Joint Trust Guideline for the Management of: Wernicke s Encephalopathy. A clinical guideline recommended for use A+E, Medical and Surgical Wards

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1 A clinical guideline recommended for use In: A+E, Medical and Surgical Wards By: For: All Medical staff Division responsible for document: Divisions 1 and 2 Patients at risk of or with features of Wernicke s Encephalopathy Key words: Wernicke s, Encephalopathy, Alcohol, Withdrawal, Thiamine, Detoxification Name of document author: Mark Tremelling Job title of document author: Name of document author s Line Manager: Job title of document author s Line Manager: Supported by: Assessed and approved by: Consultant Gastroenterologist Francesca Swords Consultant Endocrinologist Date of approval: 04 January 2016 Ratified by or reported as approved to the: To be reviewed before: 04 January 2019 To be reviewed by: Dr Ajay Wagle, Lead Clinician, TADS, NWMHFT Dr Paul Banim Consultant Gastroenterologist, JPUH Approved by Chairs Action 04 January 2016 Clinical Guidelines Assessment Panel (CGAP) Accepted by James Paget University Hospital under the Tri-Hospital Clinical Guidelines Assessment Panel (THCGAP) Clinical Standards Group and Effectiveness Sub- Board Mark Tremelling Reference and/or Trustdocs ID No: JCG0052 ID No: 1352 Version No: 2 Description of changes: No clinical changes new front page and footers added Compliance links: None If Yes does the strategy/policy deviate from the recommendations of NICE? N/A If so, why? This guideline has been approved by the Trust's Clinical Guidelines Assessment Panel as an aid to the diagnosis and management of relevant patients and clinical circumstances. Not every patient or situation fits neatly into a standard guideline scenario and the guideline must be interpreted and applied in practice in the light of prevailing clinical circumstances, the diagnostic and treatment options available and the professional judgement, knowledge and expertise of relevant clinicians. It is advised that the rationale for any departure from relevant guidance should be documented in the patient's case notes. The Trust's guidelines are made publicly available as part of the collective endeavour to continuously improve the quality of healthcare through sharing medical experience and knowledge. The Trust accepts no responsibility for any misunderstanding or misapplication of this document. Joint Trust Guideline for: Management of Available via Trust Docs Version: 2 Trust Docs ID:1352 Page 1 of 7

2 Quick reference Guide Joint Trust Guideline for the Management of: ALGORITHM FOR THE PREVENTION, IDENTIFICATION AND MANAGEMENT OF WERNICKE S ENCEPHALOPATHY ASSOCIATED WITH ALCOHOL MISUSE ON MEDICAL AND SURGICAL WARDS For the use of all Medical Staff (full guideline available on intranet) Is a medical emergency and should be considered in all patients where alcohol misuse is suspected (Associated mortality rates of up to 20% and permanent brain damage (Korsakoff s syndrome) in up to 84% of survivors.) Diagnosis Based on clinical judgement. There are no diagnostic tests. The classical (confusion, ataxia and opthalmoplegia) triad is rare therefore diagnosis is based on the presence of 2 of the following in the presence of suspected alcohol misuse Altered mental state (present in 82% Oculomotor signs (present in 29%) Cerebellar dysfunction (present in 23%) Background of dietary deficiency Treatment Pabrinex IV two pairs of ampoules three times daily for 2-3 days. Ensure magnesium levels are within normal range After 2-3 days if improving continue with one pair of ampoules once daily for 3-5 days until improvement ceases. If no improvement discontinue treatment. Prophylaxis During alcohol detoxification: - Pabrinex 1 pair of ampoules IM or IV daily, for 3-5 days. Give first dose prior to the emergence of withdrawal symptoms. Consider increasing to twice daily for 3-5 days if: Severe alcohol dependence Poor diet Abnormal liver function Not prescribed or not taking oral thiamine treatment Symptoms of peripheral neuropathy / Impaired memory Concurrent physical illness Magnesium deficiency Prophylactic thiamine should also be given to the following groups where alcohol misuse is thought to be implicated:- HYPOGLYCAEMIA thiamine must be given before IV glucose as this can precipitate Wernicke s in those with thiamine deficiency HEPATIC ENCEPHALOPATHY Wernicke s more difficult to diagnose in this high-risk group. Joint Trust Guideline for: Management of Available via Trust Docs Version: 2 Trust Docs ID:1352 Page 2 of 7

