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2025
Acute Complications of Central Line Placement in
Profoundly Thrombocytopenic Cancer Patients
Rafael Barrera, M.D.'
Bushra Mina, M.D.'
Ying Huang, Ph.D.2
Jeffrey S. Groeger, M.D.'
'
Critical Care Medicine Service, Department of
Anesthesiology and Critical Care Medicine, Memorial Sloan-Kettering Cancer Center Cornell
University Medical College, New York, New
York.
* Biostatistics Service, Department of Epidemiology and Biostatistics, Memorial Sloan-Ketteriiig Cancer Center, Cornell University Medical
College, New York, New York.
BACKGROUND. Morbidities associated with the insertion of central venous catheters
in severely thrombocytopenic cancer patients were analyzed in this prospective
observational study. One hundred fifteen consecutive thrombocytopenic patients
requiring central venous access (internal jugular or subclavian vein cannulation
by a modified Seldinger technique) were evaluated.
METHODS. One hundred fifteen catheters were inserted. For each patient, the following factors were documented: age; sex; diagnosis; previous catheterization;
prior neck, chest, breast, or axillary surgery or radiation therapy; presence of other
lines prior to venipuncture; site and indication for line insertion; complications;
PT and PTT; platelet counts; and hematocrit.
RESULTS. Of the total number of catheters inserted, 63 (55%) were subclavian and
52 (45%) were internal jugular. Successful cannulations with no complications (n
= 91; 79% of the total) were achieved with 1.2 5 0.5 attempts. Twenty-four major
and minor complications (20%) occurred with an average of 1.6 i 1 attempts ( P
= 0.003). The mean preprocedure platelet counts were 14.8 5 4.5 x 10y/Lfor the
subclavian group and 14.3 t 4.8 x 109/L for the internal jugular group. With
platelet transfusion, the mean postprocedure platelet counts for the subclavian
and internal jugular groups were 23.9 2 12.8 x 109/L and 24.6 2 15 x 10"/L,
respectively. In the subclavian group, seven patients (6%)experienced minor complications. There were 17 minor complications (15%)and 1 pneumothorax in the
internal jugular group. Patients experiencing more than one attempt at cannulation
had more complications ( P = 0.003).
CONCLUSIONS. With the appropriate precautions and platelet transfusions, central
venous catheters can be inserted safely with minimal complications into thrombocytopenic cancer patients. Fewer attempts are associated with fewer complications.
High risk procedures should be attempted only by experienced personnel or under
their direct and strict supervision. Cancer 1996; 782025-30.
0 1996 American Cancer Society.
KEYWORDS: central line, thrombocytopenia, complications, catheterization.
T
Address for reprints: Jeffrey S. Groeger, M.D.,
Medical Director, Special Care Unit, Memorial
Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.
Received July 15, 1996; revision received August 1, 1996; accepted August 1, 1996.
0 1996 American Cancer Society
he nature and the magnitude of complications associated with
central venous catheterization are related to the invasiveness of
the procedure, the operator's experience, and the patient's clinical
condition. Common complications are bleeding and hematoma.',2
Reports of mechanical complications after initial insertion vary from
1.3%to 11%,and may include pneumothorax, hemothorax, and injury
to great vessel^.^-'^
A quantitative relationship between the platelet count and the
occurrence of spontaneous hemorrhage exists. The incidence of spontaneous hemorrhage is greater than 50% with platelet counts < 20 x
109/Lin patients with acute leukemia,15whereas in patients with solid
2026
CANCER November 1, 1996 / Volume 78 / Number 9
tumors, the incidence is below 12% with platelet
counts > 10 x io9/L.l6
Thrombocytopenic cancer patients present a dilemma for central venous access. Some investigators
consider the safest sites, with the least potential for
bleeding complications, to be a percutaneous approach into the external jugular vein or the antecubital
fossa, or via a cutdown. Although a cutdown offers
advantages for prevention and control of hemorrhage,
in neutropenic patients it presents a significant risk
for infe~tion.'~
Insertion of a femoral vein line is reasonably safe, particularly if a low femoral approach
is used. However, the incidence of contamination is
frequent.' Some investigators have demonstrated that
central venous catheterization can be performed safely
in the thrombocytopenic patient without an increase
in complications.'4"8Although it is impossible to specify an absolute platelet count below which the risk
of hemorrhage contraindicates a surgical or invasive
procedure, a platelet count > 50 x 109/L is recommended during any inter~ention.'~
The aim of this study was to evaluate the incidence
of complications related to venous cannulation in severely thrombocytopenic patients described as having
a platelet count 5 20 x i09/L.
