Alcohol Detox: loading or sliding dose better? Gen Hosp Psy Nov 2012


Alcoholism and withdrawal states are common both in acute psychiatric and general medical settings.For last 50 yrs or so benzodiazepines have remained  as first line agents for treating withdrawal states. Cochrane review (2010) demonstrated that benzodiazepines are superior to placebo for all alcohol withdrawal symptoms, particularly seizures. One ongoing debate/difference in practice is about the way we use benzodiazepines.

There are two schools of thought.

1. Loading method:   use  a long-acting agent (e.g., diazepam, onset of action=1–1.5 h, T1/2=20–100 h, plus 36–200 additional h of active metabolites) which is administered until there has been significant improvement in withdrawal symptoms . Benefits:  a. agents with long half-lives will allow for self-tapering b. ease of administration c. avoidance of breakthrough symptoms due to under sedation.d. less risk of seizures.

Example as used in this study: On day 1: Load with diazepam 20 mg by mouth every 2 h × 3 doses. (For parenteral treatment, load with diazepam 10 mg intravenously every 1 h × 6 doses). Hold for excessive sedation or Resp Rate below 10.
Additional diazepam 10 mg by mouth or intravenously may be administered every 2 h as needed for residual withdrawal symptoms (e.g., CIWA-Ar or vital signs alteration suggestive of a hyper adrenergic state, such as Systolic BP above 140, Diastolic BP above 90, Heart rate above 100). Hold for excessive sedation or Resp rate below 10.

2.Symptom-triggered method ( Sliding Scale method) :  Use of short-acting agents (e.g., lorazepam, onset of action=2–4 h, T1/2=10–15 h, no active metabolites) administered in accordance with regular symptom monitoring [e.g., Clinical Institute Withdrawal Assessment for Alcohol-Revised scale (CIWA-Ar)]. Benefits: 1.avoids under or oversedation as need is assessed real time medication given only if required. 2.Faster resolution of symptoms, a reduction in the duration of treatment and quantity of medication use, and earlier discharge from the hospital. 3. less hepatic stress. Criticism: a. “breakthrough” withdrawal b. need for constant monitoring  c. frequent medication administration d. greater risk of developing benzodiazepine dependence.

Example as used in this study: Lorazepam 1 to 2 mg, by mouth or intravenously, may be administered every 2 h as needed for active withdrawal symptoms (e.g., CIWA-Ar above 8 or vital signs alteration suggestive of a hyper adrenergic state, such as SBP above 140, DBP above 90, HR above 100). Hold for excessive sedation or RR below 10.

This study compares these two widely used approaches  in a “real-life” scenario. This is an open, prospective, randomized clinical trial conducted over a 12-month period at two tertiary care medical facilities, Stanford University Medical Center (SUMC) and the Palo Alto Veterans Affairs (PAVA) Healthcare System, in patients who presented with alcohol withdrawal symptoms.The primary outcome measure was the baseline scores and rates of change of the CIWA-Ar. 47 inpatients who presented with alcohol withdrawal symptoms completed the study.The two treatment groups were similar with respect to age, sex, race, body mass index, primary reason for hospitalization, hospital site, hospital service and initial CIWA-Ar score

55.3% of all study patients were free of withdrawal symptoms within 72 h of admission: 69.6% in the loading group and 41.7% in the symptom-triggered group. This difference in proportions, however, did not reach statistical significance (P=.08)There was no significant difference in the average total benzodiazepine usage between the two groups (P=.05), with 103.8 mg (S.D. 71.5) for the loading group and 92.4 mg equivalents (S.D. 103.5) for the symptom-triggered group.There was more rapid resolution of symptoms with the diazepam loading protocol in that a greater percentage of patients were free of symptoms within 72 h in the diazepam group, but the difference was not statistically significant.Limitations

Unblinded design,  small sample size.

Cohort had less over all comorbid medical problems limiting generalisability.

Clinical Practice: Either protocol is efficient in achieving the desired outcome. Having a well defined protocol with strict adherence to the monitoring and prescribing is key to safe and efficient detox in any setting.

Cochrane 2010 review found 1. Comparing different benzodiazepines among themselves, (18 studies included) results never reached statistical significance but chlordiazepoxide performed better 2.In the comparison of fixed-schedule versus symptom-triggered regimens: limited studies to make conclusions (Dappen 2002, Saitz 1994, Spies 2003)

Benzodiazepine loading versus symptom-triggered treatment of alcohol withdrawal: a prospective, randomized clinical trial.Maldonado JR, Nguyen LH, Schader EM, Brooks JO 3rd.Gen Hosp Psychiatry. 2012 Nov;34(6):611-7.

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