Literature Reviews

Paper #1

Bhatt M, Kennedy RM, Osmond MH, Krauss B, McAllister JD, Ansermino JM, Evered LM, Roback MG; Consensus Panel on Sedation Research of Pediatric Emergency Research Canada (PERC) and the Pediatric Emergency Care Applied Research Network (PECARN). Consensus-based recommendations for standardizing terminology and reporting adverse events for emergency department procedural sedation and analgesia in children. Ann Emerg Med. 2009 Apr;53(4):426-435.e4

Abstract:
Children commonly require sedation and analgesia for procedures in the emergency department. Establishing accurate adverse event and complications rates from the available literature has been difficult because of the difficulty in aggregating results from previous studies that have used varied terminology to describe the same adverse events and outcomes. Further, serious adverse events occur infrequently, necessitating the study of large numbers of children to assess safety. These limitations prevent the establishment of a sufficiently large database on which evidence-based practice guidelines may be based. We assembled a panel of pediatric sedation researchers and experts to develop consensus-based recommendations for standardizing procedural sedation and analgesia terminology and reporting of adverse events. Our goal was to create a uniform reporting mechanism for future studies to facilitate the aggregation and comparison of results.

Commentary:
Studies that evaluate pediatric sedation drugs and techniques report a wide range of “complications” or “adverse events” associated with the use of specific drugs or techniques.  Historically there has been little consistency between the adverse events that are reported from one study to the next.  More importantly, there has never been agreement between investigators as to what type of event actually reaches the “threshold” to be considered an anverse event.  This study reports on the efforts of two research groups involved in emergency care to come up with a set of specific set of terminology for adverse events.  The authors propose that this standard terminology will be accepted by all emergency medicine researchers resulting in more consistant reporting in the future.  The methodology used included extensive review of the available literature along with consensus among the expert panel of authors.  The results of this effort are divided into three sections including general Sedation Terminology (depth of sedation, efficacy of sedation), Sedation Intervals (Presedation, Postsedation), and Adverse Event Terminology (Oxygen desaturation, Apnea, Laryngospasm).  The authors take a very forward thinking approach in defining (particularly) the adverse events in that they have included both the objective findings (such as the absolute oxygen saturation level) plus and analysis of the interventions that were made at the time of the event to prevent or “fix” the adverse event.  This is extremely important since the progress of any adverse event in sedation is so greatly impacted by the actions of the sedation providers.  We must know the intervention that was engendered by the event in order to understand its gravity. A similar approach was taken by the Pediatric Sedation Research Consortium in reporting both the adverse events (desaturation episodes) in a large group of sedation encounters (50,000) as well as the unexpected airway management interventions required among these encounters (1).

As the outcomes of this paper are not “absolute”, there will undoubtedly be quibbling over the exact nature of the standard terminology that has been chosen by these researchers.  On the other hand, there can be no doubt that Bhaat and colleagues have done a lot of work to solve a very vexing problem in this area of clinical research – that of defining the outcomes that are meaningful and trying to standardize reporting of this work so that all sedation providers can understand the relative effective safety and effectiveness of the various sedation methods that are studied in the future.

1. Cravero JP, Beach ML, Blike GT, Gallagher SM, Hertzog JH. The Incidence and Nature of Adverse Events during Pediatric sedation/anesthesia with Propofol for Procedures outside the Operating Room, Report from the Pediatric Sedation Research Consortium. Anesthesia Analgesia, 2009 108795-804

Paper #2

Green SM, Roback MG, Krauss B, Brown L, McGlone RG, Agrawal D, McKee M, Weiss M, Pitetti RD, Hostetler MA, Wathen JE, Treston G, Garcia Pena BM, Gerber AC, Losek JD; For the Emergency Department Ketamine Meta-Analysis Study Group Predictors of Airway and Respiratory Adverse Events With Ketamine Sedation in the Emergency Department: An Individual-Patient Data Meta-analysis of 8,282 Children. Ann Emerg Med. 2009 Feb 5. [Epub ahead of print]

Abstract:

Introduction: Although ketamine is one of the most commonly used sedatives to facilitate painful procedures for children in the emergency department (ED), existing studies have not been large enough to identify clinical factors that are predictive of uncommon airway and respiratory adverse events.

