Evaluation of a symptom-triggered front-loading detoxification technique for alcohol dependence: a pilot study

AIMS AND METHODS

A pilot study was set up to compare a symptom-triggered ‘front-loading’detoxification technique with the usual fixed dosage method.A group of 23 in-patients with alcohol dependence were randomisedto receive either the intervention technique using diazepamor the standard chlordiazepoxide taper over 10 days.

RESULTS

The intervention group received a mean dosage of 74 mg diazepam(equivalent to 222 mg chlordiazepoxide) compared with 700 mgchlordiazepoxide in those receiving usual treatment. Therewas no statistical difference in the severity of alcohol withdrawalsymptoms in the two groups, and the intervention group wereslightly more satisfied with their treatment than the groupundergoing the usual detoxification treatment. Feedback fromthe nursing staff was positive towards the new approach buthighlighted some potential problems for its wider implementation.

CLINICAL IMPLICATIONS

It was possible to use a simple randomised trial design to introducea new technique for alcohol detoxification to a specialistunit. Symptom-triggered front-loading detoxification usingdiazepam was as effective as a standard taper technique interms of withdrawal severity reduction, and was acceptable toboth patients and staff. This is potentially a useful techniquefor busy acute psychiatric wards.

Introduction

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Introduction

The abrupt cessation of alcohol intake in dependent individualsresults in a withdrawal syndrome. In some cases this may developinto the more serious consequence of delirium tremens, butthis is now uncommon owing to the widespread use of benzodiazepinesto attenuate the severity of the withdrawal symptoms (Mayo-Smith, 1997;Williams & McBride, 1998). Research from the USA,combined with anecdotal evidence in the UK, suggests that themost common method of administering benzodiazepines is by afixed dosage schedule, with or without additional medicationon demand (prn) (Saitz et al, 1995). This means that the dosageof medication used and the rate of reduction are determinedbefore the detoxification process starts. However, because the severity of alcohol withdrawal varies between individuals,these regimens often do not allow individualisation of treatment.Some patients may not receive sufficient medication to preventwithdrawal symptoms, thus putting them at risk of stoppingtheir detoxification programme or experiencing seizures. Othersmay be at risk of over-sedation, and prescribing medication where it is not needed runs the risk of creating a benzodiazepinedependence syndrome in a vulnerable population.

A further disadvantage of fixed dosage regimens is the lengthof time that they take. In cases in which the expected severityof alcohol withdrawal symptoms merits admission to hospital,it is not uncommon for the medication taper to take 5–10days. An alternative is the use of a ‘front-loading’approach, whereby diazepam is administered at intervals of1–2 hours until the patient is asymptomatic (Heinala et al, 1990).Such an approach is refined by using a symptomseverity rating scale such as the Clinical Institute WithdrawalAssessment for Alcohol – Revised version (CIWA–Ar;Sullivan et al, 1989) to assess the severity of withdrawalsymptoms, the results of which dictate the amount of benzodiazepineprescribed. Such regimens may counter many of the problemswith traditional fixed dosage techniques highlighted above,with the added bonus of standardised regular monitoring ofpatients. Furthermore, a number of studies suggest that front-loadingregimens use less medication and have a shorter duration, as well as rein-forcing the fact that many cases of alcohol withdrawalcan be managed without medication at all (Sellers et al, 1983; Wartenberg et al, 1990; Saitz et al, 1994; Wasilewski et al, 1996; Silpakit et al, 1999; Reoux & Miller, 2000).

Although front-loading detoxification techniques have been reported throughout the world, no clinical trial evidence could be foundfrom a UK centre. There are few reports of randomised controlledtrials, and most studies have involved only male patients.Furthermore, it has been usual to exclude patients with a pasthistory of seizures, even though there is other evidence tosuggest that this technique is safe in this patient group (Devenyi & Harrison, 1985).This is significant in the in-patientsetting, as a past history of alcohol withdrawal seizures isoften a reason for choosing a hospital rather than a home detoxificationprocess. Few of the studies reported any evaluation of patientor staff views about the process.

As a way of introducing this technique in a unit that had previouslyonly ever used fixed dosage chlordiazepoxide schedules withoutsymptom monitoring, we devised a randomised controlled trialto compare the new technique with standard practice. It wasdecided to use diazepam because of its long half-life, andso the use of a symptom-triggered regimen within the first 24 hours of the detoxification led to therapeutic concentrationsof the drug being maintained for over 72 hours. Chlordiazepoxidealso has a long half-life, but a regimen using diazepam hadpreviously been shown to be safe and effective by another UKcentre (Williams, 2001).

