Safety and effectiveness of adding fentanyl or sufentanil to spinal anesthesia: systematic review and meta-analysis of randomized controlled trials

Abstract

Introduction: Spinal infusions of either fentanyl or sufentanil have been reported in international reports, articles, and scientific events worldwide. This study aimed to determine whether intrathecal fentanyl or sufentanil offers safety in mortality and perioperative adverse events.

Methods: MEDLINE (via PubMed), EMBASE, CENTRAL (Cochrane library databases), gray literature, hand-searching, and clinicaltrials.gov were systematically searched. Randomized controlled trials with no language, data, or status restrictions were included, comparing the effectiveness and safety of adding spinal lipophilic opioid to local anesthetics (LAs). Data were pooled using the random-effects models or fixed-effect models based on heterogeneity.

Results: The initial search retrieved 4469 records; 3241 records were eligible, and 3152 articles were excluded after reading titles and abstracts, with a high agreement rate (98.6%). After reading the full texts, 76 articles remained. Spinal fentanyl and sufentanil significantly reduced postoperative pain and opioid consumption, increased analgesia and pruritus. Fentanyl, but not sufentanil, significantly reduced both postoperative nausea and vomiting, and postoperative shivering; compared to LAs alone. The analyzed studies did not report any case of in-hospital mortality related to spinal lipophilic opioids. The rate of respiratory depression was 0.7% and 0.8% when spinal fentanyl or sufentanil was added and when it was not, respectively. Episodes of respiratory depression were rare, uneventful, occurred intraoperatively, and were easily manageable.

Conclusion: There is moderate to high quality certainty that there is evidence regarding the safety and effectiveness of adding lipophilic opioids to LAs in spinal anesthesia.

Keywords: Anesthesia, spinal; Drug-related side effects and adverse reactions; Fentanyl; Safety; Sufentanil.

Conflict of interest statement

Conflicts of interest The authors declare no conflicts of interest.

Copyright © 2021 Sociedade Brasileira de Anestesiologia. Published by Elsevier España, S.L.U. All rights reserved.

Figures

Figure 1

Flow diagram.

Figure 2

Meta-analysis of the rescue analgesia up to 24h. (1.1.1) Rescue analgesia of patients received fentanyl vs local anesthetic alone, fixed-effect model was used. (1.1.2) Rescue analgesia of patients received sufentanil vs local anesthetic alone, fixed- effect model was used.

Figure 3

Meta-analysis of the length to discharge from the PACU (measured in minutes). (1.4.1) Rescue analgesia of the length to discharge from the PACU received fentanyl vs local anesthetic alone, fixed- effect model was used. PACU, post-anesthesia care unit.

Figure 4

Meta-analysis of respiratory depression events (number of patients) up to 24 h. (1.12.1) Patients who received fentanyl vs local anesthetic alone with respiratory depression up to 24 h; random-effect model was used. (1.12.2) Patients who received sufentanil vs local anesthetic alone with respiratory depression up to 24 h; random-effect model was used.

Figure 5

Meta-analysis of the number of patients with urinary retention up to 24 h. (1.10.1) Patients who received fentanyl vs local anesthetic alone with urinary retention up to 24 h; fixed-effect model was used. (1.10.2) Patients who received sufentanil vs local anesthetic alone with urinary retention up to 24 h; fixed-effect model was used.

Figure 6

Meta-analysis of the number of PONV episodes during the 24 hours following surgical procedure. (1.9.1) Patients with PONV episodes during the 24 hours following surgical procedure received fentanyl vs local anesthetic alone, fixed- effect model was used; (1.9.2) Patients with PONV episodes during the 24 hours following surgical procedure received sufentanil vs local anesthetic alone, fixed- effect model was used. PONV, postoperative nausea and vomiting.

Figure 7

Meta-analysis of the pruritus episodes during the 24 hours following surgical procedure. (1.7.1) Patients with pruritus episodes during the 24 hours following surgical procedure received fentanyl vs local anesthetic alone, fixed- effect model was used; (1.7.2) Patients with pruritus episodes during the 24 hours following surgical procedure received sufentanil vs local anesthetic alone, fixed- effect model was used.

Figure 8

Meta-analysis of the shivering episodes during the 24 hours following a surgical procedure. (1.8.1) Patients with shivering attacks during the 24 hours following surgical procedure received Fentanyl vs. local anesthetic alone, fixed-effect model was used; (1.8.2) Patients with shivering episodes during the 24 hours following surgical procedure Sufentanil vs. local anesthetic alone, fixed- effect model was used.