Sickle Cell Disease Anaesthesia

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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 Stud y of Sickle Cell Disease

From 1978 t o 1988, The Cooperative Study of Sickle CellDisease observed 3,765 patients with a mean follow-up of5.3 k 2.0 years. One thousand seventy-nine surgical proce-dures were conducted on 717 patients (77 sickle cell ane-mia [SS], 14 sickle hemoglobin C disease [SC], 5.7 Spothalassemia, 39'0 Sp+ thalassemia). Sixty-nine percent had asingle procedure, 219'0 had two procedures, and the re-maining 11 had more han t w o procedures during hestud y follow-up. The mos t frequent procedure was abdomi-nal surgery for cholecystectomy or splenectomy (2496 of allsurgical procedures, N = 258). Of these, 939'0 received bloodtransfusion, and there was no ssociation between preoper-ative hemoglobin A level and complication rates (except re-duction in pain crisis). Overall morta lity with in 30 days of asurgical procedure was 1.1 (12 deaths after 1,079 surgicalprocedures). Three deaths were considered to be related othe surgical procedure andlo r anesthesia (0.3 ). No deathswere reported in patients younger than 14 years of age.

ATIENTS WITH sickle cell disease (SCD; which n-cludes sickle cell anemia [SS], sickle hemoglobin C

disease [SC], and the sickle 0 thalassemias) who undergosurgery are generally considered to be at greater risk forperioperative complications than otherwise healthy patientswithout this hematologic disorder.' ' Favorable outcomeshave been reported without transfusion, but perioperativetransfusion is commonly used to prepare SCD patients forsurgery and to treat complications of sickle cell di se a ~ e . 4 , ~ . ~ ~ ~Although the optimal level of sickle hemoglobin (Hb) to beachieved is unknown, most sickle cell centers adhere to someform of transfusion protocol for SCD patients undergoing

The Cooperative Study of Sickle Cell Disease (CSSCD)was a natural history study that observed 3,765 patients from1978 to 1988.26.27 his report analyzes the course and out-come of the 1,079 surgical procedures performed on 717patients during this time period.

P

sUrgery.l.18.20-25

From the University of Illinois, C hicago, IL; New England R e-search Institutes, Wa tertown, MA; the Departm entof Pediatrics,State University of New York Health Science C enter at Brooklyn,Brooklyn, NY; the Departmentof Pediatrics, Children's Hospital,Oakland , CA; the Columb ia University College of Physicians andSurgeons and Harlem Hospital Center, New York, NY; the Depart-ment of Pediatrics, Duke U niversity 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 Instituteo the National Insti-tutes of Health.

Address reprint requests to Mabel Koshy, MD, University of Illi-nois at Chicago , Division of Hema tology(M/C 787), 8 4 0 S WoodSt, Room 314 CSB, Chicago,IL 60612.

The publication costsof his article w ere d efrayedn par t by pagecharge payment. This article must therefore be hereby marked

advertisement in accordance with18 U.S.C. section 1734 solely toindicate this fac t.

995 by The American Society of Hematolog y.

0006-4971/95/8610-0012 3.00/0

3676

Sickle cell disease (SCD)-related complications after surgerywere more frequent in SS patients who received regionalcompared with general anesthesia (adjusted for risk level ofth e surgical procedure, pat ient age, and preoperative trans-fusion status, P = .058). Non-SCD-related postoperativecomplications were higher in both SS and SC patie nts whoreceived regional compared with those who received gen-eral anesthesia (P .095). Perioperative transfusion was as-sociated with a lo wer rate of SCD-related postoperativecomplications for SS patients undergoing low-risk proce-dures (P .006, adjusted for age a nd type of anesthesia),with crude rates of 12.9 wit ho ut transfusion comparedwith 4.8 with transfusion. In SC patients, preoperativetransfusion w as beneficial for all surgical risk levels ( P =.0091. Thus, surgical procedures can be performed safely inpatients with SCD.

1995 by The American Society of Hematology

MATERIALS ANDMETHODS

Patients

The goals, objectives, design, and enrollment procedures of theCooperative Study of Sickle Cell Disease have been described else-where.26-28 From ctober 1978 to October 1988, 3,765 patients from23 clinical centers across the continental United States participatedin the CSSCD. The median length of patient follow-up was 6.0years. Of the total study cohort, 67.5% of the patients had SS, 22.4%had SC, 5.0 had sickle o thalassemia (Soo thal), and 5.1% hadsickle p thalassemia (So' thal). The Hb phenotype was establishedby the Centers for Disease Control using standard laboratorymethods.

Data Collection

A standardized CSSCD data collection form was completed eachtime a patient underwent a surgical procedure. Because of limitationsin data collection procedures, only one surgical procedure was re-corded per operation. Medical history, laboratory data, and perioper-ative course were recorded on this form. Separate forms were com-pleted documenting blood transfusions and acute and chronic clinicalevents. Transfusion data for the 30-day period before surgery andacute event data for the 7-day period after surgery were used in thisreport. All deaths within 30 days after a surgical procedure aresummarized in this report. Deaths occurring within 7 days of surgerywere defined as postoperative complications.

