Wednesday, March 18, 2015

Sprinkle on a little ketamine

A middle aged patient with a longstanding history of asthma (multiple intubations and ICU stays) presents with 3 days of worsening dyspnea, refractory to home bronchodilators, speaking in 2 word sentences and in tripod position. As oxygen saturations hover in the low 90s, the patient is transferred to critical care area for BiPAP.  As the patient rolls by you plan on BiPAP, solumedrol, epinephrine, and magnesium, and you and your attending think “why don’t we try some ketamine?” 

Severe Respiratory distress (Source imgkid)

Clinical Question: Can ketamine be used as a bronchodilator improve outcomes in patients with severe asthma?

Literature Review: In the review article from 2013 by Goyat et al, 20 articles were examined looking at ketamine for bronchospasm (case series, RCTs, observational, retrospective studies) 3 of which were in the ED.  Ketamine was used as a rescue agent in all studies; general doses were 0.1-0.2mg/kg IVP followed by infusion at 0.15-0.25mg/kg/hr.  Eighteen articles showed a “favorable response”, and 2 studies showed insufficient response.  No major adverse events were reported.  

To review, ketamine has 2 enantiomers: the S is more potent and faster acting, and the R enantiomer may be associated with more emergence reactions.  Most preparations are 1:1 S:R. Peak onset is at 60 seconds with a duration of 10-15 minutes. The distribution half-life is approximately 7-11 minutes and is cleared via the hepatic route with half life of 2-3 hours.  Several mechanisms have been proposed for its effect on bronchospasm: improved airway mechanics, anti-inflammatory properties, airway relaxation, reduction of nitric oxide, inhibition of reuptake of catecholamines at the synapse, and anticholinergic effects.

The first case report of ketamine use for reactive airway disease was in 1972 of a child who had anaphylaxis during skin testing that improved after ketamine, followed by a non-controlled trial in children intubated for asthma that showed a significant difference in PaO2/FiO2 and dynamic compliance after initiation of ketamine infusion.  The first controlled double blind trial in 1994 showed an improvement in “stethoscopic exam” and in Po2 and PCO2.  While it is worth noting the significant change in these objective data points, they are not exactly patient centered outcomes.

One observational study looked at pediatric ED patients. It enrolled 10 patients who were unresponsive to traditional therapy; no change in peak expiratory flow (PEF) was noted at 1 hour, but a significant change in the patients’Asthma Scores and respiratory rates (RR) was noted. 

The next prospective, double blind RCT (Howton, 1996) showed no benefit with ketamine.  Fifty-three consecutive patients with peak flows less than 40% after 3 does of albuterol were enrolled, all were given continuous albuterol, methylpredisolone and oxygen and then either a 0.2mg/kg ketamine bolus followed by 0.5mg/kg/hr x 3 hours, or an equivalent saline dose.  While there was a significant improvement in PEF, RR, FEV-1 in both groups over time, there was no difference between the groups. 

Similarly, a follow up RCT in kids (Allen, 2005), looked at 62 consecutive patients randomized to saline or the same ketamine doses as above, without improvement in pulmonary scores.

 Take-Home Points:
The conclusions of the above review are that ketamine is cheap, has a physiologic rationale, has few adverse effects and has been shown to improve asthma in case series and observational trials, though this has not been born out in the two small RCTs undertaken.  Their suggestion is that it should remain in the ED physicians armamentarium for refractory status asthmaticus and, as always, “further well-designed studies are warranted”.  It is probably not unreasonable for ketamine to be the induction agent of choice for asthmatics, and should be considered whenever NPPV is considered for status asthmaticus. 

Allen JY, Macias CG. The efficacy of ketamine in pediatric emergency department patients who present with acute severe asthma. Annals of Emergency Medicine 2005, 46 (1): 43-50

Howton JC, Rose J, Duffy S, Zoltanski T, Levitt MA. Randomized, double-blind, placebo-controlled trial of intravenous ketamine in acute asthma. Annals of Emergency Medicine 1996, 27 (2): 170-5

Shweta Goyal, Amit Agrawal.  Ketamine in status asthmaticus: A review.  Indian Journal of Critical Care Medicine 2013, 17 (3): 154-61

Submitted by Wes Watkins, PGY-4 
Edited by Louis Jamtgaard, PGY-3 @Lgaard

Faculty Review by Joan Noelker


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