1. Healthcare

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Surgery and Anesthesia in Sickle Cell Disease
By Mabel Koshy, Steven J. Weiner, Scott T. Miller, Lynn A. Sleeper, Elliott Vichinsky, Audrey K. Brown,
Yusuf Khakoo, Thomas R. Kinney, and The Cooperative Study of Sickle Cell Disease
From 1978 t o 1988, The Cooperative Study of Sickle Cell
Disease observed 3,765 patients with a mean follow-up of
5.3 k 2.0 years. One thousand seventy-nine surgical procedures were conducted on 717 patients (77% sickle cell anemia [SS], 14% sickle hemoglobin C disease [SC], 5.7% Spo
thalassemia, 39'0Sp+ thalassemia). Sixty-nine percent had a
single procedure, 219'0 had t w o procedures, and the remaining 11% had more than t w o procedures during the
study follow-up. The most frequent procedure was abdominal surgery for cholecystectomy or splenectomy (2496 of all
surgical procedures, N = 258). Of these, 939'0 received blood
transfusion, and there was no
association between preoperative hemoglobinA level and complication rates (except reduction in pain crisis). Overall mortality within 30 days of a
surgical procedure was 1.1% (12 deaths after 1,079 surgical
procedures). Three deaths were considered t o be related t o
the surgical procedure andlor anesthesia (0.3%). No deaths
were reported in patients younger than 14 years of age.
Sickle cell disease (SCD)-relatedcomplications after surgery
were more frequent in SS patients who received regional
compared with general anesthesia (adjusted for risk level of
the surgical procedure, patient age, and preoperative transfusion status, P = .058). Non-SCD-related postoperative
complications were higher in both SS and SC patients who
received regional compared with those who received general anesthesia (P= .095). Perioperative transfusion was associated with a lower rate of SCD-related postoperative
complications for SS patients undergoing low-risk procedures (P = .006, adjusted for age and type of anesthesia),
with crude rates of 12.9% without transfusion compared
with 4.8% with transfusion. In SC patients, preoperative
transfusion was beneficial for all surgical risk levels ( P =
.0091. Thus, surgical procedures can be performed safely in
patients with SCD.
0 1995 by The American Societyof Hematology.
P
ATIENTS WITH sickle cell disease (SCD; whichinMATERIALSANDMETHODS
cludes sickle cell anemia [SS], sickle hemoglobin C
Patients
disease [SC], and the sickle 0 thalassemias) who undergo
The goals, objectives, design, and enrollment procedures of the
surgery are generally considered to beat greater risk for
Cooperative Study of Sickle Cell Disease have been described elseperioperative complications than otherwise healthy patients
where.26-28 From
October 1978 to October 1988, 3,765 patients from
without this hematologic disorder.'"' Favorable outcomes
23 clinical centers across the continental United States participated
have been reported without transfusion, but perioperative
in the CSSCD. The median length of patient follow-up was 6.0
transfusion is commonly used to prepare SCD patients for
years. Of the total study cohort, 67.5% of the patients had SS, 22.4%
surgery and to treat complications of sickle cell d i s e a ~ e . 4 , ~ . ~ ~had
" ~ SC, 5.0% had sickle Po thalassemia (Soo thal), and 5.1% had
sickle p' thalassemia (So' thal). The Hb phenotype was established
Although the optimal level of sickle hemoglobin (Hb) to be
by the Centers for Disease Control using standard laboratory
achieved is unknown, most sickle cell centers adhere to some
methods.
form of transfusion protocol for SCD patients undergoing
sUrgery.l.18.20-25
The Cooperative Study of Sickle Cell Disease (CSSCD)
was a natural history study that observed 3,765 patients from
1978 to 1988.26.27
This report analyzes the course and outcome of the 1,079 surgical procedures performed on 717
patients during this time period.
From the University of Illinois, Chicago, IL; New England Research Institutes, Watertown, MA; the Department of Pediatrics,
State University of New York Health Science Center at Brooklyn,
Brooklyn, NY; the Department of Pediatrics, Children's Hospital,
Oakland, CA; the Columbia University College of Physicians and
Surgeons and Harlem Hospital Center, New York, NY; the Department of Pediatrics, Duke University Medical Center, Durham, NC.
Submitted February 21, 1995; accepted July 3, 1995.
Supported by the Division of Blood Diseases and Resources of
the National Heart, Lung, and Blood Institute of the National Institutes of Health.
Address reprint requests to Mabel Koshy, MD, University of Illinois at Chicago, Division of Hematology (M/C 787), 840 S Wood
St, Room 314 CSB, Chicago, IL 60612.
The publication costsof this article were defrayedin part by page
charge payment. This article must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. section 1734 solely to
indicate this fact.
0 1995 by The American Society of Hematology.
0006-4971/95/8610-0012$3.00/0
3676
Data Collection
A standardized CSSCD data collection form was completed each
time a patient underwent a surgical procedure. Because of limitations
in data collection procedures, only one surgical procedure was recorded per operation. Medical history, laboratory data, and perioperative course were recorded on this form. Separate forms were completed documenting blood transfusions and acute and chronic clinical
events. Transfusion data for the 30-day period before surgery and
acute event data for the 7-day period after surgery were used in this
report. All deaths within 30 days after a surgical procedure are
summarized in this report. Deaths occurring within 7 days of surgery
were defined as postoperative complications.