Class cation o Surgeries, Anesthesia, Transfusion, andComplications

Surgeries were defined using the International Classification ofDiseases (9th revision) diagnosis codes for procedures. For the pur-poses of analysis, surgical procedures were categorized into threegroups by level of ri sk low, moderate, and high.29 Low-risk proce-dures are those of the eyes, skin, nose, ears, and distal extremitiesas well as those pertaining to the dental, perineal, and inguinalareas (eg, inguinal hernia repair, myringotomy, and dilatation andcurettage). Moderate-risk procedures are those of the throat, neck,spine, proximal extremities, genitourinary system, and intra-abdomi-nal areas, such as onsillectomy, Cesarean section, splenectomy, cho-lecystectomy, and hip replacement. High-risk procedures are thosepertaining to the intracranial, cardiovascular, and intrathoracic sys-

tems (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

In addition to ove rall analyses stratified y risk level, six specificclasses of the most common surgical procedures wereanalyzed (1)cholecystectomy or splenectomy (N = 222and 36, respectively;23.9% of all surgical procedures); (2) dilation and curettage(N =97; 9.0 ); 3) Cesarean section or hysterectomy (N = 87; 8.1%);(4) tonsillectomyand/oradenoidectomy(N = 46; 4.3%); 5 ) hipreplacement, removal, or revision (N = 4 4 ; 4.1 ); nd (6) myrin-gotomy (N = 30; 2.8%). The frequencies of the remaining surgicalprocedures (47.8%) are listed in the Appendix.

Anesthesia was classified as general, regional, and local. Generalanesthesia refers to that inducedy the inhalation f gas and balancedintravenous methods. Regional anesthesia refers to spinal, epidural,and nerve block anesthesia. The type of anesthesia and its methodof adm inistration were not prescribed by the CSSCD protocol.

Patients were defined as p reoperatively transfused if at least onetransfusion was administered within 30 days before surgery. Postop-erative complication ratesor patients who were perioperatively (ei-ther preoperatively or intraoperatively) ransfused were comparedwith those who were not transfused. Total Hb concentrations andHb A percentages presented in this report were obtained after trans-fusion and before surgery. The CSSCD was natural history study,

thus noprotocolwasspecified for perioperative management; allpatients were treated according to institutional practices.Postope rative com plications were defined as complications hat

occurred within 7 days after surgery. These complications were cate-gorized nto hree groups: (1) SCD -related, (2) non-SCD-related,and (3) other. SCD-related complications were defined as painfulcrisis, acute chest syndrome (ACS), and cerebrovascular accident(CVA). Non-SCD-related complicationswere defined as fever , in-fection (excluding ACS), bleeding, thrombosis, embolism, and death.Other postoperative complications included transfusion reactions andunspecified complications. Painful crisis was defined as pain in theextremities, back, abdomen, chest, or head for whicho other expla-nation (eg, osteomyelitisor appendicitis) could be found. ACS wasdefined as the new appearance of an infiltrate on chest radiographor abnorm alities on a radioisotope ungscan n hepresence of

symptoms.Statistical Methods

Because many patients underwent more than one surgical proce-dure, hesurgeryserved as heunitof analysis;eg,percentagesreported refer to the percentage of surgeries withparticular charac-teristic, rather than the percentagef patients. Complication rates arecomputed as the number of surgeries w itha particular complicationdivided by he oal number of surgeries. Descriptive statistics arepresentedaspercentagesandmeans -C 1 standarddeviation.Allhypothesis tests and confidence intervals are two-sided.two-sidedP value of .05 or less was considered to bea statistically significantresult. Postoperative complication rates with and without periopera-tive transfusion were compared using logistic regression, with adjust-ments for phenotype, ypeof anesthesia, surgical risk evel, and

age. The logistic regression model provided robust standard errorestimatesfor the model parameters that accountedor the correlationbetween different surgical procedures on hesame patient.30 Theassociation between postoperative complication rates and anesthesiawas also examined using logistic regression. Where there wereuf-ficient data, the association between postoperative complication ratesand (1) total Hb concentration and (2) HbA percentage was exam-ined using logistic regression. Mean totalHb concentrations of pa-tients with and without postoperative complications were comparedusing the Students t-test.

R E S U LT S

General Cha racteristics

There were 717 pat ien t s who had one or more surgical

procedures. Of these patients, 77.1%(N=

5 5 3 ) were SS,

14.2% (N = 102)were SC, 5.7% (N = 41) wereSpa hal , and2.9% (N = 21) wereSp+ thal. This group has roportionatelymore SS and f ewer S C an dSO+ thal patients than th e totalCSSCD cohor t (see Mater ia l s and Methods) .ixty-nine per-cent (N = 495) of the pat ients underwent one, 20.5%(N =147) had two,6.0 (N = 43) had three, and 4.5% (N= 32)

had four or more surgical procedures during the fol low-upperiod. Forty-eight percent(N = 520) of the 1,079 reportedsurgical procedu res were classified as low-risk,50% (N =543) as moderate-risk, and 2%(N = 16) as high-risk proce-dures.Seventy-fivepercent (N = 806)wereelectiveand25% (N = 271) wereemergent surgicalprocedures. Themean age a t the t ime f surgery was22.0 11.6 years, with17% being less than 10 years of age, 25% being 10 to 19years of age, 52% being20 to 39 years f age, and 6% being40 years of age and older. Female pat ients underwent1(N = 660) of thesurgicalproceduresandmale patientsunderwent the remaining 39% (N = 419).

