Clinical Guideline Guidelines for the use of opioid analgesics in the management of acute pain in adults Document detail Document location West Kent and MTW Formulary Version 1.0 Effective from July 2017 Review date July 2020 Owner Directorate of Critical Care Author Consultant in Anaesthesia & Pain Medicine Approved by Pain Management Steering Group Date June 2017 MTW Medicines Management Committee May 2017 West Kent Medicines Optimisation Group April 2017 Ratified by Trust Clinical Governance Committee Date 14 th September 2017 Superseded documents Prescribing Guidelines > Central nervous system Guidelines Opioid analgesics in the management of acute pain 2014 Related documents Neuropathic Pain Guidelines Chronic Pain Guidelines Palliative Care Pain Guidelines Change history Date Change details Approved by Version no.: 1.0 Page 1 of 14
Contents Page Abbreviations 2 Aim of guidelines 3 References 3 Oral analgesia flowchart 4 Paracetamol 5 NSAIDs 5 Opioids 5 Alternative opioids (oxycodone, codeine, tramadol, buprenorphine) 6 Patient factors 7 Opioid equivalences 7 Parenteral analgesia flowchart 8 Intravenous (IV) paracetamol 9 Parenteral opioids 9 Opioid patches 9 Naloxone 9 Appendix 1: Additional drug information 11 PRN IV IM SC NSAID PPI SSRI SNRI AKI CKD Abbreviations Pro re nata (as required) Intravenous Intramuscular Subcutaneous Non-Steroidal Anti-inflammatory Drug Proton Pump Inhibitor Selective Serotonin Reuptake Inhibitor Selective Noradrenaline Reuptake Inhibitor Acute Kidney Injury Chronic Kidney Disease Version no.: 1.0 Page 2 of 14
Aim of guideline To provide a general framework that should be widely applicable when prescribing opioid analgesia for the management of acute pain in adults To standardise clinical practice as far as possible - safe and effective practice is likely to be achieved by familiarity Not to undermine the autonomy or freedom of clinicians to make their own decisions regarding the clinical management of patients in their care. References: Core Standards for Pain Management Service in the UK (2015) Faculty of Pain Medication http://fpm.anzca.edu.au/resources/publications 2015 Opioid Aware: A resource for Patients and Healthcare professional to support prescribing of Opioid Medication for pain. http://www.fpm.ac.uk/faculty-ofpain-medicine/opioid-aware Opioids for persistent pain: Good Practice. (2010). http://www.britishpainsociety.org/book_opioid_main.pdf Long-term opioid management for chronic non cancer pain.noble M, Treadwell JR, Tregear SJ, Coates VH, Wiffen PJ, Akafomo C, Schoelles KM. Cochrane Database of Systematic Reviews 2010, Issue 1. http://www.palliativedrugs.com/palliative-care-formulary.html Version no.: 1.0 Page 3 of 14
Oral analgesic flowchart Analgesia should be prescribed orally unless this route is unavailable (e.g. nil by mouth, ileus) Co-prescribe baseline analgesia for all patients unless contraindicated; this will minimise the amount of opioid required to effectively manage pain. Figure 1: Oral analgesia flowchart for acute pain Mild Pain Regular paracetamol +/- regular or PRN NSAID add in Moderate Pain or or Morphine immediate release PRN (1 st line) Codeine phosphate PRN (2 nd line) Tramadol PRN (3 rd line) switch to Regular morphine modified release + morphine immediate release PRN 1 st line Severe Pain or or or Regular oxycodone modified release + oxycodone immediate release PRN 2 nd line (but 1 st line in renal impairment or true morphine allergy) Buprenorphine tablets sublingually PRN 3rd line Fentanyl seek advice from pain team 4 th line Parenteral route should be used for speed of onset of action for chest pain/trauma. Version no.: 1.0 Page 4 of 14
