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Original article

Effect of delaying same-admission cholecystectomyon outcomes in patients with diabetes

R. Gelbard1, E. Karamanos1, P. G. Teixeira1, E. Beale2, P. Talving1, K. Inaba1 and D. Demetriades1

1Department of Surgery, Division of Acute Care Surgery, and 2Division of Endocrinology, Department of Medicine, Los Angeles County and Universityof Southern California Medical Center, Los Angeles, California, USACorrespondence to: Professor D. Demetriades, Division of Trauma, Emergency Surgery and Surgical Critical Care, Los Angeles County and University ofSouthern California Medical Center, 2051 Marengo Street, C5L100, Los Angeles, California 90033, USA (e-mail: [email protected])

Background: Recent studies have suggested that same-admission delayed cholecystectomy is a safeoption. Patients with diabetes have been shown to have less favourable outcomes after cholecystectomy,but the impact of timing of operation for acute cholecystitis during the same admission is unknown.Methods: This was a retrospective analysis of patients undergoing laparoscopic cholecystectomy foracute cholecystitis between 2004 and 2010, from the American College of Surgeons National SurgicalQuality Improvement Program database. Patients with no significant co-morbidities (American Societyof Anesthesiologists grade I or II) were included. Propensity score matching (PSM) was used to matchpatients with diabetes with those who did not have diabetes, in a ratio of 1 : 3, to ensure homogeneity ofthe two groups. Logistic regression models were applied to adjust for differences between early (within24h) and delayed (24h or more) surgical treatment. The primary outcome was development of localand systemic infectious complications. Secondary outcomes were duration of operation and length ofhospital stay.Results: From a total of 2892 patients, 144 patients with diabetes were matched with 432 withoutdiabetes by PSM. Delaying cholecystectomy for at least 24h after admission in patients with diabetes wasassociated with significantly higher odds of developing surgical-site infections (adjusted odds ratio 411,95 per cent confidence interval 111 to 1522; P = 0034) and a longer hospital stay. For patients with nodiabetes, however, delaying cholecystectomy had no impact on complications or length of hospital stay.Conclusion: Patients with diabetes who undergo laparoscopic cholecystectomy 24h or more afteradmission may have an increased risk of postoperative surgical-site infection and a longer hospital staythan those undergoing surgery within 24h of admission.

Paper accepted 24 October 2013Published online 16 December 2013 in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.9382

Introduction

Gallstone-related disease is more prevalent among patientswith diabetes than in the general population13. Thefrequency of diabetes in patients undergoing surgery forgallstone-related diseases, including acute and chroniccholecystitis, is about 10 per cent46. There is evidencethat patients with diabetes and biliary disease have poorersurgical outcomes than those without diabetes, as well ashigher rates of intraoperative complications and conver-sion from laparoscopic to open cholecystectomy4,611. Arecent study12 found not only that 141 per cent of patientsundergoing cholecystectomy for acute cholecystitis haddiabetes but also that diabetes was an independent riskfactor for death, infectious complications, cardiovascularevents and renal failure after cholecystectomy.

There has been a great deal of controversy over theoptimal timing of laparoscopic cholecystectomy for acutecholecystitis1325. It was initially thought that conservativemanagement with interval elective surgery would avoidsevere complications and high conversion rates in thesetting of acute inammation. However, current evidencesuggests that patients with acute cholecystitis should actu-ally undergo cholecystectomy early on during their initialhospital admission1416,18,20,23,24. Previous research15

has also suggested that delaying cholecystectomy duringthe same admission prolongs hospital stay but has noeffect on complications. However, the effect of timingof same-admission cholecystectomy on outcomes has notbeen studied specically in patients with diabetes. Thepresent study aimed to determine whether or not delaying

2013 BJS Society Ltd BJS 2014; 101: 7478Published by John Wiley & Sons Ltd

Delaying cholecystectomy in diabetic patients 75

Table 1 Demographic and preoperative clinical data

Diabetic Non-diabetic(n= 144) (n= 432) P

Age (years)* 45(15) 44(14) 0876Sex ratio (M : F) 62 : 82 187 : 245 1000ASA fitness grade

