Effect of Intrathecal Lipophilic Opioids on the Incidence of Shivering in Women Undergoing Cesarean Delivery after Spinal Anesthesia: A Systematic Review and Bayesian Network Meta- analysis of Randomized Controlled Trials.
Authors: Subramani Yamini , Nagappa Mahesh , Kumar Kamal , Fochesato Lee-Anne , Chohan Moaz Bin Yunus , Zhu YunFei , Armstrong Kevin , Singh Sudha (Indu) 
Published: May 2020

Background
Shivering is a common side effect in women having cesarean delivery (CD) under spinal anesthesia. It may be bothersome and can also interfere with perioperative monitoring. The intrathecal (IT) addition of a lipophilic opioid to local anesthetics has been shown to decrease the incidence of shivering in several studies in literature.
Objective
We performed this meta-analysis to evaluate the effects of intrathecal lipophilic opioids in preventing the incidence of shivering in patients undergoing CD.
Methods
This review was planned according to the PRISMA for Network Meta-Analysis (PRISMA-NMA) guidelines. An English literature search of multiple electronic databases was conducted. We included randomized controlled trials (RCTs) that reported on the incidence of shivering, with study groups receiving either IT fentanyl, sufentanil, or meperidine in women undergoing CD under spinal anesthesia. Quality of the studies was assessed using the modified oxford scoring system. Dichotomous data were extracted and summarized using Odds Ratio (OR) with 95% Credible intervals (CrI) using random-effects modeling. Statistical analysis was conducted using R studio version 1.0.153 - Inc.
Results
Twenty-one studies consisting of 1433 patients (Control group: 590 patients in twenty-one studies; Fentanyl group:199 patients in seven studies; Sufentanil group: 156 patients in five studies; Meperidine group: 488 patients in ten studies) met inclusion criteria for intrathecal lipophilic opioids to prevent the incidence of shivering in women undergoing cesarean delivery under spinal anesthesia. Methodological validity scores ranged from 3 to 7. The bayesian mixed network estimate showed the incidence of shivering was significantly lower with IT fentanyl (Pooled Odds Ratio (OR): 0.13; 95% Credible Interval (CrI): 0.04 to 0.35; P = 0.0004) and IT meperidine (OR: 0.12; 95% CrI: 0.05 to 0.29; P < 0.00001), but not with IT sufentanil (OR: 0.37; 95% CrI: 0.11 to 1.22; P = 0.23). The IT fentanyl group had a significantly lower incidence of intraoperative discomfort (RR: 0.19; 95% CI: 0.10–0.35; P < 0.00001), The IT sufentanil group had a significantly higher incidence of pruritus (RR: 6.18; 95% CI: 1.18–32.46; P = 0.03) The IT Meperidine group had a significantly lower incidence of intraoperative discomfort (2.7% vs. 13.6%; RR: 0.22; 95% CI: 0.09–0.55; P = 0.001), but there was a significant increase in nausea and vomiting (IT meperidine group vs. Control group: 42.7% vs. 19.4%; RR: 2.56; 95% CI: 1.14–5.75; P = 0.02). Meta-regression analysis based on the opioid dose and quality of the study did not impact the final inference of our result.
Conclusion
IT fentanyl significantly decreased the incidence of shivering in women undergoing CD under spinal anesthesia without increasing maternal adverse events, confirming that routine use in this patient population is a good choice. IT sufentanil did not decrease the incidence of shivering. IT meperidine also decreased the incidence and severity of shivering, but it was associated with significant nausea and vomiting.