Case Report

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American Journal of Emergency Medicine

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Propofol for benzodiazepine-refractory alcohol withdrawal in a non-mechanically ventilated patient

Abstract

Long-term alcohol use confers neurochemical changes in response to alcohol’s exogenous inhibitory effects. Downregulation and decreased sensitivity of ?-aminobutyric acid receptors render benzodiazepines less effective at controlling psychomotor agitation. Propofol has been reported to have successfully relieved alcohol withdrawal syndrome (AWS) symptoms in part because of activation of ?-aminobutyric acid channels in combination with antagonism of excitatory amino acids such as N-methyl-D-aspartate. Successful use of propofol in refractory AWS in patients with endotracheal intubation and mechanical ventilation has been reported. We present a case of resolution of AWS symptoms in a benzodiazepine-refractory, nonintubated, non-mechanically ventilated alcohol withdrawal pa- tient with low-dose, continuous-infusion propofol.

Alcohol is the most widely abused drug in the world [1]. Long-term alcohol use upregulates excitatory glutaminergic neuroreceptors, such as N-methyl-D-aspartate (NMDA), and downregulates inhibitory neuroreceptors, including ?-aminobutyric acid (GABA). These changes are necessary to maintain neurotransmitter equilibrium during extended periods of alcohol use because of alcohol’s exogenous inhibitory effects on GABA [2,3]. Following abrupt discontinuation of alcohol use, neuronal hyperactivity occurs, char- acterized as alcohol withdrawal syndrome (AWS) including tremu- lousness, diaphoresis, palpitations, and hallucinations [2].

Benzodiazepines have been shown to reduce the incidence of AWS seizure and to alleviate autonomic hyperactivity and agitation associated with AWS. drug therapy with benzodiazepines is the currently accepted standard of practice for the treatment of AWS. Benzodiazepines potentiate the effects of GABA by allosterically binding to the GABA-a receptor, thus increasing GABA-mediated inhibitory neurotransmission [3]. Severe alcohol withdrawal can be refractory to high-dose benzodiazepines (doses >=40 mg lorazepam equivalents without relief of psychomotor agitation) as defined in case reports and case series [4]. Propofol is an attractive agent for benzodiazepine-refractory AWS and has been reported to have successfully relieved AWS symptoms in part because of activation of GABA channels and antagonism of excitatory amino acids such as NMDA [5,6]. Previous reports of propofol use in refractory AWS were in patients with endotracheal intubation and mechanical ventilation. We report resolution of AWS symptoms in a benzodiazepine- refractory, nonintubated alcohol withdrawal patient with low-dose, continuous-infusion propofol.

A 42-year-old Hispanic man was brought to the emergency department (ED) via emergency medical services for alcohol

withdrawal. The patient had been arrested 4 days prior and presented to the ED from jail with gradual-onset altered mental status. The patient was oriented to self and place only and reported seeing crawling scorpions and “nanos” (mechanical insect hallucinations from formications) all over his arms, feet, and legs (Fig. 1). He reported usually drinking 24 beers per day for many years, and his last drink was 4 days prior to presentation. Initial vitals signs in the ED were as follows: oral temperature, 36.6?C (97.8?F); heart rate, 98 beats per minute; blood pressure, 126/84 mm Hg; and respiratory rate, 13 breaths per minute. Initial comprehensive metabolic profile, serum osmolality, liver function tests, and complete blood count were all within normal limits except for a serum potassium level of 2.8 mmol/L and alanine aminotransferase/aspartate aminotransferase levels of 285 and 283 IU/L, respectively. serum ethanol level was less than 3 mg/dL. Intravenous sodium chloride 0.9%, thiamine, folic acid, multivitamin, and potassium chloride were initiated in addition to the Clinical Institute Withdrawal Assessment for Alcohol (CIWA). The initial CIWA score was 14 (mild tremor, 3; mild anxiety, 1; agitation, 1; tactile disturbance, 1; auditory hallucination, 4; and

visual disturbance, 4) (Fig. 2).

