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Three Part Question

In [pediatric patients presenting with an acute asthma exacerbation who have failed standard treatments], is [ketamine] effective in [reducing airway distress, intubation, and hospital admissions]?

Clinical Scenario

A pediatric patient presents to the ED in acute respiratory distress, with increased work of breathing and reduced oxygen saturation. The patient is treated with multiple rounds of nebulized albuterol, ipratropium, oxygen supplementation, and parental steroids, with none to minimal improvement in clinical and objective evidence of respiratory distress. You have heard that ketamine is the anesthesia of choice in pediatric and adult patients with bronchospasm of history of reactive airway disease. However, you wonder if ketamine’s bronchodilatory effects can reduce patient’s airway distress, prior to the need for intubation or admission, when added to standard therapies.

Search Strategy

1. Search Ovid Medline 1960- 1st week June, 2009 database through OHSU library, beginning 6/21/09. Search under “asthma or acute asthma or reactive airway disease” and “ketamine” then further limited to “pediatrics and child,” English language and human only articles.
2. Search PubMed database through OHSU library, beginning 6/21/09. Search under “asthma and ketamine,” further narrowed by adding “and pediatrics.”
3. The references of each of relevant articles was reviewed to look for additional articles.

Search Outcome

- Using criteria #1, yielded 46 narrow to 13 results for pediatric patients,3 were found to be relevant to usage of ketamine within the ED, others excluded mainly for usage of ketamine after intubation or after ED triage to ICU.
- Using criteria #2, yielded 20 results narrowed to 7 pediatric results, 3 which were relevant, and already included in search #1.
- Using criteria #3, an additional, 11 other article abstracts were reviewed, regarding overall approach and treatment of patients with severe asthma exacerbations, or use of ketamine with asthmatic patients. None were added either for failure to use ketamine, non-pediatric patients, ketamine after intubation, or for use of ketamine after ED triage to ICU.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Allen, Joseph Y and Charles G Macias July 2005 USA	68 patients, aged 2-18, present, at single center ED, present with acute asthma exacerbation, no fever, focal on CXR, or steroids within 72 hrs	Double-blinded, randomized, placebo-controlled trial	Pulmonary Index score after 2 hour infusion of ketamine	No significant improvement in PIS between ketamine and placebo group	Large age range; Small limited number of patients; overall low power; Despite PIS usage – subjective nature to scoring; did not measure all outcomes in clinical question
			Adverse Effects	No adverse effects requiring discontinuation of ketamine or withdrawl from study
			Intubations	No Intubations necessary
			Hospital Admission	6/68 removed prior to completion of treatment, 3/68 admitted to hospital
Denmark, T Kent, et.al 2006 USA	2 children, 1 9 yo boy, 1 4 yo boy	2 Case Reports	Respiratory Distress	Clinical improvement in respiratory distress in both patients after ketamine treatment	Case reports, not RCT, with only 2 cases so limited power; No indications or parameters designating failing standard treatments; no standardized objective data for improvement in respiratory state
			Adverse Effects	- nystagmus - confusion, non-dissotiative - both patients were able to control salivations
			Intubations	Neither patient intubated
			Admission	Neither patient admitted
Petrillo, Toni M., et.al. 2001 USA	10 patients, aged 5-16 years, unresponsive to “standard” therapy, at 2 centers	Prospective Observational Study	Clinical Asthma Score (CAS)	Significant decrease in CAS following infusion, from 14.2 to 10.5 to 9.5	Large age range; small population size; non-controlled/standardized treatment prior to ketamine initiation; Did not comment of number of patients intubated
			Vital Signs	25% reduction in respiratory rate, O2 saturation improved from 89% to 95%
			Peak Expiratory Flow (PEF)	No difference in PEF
			Adverse Effects	4 reported, 3 discontinued ketamine treatment, 2 for hallucinations, 1 HTN, 1 Flushing
			Admission	8/10 Admitted, 4 ICU, 4 Wards

Comment(s)

The usage of ketamine in pediatric patients who are suffering moderate to severe respiratory distress despite the standard interventions (albuterol, ipratropium, oxygen, steroids, etc.) still needs to be further investigated before clear clinical indications and guidelines for usage can be established. Ketamine does have proven bronchodilation effects and is the anesthesia of choice for patients in respiratory distress. Also given a brief review of the associated literature, ketamine does appear to have a beneficial role in reducing the length of intubation/hospital admission and level of respiratory distress in pediatric asthma patients already intubated or admitted to the ICU using multiple standard and non-standard treatment modalities. However, in review of the literature for usage of ketamine within the Emergency Department, there appears to be conflicting evidence. Not included in the above review were other case reports of the use of ketamine overall improving respiratory status but articles either were not in English, patients were intubated, or ketamine was not administered in the ED. Per this review, there is prospective data in a small patient group and case reports, that indicates ketamine did improve clinical respiratory distress, and may have decreased intubation and admissions; however, in the one RCT there was no difference in the ketamine vs. placebo group. Several limitations were identified in each study, including small group size, non-standardized treatment dosages (lower dose in RCT than in the prospective), and missing data objects/variable end-points analyzed. As such the efficacy of ketamine in improving investigated outcomes appears questionable.

Clinical Bottom Line

In practice if a patient appears to be refractory to standard treatments, ketamine is a viable additional treatment modality such as magnesium sulfate, heliox, etc. but currently more research into ketamine’s efficacy needs to be performed before recommending ketamine as a standard treatment. Review of recent asthma guidelines support this conclusion.

References

1. Allen, Joseph Y. and Charles G. Macias The Efficacy of Ketamine in Pediatric Emergency Department Patients Who Present with Severe Acute Asthma Annals of Emergency Medicine Vol. 46, No.1, July 2005, 43-50
2. Denmark, T. Kent, et.al. Ketamine to avoid mechanical ventilation in severe pediatric asthma The Journal of Emergency Medicine Vol.30, No. 2, 2006, pp163-166
3. Petrillo, Toni M. et.al. Emergency Department Use of Ketamine in Pediatric Status Asthmaticus Journal of Asthma 38(8), 2001, 657-664