  total  of  231  patients  were  scheduled  for  elective  cardiac  surgery  and  enrolled  into  this  study.   ICU  delirium  was  assessed  by  the  CAM  ICU  criteria  on  the  first  three  ICU  days  after  cardiac  surgery.   ScO2  (cerebral  oximetry)  values  were  obtained  on  the  day  before  surgery,  immediately  before  surgery,  and  throughout  the  surgical  procedure.   Preoperative  cognitive  function,  demographics,  surgery  related/intraoperative/postoperative  physiological  data  were  all  registered.   Patients  with  delirium  had  lower  pre  and  intra-­‐operative  ScO2  readings,  were  older,  had  lower  mental  status  examination  scores,  and  lower  preoperative  hemoglobin  levels.   The  binary  regression  identified  older  age,  lower  MMSE,  neurological  or  psychiatric  disease,  and  lower  preoperative  ScO2  as  independent  predictors  of  postoperative  delirium.   Thus,  a  low  preoperative  ScO2  is  associated  with  postoperative  delirium  after  on  pump  cardiac  surgery.      Prevention  of  Delirium:   A  great  deal  of  emphasis  has  been  placed  on  trying  to  determine  if  delirium  can  be  prevented.   Efforts  to  evaluate  the  effects  of  perioperative  medications  on  the  incidence  of  delirium  has  been  receiving  the  greatest  focus.(2)   Given  the  changes  in/excess  of  neurotransmitters  like  dopamine,  norepinephrine,  and  epinephrine  in  the  perioperative  state,  attention  is  being  focused  on  pharmacology  as  a  means  of  modifying  the  risks  for  postoperative  delirium.(2)   Attention  has  been  paid  to  drugs  that  have  anticholinergic  properties  (digoxin,  furosemide,  or  nefedipine)  that  might  play  a  role  in  delirium.(2)   Also,  selective  serotonin  reuptake  inhibitors  (SSRIs),  antipsychotics,  and  benzodiazepines  may  also  play  important  contributors  to  delirium  etiology  though  neurotransmitter  pathways.(2)   One  drug,  postoperative  risperidone  (taken  upon  awakening)(2)  has  shown  to  help  in  the  prevention  of  postoperative  post  cardiac  surgical  delirium.   Preoperative  drug  administration.    Mixed  results  on  drug  effect  on  postoperative  delirium  were  seen  with  the  following  drugs:   statins,  anticholinergic  agents,  antidepressants,  selective  serotonin  reuptake  inhibitors  (SSRI),  and  benzodiazepines.   No  effect  on  postoperative  delirium  was  seen  for  the  use  of  cholinesterase  inhibitors,  opioids,  diuretics,  calcium  channel  blockers,  Beta  blockers,  ACE  inhibitors,  angiotensin  receptor  blockers,  Nitrates,  or  benzodiazepines.   Increased  risk  of  postoperative  delirium  was  seen  when  antipsychotics  were  used  in  a  patient  in  the  weeks  that  led  up  to  the  date  of  surgery.(2)   Intraoperative  drug  administration.   No  effect  on  postoperative  delirium  was  seen  with  intraoperative  diazepam.   Mixed  results  have  been  seen  with  fentanyl.   Possible  decreased  incidence  of  postoperative  delirium  has  been  seen  with  ketamine.(2)   Postoperative  administration  of  these  drugs:   Mixed  results  were  seen  for  effects  on  postoperative  delirium  with  the  use  of  dexmedetomidine.   No  effect  on  postoperative  delirium  was  seen  with  the  use  of  morphine  or  opioids.   Increased  risk  of  postoperative  delirium  was  seen  with  the  use  of  inotropes  postoperatively.(2)   Prophylactic  regimens:   Decreased  incidence  of  postoperative  delirium  with  the  immediate  postoperative  use  of  risperidone.(4)    Prevention  of  Delirium  postoperatively  with  Risperidone:(4)   Randomized  double  blind  placebo  controlled  study  of  126  patients  after  cardiopulmonary  bypass.   Patients  were  to  receive  either  1  mg  of  risperidone  (sublingual  administration)  or  placebo  when  they  regained  consciousness  in  the  ICU.   