Despite intravenous administration of 62 mg of lorazepam, 10 mg of diazepam, and 5 mg of haloperidol, the patient became increasingly symptomatic of his AWS with increasing CIWA score of 46 (tremors, 7; paroxysmal sweats, 1; anxiousness, 7; agitation, 6; tactile disturbance, 7;

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Fig. 1. CIWA score over the ED clinical course.

0735-6757/$ - see front matter (C) 2013

encourage prospective studies of propofol for the treatment of benzodiazepine-resistant AWS.

Darrel W. Hughes PharmD Department of Pharmacy Services University Health System

San Antonio, TX, USA Pharmacotherapy Division College of Pharmacy

The University of Texas at Austin

TX, USA

Pharmacotherapy Education and Research Center

School of Medicine The University of Texas Health Science Center at San Antonio

San Antonio, TX, USA E-mail address: [email protected]

Fig. 2. Formication. This patient hallucinated during AWS that his scorpion tattoos were entering his body.

auditory disturbance, 7; visual disturbance, 7; orientation, 4) during the first 2 hours of treatment. In view of the refractory nature of AWS in the face of high-dose benzodiazepines, we initiated low-dose, continuous infusion of propofol at 5 ug/(kg min) at 2:35 PM. Continuous end-tidal carbon dioxide (ETCO₂) monitoring was ordered in addition to previously placed continuous cardiac and oxygen saturation monitoring. Approximately 1 hour later at 3:25 PM, the propofol had been titrated up to 25 ug/(kg min) based on bedside assessment. Vital signs were as follows: respiratory rate, 16 breaths per minute; 97% oxygen saturation on 2-L nasal cannula; heart rate, 83 beats per minute; blood pressure, 114/69 mm Hg; ETCO₂, 38 mm Hg; and CIWA score, 2 (tremors, 0; paroxysmal sweats, 1; anxiousness, 0; agitation, 0; tactile disturbance, 0; auditory disturbance, 0; visual disturbance, 0; orientation, 1). The propofol infusion was then terminated, and the patient remained hemodynamically stable and withdrawal symptom free for 1 hour. Approximately 1 1/2 hours after stopping the propofol infusion, the patient began to exhibit Withdrawal symptoms; and his CIWA score rose to 46. Because of returning signs and symptoms of alcohol withdrawal, the propofol drip was restarted at 5 ug/(kg min) and titrated by 5 ug/(kg min) every 10 minutes up to 20 ug/(kg min), which abated the patient’s symptoms; and the CIWA score returned again to 2. The patient remained hemodynamically stable with minimal signs/symptoms of alcohol withdrawal until 11:00 PM, at

which time he was transferred to the medical intensive care unit.

Our case adds to the small body of literature that describes the use of propofol for benzodiazepine-refractory AWS. Additionally, we add to published reports by demonstrating the use of propofol in a patient without endotracheal intubation and mechanical ventilation, but with ETCO₂ monitoring. Propofol relieves AWS symptoms in part because of activation of GABA channels and antagonism of excitatory amino acids such as NMDA. Practitioners should be cautious of hypotension, respiratory depression, and propofol-related infusion syndrome. We

Elizabeth VanWert PharmD Department of Pharmacy Services University Health System

San Antonio, TX, USA Pharmacotherapy Division College of Pharmacy

The University of Texas at Austin

TX, USA

Pharmacotherapy Education and Research Center

School of Medicine The University of Texas Health Science Center at San Antonio

San Antonio, TX, USA Department of Pharmacy Practice

University of the Incarnate Word Feik School of Pharmacy

San Antonio, TX, USA

Lauren LePori PA Bruce D. Adams MD

Department of Emergency Medicine

School of Medicine The University of Texas Health Science Center at San Antonio

TX, USA

http://dx.doi.org/10.1016/j.ajem.2013.08.044

References

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6. Coomes TR, Smith SW. Successful use of propofol in refractory delirium tremens. Ann Emerge Med 1997;30:825.