Method

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Method

The Church Road in-patient unit in Birmingham is a 12-beddedsubstance misuse treatment service with resident psychiatricnursing staff and 24-hour specialist medical cover. Half ofthe beds are dedicated to alcohol detoxification, and admissionrequires at least one of the following five inclusion criteria:

a history of seizures related to alcohol withdrawal;
a historyof delirium tremens;
more than three previous unsuccessfulattempts at home detoxificationin the past;
physical orpsychiatric comorbidity, making community detoxification unsafe;
lack of social support for a community detoxification.

All patients meeting ICD–10 criteria for alcohol dependence (World Health Organization, 1992) and requiring inpatientdetoxification were considered for randomisation during the4-month pilot phase. People dependent on substances other thanalcohol, or with current severe liver impairment or other major physical illness were excluded, and those unable or unwillingto give informed consent to enter the study were given treatmentas usual. All patients attended a pre-admission group meetingduring which the study was explained to them and an informationleaflet was distributed. On arrival at the unit all patientswere assessed with the CIWA–Ar and were invited to jointhe study. If the patient gave informed consent the researcherconducted a short structured interview and administered theSeverity of Alcohol Dependence Questionnaire (SADQ; Stockwellet al, 1983). The researcher then telephoned a remote randomisationservice and the patient was allocated to either symptom-triggeredfront-loading detoxification or usual treatment. The admittingdoctor then completed a full medical assessment, physical examinationand blood tests. The study was approved by the local research ethics committee.

The main outcome measures were the amount of medication usedin each treatment group, the duration of the detoxificationperiod (defined as the time between the administration of thefirst and last medication) and the development of any adverseevents. Other outcomes of interest were the level of patientsatisfaction with symptom control during the detoxificationperiod, and the views of the nursing staff administering themedication. All data analysis was carried out using the StatisticalPackage for the Social Sciences, version 10.0. Continuous variablesthat were normally distributed were compared using a t-test,and non-parametric continuous data were analysed using theMann–Whitney U-test.

Intervention
All qualified nursing staff working on the in-patient unit attendeda training session on how to use the CIWA–Ar, at whichan introductory lecture was followed by a series of video recordingsof patients at various stages of alcohol withdrawal. The staffwere asked to rate these cases using the CIWA–Ar, andthe results were discussed and compared with a gold standardrating. The staff then practised rating patients admitted tothe unit prior to the start of the trial, and the results werediscussed during the weekly ward review.

Participants in the intervention group were assessed every 90minutes using the CIWA–Ar, with each assessment takingapproximately 10 minutes. Those scoring 11 or more received20 mg of diazepam, whereas those with a score of 10 or lessreceived no medication. The process was discontinued when the patient scored 10 or less on two consecutive occasions, afterwhich no further medication was administered. Participantsin the control group received 30 mg of chlordiazepoxide every6 hours on the first day, with the dose tapering to zero accordingto a defined regimen over a 10-day period. Nursing staff were also able to dispense up to an additional 20 mg of chlordiazepoxideevery 6 hours if they judged that the patient required it.The CIWA–Ar was used to assess all patients twice dailyprior to the administration of medication for the first 10days of the period of admission.

Results

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Results

The pilot phase ran for 4 months, and during this time 39 patientswere admitted to the unit for alcohol detoxification. A totalof 16 patients (10 men, 6 women) were excluded from the study:5 were unable or unwilling to give informed consent to takepart in the trial; 4 had severe current mental health problems;3 had alcohol-related liver disease; 2 had completed their detoxificationprior to admission; 1 was dependent on cocaine; and 1 was excludedowing to the lack of a trained CIWA–Ar rater at the timeof admission.

