Antibiotic prophylaxis in sever Acute PanceriatitisPresentation Transcript
Antibiotic prophylaxis is not protective in severe acute pancreatitis: a systematic review and meta-analysis Dr Mohammed Al-Shehri KFHU – Khobar General Surgery 2010
Definition It is an inflammatory disorder of previously normal pancreas. Typically cause pain and interfere with the exocrine function of the gland. Cause local, adjacent and remote organs involvement.
Can be done at 24 hrs, can be repeated
Ranson’s Criteria (1974!)
Needs to be done at 24 and 48 hrs
Balthazar’s (CT scan criteria)
Single Markers of Severity
Ranson Criteria Admission Age > 55 WBC > 16,000 Glucose > 200 LDH > 350 AST > 250 During first 48 hours Hematocrit drop > 10% Serum calcium < 8 Base deficit > 4.0 Increase in BUN > 5 Fluid sequestration > 6L Arterial PO2 < 60 5% mortality risk with <2 signs 15-20% mortality risk with 3-4 signs 40% mortality risk with 5-6 signs 99% mortality risk with >7 signs
APACHE II http://www.sfar.org/scores2/apache22.html ≥ 8 is severe.
The American Journal of Surgery (May 2009) 197, 806-813 Review Antibiotic prophylaxis is not protective in severe acute pancreatitis: a systematic review and meta-analysis Nadim S. Jafri, M.D., M.Sc.a,b, Suhal S. Mahid, M.D., Ph.D.c, Spencer R. Idsteinc, Carlton A. Hornung, Ph.D., M.P.H.a,b, Susan Galandiuk, M.D.c,* aDivision of Internal Medicine, Department of Medicine, bDepartment of Epidemiology and Population Health, cPrice Institute of Surgical Research and the Section of Colorectal Surgery, Department of Surgery, University of Louisville, School of Medicine, Louisville, KY 40292, USA
in US , 20% of pts admitted with AP develop severe acute pancreatitis (SAP).
may lead to life threatening conditions .
SAP usually develops when part of the pancreas become necrotic and many complications are associated with the presence of this dead pancreatic tissue.
It requires intensive and aggressive management.
International symposium on AP described SAP as being associated organ failure and/or local complications such as abscess ,necrosis, or pseudocyst.
SAP is diagnosed if any of the following 4 criteria are met:
organ failure with 1 or more of the following: shock (SBP < 90mmHg). Pulmonary insufficiency(PaO2<60). Renal failure (creatinine>2mg /dL after rehydration). GIT bleeding ( >500 ml in 24 hrs ) . local complications such as necrosis, abscess or pseudo cyst. at least 3 of Ranson criteria.
Cont…. at least 8 of APACHE II criteria.
mortality in SAP ranging from 10% -25% .
The disease process comprises 2 stage :
the initial phase is characterized by SIRS that can lead to multi-organ failure and ultimately death. The later phase compromises secondary bacterial infection of devitalized tissues primarily caused by gut organism.
These invading organism involving aerobic and anaerobic bacteria.
Sterile necrosis can be infected with gut bacteria in up to 70% .
To assess the clinical out come of pts with SAP treated with prophylactic antibiotics with that of pts not treated with antibiotics.
Method STUDY SELECTION
MEDLNE ,EMBASE(1966-May2008) and the Cochrane Central Register of Controlled Trials, using PubMed and Ovid as search engines, in addition to Google Scholar.
Limited to the human studies without language restrictions.
Hand –searched the references of review articles , evaluated symposia proceeding, poster presentations and abstracts from major gastrointestinal and surgical meetings.
Cont….. INCLUSION CITERIA
all studies were RCTs .
SAP was diagnosed with contrast enhanced CT scan and any of the following : APACHE II, Imrie classification and increased C-reactive protein levels > 120 mg /Dl.
Necrosis by CT scan.
Prophylactic antibiotics were administered IV .
Defined length of antibiotics treatment.