The reported sample includes surgical procedures of dif-

fering risk levels performed on patientsof varying ages.Therisk of postoperative comp lications significantly increasedwith age (estimated odds ratio, 1.3 times increased riskofpostoperat ive complicat ions per10 years of age,P < . m o l ) .Com parisons of postoperative complication rateswere there-fore adjusted fo r pa tient ag e a s well as surgical risk leve l tocorrect for the potential c onfounding effects of these twofactors.

Postoperative Deaths

There were 12 postoperat ive deaths (10 SS, 1 SC, and 1Spa hal) within 30 days of a surgical procedure (Table1).Notably, therewere no dea ths amon g atients under14 yearsof age and only 2 in patients betwee n 14 and 20 years ofage. The mean age at death was 27.4 - 10.4 years (range,14 to 54 years). Eleven of these patients were transfused.There were8 minor and4 major intra-abdominal procedu res.The deaths in the first 9 patients appear o be related tocomo rbid medic al comp lications and SCD-related multior-gan failure. The deaths in the rema ining 3 patients appea rto be related to the surgical procedure: patient no.10 f romprofound anem ia seconda ry to delayed transfusion reaction;patient no. 11 from an ntra-abdominal hem orrhage requiring18 U of packe d red blood cells; and patientno. 12 fromrupture of the prosthetic mitral valveeplaced 38 days earlier(the surgical procedure was diagnost ic rightheart catheter-ization 1 day before death).

The overal l 30-day postoperat ive ortal ity rate was1 l%(12 dea ths of 1,07 9 surgicalprocedures). The actual mortal-ity rate of the 3 deaths related to the urgical procedure wasonly 0.3%.

A Projile of Most Frequently Performed Procedures

A description of six classes of surgical procedu res mostfrequently performed during he course of the CSSC D sdisplayed in Table 2. There were few procedures performedon SC patients; hus, no formal statistical compa risons ofthe outcome of SS and SC patients were made. Analyses

of therelationshipbetweenpreoperat ive Hb A leveland


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3678 KOSHY ET AL

Table 1. Pos topera t ive Dea ths Occurr ing W ith in 0 Days o f S urgery

No. of Units o f PreopPatient Age/ Hb Clinical Status a t

SurgeryPRBC Transfused Hb A to Death

No. Sex Diag. Surgery Surgical Procedure Within 30 d of Death Anesthesia ( d ) Cause of Death

1

2

3

4

5

6

7

8

9

10

11

12

21lF

36lF

28lF

27lF

23lM

2OlF54/F

17lF

26/F

14lF

32lM

2 4lF

ss

ssss

ss

ss

ssss

ss

scssSO0

ss

Cirrho sis DIC,MOF, CRF

FeverMOFlseps is, CRFI

DIC peritonitis1pneumonia

CRF/SP renaltransplant

CRF infected graft,

CVA, comatoseAcute abdomen,

Bili 26, CHFSepsislacidosis,

SepsisIMOFRenal abscess

Liver disease, Bili

dialysis

MOF, DIC, ARF

30, sepsisMV replacement

Bronchoscopy,

Tendon repairTenkhoff catheter

mediastinoscopy

Clotted venous graftremoval

Graft removal

Dental extractionExploratory cholecyst.

Exploratory laparotomy

A-V fistulaDrainageCholecys tec tomy

RH catheter

2

2

30

4

Dialysis

05

10

0

6

18

0

95

70

71

53

90

17

lnhal

lnhallnhal

Local

Local

Locallnhal

lnhal

Locallnhallnhal

Local

18 ARDS

26 ARF9 Sepsis, DIC

15 DOA

29 Sepsis, M. TB

12 DOA4 ARF

2 DIC, Sepsis

5 Sepsis8 DTR, severenemia2 Intra-abdominal

hemorrhage1 (38) M Vupture

Abbreviations: DIC, disseminated IN coagulation; ARF, acute renal failure; DOA, dea d on arrival; MOF, m ultior gan failure; TB, tuberculosis;ARDS, adult respiratory distress syndrome; CRF, chronic renal failure; DTR, delaye d trans fusion reaction; PRBC, packed RBCs; MV, m itral valve;CHF, congestive he art failure.

postoperative complications were conducted only for twoof the groups, ie, abdominal surgery (cholecystectomy andsplenectomy) and orthopedic procedures of the hip. Only forthese two groups were posttransfusion Hb A data availablefor at least 80 of the surgical procedures on SS patients.

