Alcohol is a commonly abused substance, and it is important that healthcare facilities properly manage alcohol withdrawal. Studies have found that the most efficient way to manage alcohol withdrawal is to use a symptom-triggered approach and only administer medications if symptoms surpass a specific threshold determined by a clinician administered rating scale. Alternatively, a standard fixed-dose medication regimen can be utilized. This study assessed if a new symptom-triggered protocol, utilizing the Clinical Institute Withdrawal for Alcohol, Revised (CIWA-Ar) scale for the assessment of symptoms, resulted in the anticipated patient outcomes of decreased length of hospital stay, less benzodiazepine administered per patient, and a shorter administration time from first dose of benzodiazepine given to last dose, when compared to the previous standard of care. A retrospective chart review was performed for 70 patients who had been treated for alcohol withdrawal. Patients who were treated with the symptom-triggered protocol had a decreased length of hospital stay when compared to the previous standard of care (−2.62 days, p = 0.0054). Both secondary efficacy outcomes were also statistically significant in favor of the symptom-triggered group. This retrospective chart review adds to the body of evidence supporting the use of symptom-triggered protocols as opposed to fixed-dose protocols in the management of alcohol withdrawal.

In 2010, the percentage of adults aged 18 and over that consumed alcohol regularly was 50.9%.1 More than 8 million Americans are dependent on alcohol, with alcohol abuse being associated with significant morbidity and mortality including increased hospital and ED admissions, violence and other forms of abuse, and suicide.2 Within the Veteran population, 55% report drinking alcohol regularly and 7% reporting heavy drinking, defined as more than 14 drinks per week for men and 7 drinks per week for women.3 With alcohol existing as a frequently used and abused substance, it is important that healthcare facilities properly manage alcohol withdrawal. Failure to do so may result in adverse outcomes such as delirium, respiratory depression, seizures, delirium tremens, coma, or even death.4 

Alcohol withdrawal occurs when the body has developed physical dependence on the substance and the use of the substance is significantly decreased or discontinued. Treatment of withdrawal consists of the administration of a medication that can effectively treat the symptoms of alcohol withdrawal and allow for a more gradual return to CNS baseline. Literature supports that the most efficient means to medically manage alcohol withdrawal is through a symptom-triggered approach where patients are only administered medication when symptoms exceed a certain threshold level as determined through the use of a clinician administered rating scale.6–11 The alternative to this method is through the use of a standard fixed-dose regimen. Although this method is typically effective, severity of withdrawal varies between patients and is difficult to predict. This opens the possibility of patients receiving unnecessary doses of benzodiazepines or conversely, withdrawal symptoms being undertreated. Over-medicating a patient may result in stupor, delirium, or the suppression of the respiratory drive.5 Under-medicating a patient may result in a seizure or delirium tremens.4 In utilizing a symptom-triggered approach as opposed to a fixed-interval approach, medication is given to the effect of meeting the needs of the patient. In this way, if a patient is symptomatic, he or she will be treated and re-evaluated for further treatment. However, if a patient is having a mild withdrawal, he or she does not end up taking unnecessary medications. Many studies have evaluated the symptom-triggered approach versus a fixed-dose type of treatment. Reoux and Miller found that the symptom-triggered protocol group had statistically significantly less benzodiazepine administered, fewer milligram equivalents of medication received, and shorter duration of medication administration compared to a fixed-dose protocol.7 Other studies have found comparable results in favor of a symptom-triggered protocol.8–12 Jaeger, Lohr, and Pankratz found similar results in comparing a symptom-triggered protocol to a fixed-dose one with an additional observation of fewer instances of delirium tremens post-implementation of the symptom-triggered protocol.7 

The practice selected for use at this rural Veterans Affairs Medical Center was a symptom-triggered protocol utilizing the Clinical Institute Withdrawal for Alcohol, Revised (CIWA-Ar) scale for the assessment of symptoms. This scale was chosen for its validity, reliability, and reproducibility in a number of settings.9,13 It was important that the scale selected could be administered quickly by trained clinicians in our Urgent Care, Specialty Care/Telemetry Unit, General Medical Unit, and Acute Psychiatry Unit as alcohol detoxification can occur in any of these units.

This new protocol went into effect June of 2012. This study was designed to assess if the new symptom-triggered protocol resulted in the anticipated patient outcomes of decreased length of hospital stay, less benzodiazepine administered per patient, and a shorter administration time from first dose of benzodiazepine given to last dose, when compared to the previous standard of care.