Class$cation of Surgeries, Anesthesia, Transfusion, and
Complications
Surgeries were definedusing the International Classification of
Diseases (9th revision) diagnosis codes for procedures. For the purposes of analysis, surgical procedures were categorized into three
groups by level of risk low, moderate, and high.29Low-risk procedures are those of the eyes, skin, nose, ears, and distal extremities
as well as those pertaining to the dental, perineal, and inguinal
areas (eg, inguinal hernia repair, myringotomy, and dilatation and
curettage). Moderate-risk procedures are those of the throat, neck,
spine, proximal extremities, genitourinary system, and intra-abdominal areas, such astonsillectomy, Cesarean section, splenectomy, cholecystectomy, and hip replacement. High-risk procedures are those
pertaining to the intracranial, cardiovascular, and intrathoracic systems (eg, craniotomy and heart valve replacement).
Blood, Vol 86, No 10 (November 15). 1995: pp 3676-3684
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RISKS OF SURGERY AND ANESTHESIA IN SICKLECELL DISEASE
3677
14.2% (N = 102) were SC, 5.7% (N = 41) were Spathal, and
In addition to overall analyses stratifiedby risk level, six specific
classes of the most common surgical procedures wereanalyzed (1)
2.9% (N = 21) wereSp+ thal. This group hasproportionately
cholecystectomy or splenectomy (N = 222and 36, respectively;
more SS and fewer SC and SO+ thal patients than the total
23.9% of all surgical procedures); (2) dilation and curettage (N =
CSSCD cohort (see Materials and Methods).
Sixty-nine per97; 9.0%); (3) Cesarean section or hysterectomy (N = 87; 8.1%);
cent (N = 495) of the patients underwent one, 20.5% (N =
(4) tonsillectomyand/oradenoidectomy(N
= 46; 4.3%); ( 5 ) hip
147) had two, 6.0% (N = 43) had three, and 4.5% (N = 32)
replacement, removal, or revision (N = 4 4 ; 4.1%);and (6) myrinhad four or more surgical procedures during the follow-up
gotomy (N = 30; 2.8%). The frequencies of the remaining surgical
period. Forty-eight percent (N = 520) of the 1,079 reported
procedures (47.8%) are listed in the Appendix.
surgical procedures were classified as low-risk, 50% (N =
Anesthesia was classified as general, regional, and local. General
anesthesia refers to that induced
by the inhalationof gas and balanced 543) as moderate-risk, and 2% (N = 16) as high-risk proceintravenous methods. Regional anesthesia refers to spinal, epidural,
(N = 806)wereelectiveand
dures.Seventy-fivepercent
and nerve block anesthesia. The type of anesthesia and its method
25% (N = 271) wereemergent surgicalprocedures. The
of administration were not prescribedby the CSSCD protocol.
mean age at the timeof surgery was 22.0 2 11.6 years, with
Patients were defined as preoperatively transfused if at least one
of age, 25% being 10 to 19
transfusion was administered within 30 days before surgery. Postop- 17% being less than 10 years
years of age, 52% being20 to 39 yearsof age, and 6% being
erative complication ratesfor patients who were perioperatively (ei40 years of age and older. Female patients underwent6 1%
therpreoperatively or intraoperatively) transfused were compared
with those who were not transfused. Total Hb concentrations and
(N = 660) of thesurgicalproceduresandmale
patients
Hb A percentages presented in this report were obtained after trans- underwent the remaining 39% (N = 419).
fusion and before surgery. The CSSCD wasa natural history study,
The reported sample includes surgical procedures of difthus noprotocolwasspecified
forperioperativemanagement;all
fering risk levels performed on patientsof varying ages. The
patients were treated according to institutional practices.
risk of postoperative complications significantly increased
Postoperative complications were definedas complications that
with
age (estimated odds ratio, 1.3 times increased risk of
occurred within7 days after surgery. These complications were catepostoperative complications per10 years of age, P < . m o l ) .
gorized into three groups: (1) SCD-related, (2) non-SCD-related,
Comparisons of postoperative complication rateswere thereand (3) other. SCD-related complications were defined as painful
crisis, acute chest syndrome (ACS), and cerebrovascular accident
fore adjusted for patient age as well as surgical risk level to
(CVA). Non-SCD-related complicationswere defined as fever, incorrect for the potential confounding effects of these two
fection (excluding ACS), bleeding, thrombosis, embolism, and death.
factors.
Other postoperative complications included transfusion reactions and
unspecified complications. Painful crisis was defined as pain in the
Postoperative Deaths
extremities, back, abdomen, chest, or head for which
no other explanation (eg, osteomyelitisor appendicitis) could be found. ACS was
There were 12 postoperative deaths (10 SS, 1 SC, and 1
defined as the new appearance of an infiltrate on chest radiograph
Spathal) within 30 days of a surgical procedure (Table 1).
or abnormalities on a radioisotopelungscaninthepresence
of
Notably, therewere no deaths amongpatients under 14 years
symptoms.
of age and only 2 in patients between 14 and 20 years of
Statistical Methods
age. The mean age at death was 27.4 +- 10.4 years (range,
Because many patients underwent more than one surgical proce14 to 54 years). Eleven of these patients were transfused.
dure,thesurgeryserved
astheunitof
analysis;eg,percentages
There were8 minor and4 major intra-abdominal procedures.
reported refer to the percentage of surgeries with
a particular characrelated to
The deaths in the first 9 patients appear to be
teristic, rather than the percentage
of patients. Complicationrates are
comorbid medical complications and SCD-related multiorcomputed as the number of surgeries with a particular complication
gan failure. The deaths in the remaining 3 patients appear
divided by the toal number of
surgeries. Descriptive statistics are
to
be related to the surgical procedure: patient no. 10 from
presentedaspercentagesandmeans
-C 1 standarddeviation.All
profound anemia secondary to delayed transfusion reaction;
hypothesis tests and confidence intervals are two-sided.