Cholecystectomy and splenectomy. Patients undergoingopen cholecystectomy had a mean age of 23.3 11. l years(range, 5 to 64 years). Patients undergoing splenectomy hada mean age of 7.8 8.5 years (range, 9 months to 30 years).All procedures were performed under general anesthesia andthe majority of patients were preoperatively transfused. The

rate of SCD-related postoperative complications was similarfor S S and SC patients (8 and 9%, respectively). Rates ofnon-SCD-related postoperative complications were 11% forS S and 23% for SC patients. The most frequent non-SCD-related complications were fever and infection (otherthan ACS).

There was no difference n the overall ates of postoperativecomplications n 203 transfused versus 13 untransfused SSpatients (21.6% 33.3%, P = .229). When examined sepa-rately, SCD-related and non-SCD-related complication rateswere again imilar for transfused and untransfused S patients.

Table 2. Profile of Six Surgical Procedures

CholecystectomyHip Replacement,

Tonsillectomy Revision, an dand Dilation and Cesarean Section and Prosthesis

Splenectomy Curettage a n d Hysterectomy Adenoidectomy Removal Myringotomy

ss sc ss sc ss sc ss sc ss sc ss scN

Risk levelMean age (yr)Age range (yr)Emergen t ( )Preoperative transfusion ( )Perioperative transfusion ( )General anesthetic ( )Postoperative complications

SCD-related ( )Non-SCD-related ( )Othe r ( )Any compl ica t ions ( )

2182

Modera te20.78.3

0, 59 7, 64

18.4 13.6

94.0 81.8

94.5 81.8

100.0 100.0

7.8 9.1

11.0 22.7

7.9 4.6

22.2 36.4

70 14

L o w23.56.2

16,348,35

21.4 35.7

42.9.1

44.3 7.1

60.9 64.3

18.6 14.3

15.7 0.02.9 0.0

27.5 14.3

65 18

Modera te25.9 27.7

17,6 16,39

64.6 72.2

81.5 61.1

90.8 72.2

77.8 72.2

16.9 11.1

26.2 33.3

13.9 11.1

41.5 50.0

35 7

Modera te11.45.5

2, 22 1, 315.7 0.0

82.9 100.0

82.9 100.0

100.0 100.0

0.0 14.3

5.74.3

2.9 0.05.74.3

34 6

Modera te28.1 41.4

9, 46 25, 62

5.9 0.097.1 100.0

100.0 100.0

97.0 100.0

2.9 0.014.7 33.3

0.0 16.7

17.7 33.3

26 3

L o w9.1.3

0, 16 2, 73.9 0.0

53.8 33.3

53.8 33.3

100.0 100.0

3.9 0.0

7.7 0.00.0 0.0

11.5 0.0


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Amon g preoperatively transfusedS S patients, the risk ofpostoperative painful crisis decreased with increasing levelsof Hb A ( P = .054). The mean Hb A percentage in thosewithout pain (N = 161) was 54.8 23.3 ,compared with34.7 29.5 in those with pain (N = 6). However, amongall S S patients (transfused and untransfused), totalHb con-centration did not differ for those with and without postope r-ative painful crisis.

There was no association between the development ofpostoperative A CS in preoperatively transfusedS S patientsand the mean Hb A percentage (P = .854). However, thetotal Hb concentration of 7 Ss patients with postoperativeACS was significantly lower than that of205 S S patientswithout ACS (9.3 2.3 v 11 .1 2.1 g/dL, P = .024),even after adjustment for age. The risk of postoperative ACSincreased as total Hb concentration decreased (estimatedodds ratio, 1.7 times increase d risk of ACS with each1 g/dL, P = .016).

Dilation and curettage. Only 44 of 70 S S patients and

7 of 14 SC patients received blood transfusion. There wasno difference in the overall rate of postoperative complica-tions in S S patients by transfusion status(23.7 of N = 38untransfused v 32.3 of N = 31 transfused, P = .662).Except for 2 patients who developed ACS (1 patient wastransfused and the other not),all SCD-related com plicationsin S S and SC patients were painful crisis. The most com monnon-SCD-related complications inS S patients were feverand infection; none was reported in S C patients.

Cesarean section and hysterectomy. These procedureswere analyzed together. Cesarean sections comprised55 ofthe 65 S S procedures (85 )and 16 of the 18 SC procedures(89 ).The mean patient age was25.3 5.3years for Cesar-

ean section and32.7 7.9years for hysterectomy. Seventy-three percent of the Cesarean sections were emergent.Ninety-one percent of the S S and 72 of the SC patientswere transfused. The postoperative complication rates w erehigh (42 for S S patients and 50% for SC patients). Although only 6 S S patients were untransfused, the overallcomplication rate inS S patients did not differ by transfusionstatus (44.1 of transfused v 16.7 of untransfused,P =.793). Themean totalHb concen tration ofall S S patients wasnot associated with the presence or absence of postoperativecomplications ( P = .836).