MATERIALS AND METHODS
A prospective quality assurance project from July 1990
to September 1993, evaluating the incidence of complications related to cannulation of the internal jugular
and subclavian veins in profoundly thrombocytopenic
patients, was performed. As per hospital policy, central
line insertion in thrombocytopenic patients is performed, upon request, by the Critical Care Medicine
Service. Profound thrombocytopenia in the current
study was defined as platelet count of 520 x 109/L
before platelet transfusion. In the current study institution, the level of expertise for venous cannulation
varied among the Critical Care fellows; however, all
fellows performed between 25 to more than 100 central line cannulations in their primary training program and were certified to perform these high risk
procedures after direct observation by a Critical Care
Medicine Service attending physician. Only central
line placements performed by the Critical Care staff
were evaluated during that period. Critical care house
staff recorded each patient's age, sex, diagnosis, previous catheter placement, neck surgery, or radiation
therapy. Site of line, complications, attempts, line tip,
transfusions, prothrombin time (PT) and partial
thromboplastin time (PTT), pre- and postprocedure
platelet count, and hematocrit were also obtained by
observation and chart review. Indications for the line
were specified for each patient. There were eight dif-
ferent inserters and their level of experience in line
placement was not recorded. The central venous catheters were inserted in patients in the combined medical-surgical intensive care unit or on the regular wards
of Memorial Sloan-Kettering Cancer Center. Catheters
were inserted by the Critical Care fellows; all insertion
attempts were observed and self-reported. Patients
with an initial platelet count 5 20 x 109/L required
platelet transfusion in an attempt to raise the platelet
count 2 20 x 109/L. The number of platelet units
transfused prior to the cannulization varied according
to the initial platelet count and the clinical setting.
The number of platelet units transfused was recorded,
as was the posttransfusion platelet count. Patients
with prolonged PT and PTT received two units of fresh
frozen plasma in an attempt to correct coagulopathies.
No posttransfusion PT and PTT were done. The site
of the venipuncture that would provide the least morbidity to the patient was selected. There was no systematic algorithm for venipuncture site selection. The
site was selected according to the patient's or the inserter's preference, viability of the site, history of previous unsuccessful or difficult attempts, and distortion
of the anatomic landmarks either due to neck/truncal
obesity or prior neck/chest/breast/axillary radiation or
surgery. The procedures were performed under local
anesthesia, without utilization of fluoroscopic or sonographic visualization. Venipuncture was performed either during or immediately after platelet transfusion.
Triple lumen central venous catheters (7 French) or
Introducer Sheaths (8 French) were inserted aseptically using a modified Seldinger technique with a 18gauge (6.35 cm) needle. After the catheter had been
successfully inserted, the site was inspected for any
evidence of bleeding, oozing, or hematoma. The puncture site and the surrounding skin were cleansed with
povidone-iodine and alcohol swabs, and sterile Tegaderm transparent dressings (3M, Medical-SurgicalDivision, St. Paul, MN) were applied. Any complications
encountered during the procedure were evaluated.
The number of attempts, defined as skin puncture and
any interventions taken, were self-recorded. Postprocedure chest radiographs were obtained for verification of the catheter's position and to evaluate the possibility of complications related to the procedure. After
24 hours, the patients were interviewed, the sites inspected, and the nurse's notes reviewed for any evidence of late complications. Major complications were
defined as bleeding from the site requiring blood
transfusion, malposition of the catheter, hydro/pneumothorax, or mediastinal hematomas. Minor complications were defined as oozing of blood and/or small
hematomas < 5 cm at the cannulation site not requiring therapy. Late occurring complications such as
Central Line Placement in Profoundly Thrornbocytopenic PatientdBarrera et al.
TiLBLE 1
Comparison of Selected Clinical Characteristics of Subclavian and
Internal JugularVein Cannulations
2027
TABLE 2
Complications bv Site
Observed complications (N = 24)
No.
