Predictors of resistant alcohol withdrawal (RAW): A retrospective case-control study.

BACKGROUND: Benzodiazepine-resistant alcohol withdrawal (RAW), defined by a requirement of ≥ 40 mg of diazepam in 1 h, represents a severe form of withdrawal without predictive parameters. This study was designed to identify risk factors associated with RAW versus withdrawal without benzodiazepine resistance (nRAW). METHODS: A retrospective cohort of adults with severe alcohol withdrawal were screened. Demographic and clinical variables, collected through chart review, underwent logistic regression to select the subset that predicst RAW. RESULTS: 736 patients (515 nRAW, 221 RAW) were analyzed. RAW patients were younger (P < 0.001), male (P = 0.008) Caucasians (P = 0.037) with histories of psychiatric illness (P < 0.001), higher serum ethanol concentrations (P < 0.007), and abnormal liver enzymes (P = 0.01). RAW patients had significantly lower platelets (P < 0.001), chloride (P = 0.02), and potassium (P = 0.01) levels; severity of illness (SAPSII) (P < 0.001) and comorbidity scores (P < 0.001). Caucasian race and male gender were found to be 3.6 and 2.6 times more likely to be RAW. For every 1-unit increase in comorbidity and severity of illness scores, patients were 22% [OR(95% CI) 0.78 (0.66-0.90)] and 4% [0.96 (0.93-0.98)] less likely to be RAW. Patients with a psychiatric history or thrombocytopenia were 2 times more likely [2.02 (1.24-3.30); 2.13 (1.31-3.50), respectively] to be RAW. CONCLUSION: These data demonstrate the predictive ability of a history of psychiatric illness, thrombocytopenia, gender, race, baseline severity of illness and comorbidity scores for developing RAW. Considering these characteristics in early withdrawal management may prevent progression to RAW outcomes.

Prospective Assessment of Inpatient Boxed Warning Prescriber Adherence.

OBJECTIVE: To evaluate medication boxed warning nonadherence in the inpatient setting. METHODS: This was a prospective cohort quality improvement project approved by our institution's Total Quality Council. General medicine and ICU patients 18 years and older were included if they were cared for by a prescriber-led multidisciplinary team that included a pharmacist. Patients were evaluated for medication orders with an actionable boxed warning; if boxed warning nonadherence occurred, the physician's reason was determined. Patients with boxed warning nonadherence were monitored for adverse drug reactions until discharge. RESULTS: A total of 393 patients (224 general medicine and 169 ICU) were evaluated for nonadherence to 149 actionable boxed warnings. There were 293 drugs (175 general medicine and 118 ICU) with boxed warnings prescribed, and more than 50% of these were medications restarted from home. A total of 23 boxed warning nonadherences occurred in general medicine patients, and NSAIDs accounted for 81% of these events. ICU patients experienced 11 boxed warning nonadherences, with nearly 54% from anti-infectives and immunosuppressants. Antipsychotics were the most commonly ordered boxed warning medication class in ICU patients. Reasons for nonadherence included knowledge deficit and an acceptable risk-to-benefit ratio. Two adverse drug reactions occurred from boxed warning nonadherences, both because of a drug-drug interaction. CONCLUSIONS: Boxed warning nonadherence is a concern in the inpatient setting, specifically with NSAID use in general medicine patients and antipsychotic use in ICU patients. More than half of boxed warning nonadherence occurred in medications restarted from home, which emphasizes the need for medication evaluation during transitions of care.

Management of benzodiazepine-resistant alcohol withdrawal across a healthcare system: Benzodiazepine dose-escalation with or without propofol.

BACKGROUND: Severe cases of alcohol withdrawal syndrome (AWS) may not resolve despite escalating doses of benzodiazepines (BZDs). Benzodiazepine-resistant alcohol withdrawal (RAW) is a subset of severe alcohol withdrawal defined by the requirement of ≥40mg of diazepam administered within one hour. Use of adjunct agents, such as propofol, may be beneficial to minimize BZD adverse effects and improve symptom control. While limited evidence suggests propofol as an effective adjunct in AWS through improved sedation, evidence is currently lacking for the addition of only propofol to BZDs for management of RAW. METHODS: Retrospective review of adult patients from January, 2009 to March, 2012 with RAW. Patients were categorized into BZD dose-escalation only or BZD plus propofol. The primary endpoint was time to resolution of AWS. Secondary endpoints included safety outcomes associated with medication use. RESULTS: Of 1083 patients with severe AWS, 66 RAW patients (n=33 BZD only, n=33 BZD plus propofol) met inclusion. Median time to AWS resolution was 5.0 and 7.0 days for BZD only vs. BZD plus propofol (p=0.025). Duration of mechanical ventilation, ICU and hospital length of stay were significantly higher with propofol (p=0.017, <0.001 and <0.001, respectively). Ten patients required intervention for management of propofol-induced adverse reactions. CONCLUSIONS: The addition of propofol for RAW treatment is associated with significant increases in clinical care. While randomized, prospective evaluations are necessary to determine the cause of this association, our data suggests use of adjunctive propofol therapy in RAW is associated with longer and more complicated hospital admissions.