3 Objective of Guideline is a medical emergency which should be considered in all patients where alcohol misuse is suspected. This guideline is intended to assist in the assessment and treatment of patients with on medical and surgical wards. Goals To minimize morbidity and mortality and maximize treatment quality through: improving recognition of ensuring prompt initiation of appropriate medical management to reduce mortality and morbidity; particularly progression to Korsakoff s Syndrome. Rationale for the recommendations This guideline has been developed to improve appropriate care and treatment of this specific patient group and is based on a review of current literature. There are very few trials of adequate quality regarding the ideal dose and timing of thiamine as prophylaxis or treatment; therefore the recommendations in this guideline are based on expert opinion from the existing literature 1,2,3. Broad recommendations Recognition and assessment Wernicke s encephalopathy (WE) is a neuropsychiatric disorder of acute onset caused by thiamine deficiency. The consequences of the disorder are significant with mortality rates reported as high as 17% and of survivors 80% progressing to Korsakoff s syndrome 4. In the acute phase the disorder responds rapidly to parenteral thiamine. However once Korsakoff s encephalopathy is established the deficit is permanent Diagnosis Traditionally Wernicke s encephalopathy is described as characterised by a triad of confusion, ataxia and opthalmoplegia. However in studies up to 90% of cases do not present with the full triad and 80% are not diagnosed prior to post mortem 5. The approximate incidence of features of the triad in Wernicke s encephalopathy and additional features of the syndrome are shown below 2. Mental status changes (82%) o Includes confusional state, mental sluggishness, apathy, impaired awareness, poor concentration and coma) Ocular abnormalities: (29%) o (Includes nystagmus, lateral rectus palsies, conjugate gaze palsies sluggish papillary reaction to light, papilloedema, retinal haemorrhages) Incoordination of gait and truncal ataxia: (23%) o (Some also have limb ataxia and dysarthria) Joint Trust Guideline for: Management of Available via Trust Docs Version: 2 Trust Docs ID:1352 Page 3 of 7

4 Additional features Peripheral neuropathy, usually confined to the legs, occurs in majority of cases Stupor pulse, blood pressure, temperature Fits Hallucinations and behaviour change Late signs Raised temperature Increased tone Choreiform dyskinesias Coma Given the poor sensitivity of the triad the following operational criteria have been developed which improve the recognition of the disorder in patients who misuse alcohol 6. Operational diagnostic criteria Two of the Following Four Signs in Patients Who Misuse Alcohol 6 Altered mental state Oculomotor signs Cerebellar dysfunction Background of dietary deficiency These criteria were found to be less sensitive in patients with hepatic encephalopathy who misuse alcohol. However this group is at high risk of and should probably therefore receive parenteral thiamine regardless 2. It should also be noted that the clinical features are difficult to distinguish acutely from signs of intoxication with alcohol and therefore a high index of suspicion should be employed when assessing acute admissions with apparent intoxication particularly in the A+E department 7. There are no diagnostic laboratory tests so the diagnosis is based on clinical suspicion and response to treatment with parenteral thiamine 2. Alcohol misuse is an important but not an exclusive cause of the disorder. It leads to thiamine deficiency by several mechanisms the replacement of vitamin-containing foods by the high calorific value of alcohol, impaired absorption of thiamine from the gut, Joint Trust Guideline for: Management of Available via Trust Docs Version: 2 Trust Docs ID:1352 Page 4 of 7

5 impairment of storage by the liver, decreased phosphorylation to thiamine pyrophosphate and excessive requirements for the metabolism of alcohol. Magnesium Magnesium is a co-factor in conversion of thiamine to its active form (thiamine pyrophosphate). Magnesium deficiency may therefore contribute to development of the disorder and lead to refractory response to thiamine therapy 2. Prophylaxis during alcohol detoxification Thiamine prophylaxis Patients undergoing inpatient detoxification from alcohol should receive prophylactic treatment: Pabrinex 1 pair of ampoules IM or IV daily, for 3 to 5 days 3. The first dose should be given prior to the emergence of withdrawal symptoms. In those with the following risk factors consider increasing to 1 pair bd for 3 to 5 days High risk 4 Severe alcohol dependence Poor diet Abnormal liver function Not prescribed or not taking oral thiamine treatment Symptoms of peripheral neuropathy Impaired memory Concurrent physical illness Magnesium deficiency Oral absorption of thiamine is rate limited in healthy adults and further reduced in those with alcohol dependence. Only 1mg will be absorbed from a single tablet greater than 30mg in a malnourished patient 8. In healthy uncomplicated individuals oral thiamine at a minimum dose of 100mg tds during detoxification may be adequate 3, however few such patients will undergo detoxification in the acute hospital therefore the decision not to use parenteral thiamine should be discussed with a senior member of the medical team. After detoxification oral thiamine 100mg bd daily should be continued for 1 month 9. Joint Trust Guideline for: Management of Available via Trust Docs Version: 2 Trust Docs ID:1352 Page 5 of 7

