• To ensure opiate dependent individuals are identified and treated adequately and in a timely manner, to allow their presenting problems to be assessed and managed appropriately.

• To guide clinical staff involved in treating opioid dependent patients in hospital who require ongoing management of their dependency.

• To promote safe and appropriate prescribing of opiate substitutes. Appropriate communication with the specialist drug and alcohol team in community is essential to provide seamless care - particularly during admission and discharge.

• Patients should NOT be discharged with opioid substitution therapy (OST) except on advice from specialist drug and alcohol team in community. This guideline does not include palliative patients on methadone for non-OST indications.

This is a controlled document. If you are using a printed copy, check it against the guidelines site to ensure you are using the latest edition. Print copies must be destroyed after use.

Abbreviations

1.1 This guideline aims to manage adult patients admitted to hospital who are opioid dependent (this does not include palliative patients on methadone for non-OST indications). It provides advice on the management of both patients who are currently on Opioid Substitution Therapy (OST) and those who are not.

1.2 The overarching aim for managing this often-complicated group of patients is to stabilise them to allow medical or surgical treatments to proceed while they are admitted to hospital, i.e.: it is not to “detox” patients.

1.3 In the context of patients receiving opioids within these guidelines it is important that the practitioner managing the prescription, dispensing or administration must familiarise themselves with the therapeutic characteristics of the opioid to be prescribed or seek appropriate advice. (NPSA 2008)

1.4 Appropriate communication between key professionals in hospital and in the community, particularly around time of entry to hospital and around discharge, is vital to ensure safe, effective and seamless care, including making appropriate plans for seamlessly and safely continuing Methadone/Buprenorphine prescribing in the community.

1.5 People who use drugs have the same entitlement as other patients to the services provided by the NHS, including access to adequate symptomatic and pain relief, and to proper discharge planning.

1.6 Pregnancy

1.6.1 Opiate withdrawal during pregnancy may induce foetal distress and lead to intrauterine death or premature labour. It is therefore important to prevent pregnant patients from developing a withdrawal state. Please refer to “Substance misuse in Pregnancy” Guideline on the Intranet (Frimley Guidelines). Contact the obstetrics team for further advice.

2.1 Opioid Withdrawal – mostly used to describe the group of symptoms that occurs upon the abrupt discontinuation/separation or a decrease in dosage of the intake of opiate based medications or recreational drugs.

2.2 Opioid toxicity – toxic effects of a potent opioid, including depression of the brainstem, causing unconsciousness and respiratory depression. Acute intoxication is characterised by euphoria, flushing, itching, and constriction of pupils, followed by reduced rate of respiration, hypotension, lowered body temperature, and abnormally slow heartbeat.

2.3 Methadone - a long-acting opiate agonist and it is the drug of choice for opioid substitution therapy in Frimley Health NHS Foundation Trust. It should always be prescribed as the 1mg/mL liquid (sugar free) preparation. Methadone is a schedule 2 controlled drug, it has a high dependency potential and a low lethal dose threshold. It is therefore imperative that appropriate assessment, titration and monitoring are performed during the initiation of methadone.

2.4 Buprenorphine - a partial agonist. It has a higher affinity for opioid mu receptors than almost any other opioid and will displace any residual drug including heroin, methadone and many other opioids. For this reason, starting buprenorphine in an opioid-dependant person may precipitate withdrawal (see appendix 4).

3.1 All suspected opioid-using adult patients must firstly undergo an initial assessment. After this, the management will vary depending on which of the two scenarios the patient falls into. There are two possible scenarios of opiate-using adult patients which may present to hospital:

• Patients established on a programme and receiving OST in the community

• Patients who are NOT enrolled in an OST programme who are misusing illicit

• substances

3.2 Initial Patient Assessment

3.2.1 A full assessment must be completed including:

• A relevant history taken, including that of substance misuse, physical health, psychiatric health, prescribed medication and allergies.

• An examination for:

  • Signs of injection

  • Signs and symptoms of withdrawal (See section 3.5)

  • Signs and symptoms of intoxication

3.3 Patients established on an OST programme (methadone or buprenorphine)

3.3.1 If the patient is receiving OST in the community, it is vital that a reliable drug history is obtained before prescribing ANY methadone or buprenorphine. This should be confirmed with one of the following sources:

• Keyworker in Drug and Alcohol Service / Clinic / Drug Dependence Unit

• Dispensing Pharmacy

• OST Prescriber

• GP

• Hospital that the patient was transferred from (if applicable)

• Prison (if applicable)

3.3.2 The following information should be confirmed for all patients:

• Dose

• Frequency of administration

• Formulation / brand

• If the supply given is supervised or unsupervised by the dispensing pharmacy

• Date and time of the last dose

• Date last prescribed / number of days remaining on FP10MDA

• Date prescription was last collected

• If the patient has any methadone or buprenorphine supply on the ward / at home

• Quantity on ward / at home (and if supplied in advance before weekends/bank holidays)

• Other medicines

• If the patient is on any concomitant weaning regimens under specialist team advice (e.g. codeine or benzodiazepines)

3.3.3 The above details should be clearly documented in the patient’s medical notes or home medication list and only once the above information has been confirmed, should the drug be prescribed on the patient’s drug chart.

