Objective To determine whether use of intermediate acting neuromuscular blocking agents during general anesthesia increases the incidence of postoperative respiratory complications.Design Prospective, propensity score matched cohort study.Setting General teaching hospital in Boston, Massachusetts, United States, 2006-10.Participants 18 579 surgical patients who received intermediate acting neuromuscular blocking agents during surgery were matched by propensity score to 18 579 reference patients who did not receive such agents. Main outcome measuresThe main outcome measures were oxygen desaturation after extubation (hemoglobin oxygen saturation <90% with a decrease in oxygen saturation after extubation of >3%) and reintubations requiring unplanned admission to an intensive care unit within seven days of surgery. We also evaluated effects on these outcome variables of qualitative monitoring of neuromuscular transmission (train-of-four ratio) and reversal of neuromuscular blockade with neostigmine to prevent residual postoperative neuromuscular blockade. ResultsThe use of intermediate acting neuromuscular blocking agents was associated with an increased risk of postoperative desaturation less than 90% after extubation (odds ratio 1.36, 95% confidence interval 1.23 to 1.51) and reintubation requiring unplanned admission to an intensive care unit (1.40, 1.09 to 1.80). Qualitative monitoring of neuromuscular transmission did not decrease this risk and neostigmine reversal increased the risk of postoperative desaturation less than 90% (1.32, 1.20 to 1.46) and reintubation (1.76, 1.38 to 2.26). ConclusionThe use of intermediate acting neuromuscular blocking agents during anesthesia was associated with an increased risk of clinically meaningful respiratory complications. Our data suggest that the strategies used in our trial to prevent residual postoperative neuromuscular blockade should be revisited. IntroductionTens of millions of people worldwide undergo general anesthesia every day. Anesthetists use a wide variety of drugs to establish the reversible state of anesthesia, which is characterised by hypnosis, amnesia, analgesia, hemodynamic stability with control of the stress response, and immobility.1 Deep anesthesia provides all components 2 3 ; however, to achieve immobility with lower levels of anesthetic agents, anesthetists may coadminister curare-type neuromuscular blocking agents. These drugs inhibit neuromuscular transmission from nerves to muscles by competitively blocking the binding of acetylcholine to its postsynaptic receptors at the motor end plate, thereby causing paralysis of the muscle.More than 400 million people receive neuromuscular blocking agents annually (Intercontinental Marketing Services (IMS) RESEARCHHealth, Multinational Integrated Data Analysis System (MIDAS), September 2010), either in the operating theatre to optimize surgical conditions, or in the intensive care unit to facilitate mechanical ventilation in those with patient-ventilator asynchrony. 4 Neuromuscular blocking a...

No a priori adjustment in methadone dosage is required during coadministration with amprenavir as there is only a small effect on R-methadone exposure and no evidence of opioid withdrawal.

No adjustment in the dosages of either methadone or fosamprenavir 700 mg-ritonavir 100 mg twice/day is required during coadministration, on the basis of the small reduction in total R-methadone exposure, no change in unbound R-methadone, no clinically important opioid effects, and no change in amprenavir exposure.