Patients  were  assessed  for  delirium  using  the  CAM  ICU.   The  incidence  of  postoperative  delirium  was  11%  percent  in  the  risperidone  group  versus  31%  in  the  control  group  (P  =  0.009).   Many  other  perioperative  factors  were  associated  with  postop  delirium  but  there  was  no  statistical  difference  between  the  two  groups  regarding  these  factors.   Final  outcome:   one  dose  of  risperidone  administered  relatively  soon  after  cardiac  surgery  reduced  the  incidence  of  postoperative  delirium.       Prediction  of  Delirium:   One  study  was  able  to  predict  postoperative  post  cardiac  surgical  delirium  using  the  combination  of  age,  Mini  Mental  Status  Exam  score,  and  length  of  cardiopulmonary  bypass  with  a  sensitivity  of  71.2%  and  a  specificity  of  26%.(3)    Dexmedetomidine  Versus  Midazolam  for  Sedation  in  ICU  Patients:  (13)   ICU  Study:   Randomized  prospective  double  blind  trial  in  5  countries  for  two  years.   Sedation  for  ICU  patients.   RASS  and  CAM  ICU  were  used  for  assessment  of  delirium.   RASS  was  targeted  to  -­‐2  to  1.   Primary  outcome  was  the  target  RASS  range.   Other  outcomes:   duration  of  mechanical  ventilation,  ICU  length  of  stay,  and  adverse  events.     Results:   No  difference  between  both  drugs  regarding  the  time  within  the  target  RASS  range.   The  prevalence  of  delirium  during  treatment  was  54%  in  the  dexmedetomidine  group  versus  76.%  in  the  midazolam  treated  patients.   Time  to  extubation  after  the  procedure  was  1.9  days  shorter  in  the  dexmedetomidine  treated  patients  and  the  ICU  stay  was  similar  between  the  two  groups.   Dexmedetomidine  treated  patients  were  more  likely  to  develop  bradycardia  with  a  non-­‐significant  increased  need  to  treat  the  bradycardia.   Overall,  no  difference  between  dexmedetomidine  and  midazolam  were  found  as  related  to  time  at  targeted  sedation  level  in  mechanically  ventilated  ICU  patients.   At  comparable  sedation  levels,  dexmedetomidine  treated  patients  spent  less  time  on  the  ventilator,  experienced  less  delirium,  and  developed  less  tachycardia/hypertension.      Lorazepam  is  an  Independent  Risk  Factor  for  Determining  to  Delirium  in  Intensive  Care  Unit  Patients(14)   This  was  a  cohort  study  in  order  to  investigate  whether  sedative  and  analgesic  mediations  independently  increased  the  probability  of  daily  transition  to  delirium.   A  total  of  198  mechanically  ventilated  patients  were  enrolled  to  determine  the  probability  of  delirium  as  a  function  of  sedative  and  analgesic  dose  during  a  drug’s  administration  during  the  previous  24  hours.    Lorazepam  was  an  independent  risk  factor  for  daily  transition  to  delirium  (OR  1.2;  P  =  0.003);  whereas  fentanyl,  morphine,  and  propofol  were  associated  with  higher  but  not  statistically  significant  odds  radios.   Increasing  age  and  Acute  Physiology  and  Chronic  Health  Evaluation  II  (APACHE  II)  scores  were  also  independent  predictors  of  transitioning  to  delirium.   Lorazepam  administration  is  an  important  and  potentially  modifiable  risk  factor  for  transitioning  into  delirium  even  after  adjusting  for  relevant  covariates.       Modifiable  Risk  Factors  in  the  Cardiac  Surgical  ICU:  (15)   This  is  a  prospective  observational  study  involving  200  patients  in  a  cardiovascular  ICU.   Patients  include  both  postoperative  cardiac  surgical  and  cardiology  ICU  patients.   Delirium  occurred  in  26%  of  the  cardiology  and  cardiac  surgical  patients.   Almost  92%  of  the  patients  with  delirium  had  the  hypoactive  form.   