Anticholinergics and Ketamine Sedation in Children: A Secondary Analysis of Atropine Versus Glycopyrrolate

Abstract

Objectives: Adjunctive anticholinergics are commonly administered during emergency department (ED) ketamine sedation in children under the presumption that drying oral secretions should decrease the likelihood of airway and respiratory adverse events. Pharmacologic considerations suggest that glycopyrrolate might exhibit a superior adverse effect profile to atropine. The authors contrasted the adverse events noted with use of each of these anticholinergics in a large multicenter observational database of ketamine sedations.Methods: This was a secondary analysis of an observational database of 8,282 ED ketamine sedations assembled from 32 prior series. The authors compared the relative incidence of six adverse events (airway and respiratory adverse events, laryngospasm, apnea, emesis, recovery agitation, and clinically important recovery agitation) between children who received coadministered atropine, glycopyrrolate, or no anticholinergic. Multivariable analysis using the specific anticholinergic as a covariate was performed, while controlling for other known predictors.Results: Atropine was associated with less vomiting (5.3%) than either glycopyrrolate (10.7%) or no anticholinergic (11.4%) in both unadjusted and multivariable analyses. Glycopyrrolate was associated with significantly more airway and respiratory adverse events (6.4%) than either atropine (3.3%) or no anticholinergic (3.0%) and similarly more clinically important recovery agitation (2.1% vs. 1.2 and 1.3%). There were, however, no differences noted in odds of laryngospasm and apnea.Conclusions: This secondary analysis unexpectedly found that the coadministered anticholinergic atropine exhibited a superior adverse event profile to glycopyrrolate during ketamine sedation. Any such advantage requires confirmation in a separate trial; however, our data cast doubt on the traditional premise that glycopyrrolate might be superior. Further, neither anticholinergic showed efficacy in decreasing airway and respiratory adverse events.ACADEMIC EMERGENCY MEDICINE 2010; 17:157-162 ª

Comparison of ketamine-propofol and remifentanil in terms of hemodynamic variables and patient satisfaction during monitored anaesthesia care

“…The most frequently seen side effect is airway and respiratory effects, larygospasm, apnoea, nausea, and agitation occurring during recovery [17]. In the studies of Badrinath et al [18] who combined different concentrations of ketamine and propofol during MAC, they showed that the increased concentrations of ketamine are associated with PONV, various psychotomimetic effects and prolonged recovery periods.…”

“…In a meta-analysis by Green et al [17], it was concluded that the addition of any kind of anticholinergic to ketamine decreases oral secretions and respiratory side effects. However, although in the current study, a low dose of atropine (0.25 mg) was administered for premedication, a cough reflex was seen in five patients in the ketamine-propofol group.…”

Management of Pain in the Emergency Department

“…Hypersalivation, vomiting, laryngospasm, and unpleasant emergence reactions are among the major nonhemodynamic issues that should be considered when ketamine is used in any dose (risk of side effects does not appear to be dose dependent) [120,[124][125][126][127][128][129][130][131]. Hemodynamically, ketamine's sympathomimetic effects are well known to be associated with increases in heart rate and blood pressure, but the latest data indicate that there is little reason for concern about the more important issue of hemodynamic stimulation's adverse impact on intracranial pressure [132,133].…”

“…First, while a coadministered benzodiazepine is not strictly required in all patients (it appears to be unnecessary for emergence reaction prevention in young children), the addition of a benzodiazepine such as midazolam is not harmful and may have additional benefits 8 ISRN Emergency Medicine (e.g., as antiemetics) besides prophylaxis against emergence [124,131,134,135]. Second, while data are variable [131,136], the best (and most recent) prospective trial evidence suggests it is worthwhile to coadminister an antisialagogue such as atropine [123]. Third, although postketamine vomiting usually occurs well after ED discharge (and thus well after there is significant risk for aspiration), the occurrence of this "nuisance" side effect may be reduced by postprocedure utilization of an antiemetic such as ondansetron at home (atropine and metoclopramide do not appear to work well for this indication) [137].…”

Ketamine and Intracranial Pressure: No Contraindication Except Hydrocephalus

“…10 Both of these maxims were later disproved when it was shown that there was no benefit to midazolam prophylaxis in children [17][18][19][20] and no increase in airway problems or clinically important secretions when an anticholinergic was omitted. [20][21][22][23] Other historical concerns-enhanced laryngospasm risk with minor oropharyngeal procedures and in children aged 3 to 12 months-have similarly been shown to have been substantially overstated. 20,22,23 So after 45 years of experience with ketamine, what do we know?…”