3.3.4 It is dangerous to prescribe methadone without confirming the dose or seeking expert advice because the dose of methadone prescribed to many patients would be lethal to a non-tolerant individual. There is also the risk of duplicate prescriptions.

3.3.5 The appropriate agency, GP and dispensing pharmacy should be notified when the patient is discharged (See section 4.0).

3.3.6 If a reliable drug history cannot be obtained e.g. patient admitted out of hours, and if the patient is displaying objective signs of withdrawal, then please refer to section 3.4 and prescribe OST in the same manner as if the patient was not on OST prior to admission. Methadone should not be initiated within 24 hours of the patient’s admission and the patient should be treated symptomatically. (see section 3.6)

3.3.7 Do not give in to pressure to prescribe a higher dose that the patient might be claiming to be taking in community. 30mg in 24 hours is sufficient to reduce withdrawal symptoms safely until a reliable drug history can be obtained (harm-minimalisation dose).

3.3.8 If an established OST patient has missed more than 72 hours of treatment, they may need a reduction or re-titration of their usual dose. During working hours, contact the patient’s Drug and Alcohol Team (D&A) for further advice (See section 6.0).

3.4 Patients NOT enrolled in an OST programme (methadone or buprenorphine) OR on an established OST programme but has missed > 72 hours of treatment

3.4.1 If patients are not currently enrolled in a substitution programme in the community, consider prescribing substitution therapy whilst an inpatient if the following criteria apply:

• Patient is using opioid drugs on a regular basis (typically daily)

• Convincing clinical evidence is present to indicate that the patient is opiate dependent (including clinical history/examination findings indicative of opiate dependence, or using the COWS score – See Appendix 1).

• The patient provides informed consent to treatment. A full discussion should be entered into with the patient detailing the issues surrounding substitution therapy and the options available including risk of overdose and the importance of compliance with treatment.

• The local D&A teams may be able to visit the patient as an in-patient if the patient wishes to commence on OST. They may be able to assess the patient and commence OST whilst the patient is still an in-patient. Contact the D&A team for further advice.

3.5. Signs and Symptoms of Opioid Withdrawal

3.5.1 Patients may present with opioid withdrawal signs and symptoms. See Table 1 for opioid withdrawal signs and symptoms. For safety, rely more on objective signs rather than subjective signs i.e. what the patient says.

Table 1: Opioid withdrawal signs and symptoms

3.5.2 Untreated heroin withdrawal symptoms typically peak 32-72 hours after administration of the last dose and symptoms will have subsided substantially after 5 days.

Note: Opioid withdrawal is NOT a life-threatening condition however opioid toxicity is. Prescribe methadone with caution.

Table 2: Signs of Opioid toxicity

3.6 When to Initiate Methadone on Admission

3.6.1 Methadone should not be initiated within 24 hours of the patient’s admission and the patient should be treated symptomatically. If methadone is initiated, discontinue benzodiazepines and zopiclone if used for symptomatic treatment. See Table 3 for drugs used to treat symptoms.

Table 3: Drugs to treat symptoms

3.6.2 Methadone should only be initiated within 24 hours of the patient’s admission providing that:

• The patient is exhibiting signs of withdrawal (e.g. severe agitation) - the COWS scale may be used to determine this

• They are not drowsy, intoxicated or suspected to be using illicit substances while an in-patient.

3.7 How to Initiate Methadone on Admission

3.7.1 After 24 hours of admission, assess the severity of the patient’s withdrawal symptoms. The COWS tool under flowsheets on Epic may be useful to assess severity (See Appendix 1 for information on how to access the flowsheet on Epic and see criteria included in flowsheet in Appendix 2).

3.7.2 If withdrawal symptoms are severe and require treatment**,** prescribe 30mg once daily of Methadone 1mg/mL sugar-free oral liquid (harm-minimalisation dose). Continue to monitor withdrawal symptoms and reassess 4 hourly. The COWS tool may be useful for assessing this.