Patients  were  prone  to  delirium  when  exposed  to  benzodiazepines  (OR  2.6,  p=0.02)  or  when  restraints  were  used  (OR  2.9,  p<0.01)  during  the  stay  in  the  cardiac  surgical  ICU.   Hemodynamic  status  was  not  associated  with  delirium  in  this  study.   Thus,  benzodiazepine  use  and  use  of  restraints  were  the  only  two  modifiable  risk  factors  identified  for  reducing  the  incidence  of  postoperative  post  cardiac  surgical  delirium.      Conclusions:   Few  modifiable  risk  factors  have  been  identified  that  could  reduce  the  likelihood  of  postoperative  post  cardiac  surgical  ICU  delirium.   One  should  consider  the  avoidance  of  benzodiazepines  for  sedation,  the  avoidance  of  restraints  in  the  ICU  after  cardiac  surgery,  the  use  of  risperidone  in  the  postoperative  period,  and  control  of  atrial  fibrillation  as  a  means  of  reducing  the  likelihood  of  delirium  after  cardiac  surgery.(1,4,6,9,11,15)   No  single  prediction  tool  for  delirium  is  going  to  be  100%.   However,  knowledge  of  all  risk  factors  will  be  there  to  help  identify  patients  at  risk.(3)      References:     1. Shadvar  K,  Baastani  F,  Mahmoodpoor  A,  Bilehjani  E.   Evaluation  of  the  prevalence  and  risk  factors  of  delirium  in  cardiac  surgery  ICU,  Journal  of  Cardiovascular  Thoracic  Research,  2013:  5(40):  157  to  161.  2. Lurdes,  TS,  Schwartz  SK,  Bowering  JB,  Moore  RL,  Burns  KD,  Richford  CM,  Osborn  JA,  Barr  AM.   Pharmacological  Risk  Factors  for  Delirium  after  Cardiac  Surgery:  A  Review.   Current  Neuropharmacology,  2012;  10:181-­‐196.  3. Guenthar  U,  Theuerkauf  N,  Frommann  I,  Brimmers  K,  Malik  R,  Stori  S,  Scheidemann  M,  Putensen  C,  Popp  J.   Predisposing  and  Precipitating  Factors  of  Delirium  after  cardiac  surgery.   A  Prospective  Observational  Cohort  Study.    Annals  of  Surgery,  2013  257(6):  1160-­‐  4. Webpage:   www.icudelirium.org/docs/CAM_ICU_worksheet.pdf.   Accessed  on  January  10,  2014.  5. Webpage:   www.wai.wisc.edu/pdf/phystoolkit/diagnosis/DSM-­‐
IV_Criteria_Delirium.pdf.   Accessed  on  January  10,  2014.  6. Kazmierski  J,  Knowman  M,  Banch  M,  Fendler  W,  Okonski  P.   Incidence  and  predictors  of  delirium  after  cardiac  surgery:   Results  form  the  IPDACS  Studey.   J  Psychosom  Re  2010;  69:179-­‐185.  7. Rudolph  YL,  Jones  RN,  Levkoff  SE,  Rockett  C,  Inouye  SK,  Selke  FW.   Derivation  and  validation  of  a  preoperative  prediction  rule  of  delirium  of  cardiac  surgery.   Circulation  2009;  119:229-­‐36.  8. Reissmuller  V,  Aguero  TH,  Vander  LJ.   Preoperative  mild  cognition  dysfunction  predicts  risk  for  post  operating  delirium  after  elective  cardiac  surgery.   Aging  Clin  Exp  Res  2007;19:172-­‐7.  9. Norkiene  I,  Misiurience  I,  Bubulis  R.  Incidence  and  precipitating  factors  of  coronary  artery  bypass  grafting.   Scan  Cardiovasc  J  2007;74:188-­‐5.  10. Chang  YL,  Tsai  YF,  Liuc  Y.   Prevalence  and  risk  factors  for  postoperative  delirium  in  a  cardiovascular  intensive  care  unit.  Am  J  Crit  Care  2008:17:31-­‐
50.  11. Banach  M,  Kazmierski  J,  Kowman  M,  Okonski  PK,  Sobow  T,  Kloszewska  I,  et  al.   Atrial  fibrillation  as  a  non-­‐psychiatric  predictor  of  delirium  after  cardiac  surgery.   Med  Sci  Monit  2008;14:CR286-­‐291.  12. Schoen  J,  Meyerrose  J,  Paramann  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.   Critical  Care  2011;  15:R218.  13. Riker  RR,  Shehabi  Y,  Bokesch  R,  Cersao  D,  Wismandle  W,  Koura  F,  Fhitten  P,  Marolis  B,  Byrne  D,  Ely  WE,  Rocha  M  (SEDCOM:  Safety  and  Efficacy  of  Dexmedetomidine  Compared  with  Midazolam)  Study  Group.   Dexmedetomidine  vs  Midazolam  for  sedation  of  critically  ill  patients:   a  randomized  trial,  JAMA  2009;  301(5):489-­‐499.  