The protocol development team consisted of two clinical pharmacy residents, clinical pharmacists in internal medicine and psychiatry, and a psychiatrist that acts as consult liaison for the facility. Several members of this team have had experience with protocol initiation, including implementing alcohol detoxification protocols. As mentioned above, the CIWA-Ar rating scale was selected to be the rating scale used at this facility. Not only was it selected due to its validity and ease of reproducibility in a number of medical settings,8,9,13 but also the team considered this scale to be best for both objective and subjective assessment of withdrawal symptoms such as diaphoresis, restlessness, hallucinations, and nausea/vomiting. This allows for the rater to use his or her own clinical judgment as well as allowing the patient to be involved in his or her own care. The rater should be able to gather an accurate assessment of the severity of symptoms, which allows for proper medication administration.

There are several benzodiazepines that can be used to successfully treat alcohol withdrawal but some may be preferred for different patient populations. Previously, at our facility, the typical benzodiazepine of choice had been chlordiazepoxide. However, there are a number of disadvantages to using chlordiazepoxide since many of our patients are of advanced age and may have some degree of liver dysfunction. Chlordiazepoxide has a half-life of 24–48 hours in a healthy patient and this is extended longer as liver function declines. This extended half-life may make it difficult for the clinician and patient to realize when the patient has returned to his/her baseline mental status as chlordiazepoxide has prolonged effects in the body. In addition, chlordiazepoxide has two active metabolites. Repeat dosing allows for accumulation of the medication, thus producing a cumulative clinical effect. This can increase the risks of adverse reactions associated with treatment including iatrogenic delirium and stupor. Lastly, there is no parenteral formulation available.14 Having a parenteral formulation available may be necessary for treatment of a patient who is actively vomiting, unable to swallow, or extremely agitated. Therefore, lorazepam was chosen as the preferred treatment for the new alcohol detoxification protocol because it is not profoundly impacted by liver dysfunction, does not have active metabolites, its elimination half-life is much shorter at 12 hours, and it is available as an intramuscular or intravenous injection.15 

In order to best assess the efficacy of treatment, it was decided that nursing staff would reassess all patients that received any dose of lorazepam 1 hour later. If a patient did not require a dose of medication, the next assessment would take place 4 hours later. The reassessment times were based on what other Veterans Affairs hospitals that utilized a symptom-triggered assessment had in place, as well as on input from the facility's nurse managers regarding their workflow.

Medication cutoff points were also decided by the protocol team. The design of the CIWA-Ar protocol with scores, doses, and times for patient evaluations can be found in Table 1. If a patient has a CIWA-Ar score >30, the nursing staff is to contact the Psychiatrist on Duty or the Psychiatry Consult Team. This is to assess if the patient has something else contributing to the symptomatology outside of alcohol withdrawal (e.g., delirium, psychosis). Other instances where nursing staff are directed to contact the Psychiatrist on Duty or Psychiatry Consult Team include patients that require 4mg of lorazepam per hour for 3 consecutive hours as the patient may be experiencing a more complicated withdrawal, or for patients that develop delirium, marked agitation, hallucinations, or disorientation that would no longer allow the patient to participate in their care and be evaluated by the CIWA-Ar.

Table 1:

CIWA-Ar dosing protocol

CIWA-Ar dosing protocol
CIWA-Ar dosing protocol

Some patients are not able to be evaluated by CIWA-Ar assessments due to psychosis, head trauma, ventilator, or other barriers to communication. These patients are placed on a fixed-dose regimen. However, it is still recommended to use lorazepam and to conduct the taper over 72 hours. Additionally, patients with historically difficult detoxifications characterized by episodes of delirium tremens or seizures could be placed on a fixed-dose protocol at the discretion of the provider in an attempt to prevent these complications before withdrawal symptoms present. In order to expedite the treatment protocol being initiated in a patient, both the CIWA-Ar medications and schedules and the fixed-dose regimen have been designed into an order set in the electronic chart for ease of ordering by the providers. Order sets also include daily vitals, weight, thiamine and folic acid supplementation, as well as the optional referral to the Substance Abuse Treatment Program or Psychosocial Rehabilitation and Recovery Treatment Program that are available onsite. Both protocols run for a maximum of 72 hours, at which point the patient should be discharged or reevaluated for further treatment. It was up to the discretion of the attending provider to reorder the protocol for further alcohol withdrawal treatment if deemed medically necessary.