6 Treatment of established or suspected Treatment should be undertaken on a medical ward. If is suspected or established the following steps should be taken: Give parenteral thiamine IV as two pairs of ampoules Pabrinex three times daily for 2-3 days. Ensure magnesium levels are within normal range After 2-3 days if there is no response discontinue treatment. Where a clinical response has been noted continue with one pair of ampoules once daily for 3-5 days until improvement ceases 2,3. IV Glucose It is mandatory that thiamine should be given prior to IV glucose where Wernicke s Encephalopathy is likely because glucose alone can precipitate the disorder in thiamine deficient individuals. This is vital for patients who present with hypoglycaemia who have been drinking alcohol. Parenteral thiamine administration is generally safe with incidence of significant allergic reaction 0.093% 10 in a series of 989 patients and 0% in a further study of Clinical audit standards a) Patients undergoing alcohol detoxification as inpatients should be prescribed thiamine prophylaxis at a level appropriate to their level of risk. b) Patients identified as established or suspected cases of Wernicke s Encephalopathy should be prescribed treatment at an adequate dose and duration. Summary of development and consultation process undertaken before registration and dissemination The authors listed above drafted this guideline at the request of Dr Phillips, Gastroenterologist. During its development it has been circulated for comment to: the membership of the TADS service governance committee and the NWMHFT Pharmacy Advisory Committee and the Consultant Gastroenterologists at NNUH. Feedback has been incorporated into the submission. Guideline reviewed with the introduction of Trust Docs and found to be current; no changes were necessary. This version has been endorsed by the Clinical Guidelines Assessment Panel. Distribution list/ dissemination method Norfolk and Norwich University Foundation Trust Intranet. Joint Trust Guideline for: Management of Available via Trust Docs Version: 2 Trust Docs ID:1352 Page 6 of 7

7 References/ source documents 1. Day E, Benthan P, Callaghan R, Kuruvilla T, George S. Thiamine for Wernicke- Korsakoff syndrome in people at risk from alcohol abuse. Cochrane Database Syst Rev 2004; 1: CD Sechi G., Serra A. Wernicke s encephalopathy: new clinical settings and recent advances in diagnosis and management Lancet Neurol 2007; 6: Lingford-Hughes AR, Welch S, Nutt DJ (2004) Evidence-based guidelines for the pharmacological management of substance misuse, addiction and comorbidity: recommendations from the British Association for Psychopharmacology Journal of Psychopharmacology 18(3) (2004) Victor M, Adams RD, Collins GH. The Wernicke-Korsakoff syndrome: a clinical and pathological study of 245 patients, 82 with post-mortem examinations. Contemp Neurol Ser 1971; 7: Cook CCH, Hallwood PM, Thomson AD. B-vitamin defi ciency and neuropsychiatric syndromes in alcohol misuse. Alcohol Alcohol Suppl 1998; 33: Caine D, Halliday GM, Kril JJ, Harper CG. Operational criteria for the classifi cation of chronic alcoholics: identification of. J Neurol Neurosurg Psychiatry 1997; 62: Thomson AD, Cook CCH, Touquet R, Henry JA. The Royal College of Physicians report on alcohol: guidelines for managing in the accident and emergency department. Alcohol Alcohol Suppl 2002; 37: Thomson A. D., Mechanism of Vitamin Deficiency in Chronic Alcohol Misusers and the development of the Wernicke-Korsakoffs Syndrome. Alcohol 2000 Alcohol Suppl 35 (suppl1): Raistrick D., Alcohol Withdrawal and Detoxification. In Heather N., Peters T., Stockwell T. (eds) International Handbook of Alcohol Dependence and Problems, 2001 pp John Wiley & sons Ltd.Chichester, UK 10.Wrenn KD, Murphy F, zidovudine Slovis CM. A toxicity study of parenteral thiamine hydrochloride. Ann Emerg Med 1989; 18: Wrenn KD, Slovis CM. Is intravenous thiamine safe? Am J Emerg Med 1992; 10: 165. Joint Trust Guideline for: Management of Available via Trust Docs Version: 2 Trust Docs ID:1352 Page 7 of 7