Tonsillectomy and adenoidectomy. All 7 SC patients and83 of the 35 S S patients were transfused. Postoperativecomplication rates were fairly low (6% or S S and 14for SC patients), with no SCD-related complications inSSpatients. The postoperative complication rates were sim ilarin 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 w ere preoperatively transfused, and onewas transfused during the intraoperative period. The rate ofnon-SCD-related complications was15 for S S and 29for SC patients. The only SCD-related complication waspainful crisis in 1 S S patient. The mean Hb A percentagewas 55.3 20.6 with no postoperative complications(N = 26) and 69.6 -C 9.8 with postoperative complica-tions (N = 5 ; P = .142) among the preoperatively transfused

S S patients.

Myringotomy. Three SC patients and26 S S patients un-derwent myringotomy. One SC patient and54 of the S Spatients were transfused. There was one SCD-related com-plication, ie, a cerebrovascular accident in a chronicallytransfusedS S patient with previous CVA . Non-SCD-relatedcomplications (fever and bleeding) occurredin 2 other S Spatients (8 ).There was no association between the overallpostoperative com plication rate and transfusion status.

Anesthesia and Postoperative Complications

For the low-risk surgical procedures,73.8 , 10.6%, and15.6 were performed under general, regional, and localanesthesia, respectively. For the m oderate-risk procedures,93.0 ,6.1%, and 1.0 , were performed under general, re-gional, and local anesthesia, respectively. Thirteenof the 15high-risk surgical procedures were performed under general(86.7 )and 2 were performed underlocal anesthesia (drain-age of a brain abscess and cardiac catheterization followed

by balloon valvuloplasty). The anesthesia data on45 surgicalprocedures(4.2 )were incomplete and excluded from anal-ysis. The effect of type of anesthesia on postoperative com-plication rates was examined with adjustment for Hb pheno-type, age, surgery risk level (low v moderate), andtransfusion status. Crude postoperative complication ratesfor S S patients are displayed in Fig1 .

Non-SCD-related complications. The most commonnon-SCD-related postoperative complication was fever.There w as a m arginally significant effect of anesthesia onnon-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 surgicalprocedures with general anesthesia compared with those w ithregional anesthesia (estimated odds ratio,0.58; P = .095)and compared with those with local anesthesia (estimatedodds ratio, 0.51; P = .100).

SCD-related complications. Painful crisis was the m ostcommon SCD-related postoperative complication. AmongS S patients, the complication rate was associated withtypeof anesthesia( P = .030), and rates were higher for surgicalprocedures with regional anesthesia compared with thosewith general anesthesia (estimated odds ratio,2.32; P =.058) and with those with local anesthesia (estimated oddsratio, 4.65; P = .014). Among SC patients, complicationrates after general versus regional anesthesia did not differ( P = l ) , but this may be due to the small number of SCpatients who received regional anesthesia (N= 18).

Perioperative Transh sion and PostoperativeComplications

The effect of blood transfusion on postoperative complica-tion rates was exam ined with adjustment forHb phenotype,age, surgery risk level (lowv mode rate), and type of anesthe-sia. Tables 3 and 4 present postoperative complication ratesby surgical risk level and perioperative transfusion status.There were no complications in the3 SC patients (2 trans-fused and 1 untransfused) undergoing high-risk surgery (notshown in Table 4).

Non-SCD-related complications. For non-SCD-re-


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3680

25

C

23.8

20.-n

V15 14.3 14 5 1 3 5

B0

2z 5

8.3

V

z

00 0

LOW ModerateRisk Level of Surgical Procedure

6.9 6.5

LOW

Risk Level of Surgical ProcedureModerate

KOSHYET AL

Fig 1. Postoperative compl ication rate in SS pa-tients by type f anesthesia. IO1 General anesthesia;1 regional anesthesia; IO) loca l anesthesia.

lated postoperative complications, the effect of transfusion erative complications than did untransfused patients ( P =depended on both surgery risk evel and phenotype ( P = .004). The crude rates of non-SCD-related postoperative.015 . There was a significant effect of transfusion only in complications were 28.1 for surgical procedures with peri-SC patients undergoing low-risk procedures. When perioper- operative transfusion and 2.1 for those without.atively transfused, these patients had higher rates of postop- SCD-relatedcomplications. For S S patients undergoing

Table 3. PostoDerative ComDlication Rates b v PerioDerative Transfusion Status SS Surgeries

Low-Risk Moderate-Risk High-Risk

No TXX No TXX No TX TXPostoperative Complications ( ) (N = 145) N = 248) N = 43) (N = 390) (N = 0) N = 12)

Pain

ACS

CVA

Any SCD complications

Non-ACS infection

Fever

BleedingThrombosisEmbolism

Death

Any non-SCD complications

Other

Any postoperative complications

12.4

1.40.012.9

2.06.20.70.00.01.48.8

1.4

18.6

4.4

0.80.44.8

3.68.92.00.0

0.4

0.411.6

5.2

17.3

2.3

2.30.04.7

2.311.60.00.00.00.0

14.0

2.3

18.6

5.4

2.80.07.9

4.99.73.10.30.30.5

13.8

7.7

23.9

8.3

8.30.016.7

0.025.0

8.30.00.00.0

33.3

8.3

41.7

Of the SS surgeries, 4 low-risk and 2 moderate-risk surgeries are missing a response to the postoperative comp lication question.~~