Before the protocol could be used in the facility, training of clinicians needed to take place. Thirty-two different training sessions were held in 1-hour intervals at the facility. Training was coordinated in conjunction with the head of nurse training at the facility with input taken from nurse managers regarding the best ways to train the staff. Training materials were designed to be interactive for the audience. A presentation was utilized to discuss background information on alcohol abuse and dependence, what the current regimen is and why we are moving to a symptom-triggered approach. It also discussed the anticipated benefits for the patients and the hospital. Most importantly, it introduced learners to the CIWA-Ar scale and how to perform the assessment. All participants in training were given a “Pocket CIWA-Ar” for easy reference on a medical floor and were able to practice their skills with case examples. Cases included both written and video examples of people in various stages of alcohol withdrawal. Training participants were able to score their “patient” and discuss 1) can the CIWA-Ar be used in this patient 2) what score 3) what medication/dose and 4) time until next assessment. Most raters found their scores to be where the protocol team had rated the case examples. By the end of the training session, all raters were utilizing the CIWA-Ar and scoring their cases with consistency.

Seventy patients were randomly selected as part of a retrospective chart review. All patients were identified through the use of the Veterans Affairs electronic medical charting system. Inclusion criteria for this study required that patients be aged 18 years or older and have an admitting diagnosis that included management of alcohol withdrawal between the dates of June 30, 2010 and December 31, 2012. This study did not have any exclusion criteria as it was designed to test the effectiveness of the symptom trigger scale at our hospital and not its efficacy which has already been established with previous studies.

Patients were divided into two treatment groups. The “standard care” group included patients who were treated at this facility for alcohol withdrawal before the initiation of the symptom-triggered protocol under the previous standard of care. The “symptom-triggered group” included patients who were treated at this facility after the initiation of the CIWA-Ar protocol beginning June 1, 2012. This symptom-triggered group includes patients assessed by CIWA-Ar as well as those who were not candidates for CIWA-Ar and placed on the new three-day fixed-dose taper of lorazepam. As patients with alcohol withdrawal are often frequently admitted, patients were allowed inclusion into both groups. If a patient was admitted between June 30, 2010 and May 31, 2012, his/her most recent admission was included into the review as part of the “standard care” group, however if that same patient was admitted on or after June 1, 2012, following the initiation of the symptom-triggered protocol, that admission could be reviewed for the symptom-triggered group.

The primary outcome assessed was length of stay in days on either the medical or psychiatric inpatient unit. Secondary efficacy outcomes assessed included total amount of benzodiazepine administered in lorazepam milligram (mg) equivalents and total duration of benzodiazepine administration from first to last dose received. Table 2 shows the equivalent doses used to convert other benzodiazepines to milligrams of lorazepam.

Table 2:

Benzodiazepine conversion;16 Benzodiazepine equivalent dosing

Benzodiazepine conversion;16 Benzodiazepine equivalent dosing
Benzodiazepine conversion;16 Benzodiazepine equivalent dosing

Safety was also assessed by comparing adverse events of alcohol withdrawal or its treatment between both treatment groups. Adverse events ranged from the more mild events such as sedation and falls to more serious outcomes such as delirium tremens and seizures. This research study was approved by the Institutional Review Board of the University Of Cincinnati in Cincinnati, OH, and the Veterans Affairs Research and Development Committee.

Fifty-two patients total, or 27 per treatment group, were needed for an α of 0.05 and 80% power. Thirty-five patients per group, or 70 patients total, were included in the study in order to allow for more robust statistics. All efficacy outcomes were assessed utilizing a two-tailed t-test. Results were reported as means with a standard deviation. Safety outcomes were assessed utilizing a chi-squared test. A p-value of < 0.05 was deemed statistically significant for all statistical tests.

Seventy charts were randomly selected and reviewed for inclusion into the study. Both groups contained 35 patients. All patients randomly selected for the symptom-triggered group were candidates for CIWA-Ar assessments and the prescribing physician did not feel a fixed-dose taper was necessary due to communication barriers or past withdrawal history. Demographics were similar for both groups (Table 3) in regards to age, past admissions for alcohol withdrawal to this facility, use of illicit substances, and history of delirium tremens or seizure.

Table 3:

Patient demographics

Patient demographics
Patient demographics

The primary efficacy outcome measure of length of stay in number of days was statistically significant in favor of the symptom-triggered protocol (−2.62 days, p = 0.0054). Average length of stay in the standard care group was 7.03 days (5.33–8.72; 95% CI) compared to 4.34 days (3.64–5.04; 95% CI) in the symptom-triggered group.