Methods: We pooled individual-patient data from 32 ED studies and performed multiple logistic regressions to determine which clinical variables would predict airway and respiratory adverse events.

Results: In 8,282 pediatric ketamine sedations, the overall incidence of airway and respiratory adverse events was 3.9%, with the following significant independent predictors: younger than 2 years (odds ratio [OR] 2.00; 95% confidence interval [CI] 1.47 to 2.72), aged 13 years or older (OR 2.72; 95% CI 1.97 to 3.75), high intravenous dosing (initial dose >/=2.5 mg/kg or total dose >/=5.0 mg/kg; OR 2.18; 95% CI 1.59 to 2.99), coadministered anticholinergic (OR 1.82; 95% CI 1.36 to 2.42), and coadministered benzodiazepine (OR 1.39; 95% CI 1.08 to 1.78). Variables without independent association included oropharyngeal procedures, underlying physical illness (American Society of Anesthesiologists class >/=3), and the choice of intravenous versus intramuscular route.

Conclusion: Risk factors that predict ketamine-associated airway and respiratory adverse events are high intravenous doses, administration to children younger than 2 years or aged 13 years or older, and the use of coadministered anticholinergics or benzodiazepines.

Commentary: Ketamine is a commonly used sedative in the emergency department setting.  Numerous reports have been published regarding the effectiveness and adverse events associated with the use of this drug in this setting. Unfortunately, the results from these reports are difficult generalize since they involve relatively small numbers of patients from individual institutions. (1,2) This study from Green and colleagues is a meta-analysis of 32 studies involving 8,282 patients receving ketamine sedation.  The authors chose these studies from 57 published reports based on the availability data on route and dose of ketamine administration as well as outcome information regarding respiratory events. All studies used in the analysis had more than twenty subjects and were limited to those in which midazolam was the only co-administered sedative. This report specifically evaluated the association of several independent predictors of airway or respiratory adverse events during sedation.  Results showed that the overall incidence of respiratory adverse events was 3.9%.  Several independent predictors were documented including age younger than 2, high intravenous dosing, coadministered anticholinergic or coadministered benzodiazepine.  Other variables that did not have predictive value included oropharyngeal procedures, ASA status, and the choice of intravenous versus intramuscular route of administration.

The study is unique in the total number of patients included in the report.  The conclusions have weight based on the power inherent in a large cohort such as this. On the other hand, there is significant heterogeneity among the studies included – most notably the inclusion of several retrospective studies along with prospective observational trials in this meta-analysis.   In addition, where data points were missing, original authors of the papers were contacted and queried to provide data, a methodology that is concerning for hindsight bias.  Finally readers will readily appreciate that not all possible predictors for adverse events are included in the analysis.  For instance, in the anesthesia literature concurrent upper respiratory infection symptoms have been implicated in perioperative events as has smoking in the living environment. Future prospective studies would do well to include similar predictive factors.

This paper represents the most complete accounting of respiratory adverse events concerning ketamine sedation in children.  While WE are concerned about the inclusion of some of the studies in this meta-analysis and with the nature of its conclusions, it is worth reading and considering with respect to the use of ketamine on children in the emergency medicine setting.

1. Pena BMG, Krauss B: Adverse events of procedural sedation and analgesia in a pediatric emergency department Ann Emerg Med 1999;34:483-490.

2. Green SM, Rothrock sg, Lynch EL et. al: Intramuscular ketamine for pediatric sedation in the emergency department: Safety profile with 1022 cases. Ann Emerg Med 1998;31:688-697

Editors:
Joseph Cravero MD
George Blike MD

Departments of Anesthesiology
and Pediatrics,
Children’s Hospital
at Dartmouth,
Dartmouth Hitchcock
Medical Center,
Lebanon, NH

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