Is there a place for oral ethanol in hospital-based alcohol withdrawal management?

Alcohol withdrawal (AWS) results following abrupt discontinuation of alcohol consumption in an individual who is dependent on alcohol. AWS may present with a range of physical and psychological symptoms ranging from sweating, tremor, agitation and palpitations to disorientation, delirium, life threatening tachycardias and seizures. Fortunately, the clinical course of AWS is predictable, can be assessed and monitored, and effectively prevented from escalating. As such the development of alcohol withdrawal related seizures or delirium tremens in a dependent individual while in hospital should be considered a failure of care.

Of those presenting to hospital with  alcohol dependence, AWS is as common, or more common, than complications of other long-term conditions, including diabetes and hypertension [1]. Around 30% of those presenting to hospital with alcohol dependence may develop AWS [2–4], and 1.7% and 1.66% of patients on general medical and surgical wards in the UK are assigned an ICD code for AWS or AWS with delirium, respectively [5].

The vast majority of patients presenting with AWS to emergency departments are successfully managed using standard treatment approaches in accordance with internationally recognised treatment guidelines. Typically, these approaches involve fixed-dose or symptom-triggered regimens of benzodiazepines such as chlordiazepoxide, lorazepam or diazepam. The evolution of alcohol care teams (ACTs) in acute hospital services has vastly improved access to effective patient pathways to address AWS. However, some patients, typically those with very high (> 30 units daily) alcohol consumption histories, do not respond well to escalating doses of benzodiazepines and as such can be considered refractory to standard approaches [6,7]. These patients are often treated with alternative medications including phenobarbital, baclofen, carbamazepine, or clonidine; many of which are used off-license, are not supported by high quality efficacy evidence [8–12], and may require high dependency or intensive care input [13].

We needed to think laterally…

In response to an emerging need to improve the management of severely alcohol dependent patients, the ACT at Sandwell and West Birmingham NHS Trust, in collaboration with senior physicians, incorporated oral ethanol into their alcohol treatment guidelines.

Alcohol, like benzodiazepines, acts as a positive allosteric modulator at GABA_A receptors. These are inhibitory receptors in the brain, that in the presence of alcohol, or benzodiazepines, are turned on, above and beyond their baseline level of activity, resulting in relaxation/sedation. Alcohol also affects other chemical messengers in the brain, including the excitatory neurotransmitter glutamate. Here, it reduces the action of excitatory receptors. In chronic alcohol use there is up-regulation of excitatory glutamate receptors to compensate for the excess inhibitory activity caused by prolonged exposure to alcohol.  The features of AWS reflect this unopposed excess excitation that follows sudden cessation of alcohol (and its inhibitory neurochemical effect). The dual mechanism of action of alcohol at inhibitory and excitatory receptors in the brain may underpin the ability of ethanol to effectively counter the neurochemical imbalance occurring during severe AWS. Furthermore, psychological factors such as salience, familiarity and prior knowledge of efficacy at addressing AWS symptoms (through self-medication of symptoms outside of the hospital setting) likely play a role in the effectiveness of alcohol to manage AWS.

Alcohol is provided at SWB as part of a comprehensive and holistic patient pathway overseen by the ACT. As part of this pathway patients are reviewed within an hour of their arrival to the accident and emergency department by a member of the ACT. During this initial assessment a detailed review of the patient’s alcohol use history and any alcohol-related physical and psychological health condition is undertaken. Alongside this assessment the ACT work with the medical team to optimise any treatment plans, oversee the monitoring and prevention of AWS symptom manifestation and will facilitate discharge and follow-up where appropriate. Only a minority of patients receive ethanol for management of their symptoms; the guidelines recommend its use for those who 1) have a history of alcohol consumption consistent with severe physical dependence (>25 units/day for women, >30 units/day for men), or 2) have a history of AWS related seizures/delirium tremens, or 3) are known to the Alcohol Care Team (ACT) to experience difficult to manage AWS. The ability for patients to demonstrate capacity and the ability to consent to receive ethanol is of paramount importance to the team. 