I 2 (14) 6 (14) 1000II 142 (986) 426 (986) 1000

Tobacco use 35 (243) 113 (262) 0875Alcohol use 5 (355) 12 (28) 0629Overweight 38 (264) 114 (264) 1000Obese 87 (604) 268 (620) 0296Admission laboratory data

Total bilirubin> 15 mg/dl 23 (160) 57 (132) 0182AST> 400 units/l 37 (257) 93 (215) 0151Alkaline phosphatase>130 units/l 21 (146) 50 (116) 0093WBC count> 11 000/l 67 (465) 214 (495) 0099Haematocrit< 30% 5 (35) 8 (19) 0067

Surgery within 24 h 63 (438) 227 (525) 0231Wound classification at end of surgery 0345

Clean 0 (0) 2 (05)Clean/contaminated 80 (556) 245 (567)Contaminated 46 (319) 147 (340)Infected 18 (125) 38 (88)

Values in parentheses are percentages unless indicated otherwise; *valuesare mean(s.d.). Body mass index 2530 and over 30 kg/m2. ASA,American Society of Anesthesiologists; AST, serum aspartateaminotransferase; WBC, white blood cell. McNemars 2 test, exceptWilcoxon signed-rank test.

surgery during a single admission would have an impact onoutcomes in patients with diabetes and acute cholecystitis.

Methods

This retrospective study used the American College of Sur-geons National Surgical Quality Improvement Program(ACS NSQIP) database. Patients with acute cholecystitiswho underwent same-admission laparoscopic cholecystec-tomy from 2004 to 2010were identied using InternationalClassication of Diseases, ninth revision, codes 574.0,574.1, 574.3, 574.6, 575.0, 575.10 and 575.12. Onlypatients coded as undergoing an emergency operation wereincluded. To eliminate possible confounding factors, onlyhealthy patients or those with mild systemic disease (Amer-ican Society of Anesthesiologists (ASA) tness grade I orII) were included in the study. The NSQIP database wasestablished in 2004 and collects data from a growing num-ber of hospitals in the USA, with over 300 participating in2011. The NSQIP is capable of documenting outcomes upto 30 days after surgery, even after discharge from hospital.

The study population was divided into two groupsaccording to diabetic status: patients with and thosewithout diabetes. These denitions were based on the long-term, chronic management of diabetes for each patient

and did not rely on measurement of glucose duringthe hospital stay. The ACS NSQIP database registersthree different conditions relating to diabetes mellitus:non-diabetic, diabetic controlled by oral medication anddiabetic controlled by insulin.

Patient variables extracted from the database were:age, sex, ASA classication, use of tobacco and alcohol,body mass index, wound classication at the end ofsurgery, admission laboratory values (total bilirubin,aspartate aminotransferase, alkaline phosphatase, whiteblood cell count and haematocrit) and time to surgeryafter hospital admission. Using propensity score matching(PSM), patients with diabetes were matched with patientswithout diabetes in a 1 : 3 ratio to ensure homogeneity ofthe two groups. Each group was subsequently divided intotwo subgroups according to the delay to surgery.

The primary outcome was the development of post-operative local and systemic complications. Secondaryoutcomes included total duration of operation, lengthof hospital stay (LOS) after surgery, and total LOSduring the initial hospital admission (preoperative andpostoperative LOS).

Statistical analysis

The cohorts with and without diabetes were compared fordifferences in demographics and clinical characteristicsusing bivariable analysis. 2 or Fishers exact testswere used to compare proportions. Continuous variableswere examined for normality of distribution using theShapiroWilk test. Students t test was used for analysisof normally distributed variables, and the non-parametricMannWhitney U test for analysis of values with a non-normal distribution.

PSM was used to minimize the effect of variability inclinical presentation on the study outcomes. Propensityscores were generated by means of binary logisticregression. Included in themodelwere all demographic andclinical variables that differed signicantly (at the P< 0050level) between patients with diabetes and patients withoutdiabetes. Each patient was matched with controls in a1 : 3 ratio within a narrow caliper (0003) of propensity,without replacement. The caliper was equal to one-quarterof the standard deviation of the generated propensityscores (caliper was 0012/4). After the matching process,McNemars 2 test was used to compare proportions andtheWilcoxon signed-rank test to comparemeans, to ensurethe suitability and applicability of the process.