14. Pandharipande  P,  Shintani  A,  Petermson  J  et  al.   Lorazepam  is  an  independent  risk  factor  for  transitioning  to  delirium  in  intensive  care  unit  patients.   Anesthesiology.   2006;  104:21-­‐26.  15. McPherson  JA,  Wagner  CE,  Boehm  LM,  Hall  JD,  Johnson  DC,  Miller  LR,  Burns,  KM,  Thompson  JL,  Shintani  AK,  Ely  EW,  Pandhvaripande  PP.   Delirium  in  the  Cardiovascular  ICU:   Exploring  Modifiable  Risk  Factors.   Critical  Care  Medicine  2013;  41:405-­‐413.     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: pratik.pandharipande@vanderbilt.edu
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 –
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
patient’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 “restful” 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 delirium’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
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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 1–6 mm and widths of 5–13 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 “bubble study”) 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 2.3–4.2).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 8–15%.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 4.7–5.6) 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 platypnea–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 “horizontalized” 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 “there is
general agreement that a PFO should be closed when development of a significant right-toleft shunt after surgery is highly likely”.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
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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. SEP’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
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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
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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
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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
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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.
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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
“evidence-based medicine”. 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 AHA’s “Get with the Guidelines” program) and the recent
ACC/AHA/STS/SCA CABG guidelines and more recently by the AABB’s Guidelines on
Blood Transfusion. 7,8
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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
Quality’s website where a large list of guidelines indexed by the responsible society is
warehoused (http://www.guideline.gov). This “guideline clearinghouse” 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 “up and coming” societies with a variety
of intentions (primarily good willed but possibly also to make themselves more visible). 9
Although there has been “rumbling” among various “end users” 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 “Clinical Practice Guidelines We Can Trust” (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 “blogosphere”. 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 “etched in stone”. 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 “blown calls” 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 “letter of concern” 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 “off the
radar”.
I think as most of us would guess that trying to scientifically prove the efficacy of
a process which is so “prolific” 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 “non-use” 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 “big data” and
“bibliometry” (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.