3.7.3 If symptoms are not controlled despite administering methadone, then seek advice from the appropriate D&A Team (See section 6.0). If the daily dose of methadone needs to be increased this can ONLY be done upon advice from a D&A Team within working hours. Ensure any changes in dose and the rationale are documented clearly in the medical notes.

3.7.4 Ensure naloxone (opioid reversal agent) is prescribed for any patients prescribed methadone. (see “Management of Opioid Induced Respiratory Depression” Guideline for dosing details – Frimley Guidelines)

3.7.5 If methadone is initiated, discontinue benzodiazepines and zopiclone if used for symptomatic treatment.

3.7.6 In cases of overdose/suspected overdose, patient must be observed for a period of up to 72 hours because of long half-life of methadone. Be prepared to give repeated large doses of naloxone (see BNF or guidance linked above).

• Be aware of possibility of illicit drug use on the ward.

• Poly-drug and alcohol misusers may develop multiple withdrawal symptoms- which methadone may mask.

• CARE especially in head injury, liver disease and respiratory depression.

3.8 OST Cautions (Methadone)

3.8.1 Intoxication

Methadone should not be given to any patient showing signs of intoxication. Risk of overdose is greatly enhanced when methadone is taken concomitantly with alcohol or other drugs causing respiratory depression. Risk factors for respiratory depression during induction are:

• Low opiate tolerance

• Concomitant use of CNS depressant drugs (e.g. benzodiazepines, alcohol)

• High starting dose

• Rapid dose increase

• Slow methadone metabolism - this can be affected by drug interactions. Some drug interactions reducing the effect of Methadone include Carbamazepine, Phenytoin and Rifampicin (See appendix 3 for more interactions).

3.8.2 Severe hepatic or renal impairment

• Both metabolism and elimination of methadone may be affected.

• Due to the extended plasma half-life, the time interval between assessing the patient for withdrawal symptoms may need to be extended

• In severe hepatic impairment a dose reduction or increase in interval between doses may be required. Liaise with the drug and alcohol teams.

• In severe renal impairment (eGFR <10mls/min) a dose reduction of 50-75% is advised and doses titrated cautiously to response as per Renal Drug Database

3.8.3 Risk of QTc interval prolongation/torsade de pointes

• Methadone can cause QTc interval prolongation which is associated with torsades de pointes and sudden cardiac death.

• Methadone used in combination with other QTc interval prolonging agents increases this risk further.

• Consider performing a baseline ECG on patients newly initiated on methadone and in patients:

  • On high dose methadone (>100mg/day)

  • With heart or liver disease

  • Electrolyte disturbances

  • On other medications which cause QTc interval prolongation

  • Or on concomitant therapy with CYP3A4 inhibitors.

• See Table 4 for guidelines on ECG monitoring

Table 4: Guidelines for ECG monitoring for patients receiving methadone

3.9 OST Cautions (Buprenorphine)

3.9.1 Interchangeability of brands

• Clarify formulation/ brand during drug history process.

• Lyophilisates and sublingual tablets are not interchangeable - lyophillosate (Espranor ®)

has a higher bioavailability than the sublingual tablets. Seek specialist advice if a switch is required.

3.9.2 Precipitated withdrawal

• The high affinity of buprenorphine for opioid receptors means it can displace (knock) other opioids off opioid receptors.

This leads to a drop in opioid effect which can cause symptoms of withdrawal in opioid-dependent patients starting on buprenorphine.

3.8.3 Risk factors for buprenorphine

• As with methadone, concomitant use of buprenorphine with:

  • benzodiazepines

  • alcohol

  • other CNS depressant drugs

can produce fatal opioid overdose, most commonly in individuals who lack opioid tolerance.

• Drug interactions can slow or speed buprenorphine metabolism or can potentiate toxicity.

• Buprenorphine is largely metabolised in the liver and the medicine’s information recommends baseline testing and then regular monitoring of liver function

3.8.4 Contra-indications

• Severe respiratory insufficiency

• Severe hepatic insufficiency

• Acute alcoholism or delirium tremens

• Hypersensitivity to buprenorphine, naloxone or to any of the ingredients

• Patients suffering chronic pain for which additional opioid analgesia is frequently used

4.1. Patients MUST NOT be discharged with a supply of methadone or buprenorphine if used for OST. This guideline does not include palliative patients on methadone for non-OST indications. Only in exceptional circumstances under the advice of the D&A team, can a limited supply of OST be given. This must be clearly documented in the patients notes, including the D&A team and keyworker who has authorised this supply. Discharges should be planned as early as possible.