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Table 4. Postoperative Co rn pl ii io n Rates by ParioporativeTransfusion Status SC Surgeries

Low-Risk Moderate-Risk

N o T X TX NoTX TXPostoperative Complications (N = 48 (N = 32) N = 21 N = 49

Pain 8.3 0.0 9.5 4.1ACS 0.0 0.0 14.3 0.0

CVA 0.0 0.0 0.0 0.0Any SCD complicat ions 8.3 0.0 19.1.1

Non-ACS infection 0.0 0.0 4.8 10.2Fever 0.0 21.9 28.60.2

Bleeding 0.0 6.3 0.0 0.0Thrombosis 0.0 0.0 0.0 0.0Embolism 0.0 0.0 4.8 2.0Death 2.1 0.0 0.0 0.0Any non-SCD complicat ions 2.18.1 28.66.3

Other 2.1 3.1 0.0 8.2

Any postoperat ivecomplicat ions 12.51.32.94.5

Of the SC surgeries, 1 low-r isk surgery is miss ing a response to thepostoperat ive complicat ion quest ion.

low-risk su rgical procedures, there w as a beneficial effect oftransfusion (estimated odds ratio for untransfusedv trans-fused, 3.28; P = .006) on SCD-related postoperative compli-cations, particularly painful crisis. The crude com plicationrates for S S patients undergoing low-risk surgical procedureswere 12.9 or surgical procedures without transfusion and4.8 or those with transfusion. Accordingly, the mean totalHb concentration of transfused patients was significantly

higher (10.3 2.3 g/ ) than that of untransfused patients(8.4 t 1.3 g/&; P = .OOOl). However, among S S patientsundergoing moderate-risk surgical procedures, no associa-tion was found between transfusion and SCD -related postop-erative com plications( P = 3 1 ) . Mean total Hb concentra-tions of S S patients undergoing moderate-risk surgicalprocedures were similar for those with and without postoper-ative painful crisis (10.6 1.9 v 10.5 ? 2.3 g/dL, P =3 8 3 ) . In contrast, the mean total Hb of12 S S patients whodeveloped ACS was9.3 ? 2.0 g/dL, comparedwith 10.5 rt2.3 g/ or 413 SS patients who did not develop postopera-tive ACS (P = .055). However, this difference did not remainafter adjusting for age.

Among SC patients there was a beneficial effect of periop-erative transfusion regardless of surgery risk level (estimatedodds ratio for untransfusedv transfused, 8.33; P = .009).The crude rate of complications after low- and moderate-risk surgeries was 2.5 with perioperative transfusion and11.6 without. The mean total Hb concentration was11.3

1.6 g/dL for untransfused SC patients and12.0 ? 2.3 gdL for perioperatively transfused SC patients. Notably,3of21 untransfused SC patients undergoing moderate-risksurgical procedures had AC S, but none of the49 transfusedpatients in this group did.

Sflo Thal and Sfl+ Thal Patients

Fifty-two surgical procedures were performed on41 Sthal patients. There were11 cholecystectomies,5 splenecto-

mies, 2 hip replacements/revisions,8 dilation and curettageprocedures,4 circumcisions,2 laparotomies,2 laparoscopicevaluations,2 tubal ligations,1 Cesarean section,1 tonsillec-tomy, 1 adenoidectomy, and 13 other surgical procedures.The SCD-related postoperative complication rate was9.6

(3 painful crises, 1 ACS, and 1 with both). The non-SCD-related complication rate was1 1S .Thirteenof 16S o o hal patients were periopera tively trans-

fused for cholecystectomy or splenectomy(81.3 ).Of thesetransfused patients,1 patient had fatal postoperative bleeding(see Postoperative Deaths), and another had a painful crisis,ACS, fever, and thrombosis after the surgical procedure.Nocomplications were reported for the3 untransfused patients.

Twenty-nine surgical procedures were performed on21S o + thal patients. There were2 splenectomies,3 Cesareansections, 2 tonsillectomies, 5 dilation and curettage proce-dures, 2 inguinal hernia repairs,1 myringotomy, 1 hip revi-sion, and 13 other surgical procedures. The perioperative

transfusion rate w as41.4 .The only SCD-related postoper-ative complication was 1 ACS event after splenectomy withintraoperative transfusion (preop erative totalH b , 13.2 g/dL).No non-SCD -related complications were reported.

DISCUSSION

Because previous studies have show n significant compli-cations for SCD patients undergoing surgical procedures,mos t centers follow protocols for use of preoperative prepar-

reported a paucity of morbidity data in untransfuse d patientsundergoing minor These increased risks arebelieved to be secondary both to acute tissue injury and

chronic organ damage produced by vaso-occlusion fromsickled red blood cells (RBCs). In addition, surgical proce-dures may be com plicated by hypo xia, acidosis, or hypothe r-mia, adding to a greater likelihood of SCD patients experi-encing an adverse event, because each of these factorspromotes erythrocyte sickling. Although RBC transfusionshave been advocated by many investigators to reduce periop-erative complications, there are no controlled trials docu-men ting their benefit. There are also significa nt risks as soci-ated with RBC ransfusions, including alloimmunization andexposure to infectious diseases.