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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
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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
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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
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Denton TA, Fonarow GC, LaBresh KA, Trento A: Secondary prevention after
coronary bypass: the American Heart Association "Get with the Guidelines"
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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
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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
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the guidelines? J Am Soc Echocardiogr 1999; 12: 343-4
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preoperative management of patients with coronary artery disease scheduled for
noncardiac surgery: effect on perioperative outcome. J Clin Anesth 2002; 14: 126-8
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vascular surgeons? Eur J Vasc Endovasc Surg 2003; 26: 623-8
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stress testing before vascular surgery using ACC/AHA guidelines: a prospective,
randomized trial. J Cardiothorac Vasc Anesth 2003; 17: 694-8
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preoperative cardiac assessment. Am J Cardiol 2003; 91: 1299-303
Siddiqui AK, Ahmed S, Delbeau H, et al.: Lack of physician concordance with
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Likosky DS, FitzGerald DC, Groom RC, et al.: The effect of the perioperative blood
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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‚·
Explain the anesthetic implications of both techniques Describe results of major trials and potential biases  Background Although not widely known, the first successful coronary artery bypass was performed in 1960 by Robert H. Goetz at the Albert Einstein College of Medicine in New York.(1)  By report, the anastomosis, using a specially designed metal ring for the internal mammary artery, took under 20 seconds.  The patient, who underwent the operation for intractable angina, returned to work as a taxi driver following an uneventful recovery and survived for more than a year afterwards.  Several years later, Vasilii Kolesov of Russia reported an anastomosis using a suture technique more closely resembling that used in modern cardiac surgery,(2) and for a period of time it was the only technique utilized.(3)  So, the birth of coronary artery bypass grafting (CABG), one of the most commonly performed elective surgical procedures in the world, actually occurred without the use of extracorporeal circulation.  It is somewhat ironic that the “gold standard” became the use of cardiopulmonary bypass (CPB) for the procedure and off‐
pump coronary artery bypass (OPCAB) surgery the “newcomer.”  CABG surgery using CPB The first successful use of CPB occurred in 1953 when John Gibbon closed an atrial septal defect in an 18 year old patient.(4)  The technology was crude at the time, however, and it was not until much later that CPB would be applied toward coronary revascularization procedures, which were also in their infancy.  The first successful coronary artery bypass using a piece of saphenous vein and extracorporeal circulation is largely credited to Rene Favaloro at the Cleveland Clinic in 1967.(5)  Enthusiasm for the procedure grew and by 1969 there were around 500 hospitals in the United States with CPB capability performing around 5,000 revascularization procedures of one type or another annually.(6)  Given that there are more than 13 million Americans with CAD, it is no surprise that this number has ballooned to 400,000 CABG procedures now performed annually,(7) with about 80% of them utilizing CPB. From an anesthetic point of view, the challenges of CPB come not during the actual CABG procedure, but from preparing for its initiation and separation.  Factors contributing to inflammatory and hemostatic activation during CPB have been extensively reviewed and the anesthesiologist’s goal is to minimize their sequelae.(8,9)  Often what is done for CABG on CPB is directly opposite to management for OPCAB.  For example, fluid restriction in the pre‐CPB period is often employed to minimize hemodilution.  For OPCABs, however, fluid loading is often required to ensure adequate pre‐load during cardiac manipulations.  The major management differences are summarized in the table below.  Major Management Differences of CABG on CPB vs OPCAB Stage of Procedure CABG on CPB Concerns OPCAB Concerns Minimize myocardial 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