M and M measured objectively .
If there were multiple publications of the same trail, only the most recent publication was considered for analysis.
Cont… EXCLUSION CRITERIA
Case repots, letters, editorials , comments, reviews and abstracts with insufficient data.
Non randomized studies.
Cont…. DATA EXTRACTION
3 independent reviewers .
Each articles scrutinized to meet the criteria.
Data abstracted independently by each reviewer using a standardized data collection to increase the uniformity of data and to reduce the reporting bias.
In discrepancy , a consensus decision was made with the help of the senior author.
The following data were abstracted form each report:
first author, year of publication, institution, single/multicenter study, number of pt in the treatment and controlled arms, etiologies, length of follow up period, name of antibiotics , dose and timing of antibiotics administration, incidence of non pancreatic infection, incidence of surgery, incidence of mortality , method of data analysis and the method of diagnosing complications.
Cont… ASSESSMENT OF STUDY QUALITY
5 –question scale :
The study is randomized. The study is double –blinded. Withdrawals are described. Randomization allocation is explained adequately. Blindness is described adequately.
Score ranging from 1 to 5 .
< 3 low study quality.
3 or more high quality, used as part of the sensitivity analysis.
Cont…. STATISTIACL ANALYSIS
Meta- analysis performed according to the quality of reporting meta-analysis guidelines.
The effect measures estimated were relative risk (RR) for dichotomous data, which we report with 95% confidence intervals (CIs).
The RR indicates the risk of an individual who received prophylactic antibiotics developing a wound infection compared with the risk of an individual not receiving prophylactic antibiotics.
Relative risk reduction (RRR), absolute risk reduction (ARR), and number needed to treat (NNT) were calculated to assess if the relative risk was clinically important.
Result STUDY CHARACTERISTICS
Cont…. PATIENTS AND ANTIBIOTCS TREATMENT
Total of 502 pts .
A total of 253 pts were randomized to the antibiotic prophylaxis group and 249 were randomized to the placebo arm.
Age ranged from 43 to 59 yrs.
60 % alcoholic , 24% biliary , and 20 % other causes.
Duration of antibiotics treatment ranged from 5 to 21 days .
Hospital stay ranged from 18 to 95 days .
Cont… Crude outcome rates are presented in Table 2. By using a fixed-effect model to evaluate mortality, antibiotic prophylaxis resulted in a RR of .76 (95% CI, .49 –1.16; I2 8.8%; indicating homogeneity among studies)
Crude outcome rate
Cont…. SENSITIVITY ANALYSIS Sensitivity analysis was conducted to determine whether infected necrosis, surgical interventions, nonpancreatic infections, class of antibiotic, or study quality (Jadad et al16 scale 3) had a significant effect on the strength and direction of the results.
7 studies evaluated infected necrosis in pts ( n=429; antibiotics , 43 0f 217; placebo,53 0f 212 ) and found no benefit of antibiotics.
Seven studies evaluated the need for surgical intervention in SAP (n 476; antibiotics, 55 of 240; placebo, 60 of 236) and collectively did not find a beneficial effect of antibiotics .
Six studies reported patients who had nonpancreatic infections in both study groups (n 407; antibiotics, 45 of 206; placebo, 71 of 201). There was a pooled benefit associated with antibiotic use (RR, .60; 95% CI, .44 –.82; I2 50.1) with a RRR of 40% (95% CI, 18%–56%; I2 50.1%), an ARR of 15% (95% CI, 6%–23%), and a NNT of 7 (95% CI, 4–17).
Cont…. TYPE OF ANTIBIOTICS
β LACTAM:4 studies .
Mortality. Four studies that used only B-lactams and evaluated mortality (n= 305; antibiotics, 18 of 152; placebo, 22 of 153) found no benefit to the use of prophylactic antibiotics. Infected necrosis. Studies that used B-lactams and evaluated infected necrosis (n= 232; antibiotics, 15 of 116; placebo, 22 of 116) found no benefit to the use of prophylactic antibiotics.
