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dc.contributor.authorKent NBen_US
dc.contributor.authorLiang SSen_US
dc.contributor.authorSmith Sen_US
dc.contributor.authorEikermann Men_US
dc.contributor.authorKhandkar Cen_US
dc.contributor.authorEikermann Men_US
dc.contributor.authorStewart PAen_US
dc.description.abstractNeostigmine reverses non-depolarising neuromuscular blockade, but may cause muscle weakness when administered after full recovery of neuromuscular function. We hypothesised that neostigmine in therapeutic doses impairs muscle strength and respiratory function in awake healthy volunteers. Twenty-one volunteers were randomised to receive two doses of either intravenous (i.v.) neostigmine 2.5 mg with glycopyrrolate 450 μg (neostigmine group, n = 14) or normal saline 0.9% (placebo group, n = 7). The first dose was administered immediately after obtaining baseline measurements, and the second dose was administered 15 min later. All 14 volunteers in the neostigmine group received the first dose, mean (SD) 35 (5.8) μ , but only nine of these volunteers agreed to receive the second dose, 34 (3.5) ? . The primary outcome was hand grip strength. Secondary outcomes were train-of-four ratio, single twitch height, forced expiratory volume in 1 s, forced vital capacity, forced expiratory volume in 1 s/forced vital capacity ratio, oxygen saturation, heart rate and mean arterial pressure. The first dose of intravenous neostigmine with glycopyrrolate resulted in reduced grip strength compared with placebo, -20 (20) % vs. +4.3 (9.9) %, p = 0.0016; depolarising neuromuscular blockade with decreased single twitch height, -14 (11) % vs. -3.8 (5.6) %, p = 0.0077; a restrictive spirometry pattern with decreased predicted forced expiratory volume in 1 s, -15 (12) % vs. -0.47 (3.4) %, p = 0.0011; and predicted forced vital capacity, -20 (12) % vs. -0.59 (3.2) %, p < 0.0001 at 5 min after administration. The second dose of neostigmine with glycopyrrolate further decreased grip strength mean (SD) -41 (23) % vs. +1.0 (15) %, p = 0.0004; single twitch height -25 (15) % vs. -2.5 (6.6) %, p = 0.0030; predicted forced expiratory volume in 1 s -23 (24) % vs. -0.7 (4.4) %, p = 0.0063; and predicted forced vital capacity, -27.1 (22.0) % vs. -0.66 (3.9) %, p = 0.0010. Train-of-four ratio remained unchanged (p = 0.22). In healthy volunteers, therapeutic doses of neostigmine induced significant and dose-dependent muscle weakness, demonstrated by a decrease in maximum voluntary hand grip strength and a restrictive spirometry pattern secondary to depolarising neuromuscular blockade.en_US
dc.subjectneuromuscular blockadeen_US
dc.subjectneuromuscular reversalen_US
dc.subjectmuscle weaknessen_US
dc.titleTherapeutic doses of neostigmine, depolarising neuromuscular blockade and muscle weakness in awake volunteers: a double-blind, placebo-controlled, randomised volunteer studyen_US
dc.typeJournal Articleen_US
dc.description.affiliatesRoyal Prince Alfred Hospital, Westmead Hospital, Sydney Adventist Hospital, Wollongong Hospital, Harvard Medical Schoolen_US
dc.type.studyortrialDouble-Blind Methoden_US
dc.contributor.anzcaPhillips, Sen_US
dc.contributor.anzcaSmith NAen_US
dc.contributor.anzcaStewart, PAen_US
Appears in Collections:Scholarly and Clinical

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