Platelets, preprocedure (1O''iL)
Platelets, postprocedure (lO'/L)
Hematocrit, preprocedure (%)
Hematocrit, postprocedure (%)
Prothrombin time (seconds)
Partial thromboplastin time (seconds)
No. complications ( P = 0.005)
Diagnosis
Solid tumor
Lymphoma
Myeloma
Leukemia
Subclavian
vein
Internal jugular
vein
63 (55%)
14.8 t- 4.5
23.9 t- 12.8
24.8 t- 4.7
23.8 ? 3.6
12.5 % 1
34.3 t 8.2
7 (6%)
52 (45%)
14.3 ? 4.8
24.6 t- 15
23.8 ? 4.7
23.9 t 5.6
12.6 .c 1.1
32.9 ? 5.1
17 (15%)
5
8
1
43
7
8
2
41
pneumothoraces, hydromediastinum, or air embolism
were also evaluated. Infection and catheter-related
sepsis were not evaluated.
Statistical analysis performed included chisquared and Student's t tests and logistic regression
with P < 0.05 considered significant. All data are presented as mean 2 standard deviation.
RESULTS
12 total of 115 catheters were inserted in 115 consecutive patients, 60 males (52%), and 55 females (48%).
In five patients, catheters were unable to be placed.
,411 of the failed attempts were internal jugular sites.
Four of these patients subsequently received a femoral
and one a right subclavian line. Only the subclavian
site was included in the final statistical analysis. Sixtythree (55%) subclaviar and 52 (45%) internal jugular
catheters were placed. The internal jugular placement
sites were divided as follows: right internal jugular
vein, 40 (35%)and left internal jugular vein, 12 (10%).
The subclavian sites were right subclavian vein, 52
(45%) and left subclavian vein, 11 (10%).
The mean age of the patients was 49 -+ 16 years
(range, 18- 100 years), 47 +- 14 years for the subclavian
site cannulation and 52 t 19 years for the internal
jugular site. All patients had a history of malignancy;
12 (10%) had a solid tumor, 16 (14%) lymphoma, 3
(2%) myeloma, and 84 (73%)leukemia (Table 1).Five
(4%) had a previous history of neck surgery, 2 (1%)
had chest surgery, and 1 (1%)patient had breast and
axillary dissection. Three (2%) had previous neck radiation. Thirty-six of the patients had previously received a central line and 39 of the patients had other
lines at the time of placement: 12 (31%)a right internal
Subclavian
Internal jugular
Major
Minor
0
7
16
1
jugular, 3 (8%) a left internal jugular, 12 (31%)a right
subclavian, 11 (29%)a left subclavian, and 1 patient an
external jugular line. Only 14 patients had a pulmonary
catheter placed simultaneously. Thirty-six (31%)of the
lines were placed for antibiotic therapy, 12 (10%)for
chemotherapy, 45 (39%)for chemo/ antibiotic therapy,
14 (12%)for hemodynamic monitoring, and 8 (7%)for
fluid administration. The pretransfusion platelet count
was 14.6 -+ 4.7 x I09/L (range, 3-20 x 10g/L),with a
posttransfusion platelet count of 24.3 -C 13.8 x log/
L (range, 2-73 x 109/L). The posttransfusion platelet
count was considered as the procedure count. A median of 6 units of platelets were transfused for 107
catheterizations resulting in an increase in the platelet
count of 9.61 i 13.2 x 109/L.Eight patients did not
receive transfusions for the procedure. There were no
reported complications related to platelet transfusions. Prolonged PT and PTT were observed in 8 patients (7%)' 4 of whom (3%) received fresh frozen
plasma transfusions prior to venipuncture. In these
four selected cases, the decision to attempt to reverse
the underlying coagulopathy by means of a fresh frozen plasma transfusion was based on the antecedent
clinical evidence of increased bleeding tendency. Posttransfusion PT and PTT were not reported.
Total major and minor complications numbered
24 (21%) (Table 2 ) . Twenty-three patients had minor
complications and only 1pneumothorax was reported.
Failed attempts were not included as a complication
but follow-up chest X-rays were done and the patients
were evaluated at 24 hours. Seven of the minor complications (6%) occurred in association with subclavian
cannulation (4 oozing, 2 hematomas, and 1 oozing
and hematoma). Cannulation of internal jugular veins
was associated with a higher incidence of minor complications (n = 17; 15%) ( P = 0.005). Sixteen instances
of oozing/hematoma and 1 pneumothorax occurred.