Once two similar groups had been formed in termsof demographics, clinical characteristics and admissionlaboratory values, separate analyses were performed foreach group. The diabetic and non-diabetic matched

2013 BJS Society Ltd www.bjs.co.uk BJS 2014; 101: 7478Published by John Wiley & Sons Ltd

76 R. Gelbard, E. Karamanos, P. G. Teixeira, E. Beale, P. Talving, K. Inaba and D. Demetriades

Table 2 Impact of delaying surgery on outcomes for patients with diabetes

Time between admission and surgery (h)Adjusted analysis#

< 24 24(n= 63) (n= 81) P Effect estimate P

Total duration of operation (min)* 851(361) 843(383) 0461 22 (51, 94) 0129Surgical-site infections 1 (2) 4 (5) 0059 411 (111, 1522) 0034Systemic infectious complications 3 (5) 2 (2) 0737 212 (051, 885) 0301Postop. LOS (days)* 19(15) 22(18) 0121 03 (01, 06) 0078Total LOS (days)* 19(15) 39(27) < 0001 20 (16, 24) < 0001

Values in parentheses are percentages unless indicated otherwise; *values are mean(s.d.); values are adjusted mean differences and odds ratios, with 95per cent condence intervals in parentheses. LOS, length of hospital stay. Fishers exact test, except Students t test. #Linear regression (duration ofoperation, LOS) and logistic regression (complications) adjusting for age, sex, American Society of Anesthesiologists classication, use of tobacco andalcohol, body mass index, wound classication and laboratory data.

Table 3 Impact of delaying surgery on outcomes for patients without diabetes

Time between admission and surgery (h)Adjusted analysis#

< 24 24(n= 227) (n= 205) P Effect estimate P

Total duration of operation (min)* 823(375) 783(330) 0404 48 (115, 18) 0155Surgical-site infections 2 (09) 5 (24) 0264 305 (058, 1603) 0189Systemic infectious complications 3 (13) 4 (20) 0713 140 (030, 643) 0667Postop. LOS (days)* 21(62) 18(21) 0313 03 (12, 06) 0477Total LOS (days)* 21(62) 32(24) < 0001 11 (02, 20) 0021

Values in parentheses are percentages unless indicated otherwise; *values are mean(s.d.); values are adjusted mean differences and odds ratios, with 95per cent condence intervals in parentheses. LOS, length of hospital stay. Fishers exact test, except Students t test. #Linear regression (duration ofoperation, LOS) and logistic regression (complications) adjusting for age, sex, wound classication, use of tobacco and alcohol, and laboratory data.

groups were each divided into two subgroups based on thetime of surgery after hospital admission: delayed (at least24 h after admission) and non-delayed (within 24 h). Thesetwo subgroups were compared for differences in baselinecharacteristics using Pearsons 2 or Fishers exact test, asappropriate, for dichotomous variables and Students t testor MannWhitney U test for continuous variables.

The impact of delaying surgery in diabetic and non-diabetic groups on the development of surgical-site infec-tions and systemic infectious complications was assessedusing binary logistic regression, adjusting for variables thatwere signicant (P< 0050) in the bivariable comparison.Linear regression models were used to assess the impact ofdelaying surgery on duration of operation, postoperativeLOS and total LOS, adjusting for variables that weresignicant (P< 0050) in the bivariable analysis and forclinically important variables. Adjusted odds ratios (ORs)with 95 per cent condence intervals (c.i.) were derivedfrom the logistic regression analysis, and adjusted meandifferences with c.i. from the linear regression analysis.

Results

A total of 2892 patients with ASA tness grade I or IIunderwent same-admission laparoscopic cholecystectomy

for acute cholecystitis in the study period and met thecriteria for inclusion in this study. Of these, 50 per centhad an established diagnosis of diabetes and 950 per centwere non-diabetic. Following PSM, 144 patients withdiabetes were matched successfully with 432 controls.