Paracetamol Reduces opioid consumption, good safety profile when taken at therapeutic doses Few contraindications to its use Avoid co-codamol (medication cannot be optimised as easily, risk that paracetamol is prescribed concurrently, codeine is not 1 st line option if an opioid is required). NSAIDs Paracetamol 1g QDS PO Use in addition to paracetamol to further reduce opioid consumption Prescribe at meal times Ibuprofen 400mg TDS PO 1 st line lowest gastrointestinal and cardiovascular risk Naproxen 500mg BD 2 nd line higher gastrointestinal risk than ibuprofen Consider gastric protection for patients prescribed a regular NSAID. e.g. omeprazole 20mg OD Risk factors include: over 65s, concurrent irritant drugs (e.g. aspirin, prednisolone, rivaroxiban), alcoholic liver disease, history of heart burn/ulceration) Contraindications and cautions to NSAIDs include: Ischaemic heart disease, cerebrovascular disease, poorly controlled hypertension, heart failure, renal impairment, hepatic impairment, hypovolaemia and dehydration, unstable asthma, gastritis, coagulopathy or haemorrhage, drug allergy and they should be used with caution in the elderly, patients co-prescribed lithium, methotrexate and warfarin. Opioids First line PRN opioid analgesia in patients with moderate to severe pain should be morphine immediate release. Morphine has a more predictable dose response curve than codeine (see note 1). Morphine immediate release 10-20mg 2-4 hourly PRN Consider 5-10mg 2-4houry PRN in elderly/frail patients Morphine has active metabolites and can therefore accumulate in renal impairment; consider oxycodone/increase dosing interval Opioid use should be reviewed regularly Increase morphine dose in small increments until pain is controlled. Patients requiring significant amounts of PRN opiates should be switched to a regular modified release preparation. This reduces the potential for undue pain and delays in administering PRN medication. Version no.: 1.0 Page 5 of 14
Calculate the total quantity of immediate release opioid administered over the last 24-hour period and divide by 2 to obtain the modified release dose. Remember to add and/or adjust breakthrough pain relief (1/6 th 1/10 th of total daily dose). Example calculation 8 x 10mg doses administered over the previous 24 hours can be switched to: Morphine modified release 40mg BD + Morphine immediate release 10-20mg 2-4 hourly PRN Likewise, patients requiring few PRN opioid doses should be reviewed with the view of weaning pain relief where appropriate. Modified release preparations Prescribe at 12 hourly intervals e.g. 08:00 + 20:00 in order to provide 24 hour cover. Morphine modified release should be 1 st line if a regular modified release opioid is required. Prescribe regular laxatives and PRN anti-emetics for all patients on regular opioids. Alternative opioid preparations Senna 15mg ON Lactulose 10mL BD Cyclizine 50mg TDS PRN Oxycodone A strong opioid Approximately twice as potent as morphine (therefore halve dose if converting from morphine to oxycodone) 5-10mg 2-4hourly PRN Codeine A weak opioid Codeine is metabolised to morphine in order to relieve pain; individuals can vary from poor metabolisers (little or no pain relief) to ultra-rapid metabolisers (excessive amounts of morphine in the blood). 30-60mg 4-6 hourly PRN (max 240mg/hours for pain) Tramadol Weak opioid + modulates serotonin/noradrenaline pathways Caution in patients prescribed other medicines which can inhibit serotonin reuptake potential risk of serotonin syndrome (SSRIs, SNRIs, mirtazapine, MAOs, tricyclic antidepressants) Caution in patients with epilepsy and in patients with other seizure threshold lowering drugs (SSRI, SNRIs, antipsychotics) Tramadol 50-100mg QDS PRN Version no.: 1.0 Page 6 of 14