Seven patients with minor complications were transfused a mean of 8 i 4.8 (range, 4-18) additional units
of platelets. Oozing was minimal and was relieved with
local pressure, and small hematomas resolved within
24 hours, neither necessitating blood transfusions. The
24 patients with complications had platelet transfusions. Among the 23 patients with oozing and/or he-
2028
CANCER November 1,1996 / Volume 78 / Number 9
matoma, 19 had a normal coagulation pattern,
whereas the remaining 4 patients had elevated PT and
PTT. Those four patients experienced minor complications: one in the internal jugular vein and three in the
subclavian vein. The other four patients with abnormal coagulopathy had no complications and required
no fresh frozen plasma transfusions. The mean pretransfusion platelet count associated with oozing and/
or hematoma was 14.8 ? 4.9 x 109/L (range, 6-20 x
109/L), and was 14.6 2 4.6 x 109/L (range, 3-20 x
109/L) in patients with no complications. The mean
posttransfusion platelet count in patients with no
complications was 23.9 c 13.2 x 109/L (range, 2-73
x 109/L).The mean posttransfusion platelet count in
patients with complications was 25.5 2 15.9 x 109/L
(range, 2-59 x 109/L).There were only 3 patients with
a platelet count above 50 x 109/L in the group with
complications and 4 in the group without complications. In patients with no complications (n = 91; 79%),
successful cannulation was achieved with 1.2 2 0.5
attempts, whereas in patients experiencing complications (n = 24; 21%), 1.6 -c_ 1 attempts occurred. Patients
experiencing more than one attempt had more complications ( P = 0.003). There was no correlation between site and number of attempts.
The catheter tip was reported in the superior vena
cava in 82 of the cases (73%), in the right atrium in 6
(5%), and in the junction of the superior vena cava
and right atrium in 13 (12%).There was no statistical
difference between the site, history of previous venous
cannulation, or concomitant presence of other lines
and the number of attempts. In the eight patients with
a prior history of neck surgery or radiation, there was
no impact on outcome.
The relationship between the complications and
prognostic factors site, and attempt was analyzed by
a logistic regression model. A relative risk of 4 (95%
confidence interval [CI], 1.46- 10.31) of minor complications for internal jugular versus subclavian sites was
found, i.e., the internal jugular site was 4 times more
likely to cause complications than the subclavian site.
Similarly, a relative risk of 4.3 (95% CI, 1.57-11.67)
was found for > 1 versus 1 attempt. After adjusting for
attempts, a relative risk of 4.6 (95% CI, 1.62-13.42)
was found for internal jugular versus subclavian sites.
Controlling for site, a relative risk of 5.5 (95%CI, 1.7615.69) was found for 2 1 attempts versus 1 attempt.
Age and malignancy were not found to be significantly
associated with the outcome variable (Table 3).
DISCUSSION
Approximately 3 million central venous catheters are
inserted annually in the U.S.*O These procedures are
associated with significant complications that are re-
TABLE 3
Logistic Regression Analysis and Odds Ratio of Internal Jugular
Compared with Subclavian Line
Odds ratio (95% CI)
IJ vs. SC
Number of attempts
Univariate
(unadjusted)
Multivariate
(adjusted]
4 (1.46-10.31)
4.3 (1.57-11.67)
4.6 (1.62-13.42)
5.5 (1.76-15.69)
CI:confidence interval: IT: internal iurmlar: S C subclavian
lated to physiologic, anatomic, or pathologic factors,
device malfunction or failure, or the experience of the
health care professional. Scott” reported that 52% of
complications and 62% of deaths were related to the
experience of the health care professional, whereas
device failure contributed to 12% of complications.