A two-sided
patient no. 11 from anintra-abdominal hemorrhage requiring
P value of .05 or less was considered to be a statistically significant
result. Postoperative complication rates with and without periopera- 18 U of packed red blood cells; and patientno. 12 from
tive transfusion were compared using logistic regression, with adjustrupture of the prosthetic mitral valve
replaced 38 days earlier
ments for phenotype,typeof anesthesia,surgicalrisklevel,and
(the surgical procedure wasa diagnostic rightheart catheterage. The logistic regression model provided robust standard error
ization 1 day before death).
estimates for the model parameters that accounted
for the correlation
The overall 30-day postoperative
mortality rate was 1.l%
betweendifferentsurgicalprocedures onthesame patient.30The
association between postoperative complication rates and anesthesia (12 deaths of 1,079 surgical procedures). The actual mortality rate of the 3 deaths related to thesurgical procedure was
was also examined using logistic regression. Where there weresufficient data, the association between postoperative complication ratesonly 0.3%.
and (1) total Hb concentration and (2) Hb A percentage was examined using logistic regression. Mean total Hb concentrations of paA Projile of Most Frequently Performed Procedures
tients with and without postoperative complications were compared
using the Student’s t-test.
A description of six classes of surgical procedures most
frequently
performed during the course
of the CSSCD is
RESULTS
displayed in Table 2. There were few procedures performed
General Characteristics
on SC patients;thus, no formal statistical comparisons of
the outcome of SS and SC patients were made. Analyses
There were 717 patients who had one
or more surgical
procedures. Of these patients, 77.1% (N = 553) were SS,
of therelationshipbetweenpreoperative
Hb A leveland
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3678
KOSHY ET AL
Table 1. Postoperative Deaths Occurring Within30 Days of Surgery
No.
Age/
Sex
Hb
Diag.
Clinical Status at
Surgery
1
21lF
ss
2
3
36lF
28lF
ss
ss
4
27lF
ss
5
23lM
ss
6
7
2OlF
54/F
ss
ss
8
17lF
ss
9
10
11
26/F
14lF
sc
ss
32lM
SO0
12
24lF
ss
Cirrhosis DIC,
MOF, CRF
Fever
MOFlsepsis, CRFI
DIC peritonitis1
pneumonia
CRF/SP renal
transplant
CRF infected graft,
dialysis
CVA, comatose
Acute abdomen,
Bili 26, CHF
Sepsislacidosis,
MOF, DIC, ARF
SepsisIMOF
Renal abscess
Liver disease, Bili
30, sepsis
MV replacement
Patient
No. of Units of
Preop
PRBC Transfused
Within 30 d of Death
Hb A
%
Anesthesia
2
-
lnhal
18
ARDS
2
30
-
lnhal
lnhal
26
9
ARF
Sepsis, DIC
4
95
Local
15
DOA
Dialysis
-
Local
29
Sepsis, M. TB
0
5
70
Local
lnhal
12
4
DOA
ARF
Exploratory laparotomy
10
71
lnhal
2
DIC, Sepsis
A-V fistula
Drainage
Cholecystectomy
0
6
18
53
90
-
Local
lnhal
lnhal
5
8
2
0
17
Local
1 (38)
Sepsis
DTR, severe
anemia
Intra-abdominal
hemorrhage
MVrupture
Surgical Procedure
Bronchoscopy,
mediastinoscopy
Tendon repair
Tenkhoff catheter
Clotted venous graft
removal
Graft removal
Dental extraction
Exploratory cholecyst.
RH catheter
Surgery
to Death
Cause of Death
(d)
Abbreviations: DIC, disseminated IN coagulation; ARF, acute renal failure; DOA, dead on arrival; MOF, multiorgan failure; TB, tuberculosis;
ARDS, adult respiratory distress syndrome; CRF, chronic renal failure; DTR, delayed transfusion reaction; PRBC, packed RBCs; MV, mitral valve;
CHF, congestive heart failure.
postoperative complications were conducted only for two
of the groups, ie, abdominal surgery (cholecystectomy and
splenectomy) and orthopedic procedures of the hip. Only for
these two groups were posttransfusion Hb A data available
for at least 80% of the surgical procedures on SS patients.
Cholecystectomy and splenectomy. Patients undergoing
open cholecystectomy had a mean age of 23.3 2 11. l years
(range, 5 to 64 years). Patients undergoing splenectomy had
a mean age of 7.8 8.5 years (range, 9 months to 30 years).
All procedures were performed under general anesthesia and
the majority of patients were preoperatively transfused. The
rate of SCD-related postoperative complications was similar
for S S and SC patients (8% and 9%, respectively). Rates of
non-SCD-related postoperative complications were 11%for
S S and 23% for SC patients. The most frequent non-SCDrelated complications were fever and infection (other
than ACS).
There was nodifference in the overallrates of postoperative
complicationsin 203 transfusedversus 13 untransfused SS
patients (21.6% v 33.3%, P = .229). When examined separately, SCD-related and non-SCD-related complication rates
were againsimilar for transfused and untransfused
SS patients.
