Dose-dependent Association between Intermediate-acting Neuromuscular-blocking Agents and Postoperative Respiratory Complications
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Duncan J McLean1, Daniel Diaz-Gil, Hassan N Farhan
1From the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts (D.J.M., D.D.-G., H.N.F., K.S.L., M.E.); Inserm Research Center for Epidemiology and Biostatistics (U897)-Team Neuroepidemiology, Bordeaux, France (T.K.); University of Bordeaux, College of Health Sciences, Bordeaux, France (T.K.); Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts (T.K.); and Universitaetsklinkum Duisburg-Essen, Essen, Germany (M.E.).
Background:
Duration of action increases with repeated administration of neuromuscular-blocking agents, and intraoperative use of high doses of neuromuscular-blocking agent may affect respiratory safety.
Methods:
In a hospital-based registry study on 48,499 patients who received intermediate-acting neuromuscular-blocking agents, the authors tested the primary hypothesis that neuromuscular-blocking agents are dose dependently associated with the risk of postoperative respiratory complications. In the secondary analysis, the authors evaluated the association between neostigmine dose given for reversal of neuromuscular-blocking agents and respiratory complications. Post hoc, the authors evaluated the effects of appropriate neostigmine reversal (neostigmine ≤ 60 μg/kg after recovery of train-of-four count of 2) on respiratory complications. The authors controlled for patient-, anesthesia-, and surgical complexity-related risk factors.
Results:
High doses of neuromuscular-blocking agents were associated with an increased risk of postoperative respiratory complications (n = 644) compared with low doses (n = 205) (odds ratio [OR], 1.28; 95% CI, 1.04 to 1.57). Neostigmine was associated with a dose-dependent increase in the risk of postoperative respiratory complications (OR, 1.51; 95% CI, 1.25 to 1.83). Post hoc analysis revealed that appropriate neostigmine reversal eliminated the dose-dependent association between neuromuscular-blocking agents and respiratory complications (for neuromuscular-blocking agent effects with appropriate reversal: OR, 0.98; 95% CI, 0.63 to 1.52).
Conclusions:
The use of neuromuscular-blocking agents was dose dependently associated with increased risk of postoperative respiratory complications. Neostigmine reversal was also associated with a dose-dependent increase in the risk of respiratory complications. However, the exploratory data analysis suggests that the proper use of neostigmine guided by neuromuscular transmission monitoring results can help eliminate postoperative respiratory complications associated with the use of neuromuscular-blocking agents.
Insights
High doses of neuromuscular-blocking agents increase the risk of postoperative respiratory complications. Proper neostigmine reversal, guided by monitoring, can mitigate these risks.
Area of Science:
- Anesthesiology
- Pharmacology
- Patient Safety
Background:
- Neuromuscular-blocking agents (NMBAs) effects can prolong with repeated doses.
- High intraoperative NMBA doses may compromise postoperative respiratory safety.
Purpose of the Study:
- To investigate the dose-dependent association between NMBAs and postoperative respiratory complications.
- To evaluate the impact of neostigmine reversal on these complications.
Main Methods:
- A hospital-based registry study of 48,499 patients receiving intermediate-acting NMBAs.
- Analysis controlled for patient, anesthesia, and surgical complexity risk factors.
- Secondary analysis assessed neostigmine dose; post hoc analysis examined appropriate reversal (neostigmine ≤ 60 μg/kg with TOF count ≥ 2).
Main Results:
- High NMBA doses correlated with increased risk of postoperative respiratory complications (OR, 1.28).
- Neostigmine administration showed a dose-dependent increase in complication risk (OR, 1.51).
- Appropriate neostigmine reversal eliminated the NMBA dose-response relationship with complications (OR, 0.98).
Conclusions:
- NMBA use is dose-dependently linked to higher postoperative respiratory complication rates.
- Neostigmine reversal also demonstrated a dose-dependent risk increase.
- Proper neostigmine use, guided by neuromuscular monitoring, may prevent NMBA-associated respiratory complications.
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