anticipation of heart manipulations  IVF administration to ensure adequate pre‐load (N/A) ACT target less well‐defined  Aspirin often administered Keep heart beating; epicardial pacing often employed  Major hemodynamic disturbances (N/A) Often able to wean pressors following distal completion  Hypothermia a problem – need active heating measures throughout operation   OPCAB Surgery From a surgical standpoint, it is more difficult to sew on a beating heart.  This problem has been ameliorated by specialized devices developed and marketed in the mid‐1990’s that help position the heart and stabilize the involved section of myocardium.  Despite these advances, communication between the surgeon and anesthesiologist is critical to determine what position the patient will or will not tolerate.  In order to alleviate some of the hemodynamic consequences of OPCAB during distal anastomoses, surgical maneuvers such as opening the pleural space to alleviate compression and employing intracoronary shunts can be used.  A 3 minute “trial” period prior to arteriotomy is helpful to avoid emergent conversion to CPB, which is associated with a significantly higher mortality rate.(10)  Outcomes of CABG with CPB versus OPCAB There are passionate proponents and opponents when it comes to this issue.  The major points of contention are generally summed up as follows:  Pro‐OPCAB Arguments 
п‚·
п‚·
Reduced neurocognitive dysfunction by avoiding cannulation and aortic cross‐clamping Avoidance of the systemic inflammatory response and its post‐op sequelae Decreased blood product use with better post‐op pulmonary and renal function Pro CABG with CPB Arguments 
п‚·
п‚·
Incomplete revascularization with OPCAB / poorer long‐term graft patency Emergency conversion of OPCAB to CPB results in higher mortality OPCAB has higher degree of technical difficulty with no proven advantages Multiple randomized controlled trials have been performed to address these arguments, but most have been insufficiently powered to detect differences in a procedure with such a low morbidity and mortality rate.  Some better‐known RCTs directly comparing CABG with (on) and without (off) the use of CPB are presented below with their latest follow‐up and limitations.  Trial (n=On/n=Off) BHACAS I & II (201/200) Octopus Study (139/142) SMART (99/98) ROOBY Study (1099/1104) CORONARY Study (2377/2375) Follow‐up / Major Conclusions 6‐8 year FU: No difference in graft patency or perceived QOL(11) 5 year FU: No difference in cognitive function or cardiac outcome(12) 6‐8 year FU: No difference in mortality or graft patency, lower costs in OPCAB(13) 1 year FU: Lower graft patency and higher mortality in OPCAB(14) 1 year FU: No significant difference in mortality, QOL, or cognitive function(15) Notes Significant improvement in OPCAB between trials I and II Low‐risk patient population only Single center; highly experienced surgeons in OPCAB Low risk males only; very high OPCAB to CPB conversion rate Largest multicenter RCT to date; planned 5 year FU  A recent Cochrane meta‐analysis of 86 trials including over ten thousand patients concluded that OPCAB provided no benefit with regard to stroke or MI and, in fact, demonstrated lower long‐term survival.(16)  However, as mentioned above, most RCTs involve only low risk patients with an expected STS mortality of 1‐2%.  In an observational analysis of the STS database (14,766 patients), Puskas and colleagues reported lower hospital mortality in the highest‐risk group with OPCAB.(17)  It is likely that the best approach to CABG will depend upon patient risk factors and surgeon experience.  Exactly what factors favor OPCAB and what surgeons are experienced enough will likely remain a matter of debate for some time.  References 1.  2.  3.  4.  5.  6.  7.  8.  9.  10.  11. Goetz RH, Rohman M, Haller JD, Dee R, Rosenak SS. Internal mammary‐coronary artery anastomosis. A nonsuture method employing tantalum rings. The Journal of thoracic and cardiovascular surgery 1961;41:378‐86. Kolesov VI, Potashov LV. [Surgery of coronary arteries]. Eksperimental'naia khirurgiia i anesteziologiia 1965;10:3‐8. Konstantinov IE. Vasilii I Kolesov: a surgeon to remember. Texas Heart Institute journal / from the Texas Heart Institute of St Luke's Episcopal Hospital, Texas Children's Hospital 2004;31:349‐