Table 2. Profile of Six Surgical Procedures
Cholecystectomy
and
Splenectomy
ss
sc
Dilation and
Curettage
ss
N
22
218
70
Risk level
Moderate
Low
28.3 20.7
26.2 23.5
Mean age (yr)
0, 59
7, 64
18,35
16,34
Age range (yr)
18.4
13.6
21.4
Emergent (%)
Preoperative transfusion (%)
7.1
42.9
81.8
94.0
44.3
81.8
Perioperative transfusion (%)
94.5
60.9
General anesthetic (%)
100.0
100.0
Postoperative complications
SCD-related (%)
18.6
7.8
9.1
Non-SCD-related (%)
15.7
11.0
22.7
2.9
Other (%)
7.9
4.6
27.5
36.4
Any complications (%)
22.2
sc
14
35.7
7.1
64.3
14.3
0.0
0.0
14.3
Cesarean Section
and Hysterectomy
ss
sc
Tonsillectomy
and
Adenoidectomy
ss
sc
65
18
35
7
Moderate
Moderate
25.9
27.7 15.5 11.4
2,22
1, 31
46
17,
16,39
0.0
64.6
72.2
5.7
100.0
82.9
81.5
61.1
100.0
82.9
90.8
72.2
100.0
77.8
72.2
100.0
16.9
26.2
13.9
41.5
0.0
11.1
33.3 14.3 5.7
2.9
11.1
50.0 14.3 5.7
14.3
0.0
Hip Replacement,
Revision, and
Prosthesis
Removal
ss
sc
34
6
Moderate
5.3
41.4
28.1
9,46
25, 62
0.0
5.9
97.1
100.0
100.0
100.0
100.0
97.0
2.9
14.7
0.0
17.7
0.0
33.3
16.7
33.3
Myringotomy
ss
sc
26
3
Low
9.1
0, 16
3.9
53.8
53.8
100.0
2, 7
0.0
33.3
33.3
100.0
3.9
7.7
0.0
11.5
0.0
0.0
0.0
0.0
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RISKS OF SURGERY AND ANESTHESIA IN SICKLECELL DISEASE
3679
Among preoperatively transfused S S patients, the risk of
postoperative painful crisis decreased with increasing levels
of Hb A (P = .054). The mean Hb A percentage in those
without pain (N = 161) was 54.8% 2 23.3%, compared with
34.7 2 29.5% in those with pain (N = 6). However, among
all S S patients (transfused and untransfused), total Hb concentration did not differ for those with and without postoperative painful crisis.
There was no association between the development of
postoperative ACS in preoperatively transfused S S patients
and the mean Hb A percentage (P = .854). However, the
total Hb concentration of 7 Ss patients with postoperative
ACS was significantly lower than that of 205 S S patients
without ACS (9.3
2.3 v 11.1 % 2.1 g/dL, P = .024),
even after adjustment for age. The risk of postoperative ACS
increased as total Hb concentration decreased (estimated
odds ratio, 1.7 times increased risk of ACS with each 1 g/
dL, P = .016).
Dilation and curettage. Only 44% of 70 S S patients and
7% of 14 SC patients received blood transfusion. There was
no difference in the overall rate of postoperative complications in S S patients by transfusion status (23.7% of N = 38
untransfused v 32.3% of N = 31 transfused, P = .662).
Except for 2 patients who developed ACS (1 patient was
transfused and the other not), all SCD-related complications
in S S and SC patients were painful crisis. The most common
non-SCD-related complications in S S patients were fever
and infection; none was reported in SC patients.
Cesarean section and hysterectomy. These procedures
were analyzed together. Cesarean sections comprised 55 of
the 65 S S procedures (85%) and 16 of the 18 SC procedures
(89%).The mean patient age was 25.3 2 5.3 years for Cesarean section and 32.7 % 7.9 years for hysterectomy. Seventythree percent of the Cesarean sections were emergent.
Ninety-one percent of the S S and 72% of the SC patients
were transfused. The postoperative complication rates were
high (42% for S S patients and 50% for SC patients). Although only 6 S S patients were untransfused, the overall
complication rate in S S patients did not differ by transfusion
status (44.1% of transfused v 16.7% of untransfused, P =
.793). Themean total Hb concentration of all S S patients was
not associated with the presence or absence of postoperative
complications (P = .836).
Tonsillectomy and adenoidectomy. All 7 SC patients and
83% of the 35 S S patients were transfused. Postoperative
complication rates were fairly low (6%for S S and 14%
for SC patients), with no SCD-related complications in S S
patients. The postoperative complication rates were similar
in transfused (N = 29) and untransfused (N = 6) S S patients
(3.5% of transfused v 16.7%of untransfused, P = .318).
Hip replacement, revision, and prosthesis removal.
Thirty-four patients were preoperatively transfused, and one
was transfused during the intraoperative period. The rate of
non-SCD-related complications was 15% for S S and 29%
for SC patients. The only SCD-related complication was
painful crisis in 1 S S patient. The mean Hb A percentage
was 55.3% 2 20.6% with no postoperative complications
(N = 26) and 69.6% -C 9.8% with postoperative complications (N = 5 ; P = .142) among the preoperatively transfused
S S patients.
Myringotomy. Three SC patients and 26 S S patients underwent myringotomy. One SC patient and 54% of the S S
patients were transfused. There was one SCD-related complication, ie, a cerebrovascular accident in a chronically
transfused S S patient with previous CVA. Non-SCD-related
complications (fever and bleeding) occurred in 2 other S S
patients (8%).There was no association between the overall
postoperative complication rate and transfusion status.
Anesthesia and Postoperative Complications
For the low-risk surgical procedures, 73.8%, 10.6%, and
15.6% were performed under general, regional, and local
anesthesia, respectively. For the moderate-risk procedures,
93.0%, 6.1%, and 1.0%,were performed under general, regional, and local anesthesia, respectively. Thirteen of the 15
high-risk surgical procedures were performed under general
(86.7%)and 2 were performed under local anesthesia (drainage of a brain abscess and cardiac catheterization followed
by balloon valvuloplasty). The anesthesia data on 45 surgical
procedures (4.2%)were incomplete and excluded from analysis. The effect of type of anesthesia on postoperative complication rates was examined with adjustment for Hb phenotype, age, surgery risk level (low v moderate), and
transfusion status. Crude postoperative complication rates
for S S patients are displayed in Fig 1.
