Effects of low-dose intraoperative fentanyl on postoperative respiratory complication rate: a pre-specified, retrospective analysis

S Friedrich; D Raub; B J Teja; S E Neves; T Thevathasan; T T Houle; M Eikermann

doi:10.1016/j.bja.2019.03.017

Effects of low-dose intraoperative fentanyl on postoperative respiratory complication rate: a pre-specified, retrospective analysis

Br J Anaesth. 2019 Jun;122(6):e180-e188. doi: 10.1016/j.bja.2019.03.017. Epub 2019 Apr 11.

Authors

S Friedrich¹, D Raub¹, B J Teja², S E Neves², T Thevathasan³, T T Houle³, M Eikermann⁴

Affiliations

¹ Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
² Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
³ Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁴ Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Universitätsklinikum Essen, Essen, Germany. Electronic address: meikerma@bidmc.harvard.edu.

PMID: 30982564
DOI: 10.1016/j.bja.2019.03.017

Abstract

Background: Fentanyl is one of the most frequently administered intraoperative drugs and may increase the risk of postoperative respiratory complications (PRCs).

Methods: We performed a pre-specified analysis of 145 735 adult non-cardiac surgical cases under general anaesthesia. Using multivariable logistic regression, we evaluated the association of intraoperative fentanyl dose and PRCs within 3 days after surgery (defined as reintubation, respiratory failure, pneumonia, pulmonary oedema, or atelectasis). We examined effect modification by patient characteristics, surgical site, and anaesthetics used.

Results: PRCs within 3 days after surgery occurred in 18 839 (12.9%) patients. In comparison with high intraoperative fentanyl doses [median: 3.85; inter-quartile range (IQR): 3.42-4.50 μg kg^-1, quartile 4 (Q4)], low intraoperative fentanyl dose [median: 0.80, IQR: 0.00-1.14 μg kg^-1, quartile 1 (Q1)] was significantly associated with lower odds of PRCs [Q1 vs Q4: 10.9% vs 16.2%; adjusted odds ratio (aOR) 0.79; 95% confidence intervals (CI) 0.75-0.84; P<0.001; adjusted absolute risk difference (aARD) -1.7%]. This effect was augmented by thoracic surgery (P for interaction <0.001; aARD -6.2%), high doses of inhalation anaesthetics (P for interaction=0.016; aARD -2.2%) and neuromuscular blocking agents (NMBAs) (P for interaction=0.001; aARD -3.4%). Exploratory analysis demonstrated that compared with no fentanyl, low-dose fentanyl was associated with lower rates of PRCs (decile 2 vs decile 1: aOR 0.82, CI 0.75-0.89, P<0.001).

Conclusions: Intraoperative low-dose fentanyl (about 60-120 μg for a 70 kg patient) was associated with lower risk of postoperative respiratory complications compared with both no fentanyl and high-dose fentanyl. Beneficial effects of low-dose fentanyl were magnified in specific patient subgroups.

Clinical trial registration: NCT03198208.

Keywords: analgesics; fentanyl; opioid; pneumonia; postoperative complications; respiratory failure; respiratory tract diseases.

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Analgesics, Opioid / administration & dosage*
Analgesics, Opioid / adverse effects
Anesthesia, General / methods
Dose-Response Relationship, Drug
Female
Fentanyl / administration & dosage*
Fentanyl / adverse effects
Humans
Intraoperative Period
Male
Middle Aged
Postoperative Complications / chemically induced
Postoperative Complications / prevention & control*
Registries
Respiration Disorders / chemically induced
Respiration Disorders / prevention & control*
Retrospective Studies
Young Adult

Substances

Analgesics, Opioid
Fentanyl

Associated data

ClinicalTrials.gov/NCT03198208