Timing of administration of prophylactic antibiotics for caesarean section: a systematic

review and meta-analysis.Baaqeel H, Baaqeel R.

Scenario

You are charged with formulating a local clinical policy in your hospital about antibiotics prophylaxis

at caesarean sections

Aims and Objectives

• Background: What do current guidelines say about the above scenario?

• What would be the best primary study design to study the above question and why?

• Sources of bias (what is the likelihood that the reported results are true?): Critically appraise, do not simply accept on face value, the methods of this systematic review and those of its constituent studies.

Aims and Objectives (2)

• What is sensitivity analysis? Is the use of sensitivity analysis in this study appropriate?

• Findings: Derive the relatively risk reduction (RRR), absolute risk reduction (ARR) and number needed to treat (NNT) of using pre-operative prophylactic antibiotics on the overall maternal infectious morbidity.

Background

• Prophylactic antibiotics reduce infectious morbidity after elective and emergency caesarean sections.

• In some countries, routine practice is to administer prophylactic antibiotics after cord-clamping to reduce fetal exposure to antibiotics.

• Conflicting reports about the neonatal impact of in-utero fetal exposure prompted this systematic review.

Other existing guidelines• National Institute for Health and Clinical Excellence. CG132: Caesarean

section Section 7.6. Available from: http://guidance.nice.org.uk/CG132/

• The Society of Obstetricians and Gynaecologists of Canada (SOGC). Antibiotic Prophylaxis in Obstetric Procedures. (SOGC clinical practical guideline no. 247). The Society of Obstetricians and Gynaecologists of Canada (SOGC); September 2010. Available from: http://www.sogc.org/guidelines/documents/gui247CPG1009E_000.pdf

• American College of Obstetricians and Gynecologists (ACOG). Use of prophylactic antibiotics in labor and delivery. (ACOG practice bulletin; no. 120). Washington (DC): American College of Obstetricians and Gynecologists (ACOG). June 2011. Available from: http://www.guidelines.gov/content.aspx?id=34024

The Review Question

In women undergoing caesarean sections, are there differences in the rates of maternal and neonatal infectious morbidity in those

receiving preoperative antibiotic prophylaxis compared with intraoperative administration?

Structured QuestionParticipants Women undergoing any type of caesarean

sectionsIntervention A single dose of prophylactic antibiotic given pre-

operativelyComparison A single dose of prophylactic antibiotic given

intra-operativelyOutcomes Maternal: febrile morbidity, endometritis, wound

infection and pyelonephritis.Neonatal: neonatal sepsis, neonatal septic work-up and neonatal intensive-care unit (NICU) admission.

Methods• Medline, Embase, Current Controlled Trials and Cochrane Central

were searched.

• Only RCTs of x1 dose of antibiotic comparing preoperative with intraoperative administration were selected.

• Independently extracted data A random effect model to estimate RRs and their 95 % CI

Conventional testing for heterogeneity was performed.

Sensitivity analysis was done if likelihood of bias is suspected.

GRADEPRO was used to grade quality of evidence. •

Events / Total Risk ratio and 95% CI (Random)

After cord Risk Lower Upper Preop clamping ratio limit limit

Endometritis 27 / 1158 47 / 1155 0.589 0.369 0.942

Pyelonephritis 13 / 956 12 / 965 1.090 0.490 2.425

Total infectious morbidity 74 / 1158 104 / 1155 0.711 0.517 0.977

Wound infection 28 / 1158 40 / 1155 0.705 0.436 1.140

0.01 0.1 1 10 100

Preoperative After cord clamping

Total

Total

Total

Total

Outcome

Heterogeneity:Endometritis Tau² = 0.00; Chi² = 3.14, df = 5 (P = 0.68); I² = 0%Pyelonephritis Tau² = 0.00; Chi² = 2.18, df = 3 (P = 0.54); I² = 0%Total infectious morbidity Tau² = 0.02; Chi² = 5.83, df = 5 (P = 0.32); I² = 14%Wound infection Tau² = 0.00; Chi² = 1.53, df = 5 (P = 0.91); I² = 0%

Neonatal pneumonia 4 / 572 0 / 561 3.361 0.552 20.470Total

Neonatal sepsis 22 / 539 27 / 541 0.814 0.469 1.412Total

Neonatal septic workup 94 / 805 101 / 799 0.929 0.714 1.208Total

NICU admissions 60 / 1126 66 / 1129 0.917 0.654 1.284Total

Neonatal pneumonia Tau² = 0.00; Chi² = 0.03, df = 2 (P = 0.98); I² = 0% Neonatal sepsis Tau² = 0.00; Chi² = 0.33, df = 2 (P = 0.85); I² = 0%Neonatal septic workup Tau² = 0.00; Chi² = 2.73, df = 4 (P = 0.60); I² = 0%NICU admission Tau² = 0.00; Chi² = 3.12, df = 4 (P = 0.54); I² = 0%

Authors’ conclusions• Implication for research:

• The review revealed no significant neonatal adverse effects with pre-operative administration. These results need to be confirmed by sufficiently powered multi-center trial.

• Implication for practice:• Any consideration of a change in practice based on the

evidence presented in this review should take into account the fact that the quality of the evidence for all reported outcomes is moderate.

Applicability of findings

• Do these results overturn the existing recommendations?

• Would you advocate the use of a) pre-operative antibiotics and b) this particular antimicrobial (a cephalosporin) based on the results this study?

Formula

• Relative risk reduction (RRR)

(CER - EER)/CER

• Absolute risk reduction (ARR)

(CER - EER)

• Number needed to treat (NNT)

1/ARR or 1/(CER - EER)

CER= control group event rate; EER= experimental group event rate