Non-SCD-related complications. The most common
non-SCD-related postoperative complication was fever.
There was a marginally significant effect of anesthesia on
non-SCD-related postoperative complication rates (P =
.095). This effect was similar for S S and SC patients (P
= .199). These complication rates were lower for surgical
procedures with general anesthesia compared with those with
regional anesthesia (estimated odds ratio, 0.58; P = .095)
and compared with those with local anesthesia (estimated
odds ratio, 0.51; P = .100).
SCD-related complications. Painful crisis was the most
common SCD-related postoperative complication. Among
S S patients, the complication rate was associated with type
of anesthesia (P = .030), and rates were higher for surgical
procedures with regional anesthesia compared with those
with general anesthesia (estimated odds ratio, 2.32; P =
.058) and with those with local anesthesia (estimated odds
ratio, 4.65; P = .014). Among SC patients, complication
rates after general versus regional anesthesia did not differ
(P = %l), but this may be due to the small number of SC
patients who received regional anesthesia (N = 18).
Perioperative Transhsion and Postoperative
Complications
The effect of blood transfusion on postoperative complication rates was examined with adjustment for Hb phenotype,
age, surgery risk level (low v moderate), and type of anesthesia. Tables 3 and 4 present postoperative complication rates
by surgical risk level and perioperative transfusion status.
There were no complications in the 3 SC patients (2 transfused and 1 untransfused) undergoing high-risk surgery (not
shown in Table 4).
Non-SCD-related complications. For non-SCD-re-
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KOSHY
3680
25
ET AL
23.8
U
C
0
f 20
-.-n
U
5 15
14 5
14.3
V
135
B
:10
2
L
8.3
V
z
5
0
z
0.0
0
Moderate
LOW
Risk Level of Surgical Procedure
,
6.5
6.9
Fig 1. Postoperative complication rate in SS patients by type
of anesthesia. IO1 General anesthesia;
1. regional anesthesia; IO) local anesthesia.
Moderate
LOW
Risk Level of Surgical Procedure
lated postoperative complications, the effect of transfusion
depended on both surgery riskleveland phenotype ( P =
.015). There was a significant effect of transfusion only in
SC patients undergoing low-risk procedures. When perioperatively transfused, these patients had higher rates of postop-
erative complications than did untransfused patients ( P =
.004). The crude rates of non-SCD-related postoperative
complications were 28.1 % for surgical procedures with perioperative transfusion and 2.1% for those without.
SCD-relatedcomplications. For S S patients undergoing
SS Surgeries
Table 3. PostoDerative ComDlication Rates bv PerioDerative Transfusion Status
Low-Risk
Moderate-Risk
High-Risk
No TX
(N = 145)
(N = 248)
No TX
(N = 43)
(N = 390)
12.4
1.4
0.0
12.9
4.4
0.8
0.4
4.8
2.3
2.3
0.0
4.7
5.4
2.8
0.0
7.9
8.3
8.3
0.0
16.7
Non-ACS infection
Fever
Bleeding
Thrombosis
Embolism
Death
Any non-SCD complications
2.0
6.2
0.7
0.0
0.0
1.4
8.8
3.6
8.9
2.0
0.0
0.4
0.4
11.6
2.3
11.6
0.0
14.0
4.9
9.7
3.1
0.3
0.3
0.5
13.8
0.0
25.0
8.3
0.0
0.0
0.0
33.3
Other
1.4
5.2
2.3
7.7
8.3
18.6
17.3
18.6
23.9
41.7
TX
Postoperative Complications (%)
Pain
ACS
CVA
Any SCD complications
Any postoperative complications
TX
0.0
0.0
0.0
No TX
(N = 0)
~~
Of the
SS surgeries, 4 low-risk and 2 moderate-risk surgeries are missing a response to the
postoperative complication question.
TX
(N = 12)
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RISKS
OF
SURGERY AND ANESTHESIA IN SICKLECELL
Table 4. Postoperative Cornpliiion Rates by Parioporative
Transfusion Status SC Surgeries
Moderate-Risk
Low-Risk
NoTX
Postoperative Complications
(N = 48)
Pain
ACS
CVA
Any SCD complications
8.3
Non-ACS infection
Fever
0.0
0.0
0.0
Bleeding
Thrombosis
Embolism
Death
28.1
Any non-SCD complications
Other
Any postoperative
24.5complications
42.9
31.3
0.0
0.0
8.3
0.0
0.0
TX
(N = 32)
NoTX
(N = 21)
0.0
0.0
9.5
14.3
0.0
19.1
0.0
4.1
0
.0
TX
(N = 49)
4.1
0.0
0.0
4.8
0.0
21.910.2 28.6
0.0
6.3
0.0
0.0
4.8
0.0
10.2
0.0
0.0
2.1
2.1
0.0
2.1
3.1
0.0
0.0
2.0
16.3 28.6
0.0
3681
DISEASE
8.2
12.5
Of the SC surgeries, 1 low-risk surgery is missing a response to the
postoperative complication question.