Various reports have estimated that complications occur in 5-20% of procedures.’2,21,22
Boyd et a1.’ reported
that hematomas (small to moderate) were present in
2.8%of cases. In 1989, the Food and Drug Administration task force issued recommendations to minimize
such complications, stating that central venous catheterization should be performed only when the benefits
appear to outweigh the inherent risks of the procedure, and must be performed only by trained personnel well versed with the anatomic landmarks, safe
techniques, and potential complications.20
Thrombocytopenia is associated with an increased risk of bleeding complications and can be a
life-threatening condition. Thrombocytopenia is a
common occurrence in intensive care units and in
cancer patients, usually due to underlying disease,
sepsis, and antineoplastic chemotherapy as independent risk factors, and is associated with an increased
mortality.23Management of thrombocytopenia must
be individualized, with a platelet count of <20 x lo9/
L commonly used as the level at which to consider
t r a n s f ~ s i o n sThrombocytopenic
.~~
patients with platelet counts < 20 x 109/L are at an increased risk for
bleeding, complicating invasive or surgical manipulations. Some investigators have reported a low rate of
bleeding with line placement ranging from 0.22%.1,22,23
A study in coagulopathic liver transplant patients showed there was no bleeding complications
with line placement despite the lack of attempts to
correct hemostatic disorders.25 Bleeding complications occurred after central line placement in 0.5%of
dialysis patients, after femoral insertion, the complication rate was 6% in patients with platelet counts > 20
x 109/L (4%).5-28In the current series of patients the
surprising finding was that after platelet transfusions
Central Line Placement in Profoundly Thrombocytopenic PatientslBarrera et al.
there was little difference in posttransfusion platelet
counts between those patients with complications and
those without. The rate of complications in patients
not receiving platelet transfusions was zero.
At Memorial Sloan-Kettering Cancer Center, a
comprehensive cancer treatment center, the etiology
of thrombocytopenia is most commonly due to antineoplastic chemotherapeutic regimens, underlying
neoplastic disorders, andlor sepsis. Adequate vascular
access is essential for the administration of various
therapeutic regimens. The indications for percutaneous short term central venous catheterization were
mostly for the administration of multiple antibiotics,
(chemotherapy, parenteral nutrition, and fluid management. The incidence of hemorrhagic complications
,are reported to be minimal with a near absence of
severe or fatal hemorrhage at platelet counts > 10-20
x 109/L.15-16 Platelets were transfused for 107 procedures, resulting in an increase in the platelet count of
9.61 ? 13 x 109/L,which provided a posttransfusion
platelet count of 24.25 2 13.79 X 109/L.A total of 24
complications (21%) occurred. A higher incidence of
minor complications occurred during cannulation of
the internal jugular vein (17) compared with the subclavian vein (7) (15%vs. 6%;P = 0.005). Minor complications occurred 50% more often with internal jugular
vein cannulation, probably because it is a more observable site. Four patients requiring fresh frozen
plasma transfusions had bleeding complications.
Bleeding complications occurred only in 4 of 8 patients
with abnormal coagulopathy, and a normal coagulation profile was evident in 19 of 23 patients with bleeding complications. One major complication, pneumothorax, was associated with an internal jugular venipuncture. Both internal jugular and subclavian veins
are associated with the same success in cannulation
rate.
Thrombocytopenia is not an absolute contraindication for any procedure. Investigators had demonstrated the safety of bronchoscopy and thoracentesis
in the presence of t h r o r n b o ~ y t o p e n i a .Even
~ ~ ~ ~in~
skilled hands, internal jugular catheterization is associated with a 2% risk for carotid artery perforation.
Subclavian catheterization is associated with increased risks for pneumothorax of 2-5%,31-35and subclavian artery puncture of 0-3.8%.14Advantages of the
subclavian site include relatively constant anatomy
(with respect to the clavicle), greater physical stability
of the catheter, and less tendency toward contamination than the internal jugular site. The detection of
more complications at the internal jugular site could
be due to its easier visualization in comparison with
the subclavian site. The greater relative risk can be
2029
explained because the internal jugular site is less stable
than the subclavian site due to soft tissue in the neck.
In patients with no complications (91) cannulation was performed successfully with fewer attempts,
in comparison with those with complications (79% vs.
21%). Successful cannulation with no complications
was achieved with 1.2 i 0.5 attempts, which is equal
to the number of punctures reported by Koski et a1?*
None of the lines in the current study were placed
using the ultrasound technique. The level of training
and experience in line catheterization varied among
the different inserters in the current study study, but
due to extensive exposure at the study institution, they
were considered qualified for line insertion of high risk
procedures. Complications are minor if catheterization is performed or supervised by experienced personnel.
CONCLUSION
Central venous catheterization can be performed
safely in thrombocytopenic patients with minimal
complications if certain precautions are taken. The
procedure should be performed by experienced personnel familiar with the anatomic landmarks. Proper
selection of the insertion site, platelet transfusions,
and fewer attempts lead to optimal results. High risk
procedures should be attempted by experienced personnel.
1.
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