The CSSCD was designed to define the natural historyof SCD and its effects on health events. The recruitment

procedures insured that participants were representative ofthe wide spectrum of clinical severity that is a hallmark ofthis disease. Because this unique population was observedprospective ly for a median of 6 years, it is ideally suitedto define the types of surgical procedures and associatedcomplications that can be observed in patients with S CD.

There w ere several interesting observations noted in thisstudy. The overall mortality rate was very low(0.3 ).Therewere only 3 deaths attributed to the surgeryor anesthesia.No deaths were observed in patients under the ageof14years, although many children had procedures associatedwith moderate surgical risk.

The SCD-related complication rates were similar forSCand S S patients undergoing abdom inal surgeries andortho-pedic procedures. The level ofHb A in the transfused pa-

ative transfusion,'~4.'2~'3*'s-19 and only aew investigators have


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3682 KOSHY ET AL

tients did not decrease postoperative complication rates, ex-cept for the decrease in the rate of postoperative pain crisisfor abdominal surgeries. There were only 21 proceduresamong S@+ hal patients enrolled in the study, and there wasno report of cholecystectomy. Although the total number of

patients was small, this low number of surgeries may bereflective of the more benign phenotype.

There was wide variation in the SCD-related complica-tions associated with the more common surgeries. The ratefor SS patients was 0% for tonsillectomy and adenoidec-tomy, 2.9 for hip surgery, 3.9 for myringotomy, 7.8for intra-abdominal surgery, 16.9 or cesarean section andhysterectomy, and 18.6 or dilation and curettage. Reasonsfor this wide variation were not identified, although the highrate of sickle cell complications after Cesarean section prob-ably is related to the increased morbidity associated withpregnancy in women with sickle cell anemia irrespective oftransfusion practice^.^ '^ At present, because laparoscopic

cholecystectomy has replaced the open procedure, the dura-tion of hospitalization, transfusion requirements, and postop-erative complications will most likely be lower than hatreported here.

We also observed that in the patients transfused beforeintra-abdominal surgery, the mean level of Hb A was higherfor those patients with no painful crisis compared with thosewho experienced painful crisis after surgery (58 v 35 ,respectively). However, prevention of painful crisis in thepostoperative period does not alone justify the use of preop-erative transfusions in light of the recognized complicationsof blood transfusion. The recently concluded randomizedcontrolled trial evaluating perioperative blood transfusion

has defined the role of preoperative blood transfusion forsickle cell patient^.^'

This study also showed that non-SCD complication ratesfor fever and infection were higher in patients receivingregional anesthesia compared with those who had receivedgeneral anesthesia but unrelated to the preoperative transfu-sion rates. Because regional anesthesia (specifically epidural)is commonly used in Cesarean sections and other assisteddeliveries, the higher complication rates observed may be areflection specifically of the higher complication rates ob-served in those obstetrical procedures.

In non-SCD patients undergoing surgery, perioperativecomplications vary from general pulmonary complications

of 3% to 70% to serious ACS-like events of less than40 Similarly, in-hospital complications for open cholecystec-tomy occur in 22.4 (unadjusted rate) of patients4' Ourdata show that SCD patients are at no greater risk for thesecomplications than the non-SCD patients.

Although not derived from a rigorously controlled trial,the data do define the types of commonly performed surger-ies on patients with SCD and provide new insights intopostoperative complications. Despite the variety of tech-niques used to manage patients and the variations in methodsof inducing anesthesia, mortality was low and there wererelatively few serious perioperative complications related toSCD. In part, this outcome can be attributed to careful atten-tion to he details of patient management by the collaborativeefforts of the hematologist, surgeon, and anesthesiologist.

However, the role of transfusion in the perioperative periodremains to be defined, but the data do suggest that not allpatients undergoing surgery should routinely receive bloodtransfusions.

During the study period, no protocol was specified for

preoperative transfusion practice. Each center continued tofollow its own preoperative preparative regimen. The pa-tient's age, disease state, multiorgan disease status, andAmerican Surgical Association (ASA) risk level were notpredetermined.

For the minor procedures, many of the patients did notreceive blood transfusions and complication rates were low.The postoperative complication rates were also low for the42 patients who underwent tonsillectomy. Six SS patientswho were untransfused had no complications after tonsillec-tomy. The paucity of complications after this procedure maybe related to the younger age of patients at the time ofsurgery.

Recent advances in intraoperative techniques and new an-esthetic agents have been touted for successful outcomes forSCD patients in postoperative periods, rather than the useof blood transfusion regimen alone.3~4~'2,20~22.25.29.35,42therscredit aggressive preoperative transfusion preparation as re-sponsible for the successful outcome of SCD patients under-going surgical procedures.'5342 he percent reduction of SHb required for transfusing patients is not well defined inthose receiving mandatory preoperative transfusion.

Surgical procedures can be performed successfully onSCD patients. Careful assessment of Hb phenotype, pastmedical history, and risk status should be documented.