Both secondary efficacy outcomes were also statistically significant in favor of the symptom-triggered group. On the measure of total amount of benzodiazepine administered in lorazepam milligram equivalents, the mean amount administered in the standard care group was 17.13 mg (12.73–21.53; 95% CI) compared to 7.63 mg (4.55–10.70; 95% CI) in the symptom-triggered group (p = 0.0009). When comparing the duration of benzodiazepine administration, the mean duration in the standard care group was 79.89 hours (55.65–104.12; 95% CI) compared to 22.31 hours (13.38–31.24; 95% CI) in the symptom-triggered group (p < 0.0001).

Regarding safety, there was no significant difference found between the groups in terms of adverse events. Six events were reported in the standard care group compared to five events in the symptom-triggered group (p = 1.0) A summary of all results can be found in Table 4.

Table 4:

Results

Results
Results

Implementing a new protocol within a hospital system can be a challenging and lengthy process. We utilized a dedicated protocol team to act as ambassadors for the new protocol which allowed for providers and other health care workers to know who to ask when questions occurred. It also allowed for the team to act as liaisons between staff, management, and other personnel required to make the protocol a reality.

The protocol team found that in order to successfully change the way our facility was managing patients with alcohol withdrawal, we needed to get the support from key personnel at the facility. This included the Chief of Staff, the Chiefs of the Mental Health and Medical/Surgical Care Lines, the Chief of Nursing, nursing education, nurse managers, and clinical pharmacists. Although there was initial resistance to a change that would be such a large undertaking, the education provided and discussion of patient-centered care helped to move the protocol forward. The team was able to begin training and implement the protocol throughout the facility. From beginning to end, including chart review, this process took about 18 months to complete.

Length of stay was selected as the primary objective of treatment because this is a good marker of the effectiveness, efficiency, and safety of the new protocol. It is beneficial to the hospital to decrease the length of stay to help decrease overall cost. Decreasing length of stay by 2.62 days on average has the potential to save the hospital thousands of dollars per patient. In the symptom-triggered group, 60% of patients' length of stay was less than 1 day and only 3% of patients were treated longer than 3 days which is the automatic stop point of the protocol. In contrast, only 9% of patients had a length of stay less than 1 day in the standard treatment group and 57% of patients were treated longer than 3 days. A limitation of utilizing length of stay as an outcome measure is it could be increased for reasons beyond treatment of alcohol withdrawal. Patients with comorbid medical and psychiatric illness often stay beyond their treatment of alcohol withdrawal for treatment of other conditions. Our facility also offers an inpatient residential substance abuse treatment program; however, a patient often has to wait a couple of days before he or she is taken for admission.

Utilizing total duration of benzodiazepine administration from first to last dose of benzodiazepine dispensed could be seen as a better estimate of duration of alcohol withdrawal treatment since this measures the amount of time treatment with medication was needed and is not skewed as much by other medical and psychiatric illness being treated. During the chart review of patients in the symptom-triggered group, it was found in several instances that a patient may receive one dose of lorazepam on the first day of admission and then did not receive another dose for the remainder of their hospital stay. In the symptom-triggered group 32% of patients received no benzodiazepines and 66% received 3 or fewer doses. In the standard treatment group 3% of patients received no benzodiazepines and 20% received 3 or fewer doses. Overall patients in the symptom-triggered group received fewer benzodiazepines and for a shorter duration, but the flexibility of the new protocol did allow the few patients with more severe withdrawal symptoms to receive higher doses within a shorter time period than would have been allowed with previous fixed-dose strategies.

As noted earlier, there were no exclusion criteria to the study. This was done intentionally to assure that this protocol fit the needs of the patients at this specific institution. Many other studies validate the benefit of utilizing a symptom-triggered approach to treating alcohol withdrawal; however, it is important to verify that the benefits are seen at the facility after the new protocol has been started.

A possible limitation of this study is that the reporting of adverse events is limited to what can be deciphered in a chart review. Adverse events in the standard care group have the potential for underreporting since outcomes such as over-sedation may be considered part of alcohol withdrawal treatment. Also, patients in the symptom-triggered group were required to have routine assessment documented into the chart making the likelihood of adverse events being reported higher. Adverse events found during chart review are reported in Table 5.

Table 5:

Adverse events reported

Adverse events reported
Adverse events reported

It can be challenging and time consuming to initiate an alcohol withdrawal protocol in a federal facility. When compared to the previous standard of care, the implementation of a symptom-triggered alcohol withdrawal protocol has resulted in a significant decrease in length of patient stay, and the amount and duration of benzodiazepine use. No difference was seen in rate of adverse events. This retrospective chart review adds to the body of evidence supporting the use of symptom-triggered protocols over fixed-dose methods when treating alcohol withdrawal.

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