Cont… Surgicalinterventions. Four studies that used B–lactams and evaluated surgical intervention (n=305; antibiotics, 30 of 152; placebo, 29 of 153) found no beneficial effect. Nonpancreaticinfections. Four studies that used B-lactams and evaluated nonpancreatic infections (n = 305; antibiotics, 29 of 152; placebo, 53 of 153) found a beneficial effect.
Five studies scored higher than 3 on the Jadad et al scale and thus were considered of high quality. Mortality. All 5 studies evaluated mortality in SAP (n= 367; antibiotics, 19 of 182; placebo, 29 of 185) and found no benefit of prophylactic antibiotics. Infectednecrosis. Four studies evaluated infected necrosis in SAP (n 294; antibiotics, 26 of 146; placebo, 29 of 148) and found no benefit of prophylactic antibiotics.
Cont… Surgicalintervention. All 5 studies evaluated surgical intervention in SAP (n 367; antibiotics, 35 of 182; placebo, 38 of 185) and found no benefit of prophylactic antibiotics (RR, .91; 95% CI, .61–1.38; I2 16.5). Nonpancreaticinfections. Four studies evaluated nonpancreatic infections in SAP (n 307; antibiotics, 35 of 152; placebo, 49 of 155) and found no benefit of prophylactic antibiotics.
Funnel plot of high-quality studies (Jadad et al16 score 3). The vertical axis represents the line of no effect with the horizontal axis representing log of RR. The 95% CI is represented by the diagonal lines. The circles represent each study
Meta-analysis of RCTs on prophylactic antibiotics versus placebo/no intervention on mortality.
Conclusion The role of systemic antibiotics in the management of acute pancreatitis remains controversial. The development of complications such as infected pancreatic necrosis, abscesses, and infected pseudocysts, herald the development of a deteriorating disease process that is associated with considerable morbidity and mortality.
Cont… The present meta-analysis does not support the use of prophylactic antibiotics to reduce the frequency of surgical intervention, infected necrosis, or mortality in patients with SAP. They may, however, be beneficial in protecting against the development of nonpancreatic infections. The mechanisms of which are not understood. This does need to be weighed against the significant adverse events associated with antibiotics, including increased bacterial resistance and fungal infections.
These limitations were inherent in the primary study design such as inclusion criteria, duration and dosing of antibiotics, assessment of severity of disease, nutritional support, and resuscitative measures.
Other notable limitations included the relatively small number of patients in each individual study, different outcome measurements, and the inclusion of low-quality studies.
Concerns over the increasing prevalence of multi drug resistant bacterial and fungal infections in the setting of often prolonged prophylactic antibiotic use in SAP have been raised because this is associated with poor outcome.
Such complications can not be evaluated because individual patient data were not available.
The use of prophylactic systemic antibiotics to prevent infection and reduce mortality in severe acute pancreatitis (SAP) remains a contentious issue.
Systemic review and meta-analysis until May 2008 was used.
Systematic search of MEDLINE ,EMBASE and Cochrane central register of controlled trial used.
Manually searched the references of original/
review articles and evaluated symposia proceedings, poster presentations, and abstracts from major gastrointestinal and surgical meetings.
Relative risk (RR) reduction, absolute risk reduction, and number needed to treat were calculated and are reported with 95% confidence intervals.
Results were subjected to sensitivity analysis to determine heterogeneity among studies.
502 patients from 8 studies.
There were 253 patients with SAP who received prophylactic antibiotics, and 249 patients were randomized to the placebo arm.
Does prophylactic antibiotic protect against infected necrosis, surgical intervention, or reducing mortality?
Answer NO The present meta-analysis presents conclusive evidence that antibiotic prophylaxis for SAP is not beneficial in protecting against infected necrosis, surgical intervention, or reducing mortality. If there is a limited benefit, it is in preventing nonpancreatic infections.