The demographics and clinical characteristics of thetwo groups after PSM are summarized in Table 1. Themean(s.d.) age of patients with and without diabetes was45(15) and 44(14) years respectively. The majority of thestudy population was obese (604 and 620 per cent ofpatients with and without diabetes respectively). Some438 per cent of patients with diabetes and 525 per cent ofthose without diabetes underwent cholecystectomy within24 h of hospital admission.

Delaying cholecystectomy for more than 24 h afteradmission in patients with diabetes was associated withsignicantly higher odds of developing a surgical-siteinfection (adjusted OR 411, 95 per cent c.i. 111 to 1522;P= 0034), but not systemic infectious complications(adjusted OR 212, 051 to 885; P= 0301). Patients whohad delayed surgery were also signicantly more likely tohave a longer total hospital stay: adjusted mean difference20 (95 per cent c.i. 16 to 24) days (P< 0001) (Table 2).

For patients without diabetes, however, delayingcholecystectomy for more than 24 h had no impact on


Delaying cholecystectomy in diabetic patients 77

the development of surgical-site infections (adjusted OR305, 058 to 1603; P = 0189) or systemic infectiouscomplications (adjusted OR 140, 030 to 643; P = 0667).However, the total LOS was longer in those who haddelayed surgery: adjusted mean difference 11 (02 to 20)days (P= 0021) (Table 3).

Discussion

This study assessed the impact of timing of same-admissioncholecystectomy on outcomes in patients with diabetes.Diabetes has already been shown to be an independent riskfactor for mortality, infectious complications, cardiovas-cular events and renal failure after cholecystectomy12,26.However, a considerable number of patients with diabeteshave major co-morbid conditions, which could becontributing to a higher incidence of complications11.To address this concern, the present study included onlypatients at low anaesthetic risk (ASA I or II). No studiesto date have looked at whether delaying same-admissioncholecystectomy among patients with diabetes leads toincreased morbidity and mortality rates. Here, delayingcholecystectomy in low-risk patients with diabetes led toan increased risk of developing surgical-site infectionsand a longer LOS compared with those in patientsundergoing surgery within 24 h of admission. Delayingthe same-admission operation in patients without diabetesdid not have any adverse effect on outcomes. Delayedcholecystectomy is common practice in the USA, owingto problems with operating room availability or plannednon-operative management that subsequently fails.

The nding that patients with diabetes are at increasedrisk of developing postoperative infections is consistentwith the results of previous studies4,12,27,28. In addition,the present study showed that patients with diabetesundergoing delayed laparoscopic cholecystectomy had afourfold increased probability of developing a surgical-site infection (including supercial and deep surgical-site infections, and abscess development) compared withthose who underwent immediate operative intervention.Immediate operation (within 24 h of admission) was almostcertainly associated with lower hospital costs owing to theshorter hospital stay.

However, these ndings need to be interpreted withcaution. Despite the use of a high-quality contemporarydatabase, this was a retrospective analysis and is thuslimited by the problems inherent to any study basedon retrospective data. As the data points analysed arenumerical and not subject to interpretation, it is hoped thatthe effect on the analysis would be minimal. Furthermore,although the group of patients with diabetes was matched

with patients without diabetes to ensure homogeneityof the two groups, there was no matching with respectto timing of cholecystectomy because of the fairly smallnumber of patients undergoing early and late operation inthe diabetes group. Themultivariable analysis adjusting forconfounding factors should, however, have minimized theeffect of group heterogeneity on comparison of outcomesbetween patients undergoing early and late operation inboth the diabetic and non-diabetic cohorts. The rates ofconversion from laparoscopic to open surgery were notdocumented in the database. In addition, data were notcollected on body temperature, oxygenation and use ofintraoperative transfusions, all of which have been foundto affect the surgical-site infection rate29. Finally, dataregarding the adequacy of perioperative glycaemic controlwere not recorded, whichmay also have affected the results.

Disclosure

The authors declare no conict of interest.

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