58. Gibbon JH, Jr. Application of a mechanical heart and lung apparatus to cardiac surgery. Minnesota medicine 1954;37:171‐85; passim. Favaloro RG. Landmarks in the development of coronary artery bypass surgery. Circulation 1998;98:466‐78. Glenn WW. Some reflections on the coronary bypass operation. Circulation 1972;45:869‐77. Epstein AJ, Polsky D, Yang F, Yang L, Groeneveld PW. Coronary revascularization trends in the United States, 2001‐2008. JAMA : the journal of the American Medical Association 2011;305:1769‐76. Levy JH, Tanaka KA. Inflammatory response to cardiopulmonary bypass. The Annals of thoracic surgery 2003;75:S715‐20. Sniecinski RM, Chandler WL. Activation of the hemostatic system during cardiopulmonary bypass. Anesthesia and analgesia 2011;113:1319‐33. Chowdhury R, White D, Kilgo P, Puskas JD, Thourani VH, Chen EP, Lattouf OM, Cooper WA, Myung RJ, Guyton RA, Halkos ME. Risk factors for conversion to cardiopulmonary bypass during off‐pump coronary artery bypass surgery. The Annals of thoracic surgery 2012;93:1936‐41; discussion 42. Angelini GD, Culliford L, Smith DK, Hamilton MC, Murphy GJ, Ascione R, Baumbach A, Reeves BC. Effects of on‐ and off‐pump coronary artery surgery on graft patency, survival, and health‐
related quality of life: long‐term follow‐up of 2 randomized controlled trials. The Journal of thoracic and cardiovascular surgery 2009;137:295‐303.  12.  13.  14.  15.  16.  17.   van Dijk D, Spoor M, Hijman R, Nathoe HM, Borst C, Jansen EW, Grobbee DE, de Jaegere PP, Kalkman CJ. Cognitive and cardiac outcomes 5 years after off‐pump vs on‐pump coronary artery bypass graft surgery. JAMA : the journal of the American Medical Association 2007;297:701‐8. Puskas JD, Williams WH, O'Donnell R, Patterson RE, Sigman SR, Smith AS, Baio KT, Kilgo PD, Guyton RA. Off‐pump and on‐pump coronary artery bypass grafting are associated with similar graft patency, myocardial ischemia, and freedom from reintervention: long‐term follow‐up of a randomized trial. The Annals of thoracic surgery 2011;91:1836‐42; discussion 42‐3. Shroyer AL, Grover FL, Hattler B, Collins JF, McDonald GO, Kozora E, Lucke JC, Baltz JH, Novitzky D. On‐pump versus off‐pump coronary‐artery bypass surgery. The New England journal of medicine 2009;361:1827‐37. Lamy A, Devereaux PJ, Prabhakaran D, Taggart DP, Hu S, Paolasso E, Straka Z, Piegas LS, Akar AR, Jain AR, Noiseux N, Padmanabhan C, Bahamondes JC, Novick RJ, Vaijyanath P, Reddy SK, Tao L, Olavegogeascoechea PA, Airan B, Sulling TA, Whitlock RP, Ou Y, Pogue J, Chrolavicius S, Yusuf S. Effects of off‐pump and on‐pump coronary‐artery bypass grafting at 1 year. The New England journal of medicine 2013;368:1179‐88. Moller CH, Penninga L, Wetterslev J, Steinbruchel DA, Gluud C. Off‐pump versus on‐pump coronary artery bypass grafting for ischaemic heart disease. The Cochrane database of systematic reviews 2012;3:CD007224. Puskas JD, Thourani VH, Kilgo P, Cooper W, Vassiliades T, Vega JD, Morris C, Chen E, Schmotzer BJ, Guyton RA, Lattouf OM. Off‐pump coronary artery bypass disproportionately benefits high‐
risk patients. The Annals of thoracic surgery 2009;88:1142‐7. 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 “clinical engine” 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
“publish or perish” model, i.e., basic science researchers. Having been inculcated with
“publication fever” 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
“service on demand” 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 member’s ability to provide compelling
documentation in areas where such documentation requires considerable creativity.
It’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 one’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 Chair’s office. The Chair
should organize mentorship within (or at times outside) the department to educate
young faculty members about how best to “work” 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
institution’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 “be at
the table” 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 “if you’re not at the table, you’re on the menu” certainly applies to the ACO
model of health care delivery in private practice.
References:
1.
The “Affordable Care Act” 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.
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