low-risk surgical procedures, there was a beneficial effect of
transfusion (estimated odds ratio for untransfused v transfused, 3.28; P = .006) on SCD-related postoperative complications, particularly painful crisis. The crude complication
rates for S S patients undergoing low-risk surgical procedures
were 12.9%for surgical procedures without transfusion and
4.8%for those with transfusion. Accordingly, the mean total
Hb concentration of transfused patients was significantly
higher (10.3 5 2.3 g/&) than that of untransfused patients
(8.4 -t 1.3 g/&; P = .OOOl). However, among S S patients
undergoing moderate-risk surgical procedures, no association was found between transfusion and SCD-related postoperative complications ( P = 3 1 ) . Mean total Hb concentrations of S S patients undergoing moderate-risk surgical
procedures were similar for those with and without postoperative painful crisis (10.6 2 1.9 v 10.5 ? 2.3 g/dL, P =
383). In contrast, the mean total Hb of 12 S S patients who
developed ACS was 9.3 ? 2.0 g/dL, compared with 10.5 rt
2.3 g
/
&
for 413 SS patients who did not develop postoperative ACS (P = .055). However, this difference did not remain
after adjusting for age.
Among SC patients there was a beneficial effect of perioperative transfusion regardless of surgery risk level (estimated
odds ratio for untransfused v transfused, 8.33; P = .009).
The crude rate of complications after low- and moderaterisk surgeries was 2.5% with perioperative transfusion and
11.6% without. The mean total Hb concentration was 11.3
5 1.6 g/dL for untransfused SC patients and 12.0 ? 2.3 g/
dL for perioperatively transfused SC patients. Notably, 3
of21 untransfused SC patients undergoing moderate-risk
surgical procedures had ACS, but none of the 49 transfused
patients in this group did.
Sflo Thal and Sfl+ Thal Patients
Fifty-two surgical procedures were performed on 41 S$
thal patients. There were 11 cholecystectomies, 5 splenecto-
mies, 2 hip replacements/revisions, 8 dilation and curettage
procedures, 4 circumcisions, 2 laparotomies, 2 laparoscopic
evaluations, 2 tubal ligations, 1 Cesarean section, 1 tonsillectomy, 1 adenoidectomy, and 13 other surgical procedures.
The SCD-related postoperative complication rate was 9.6%
(3 painful crises, 1 ACS, and 1 with both). The non-SCDrelated complication rate was 1 1 S%.
Thirteen of 16 Soo thal patients were perioperatively transfused for cholecystectomy or splenectomy (81.3%).Of these
transfused patients, 1 patient had fatal postoperative bleeding
(see Postoperative Deaths), and another had a painful crisis,
ACS, fever, and thrombosis after the surgical procedure. No
complications were reported for the 3 untransfused patients.
Twenty-nine surgical procedures were performed on 21
S o + thal patients. There were 2 splenectomies, 3 Cesarean
sections, 2 tonsillectomies, 5 dilation and curettage procedures, 2 inguinal hernia repairs, 1 myringotomy, 1 hip revision, and 13 other surgical procedures. The perioperative
transfusion rate was 41.4%. The only SCD-related postoperative complication was 1 ACS event after splenectomy with
intraoperative transfusion (preoperative total H b , 13.2 g/dL).
No non-SCD-related complications were reported.
DISCUSSION
Because previous studies have shown significant complications for SCD patients undergoing surgical procedures,
most centers follow protocols for use of preoperative preparative transfusion,'~4.'2~'3*'s-19 and only afew investigators have
reported a paucity of morbidity data in untransfused patients
undergoing minor
These increased risks are
believed to be secondary both to acute tissue injury and
chronic organ damage produced by vaso-occlusion from
sickled red blood cells (RBCs). In addition, surgical procedures may be complicated by hypoxia, acidosis, or hypothermia, adding to a greater likelihood of SCD patients experiencing an adverse event, because each of these factors
promotes erythrocyte sickling. Although RBC transfusions
have been advocated by many investigators to reduce perioperative complications, there are no controlled trials documenting their benefit. There are also significant risks associated with RBC transfusions, including alloimmunization and
exposure to infectious diseases.
The CSSCD was designed to define the natural history
of SCD and its effects on health events. The recruitment
procedures insured that participants were representative of
the wide spectrum of clinical severity that is a hallmark of
this disease. Because this unique population was observed
prospectively for a median of 6 years, it is ideally suited
to define the types of surgical procedures and associated
complications that can be observed in patients with SCD.
There were several interesting observations noted in this
study. The overall mortality rate was very low (0.3%).There
were only 3 deaths attributed to the surgery or anesthesia.
No deaths were observed in patients under the age of14
years, although many children had procedures associated
with moderate surgical risk.
The SCD-related complication rates were similar for SC
and S S patients undergoing abdominal surgeries and orthopedic procedures. The level of Hb A in the transfused pa-
From www.bloodjournal.org by guest on February 6, 2015. For personal use only.
3682
tients did not decrease postoperative complication rates, except for the decrease in the rate of postoperative pain crisis
for abdominal surgeries. There were only21 procedures
among S@+thal patients enrolled in the study, and there was
no report of cholecystectomy. Although the total number of
patients was small, this low number of surgeries maybe
reflective of the more benign phenotype.
There was wide variation in the SCD-related complications associated with the more common surgeries. The rate
for SS patients was 0% for tonsillectomy and adenoidectomy, 2.9% for hip surgery, 3.9% for myringotomy, 7.8%
for intra-abdominal surgery, 16.9%for cesarean section and
hysterectomy, and 18.6%for dilation and curettage. Reasons
for this wide variation were not identified, although the high
rate of sickle cell complications after Cesarean section probably is related to the increased morbidity associated with
pregnancy in women with sickle cell anemia irrespective of
transfusion practice^.^"'^ At present, because laparoscopic
cholecystectomy has replaced the open procedure, the duration of hospitalization, transfusion requirements, and postoperative complications willmost likely be lower thanthat
reported here.