4.2. If the patient wants advice on how they can be entered into a local programme the patient should be advised to contact their local drug service. Patients should be made fully aware of their discharge arrangements with regards to their methadone treatment.

4.3. For patients who are discharged with additional opioid analgesia, be mindful of duration and the quantity supplied.

4.4. Patients already receiving substitutive pharmacotherapy

4.4.1 The relevant community provider (D & A Team and community pharmacy) should be contacted during discharge planning to arrange for the patient to reinitiate their normal supply arrangements.

4.4.2 The patient should be directed as to where they should attend on discharge to obtain a prescription for their OST; this is usually their normal provider.

4.4.3 The patient should be given a printed copy of their electronic discharge letter and AVS (must include dose and time of last dose administered in hospital) to take with them when attending a community service to obtain a supply of OST.

4.4.4 If there are any concerns regarding obtaining supplies of OST on discharge, this should be discussed with the ward pharmacist.

4.4.5 Discharge over the weekend or bank holidays

• D&A team are not contactable out of hours.

• The patient should be administered their dose of methadone by the nursing team before the patient is discharged from hospital

• The patient would need to come back to the ward daily for supervised consumption, until the D&A team is open and can continue the patient’s methadone supply.

• The patient must be left as “In-Transit” on Epic so that the nursing team are able to sign and administer the methadone prescription for the patient.

• The patient must be informed to contact their D&A team when they are open again, for further methadone supplies

4.5 Patients with No Fixed Abode (NFA)

• Involve the Discharge Co-ordinator as soon as possible to plan for discharge. The patient DOES NOT require a GP to be on an OST program. To aid identifying a D&A team local to the patient, check where the patient will be going post-discharge or if there is a record of recent GP registration.

• Liaise with Local D&A team/ key-worker IF the patient was on an established OST prior to admission.

4.6 Patients being discharged into police custody on OST

• Thames Valley Police (TVP) do not have prescribers and are unable to prescribe OST

• TVP can collect and administer doses of OST if detailed in the TTA

• Liaise with the community D&A team as per discharge process above and only supply OST as per the advice of the D&A Team.

• The discharge letter would need to confirm/explain that the pharmacy that they usually collect OST from has been informed as well as the community prescriber to avoid the risk of double dosing if a patient were to leave custody and then collect their normal dose.

• The appropriate police department can be contacted via switchboard if needed.

• For Surrey Police or Hampshire Police, discuss with the relevant police station the patient is in custody with at the time of discharge.

5.1 Acute pain requires full analgesic management in patients dependent on opioids. These patients may have a lower tolerance of pain together with a higher tolerance of opioid analgesic effects. If pain is mild to moderate, non-opioid analgesia (Paracetamol, NSAIDs) is the initial treatment of choice.

5.2 For more severe pain or chronic pain, if opioid analgesia is indicated, pain relief should be prescribed in addition to the usual opioid treatment dose and the amount of pain relief medication titrated against pain while monitoring respiratory function. AVOID increasing the patient’s methadone dose.

5.3 In cases where patients are achieving inadequate pain control/ sedation and are receiving concomitant OST, pharmacy or the pain team should be contacted for advice.

5.4 For patients on OST experiencing continuing pain, it is recommended that the daily dose could be divided as part of the wider pain management plan – taken 8 or 12 hourly. Review pain control regularly and revert to once daily dosing of their OST as soon as possible. The patient must be changed back to ONCE daily of their OST on discharge.

5.5 If the patient is on buprenorphine, be cautious of precipitated withdrawal (See section 3.9). Seek specialist advice (D&A team, Pain Team or Pharmacy).

Drug & Alcohol Teams

Contact details are available on public facing websites but have been included in this guideline for convenience.

1. Click on flowsheets

2. Click on the search in the right-hand corner of the page as shown below, this will bring up a pop-up screen for different flowsheet templates

3. Select the Database list from along the panel below the search bar then type COWS and enter to search for flowsheet. Select “BH CLINICAL OPIATE WITHDRAWAL SCALE”.

List of criteria in flowsheet on Epic.

On Epic, for each item - write in the number that best describes the patient’s signs or symptom. Rate on just the apparent relationship to opiate withdrawal. For example, if heart rate is increased because the patient was jogging just prior to assessment, the increased pulse rate would not add to the score.

Enter scores at time zero, 30min after first dose, 2h after first dose, etc.

Total Score:

5-12 = mild;

13-24 = moderate;

25-36 = moderately severe;

more than 36 = severe withdrawal

Appendix 4: Buprenorphine products