Page 79 - JSOM Summer 2019

Impact of Continuous Ketamine Infusion Versus Alternative Regimens
on Mortality Among Burn Intensive Care Unit Patients

Implications for Prolonged Field Care

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Steven G. Schauer, DO, MS *; Michael D. April, MD, DPhil ;
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James K. Aden 3rd, PhD ; Matthew Rowan, PhD ; Kevin K. Chung, MD 5
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ABSTRACT

Background: The military is rapidly moving into a battlespace prehospital providers may have to care for multiple casualties
in which prolonged holding times in the field are probable. simultaneously over long periods of time.
Ketamine provides hemodynamic support and has analgesic
properties, but the safety of prolonged infusions is unclear. Case reports of prolonged infusions of ketamine date back sev-
We compare in-hospital mortality between intubated burn eral decades for the treatment of status asthmaticus. Rock et
4–7
intensive care unit (ICU) patients receiving prolonged ket- al. published a case series of two patients placed on a continu-
amine infusion lasting ≥7 days or until death versus controls. ous infusion for 24–36 hours, noting only increased secretions
Methods: We conducted a before/after cohort study of patients and no apparent deleterious effects. Tobias et al. published
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undergoing admission to a burn ICU with intubation within a case series of five patients who received a bolus dose fol-
the first 24 hours as part of treatment for thermal burns. In lowed by infusion, noting improved laboratory markers with
January 2012, this ICU implemented a novel continuous ket- no change in mean arterial pressure or vasopressor use. Sarma
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amine infusions protocol. We performed a preintervention and published a case series of two patients who received multiple
postintervention cohort analysis. Results: We identified 2394 boluses followed by an infusion that reduced bronchospasm
patients meeting our inclusion criteria—475 in the ketamine in acute asthma. Shulman et al. (n = 9) and Mankikan et al.
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group and 1919 in the control group. Regarding burn total (n = 14) found no changes in respiratory measurements in
body surface area (TBSA) involvement, there were 1533 in the their small prospective case series studies. 11,12 Tokics et al.
<10% group, 586 in the 11–30% group, and 281 in the >31% found no changes in hemodynamic parameters in a small pro-
group. The median number of ventilator-free days within the spective case series (n = 8) of patients undergoing routine mi-
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first 30 days did not vary significantly between the ketamine nor surgery. Heshmati et al. conducted a prospective case
group and the control group: 8.5 days (interquartile range series (n = 11) that found improvement in blood gas markers
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[IQR] 1–16 days) versus 8 days (IQR 3–13 days, p = .442). in asthmatic patients. Hijazi et al. found no changes in hemo-
Subjects receiving ketamine had higher mortality rates: 59.4% dynamic markers in a case series (n = 12) of ICU patients with
(n = 117) versus 40.6% (n = 80, p < .001), with an odds ra- traumatic brain and spinal cord injuries. 15
tio for in-hospital mortality of 7.51 (95% CI 5.53–10.20,
p < .001). When controlling for TBSA category, ventilator Several randomized controlled trials (RCTs) have since ex-
days and vasopressor administration, there was no association amined the use of prolonged infusions of ketamine. Bourgoin
between ketamine and in-hospital mortality (0.66, 0.41–1.05, et al. conducted a prospective RCT of 25 patients comparing
p = .08). Conclusions: When controlling for confounders, we combination ketamine-midazolam to sufentanil-midazolam
found no difference in in-hospital mortality between the pro- and found no changes in intracranial pressure (ICP) and cere-
longed ketamine infusion recipients versus non-recipients. bral perfusion pressure (CPP). Howton et al. conducted an
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RCT (n = 53) and found no difference in respiratory function
Keywords: ketamine; prolonged; military; trauma; analgesia markers after a 3-hour infusion of ketamine in patients with
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refractory status asthmaticus. Allen et al. found no difference
in pulmonary index scores in an emergency department (ED)-
based RCT (n = 68) of pediatric patients with acute severe
Introduction
asthma. 18]
Background
Ketamine is a first-line agent in the TCCC guidelines for anal- Current data on the use of prolonged ketamine infusions are
gesia on the battlefield. Ketamine has a well-established safety insufficient for interpretation for broader use, specifically
record when used as bolus intravenous and intramuscular trauma/burns, because most of the current literature is limited
doses and even in the setting of massive overdoses. How- to patients with acute asthma exacerbations. The endpoints
1–3
ever, the prolonged field care (PFC) model of care brings with in these studies are similarly limited to that population. We
it a need for continuous infusions of analgesic agents since expand on the existing literature by evaluating the safety of

*Correspondence to Steven G. Schauer, 3698 Chambers Pass, JBSA Fort Sam Houston, TX 78234; steven.g.schauer.mil@mail.mil
1 MAJ Schauer is affiliated with the US Army Institute of Surgical Research, JBSA Fort Sam Houston, TX; 59th Medical Wing, JBSA Lackland Air
Force Base, TX; and San Antonio Military Medical Center, JBSA Fort Sam Houston, TX. MAJ April is affiliated with the San Antonio Military
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Medical Center, JBSA Fort Sam Houston, TX. Dr Aden is affiliated with San Antonio Military Medical Center, JBSA Fort Sam Houston, TX.
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4 Dr Rowan is affiliated with the US Army Institute of Surgical Research, JBSA Fort Sam Houston, TX. COL Chung is affiliated with Uniformed
Services University of the Health Sciences, Bethesda, MD.
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