We also observed that in the patients transfused before
intra-abdominal surgery, the mean level of Hb A was higher
for those patients with no painful crisis compared with those
who experienced painful crisis after surgery (58% v 35%,
respectively). However, prevention of painful crisis in the
postoperative period does not alone justify the use of preoperative transfusions in light of the recognized complications
of blood transfusion. The recently concluded randomized
controlled trial evaluating perioperative blood transfusion
has defined the role of preoperative blood transfusion for
sickle cell patient^.^'
This study also showed that non-SCD complication rates
for fever and infection were higher in patients receiving
regional anesthesia compared with those who had received
general anesthesia but unrelated to the preoperative transfusion rates. Because regional anesthesia (specifically epidural)
is commonly used in Cesarean sections and other assisted
deliveries, the higher complication rates observed may be a
reflection specifically of the higher complication rates observed in those obstetrical procedures.
In non-SCD patients undergoing surgery, perioperative
complications vary from general pulmonary complications
of 3% to 70% to serious ACS-like events of less than
40 Similarly, in-hospital complications for open cholecystectomy occur in 22.4% (unadjusted rate) of patients4' Our
data show that SCD patients are at no greater risk for these
complications than the non-SCD patients.
Although not derived from a rigorously controlled trial,
the data do define the types of commonly performed surgerieson patients with SCD and provide new insights into
postoperative complications. Despite the variety of techniques used to manage patients and the variations in methods
of inducing anesthesia, mortality was low and there were
relatively few serious perioperative complications related to
SCD. In part, this outcome can be attributed to careful attention tothe details of patient management by the collaborative
efforts of the hematologist, surgeon, and anesthesiologist.
KOSHY ET AL
However, the role of transfusion in the perioperative period
remains to be defined, but the data do suggest that not all
patients undergoing surgery should routinely receive blood
transfusions.
During the study period, no protocol wasspecified for
preoperative transfusion practice. Each center continued to
follow its own preoperative preparative regimen. The patient's age, disease state, multiorgan disease status, and
American Surgical Association (ASA) risk level were not
predetermined.
For the minor procedures, many of the patients did not
receive blood transfusions and complication rates were low.
The postoperative complication rates were also low for the
42 patients who underwent tonsillectomy. Six SS patients
who were untransfused hadno complications after tonsillectomy. The paucity of complications after this procedure may
be related to the younger age of patients at the time of
surgery.
Recent advances in intraoperative techniques and new anesthetic agents have been touted for successful outcomes for
SCD patients in postoperative periods, rather than the use
of blood transfusion regimen alone.3~4~'2,20~22.25.29.35,42
Others
credit aggressive preoperative transfusion preparation as responsible for the successful outcome of SCD patients undergoing surgical procedures.'5342The percent reduction of S
Hb required for transfusing patients is not well defined in
those receiving mandatory preoperative transfusion.
Surgical procedures can be performed successfully on
SCD patients. Careful assessment of Hb phenotype, past
medical history, and risk status should be documented.
Blood transfusion therapy will continue to be part of the
preoperative evaluation and preparation of patients. Simple
transfusion to increase the Hb level to 10 g/&, blood replacement for profound anemia of Hb less than 5 g/dL, and
intraoperative hemorrhage appears appropriate. Transfusion
still carries with it the complications of alloimmunization,
delayed transfusion reaction, transmission of viral infection,
hepatitis, and iron o~erload?~,"
These complications should
be considered when counseling patients and family before
the surgical procedure.
ACKNOWLEDGMENT
TheauthorsareindebtedtoPamelaMoore,ShaheenIslam,and
Susan Weaver for their assistance in preparing this manuscript. The
following were senior investigators in the CSSCD: Clinical centers:
R. Johnson, Aka Bates Hospital (Berkeley, CA); L. McMahon, Boston City Hospital (Boston, MA); 0. Platt, Children's Hospital (Boston, MA); F. Gill and K. Ohene-Frempong,Children'sHospital
(Philadelphia, PA); G. Bray, J. Kelleher, and S. Leikin, Children's
NationalMedicalCenter(Washington, DC); E. Vichinsky and B.
Lubin, Children's Hospital (Oakland,CA); A. Bank and S. Piomelli,
Columbia Presbyterian Hospital (New York, NY); W. Rosse, J. Fdletta,and T. Kinney,DukeUniversity(Durham,
NC); L. Lessin,
George Washington University (Washington, DC); J. Smith and Y.
Khakoo, Harlem Hospital (New York, NY); R. Scott, 0.Castro, and
C. Reindorf,HowardUniversity(Washington,
DC); H. Dosik, S.
Diamond,andR.
Bellevue, InterfaithMedicalCenter
(Brooklyn,
NY); W. Wangand J. Wilimas, LeBonheurChildren'sHospital
(Memphis, TN);P. Milner, Medical College of Georgia (Augusta,
GA); A. Brown, S. Miller, R. Rieder, andP. Gillette, State University
of New York Health Science Center at Brooklyn (Brooklyn, NY);
From www.bloodjournal.org by guest on February 6, 2015. For personal use only.
