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