Blood transfusion therapy will continue to be part of the

preoperative evaluation and preparation of patients. Simpletransfusion to increase the Hb level to 10 g/&, blood re-placement for profound anemia of Hb less than 5 g/dL, andintraoperative hemorrhage appears appropriate. Transfusionstill carries with it the complications of alloimmunization,delayed transfusion reaction, transmission of viral infection,hepatitis, and iron o~ er lo ad ?~ , hese complications shouldbe considered when counseling patients and family beforethe surgical procedure.

ACKNOWLEDGMENT

The authors are ndebted to Pamela Moore, Shaheen Islam, andSusan Weaver for their assistance in preparing this manuscript. Thefollowing were senior investigators in the CSSCD : Clinical centers:R. Johnson, Aka Bates Hospital (Berkeley, CA); L. McMahon, Bos-ton City Hospital (Boston, M A); 0 Platt, Children's Hospital (Bos -ton, MA); F. Gill and K. Ohene-Frempong,Children'sHospital(Philadelphia, PA); G. Bray, J . Kelleher, and S . Leikin, Children'sNational Medical Center (Washington, DC); E. Vichinsky and B .Lubin, Children's Hospital (Oakland, CA); A . Bank and S. Piomelli,Columbia Presbyterian Hospital (Ne w York, NY ); W. Rosse , J. Fd-letta,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, andC. Reindorf,Howard University W ashington, DC); H. Dosik, S.Diamond,andR. Bellevue , InterfaithMedicalCenter (Brooklyn,NY); W . Wangand J. Wilimas, LeBonheurChildren'sHospital(Memphis, TN); . Milner, Medical College o f Georgia (Augusta,GA); A. Brown, S. Miller, R. Rieder, and . Gillette, State Universityof New York Health Science Center at Brooklyn (Brook lyn, NY );


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W. Lande, S . Embury, and W. Mentzer, San Francisco GeneralHospital (San Francisco, CA); D. W ethers and R. Grover, St Lukes-Roosevelt Medical Center (New York, NY);M. Koshy and N. Tali-shy, University of Illinois (Chicago,L ; C. Pegelow, P. Klug, andJ. Temple, University of Miami (M iami,FL); M. Steinberg, Univer-sity of Mississippi (Jackson, MS); A . Kraus, University of Tennessee

(Memphis,TN);

H. Zarkowsky, Washington University (St Louis,MO); C. Dampier, Wyler Ch ildrens Hospital (Chicago); H. Pearsonand A.K. Ritchey, Yale University (New Haven, CT); StatisticalCoordinating Centers: P. Levy, D. Gallagher, A. Korand a, Z. Flour-noy-Gill, and E. Jones, University of Illinois School of Pub lic Health(Chicago, I L ; 1979-89); S . McKinlay, O.Platt, D. Gallagher, D.Brambilla, and L. Sleeper, New Englan d Research Institutes (Water-town, MA; 1989-1995); M. Espeland, Bowman-Gray School ofMedicine (Winston-Salem, NC); Program Administration: M. Gas-ton, C. R eid, and J. Verter, National Heart, Lung, and Bloo d Institute(Bethesda, MD).

APPENDIX

Descriptiodlocation of 1,079 surgical procedures. Twohundred twenty-two cholecystectomy, 2 cholecystotomy, 3obstruction of gall bladder, 36 splenectomy, 107 dilationand curettage for pregnancy termination and miscellaneouscomplications, 7 dilation and curettage postpartum and forectopic pregnancy, 75 Cesarean section, 12 hysterectomy,46 tonsils and adenoids, 21 hip replacement, 19 hip revision,3 hip prosthesis removal, 30 myringotomy, 5 craniotomy, 4spinal canal, 4 miscellaneous nervous system, 6 retina, 4scleral buckling, 12 miscellaneous eye, 1 myringoplasty, 1tympanoplasty, 2 radical mastoidectomy, 3 sinus, 11 dentalexiraction and restoration, 2 cleft palate correction, 5 bron-chial and pulmonary biopsy, 6 miscellaneous respiratory, 20vascular access, 7 miscellaneous cardiovascular, 5 lymphaticnode biopsy, 10 appendectomy, 3 hemorrhoidectomy, 16inguinal hernia repair, 8 umbilical hernia repair, 19 laparot-omy and laparoscopy, 5 miscellaneous digestive system, 3kidney transplant, 10 miscellaneous urinary system, 4 unde-scended testes, 6 penile prosthesis, 17 priapism surgery, 22circumcision, 4 miscellaneous male genital organ, 4 ovariesand Fallopian tubes, 20 tubal ligation, 3 breast reduction/enhancement, 8 miscellaneous breast surgery, 6 miscellane-ous gynecological, 8 incision and drainage of long bones, 5osteotomy, 18 bone excision and biopsy, 5 bone graft, 8open reduction and treatment of fractures, 4 joint fusion, 2shoulder and wrist replacement, 4 clubfoot release, 6 tendonand sheath repair, 12 miscellaneous musculoskeletal, 31 skindebridement, 21 skin and subcutaneous, 38 skin graft, 2parathyroidectomy, 49 diagnostic procedures.

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