DISEASE
3683
W. Lande, S . Embury, and W. Mentzer, San Francisco General
Hospital (San Francisco, CA); D. Wethers and R. Grover, St Luke’sRoosevelt Medical Center (New York, NY); M. Koshy and N. Talishy, University of Illinois (Chicago, L);C. Pegelow, P. Klug, and
J. Temple, University of Miami (Miami, FL);M. Steinberg, University of Mississippi (Jackson, MS); A. Kraus, University of Tennessee
(Memphis, TN); H. Zarkowsky, Washington University (St Louis,
MO); C. Dampier, Wyler Children’s Hospital (Chicago); H. Pearson
and A.K. Ritchey, Yale University (New Haven, CT); Statistical
Coordinating Centers: P. Levy, D. Gallagher, A. Koranda, Z. Flournoy-Gill, and E. Jones, University of Illinois School of Public Health
(Chicago, IL; 1979-89); S . McKinlay, O.Platt, D. Gallagher, D.
Brambilla, and L. Sleeper, New England Research Institutes (Watertown, MA; 1989-1995); M. Espeland, Bowman-Gray School of
Medicine (Winston-Salem, NC); Program Administration: M. Gaston, C. Reid, and J. Verter, National Heart, Lung, and Blood Institute
(Bethesda, MD).
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abnormalities and on recurrence of stroke in sickle cell disease.
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Partial exchange transfusion in sickle cell anemia. Am J Dis Child
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10. Brody JI, Goldsmith MH, Park SK, Soltys H D Symptomatic
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1I. Green M, Hall RJC, Huntsman RG, Lawson A, Pearson TCF,
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Menzel DM: Prophylactic transfusions in pregnant patients with
sickle hemoglobinopathies: Benefit versus risk. Obstet Gynecol
56:274, 1980
16. Nagey DA, Garcia J, Welt S : Isovolumetric partial exchange
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17. Coker NJ, Milner PF: Elective surgery in patients with sickle
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18. Fullerton MW, Philippart AI, Samaik S , Lusher JM: Preoperative exchange transfusion in sickle cell anemia. J Pediatr Surg
16:197, 1981
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in children with sickle cell disease. Surg Clin North Am 5655, 1976
20. Lagarde MC, Tunell WP: Surgery in patients with hemoglobin-S disease. J Pediatr Surg 13:605, 1978
21. Homi J, Reynolds J, Skinner A, Hanna W, Serjeant G: General
anesthesia in sickle-cell disease. Br Med J 16:1599, 1979
22. Serjeant G: Sickle Cell Disease. London, UK, Oxford, 1985,
p 371
23. Davis JR, Vichinsky EP, Lubin BH: Current treatment of
sickle cell disease. Curr Probl Pediatr lO:l, 1980
24. Lessin LS, Kurantsin-Mills J, Klug PP, Weems HB: Determination of continuous flowblood cell separator. J Clin Apheresis
1:64, 1978
25.Griffin TC, Buchanan G: Elective surgery in children with
sickle cell disease without pre-operative blood transfusion. J Ped
Surg 28:681, 1993
26. Gaston M, Smith J, Gallagher D, Flournoy-Gill Z, West S ,
Bellevue R, Farber M, Grover R, Koshy M, Ritchey AK, Wilimas
J, Verter J, and the CSSCD Study Group: Recruitment in the Cooperative Study of Sickle Cell Disease (CSSCD). Controlled Clin Trials
8:131S, 1987
27. Farber MD, Koshy M, Kinney TR, and the Cooperative Study
of Sickle Cell Disease: Cooperative Study of Sickle Cell Disease:
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RISKS OF SURGERY AND ANESTHESIA IN SICKLECELL
APPENDIX
Descriptiodlocation of 1,079 surgical procedures. Two
hundred twenty-two cholecystectomy, 2 cholecystotomy, 3
obstruction of gall bladder, 36 splenectomy, 107 dilation
and curettage for pregnancy termination and miscellaneous
complications, 7 dilation and curettage postpartum and for
ectopic pregnancy, 75 Cesarean section, 12 hysterectomy,
46 tonsils and adenoids, 21 hip replacement, 19 hip revision,
3 hip prosthesis removal, 30 myringotomy, 5 craniotomy, 4
spinal canal, 4 miscellaneous nervous system, 6 retina, 4
scleral buckling, 12 miscellaneous eye, 1 myringoplasty, 1
tympanoplasty, 2 radical mastoidectomy, 3 sinus, 11 dental
exiraction and restoration, 2 cleft palate correction, 5 bronchial and pulmonary biopsy, 6 miscellaneous respiratory, 20
vascular access, 7 miscellaneous cardiovascular, 5 lymphatic
node biopsy, 10 appendectomy, 3 hemorrhoidectomy, 16
inguinal hernia repair, 8 umbilical hernia repair, 19 laparotomy and laparoscopy, 5 miscellaneous digestive system, 3
kidney transplant, 10 miscellaneous urinary system, 4 undescended testes, 6 penile prosthesis, 17 priapism surgery, 22
circumcision, 4 miscellaneous male genital organ, 4 ovaries
and Fallopian tubes, 20 tubal ligation, 3 breast reduction/
enhancement, 8 miscellaneous breast surgery, 6 miscellaneous gynecological, 8 incision and drainage of long bones, 5
osteotomy, 18 bone excision and biopsy, 5 bone graft, 8
open reduction and treatment of fractures, 4 joint fusion, 2
shoulder and wrist replacement, 4 clubfoot release, 6 tendon
and sheath repair, 12 miscellaneous musculoskeletal, 31 skin
debridement, 21 skin and subcutaneous, 38 skin graft, 2
parathyroidectomy, 49 diagnostic procedures.
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1995 86: 3676-3684
Surgery and anesthesia in sickle cell disease. Cooperative Study of
Sickle Cell Diseases
M Koshy, SJ Weiner, ST Miller, LA Sleeper, E Vichinsky, AK Brown, Y Khakoo and TR Kinney
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