We wanted to do things properly.

At SWB ethanol is part of the trust formulary and is prescribed as an unlicensed medicinal product following approval by a consultant clinician who is part of the alcohol team. Ethanol for the purpose of AWS management has been reviewed and approved by our local drugs and therapeutics committee. For audit and governance purposes ethanol is handled as a controlled drug within the trust and its use is tracked using an electronic prescribing system. Ethanol is provided at SWB as unit measures of vodka (37.5% ABV). Vodka was selected due to its palatability, ABV strength, familiarity among patients and its comparative price and reduced risk profile compared with alternatives such as absolute vials of medicinal ethanol.

What we’ve learnt so far.

We have published a number of studies that have demonstrated our outcomes from the ethanol prescribing work taking place at SWB. So far we know:

• The current evidence-base in the existing literature surrounding ethanol use for AWS management is limited, and of poor quality [14]. However, among these studies, the majority demonstrate that ethanol is as effective or more effective than alternative treatments.
  
  
• Compared with those managed with benzodiazepines at SWB, patients whose AWS were managed with oral ethanol were less likely to undergo unplanned admission to hospital [15].
  
  
• Oral ethanol treatment did not lead to an increased documentation of seizure activity [15], and is not associated with increased subsequent hospital attendance or admission for an alcohol-related cause in the year following initial treatment compared with those receiving BZPs [16].
  
  
•  Oral ethanol is well received by patients, and is perceived as effective symptom control [17].
  
  
• Oral ethanol prescribing does not appear to lead to alcohol seeking behaviours among SWB’s service-users, and has not been associated with any governance, reputational, or complaints issues [18].

Our hopes for the future (we are not alone!)

Despite the evolving evidence surrounding the use of alcohol as a medicine for AWS and the pressing need to more effectively manage severe AWS in acute settings, no other NHS sites in the UK are currently employ ethanol for AWS. This may, in part, be due to the use of ethanol as a medicine being viewed as controversial by some healthcare professionals and service users.

We have however received a great deal of interest in our work from both service users and healthcare professionals at other NHS sites and community or third sector treatment providers. We have also connected with other non-NHS organisations using tapered alcohol provision for detoxification, and are learning a lot from each other!

Ultimately, we need more evidence to demonstrate cost and clinical effectiveness; this would come from a randomised controlled trial. We are in the process developing a programme of work that will review the acceptability and feasibility of alcohol being used more broadly as a medicine. 

Where you come in!

We have performed some patient and healthcare professional perspectives studies at SWB. However, we would like to know more about both service users’ opinions, and healthcare professionals’ opinions on the use of alcohol as a medicine more broadly. As such we have two national surveys that are now open:

A patient and service user perspectives survey

A healthcare professional perspectives survey

We would also like to hear from healthcare professionals through a more in-depth interview process about the potential concerns, barriers and solutions to overcome these barriers. If you would like to take part in this study please contact: darren.quelch2@nhs.net for more information.

Putting the patient first

Our experience tells us that oral ethanol represents a potential effective solution to prevent the development of life-threatening complications in a group that would otherwise face extended and repeated hospitalisation, and a long-term poor prognosis. We want to share our journey and optimise our practices through an open and transparent conversation with partners. We acknowledge that our practices may be context and service-specific, but also that the potential benefits of translation to broader settings warrants investigation.

Finally, we recognise that the provision of ethanol in a medical context may be considered taboo. However, medicinal ethanol has been used safely and effectively for many years in the management of methanol and ethylene glycol poisoning. Furthermore, we have observed that the volume of alcohol required to effectively control or prevent the escalation of symptoms of AWS in this at-risk population is many times less than the number of units being consumed outside of hospital. As such where sobriety is not the ultimate goal in some patients, an educational, or ‘teachable moment’, harm reduction approach is often employed by the ACT using patient-specific evidence surrounding symptom control and patterns of consumption.

Patient + HCP Perspectives Study Poster