title: Intermediate-Acting Nondepolarizing Neuromuscular Blocking Agents and Risk of Postoperative 30-Day Morbidity and Mortality, and Long-term Survival.
abstract: Nondepolarizing neuromuscular blocking drugs (NNMBDs) are commonly used as an adjunct to general anesthesia. Residual blockade is common, but its potential adverse effects are incompletely known. This study was designed to assess the association between NNMBD use with or without neostigmine reversal and postoperative morbidity and mortality.
  
  
  
  This is a retrospective observational study of 11,355 adult patients undergoing general anesthesia for noncardiac surgery at 5 Veterans Health Administration (VA) hospitals. Of those, 8984 received NNMBDs, and 7047 received reversal with neostigmine. The primary outcome was a composite of respiratory complications (failure to wean from the ventilator, reintubation, or pneumonia), which was "yes" if a patient had any of the 3 component events and "no" if they had none. Secondary outcomes were nonrespiratory complications, 30-day and long-term all-cause mortality. We adjusted for differences in patient risk using propensity matched (PM) followed by assessment of the association of interest by logistic regression between the matched pairs as our primary analysis and multivariable logistic regression (MLR) as a sensitivity analysis.
  
  
  
  Our primary aim was to assess the adverse outcomes in the patients who had received NNMBDs with and without neostigmine. Administration of an NNMBD without neostigmine reversal compared with NNMBD with neostigmine reversal was associated with increased odds of respiratory complications (PM odds ratio [OR], 1.75 [95% confidence interval [CI], 1.23-2.50]; MLR OR, 1.71 [CI, 1.24-2.37]) and a marginal increase in 30-day mortality (PM OR, 1.83 [CI, 0.99-3.37]; MLR OR, 1.78 [CI, 1.02-3.13]). However, there were no statistically significant associations with nonrespiratory complications or long-term mortality. Patients who were administered an NNMBD followed by neostigmine had no differences in outcomes compared with patients who had general anesthesia without an NNMBD.
  
  
  
  The use of NNMBDs without neostigmine reversal was associated with increased odds of our composite respiratory outcome compared with patients reversed with neostigmine. Based on these data, we conclude that reversal of NNMBDs should become a standard practice if extubation is planned.
authors.affiliation: From the *Adult and Child Consortium for Health Outcomes Research and Delivery Science; †Surgical Outcomes and Applied Research; ‡Department of Biostatistics and Informatics, University of Colorado School of Medicine, Aurora, Colorado; §Department of Anesthesiology and Perioperative Medicine, University of Missouri, Columbia, Missouri; ‖Department of Anesthesiology, Durham VA Medical Center, Durham, North Carolina; ¶Department of Surgery, University of Alabama Birmingham, Birmingham VA Medical Center, Birmingham, Alabama; #Department of Anesthesiology, Baylor College of Medicine, Michael E. DeBakey VA Medical Center, Houston, Texas; **Department of Anesthesiology and Pain Management, University of Texas, Southwestern Medical Center, VA North Texas Health Care System, Dallas, Texas; ††Department of Anesthesiology, University of Pittsburgh School of Medicine, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania; and ‡‡Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bronsert
authors.forename: William G
authors.initials: WG
authors.lastname: Henderson
authors.forename: Terri G
authors.initials: TG
authors.lastname: Monk
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Richman
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Nguyen
authors.forename: John T
authors.initials: JT
authors.lastname: Sum-Ping
authors.forename: Michael P
authors.initials: MP
authors.lastname: Mangione
authors.forename: Binh
authors.initials: B
authors.lastname: Higley
authors.forename: Karl E
authors.initials: KE
authors.lastname: Hammermeister
mesh_terms: D000328:Adult; D000368:Aged; D000762:Anesthesia Recovery Period; D002800:Cholinesterase Inhibitors; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009388:Neostigmine; D019148:Neuromuscular Blockade / Q000009:adverse effects*; D003473:Neuromuscular Nondepolarizing Agents / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D011183:Postoperative Complications / Q000453:epidemiology* / Q000401:mortality*; D012140:Respiratory Tract Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000401:mortality; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; D003473:Neuromuscular Nondepolarizing Agents; D009388:Neostigmine