Analysis of Safety and Efficacy of Dexmedetomidine as Adjunctive Therapy for Alcohol Withdrawal in ICU Vincent Rizzo MD MBA FACP Ricardo Lopez MD FCCP Nagalli, S., Kachalia, A., Kachalia, K, Rahman, H.

Disclosures Nothing to disclose

Introduction Alcohol consumption In 2012 the National Survey on Drug Use and Health 84% of Americans 18-25 years of age and 88% of Americans 26 and older have consumed alcohol in their lifetime 60% & 55% respectively consumed in the past month Inhibits NDMA receptors and activates GABA-A receptors 8 Million alcohol dependant people in the US 500,000 episodes per year of withdrawal severe enough to require pharmacologic treatment http: //www.drugabuse.gov/national-survey-drug-use-heatlh NEJM 2003;348(18):1786

Introduction Four clinical states of alcohol withdrawal Autonomic hyperactivity, hallucinations, neuronal excitation, Delirium Tremens (DT) 5% of patients will develop DT, usually between 48-96 hours after their last drink. Risk factors include History of sustained drinking, history of previous DT, age >30, the presence of a concurrent illness, the presence of significant alcohol withdrawal with an elevated alcohol level, a longer period since the last drink Mortality has decreased from 37% in the early 20th century to 5%

Rationale Patients with severe alcohol withdrawal often require escalating doses of benzodiazepines and intubation with mechanical ventilation which leads to prolonged Intensive Care Unit(ICU) stays and increasing healthcare costs. Average daily costs in the ICU are $2,278-$3,518 Case studies suggest dexmedetomidine is effective in reducing benzodiazepine dosage and autonomic symptoms seen in alcohol withdrawal. We report a retrospective analysis of 53 ICU patients treated for alcohol withdrawal conducted to compare treatment with benzodiazepine alone to those receiving dexmedetomidine as escalation or substitution therapy Semin Resp Crit Care Med 2013;34:529-536

Dexmedetomidine Alpha 2 Adrenergic Agonist; Sedative Activates G-proteins by alpha 2a adrenoreceptors in brainstem Inhibits norepinephrine release Metabolized by CYP2A6 Significant Adverse Reactions: Hypotension, Bradycardia, Constipation, Nausea Rebound Hypertension and Tachycardia Weakly inhibits CYP1A2, CYP2C9 and CYP3A4. Route IV. No dose adjustments for renal impairment. Consider dose reduction for hepatic impairment.

Methods Retrospective study using records from a 17 bed mixed medical-surgical ICU were analyzed from January 2008 to December 2012 for patients treated with alcohol withdrawal. Inclusion criteria: Clinical Institute Withdrawal Scale(CIWA)>14 and received >16mg benzodiazepine over a 4 hour period. 2 Groups: (1) Benzodiazepine alone and (2) Dexmedetomidine for benzodiazepine refractory withdrawal either as substitution or escalation therapy. Analysis was performed using t tests and Fischer’s exact test

Results Benzodiazepine alone Dexmedetomidine Number of patients 30 23 Average age 43.53 40.52 Patients requiring intubation 5 (16.67%) 6 (26.09%) Average time receiving Dexmedetomidine 31.35 hours Used as escalation therapy 21 (91.3%) Used as substitution therapy 2

Results Attributes Benzodiazepine group, n=30 (%, SD/SEM) Dexmedetomidine group, n=23 (%) Change P value (Fischer’s exact test, t test) Average age 43.53 (11.11) 40.52 (11.15) 0.33 Incidence of intubation after initiation 10 (33.33%) 1 (4.34%) 28.98% 0.01 Average no. of days intubated after initiation 7.267 (5.573, n=15) 0.857 (0.899, n=7) 88.20% 0.0073 LOS ICU after initiation in days 7.967(1.459) 4.043(0.4422) 49.25% 0.0263 LOS hospital in days 18.533 (4.039) 13.739 (1.24) 25.87% 0.317 Incidence Bradycardia episodes after initiation 4 (13.33%) 8 (34.78%) 31.45% 0.098 Incidence seizure episodes after initiation 1 (3.3%) 2 (8.7%) 5.4% 0.57 One pt had dexmedetomidine dc’d due to symptomatic bradycardia.

Results

Results

Conclusions Adjunctive dexmedetomidine therapy for benzodiazepine refractory alcohol withdrawal results in statistically significant reductions for incidence of intubation, average number of days of intubation after initiation and ICU LOS. Reduction in ICU stay can be attributed to faster weaning off mechanical ventilation and better control of hyper-adrenergic symptoms Hospital LOS is reduced but statistically significance was not achieved. Dexmedetomidine resulted in higher incidence of bradycardia episodes and seizure episodes although findings are not statistically significant. One of 20 patients on dexmedetomidine suffered two 9-second asystolic pauses, which did not recur after dexmedetomidine discontinuation.

Conclusions Dexmedetomidine proves to be an effective agent for benzodiazepine refractory alcohol withdrawal. Helps to reduce health care costs by minimizing utilization of resources.

Potential for the Future 91.3% cases used dexmedetomidine as escalation therapy for benzodiazepine refractory alcohol withdrawal. This may contribute to the occurrence of adverse events before initiation of dexmedetomidine, increasing inpatient LOS and subsequently increasing healthcare costs. Early initiation of dexmedetomidine alongside conventional sedatives as compared to awaiting an escalation point may help alleviate the hyper-adrenergic manifestations of alcohol withdrawal and lead to better results with respect to LOS, mechanical ventilation, patient comfort and decreased costs.