Detoxification process
A total of 23 participants were randomised: 11 to the interventionand 12 to treatment as usual. The characteristics of the twogroups at baseline assessment are shown in Table 1, with thegender mix the only difference reaching statistical significance.Nine of the sample had well-documented evidence of previous seizures related to alcohol withdrawal, and the mean SADQ scoreof the whole sample (40.4) suggested severe alcohol dependence (Stockwell et al, 1983). All 23 participants completed thefull detoxification process, and no one left the unit prematurely.The intervention group received a mean dose of 74 mg of diazepam(equivalent to 222 mg chlordiazepoxide; Bazire, 2000), comparedwith 700 mg of chlordiazepoxide in the control group (P<0.001).The mean length of the detoxification period (as defined byadministration of medication) was 8.2 hours, compared with242 hours in the control group (P<0.001). However, despitethese differences, there was little difference in the severityof alcohol withdrawal between the two groups throughout the10 days studied (Fig. 1). Comparison of the two groups at eachtime point using a Mann–Whitney U-test confirmed thenull hypothesis.

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Table 1. Characteristics of the two treatment groups at baseline assessment

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Fig. 1. Mean daily score on the Clinical Institute Withdrawal Assessment for Alcohol – Revised scale (CIWA–Ar) for patients undergoing symptom-triggered front-loading detoxification ( ${blacksquare}$ ) compared with the usual fixed dosage regimen ( ${diamondsuit}$ ).

Only one patient in the study had any significant complicationsduring the detoxification: this was a 39-year-old woman inthe intervention group who was observed to have a generalisedtonic–clonic seizure during the evening of the firstday of admission to the unit. At this point the level of severity of the patient’s withdrawal symptoms had been measuredevery 90 minutes and no symptom of alcohol withdrawal had beennoted (CIWA–Ar score <5). On more detailed questioningthe patient admitted to a history of heavy zopiclone use whichhad stopped abruptly 2 days prior to admission, and furthermoreshe had experienced epileptic seizures during periods of abstinencefrom alcohol in the past.

Patient satisfaction
At the end of the detoxification period (10 days after admissionto the unit) participants were asked to complete a PatientSatisfaction Questionnaire anonymously. The participants ratedthe number of days out of the past 10 that they had been troubledby 10 different withdrawal symptoms, giving a maximum scoreof 100. The intervention group reported a lower median levelof adverse symptoms than did the group receiving the traditionaldetoxification (14.0 v. 29.5, P=0.267). In addition, the participantsrated their satisfaction with the staff, the medication andthe detoxification process as a whole on a scale of 1 to 10.Despite the shorter period of administration of medicationin the intervention group, their mean satisfaction rating was slightly higher than that of the control group (28.0 v. 27.3, P=0.152).

Nursing staff
Five of the six members of the nursing staff directly involvedwith the care of patients in the study were interviewed todetermine their opinions about the use of symptom-triggeredfront-loading detoxification and its results. Only one memberof staff had been aware of the front-loading detoxificationtechnique prior to the start of the study. All the staff felt that the technique gave the patients better symptom control,and they were positive about the reduced duration of detoxificationand the lower doses of medication used. Participants were alsonoted to be less sedated throughout the detoxification period,and were able to engage in psychological group work at an earlierstage than with the traditional approach. The technique wasfelt to be empowering for nursing staff, giving them more directcontrol over the care of their patients. Many of the problemsanticipated by the nursing staff did not arise, but a needfor ongoing training was highlighted and some problems withlow staffing levels during the trial period were also exposed.

Discussion

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Discussion

This was a pilot study to test the efficacy and feasibilityof introducing a new medical treatment of the alcohol withdrawalsyndrome, and as such it had a number of methodological limitations,including the need to use different medications in the twotreatment groups and the lack of either single or double masking.However, the study clearly demonstrated that the symptom-triggeredfront-loading detoxification technique resulted in less medicationusage and a shorter duration of medical treatment without an increase in objectively measured withdrawal severity or complications. Furthermore, the sample included high proportions of womenand of participants with a history of alcohol withdrawal-relatedseizures. Patients and nursing staff were both satisfied withthe new procedure, and the results were so positive that thepilot was terminated after the initial 4-month phase. It is now hoped that by introducing the technique in the form ofa clinical trial it will be easier to implement it in everydaypractice.

Front-loading detoxification techniques appear to yield potentially significant benefits in terms of bed occupancy. All patientsin this study were allowed to complete the full 3-week in-patientperiod, as this was the duration of admission promised whenthey were initially placed on the waiting list for treatment.However, the reduced length of the medication period with thistechnique allows the option of a much shorter admission period,or less cognitive impairment for patients entering the relapseprevention group programme also available in the unit. Suchtechniques might be well suited to other services such as acutemedical units (Lange-Asschenfeldt et al, 2003), where an initialinvestment in training might be rewarded by shorter durationsof admission.

References

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