Buprenorphine A partial opioid agonist Do not prescribe concurrently with other high dose opioids (can potentially precipitate withdrawal) 200micrograms buprenorphine is equivalent to 15mg oral morphine. 200-400micrograms sublingually TDS PRN Patient factors In true morphine allergy consider oxycodone as an alternative opioid. Nausea and vomiting are side effects; consider prescribing antiemetics and laxatives to counteract these. Morphine has active metabolites and can therefore accumulate in severe CKD or AKI. Consider alternative opioid to manage pain and increase dosing interval. o 1 st line - Oxycodone immediate release PRN 4-6 hourly o 2 nd line - Buprenorphine o 3 rd line - Fentanyl (contact pain team for advice) Liver impairment consider dosage of opioid Opioid equivalences Table 1: Oral Opioid Equivalences (RCoA Opioid Aware Project) Drug Potency Ratio with Equivalent Dose to 10mg Oral Morphine oral morphine Morphine 1 10mg Codeine Phosphate 0.1 but variable 100mg Tramadol 0.15 but variable 67mg Oxycodone 2 5mg Drug Table 2: Patch preparation opioid equivalences Patch Size (micrograms/hour) Buprenorphine 5 12mg 10 24mg 20 48mg Fentanyl 12 45mg 25 90mg 50 180mg Oral Morphine equivalent/ 24 hours Version no.: 1.0 Page 7 of 14
Parenteral therapy flowchart Parenteral analgesia should be considered only when the practicality and appropriateness of other routes of administration have been excluded. Parenteral opioids should be administered by staff, who have received appropriate training. Figure 2: Parenteral medication flowchart for acute pain Mild Pain Regular paracetamol add in Severe Pain First Line- Second Line- IV morphine immediate release injection 2mg aliquots titrated up to 10mg 2mg every 5 mins with more given as needed Baseline observations pre-dose Further observations every 5 mins for 30 mins Oxygen saturations, respiratory rate and blood pressure See Note 1 IV oxycodone immediate release injection 2mg aliquots titrated up to 10mg 2mg every 5 mins with more given as needed Baseline observations pre-dose Further observations every 5 mins for 30 mins Oxygen saturations, respiratory rate and blood pressure See Note 4 Consider whether a PCA (patient controlled analgesia) may be suitable contact pain team. Palliative care patients refer to Palliative care team. http://www.palliativedrugs.com/palliative-care-formulary.html Version no.: 1.0 Page 8 of 14
IV Paracetamol Weight >50kg 1g IV QDS Weight <50kg 15mg/kg QDS Weight >50kg with additional risk factors for toxicity 3g/day max (hepatocellular insufficiency, severe renal insufficiency, chronic alcoholism, chronic malnutrition, dehydration) Strong IV opioids Do not prescribe PO/IV. The bioavailability of oral and parenteral opioids are not equivalent; this should be considered and different doses prescribed depending upon the drug (see appendix 1 for additional information). Prescribe PRN anti-emetic s for all patients prescribed regular IV opioids. Transdermal patches Buprenorphine and Fentanyl exist as a transdermal preparation Patches take up to 48hours to reach steady state and also after removal up to 30hours for drug levels to drop 50%. Therefore there is a slow onset and slow offset of analgesia and side effects and are therefore generally unsuitable for the management of acute pain. Fentanyl patches should only be initiated following assessment by the pain team. Heat can increase drug absorption from opioid patches. Monitor for toxicity in febrile patients dose adjustment may be required. Avoid exposing the application site to heat, e.g. a heat pad or hot bath as this can have the same effect. Naloxone All patients prescribed strong opioids (IV and oral) should have when required naloxone prescribed. If respiratory rate is persistently 8 or less and sedation score is 3 or less call the pain team, primary medical team or on-call anaesthetist. Version no.: 1.0 Page 9 of 14
To prepare: Add 1mL of naloxone 400micrograms/mL to 9mL sodium chloride 0.9%. This produces a concentration of 40micrograms/mL. Naloxone should be given titrated 40micrograms (1mL) at a time in approximately 5 minute intervals. Be aware that naloxone will not only reverse opioid side-effects but analgesic effect also. In addition naloxone has a very short half-life and respiratory depression may recur therefore, close monitoring must continue. Naloxone should be given in carefully as side effects include: nausea, vomiting, hypotension, hypertension, tachycardia, headache, dizziness; less commonly diarrhoea, dry mouth, bradycardia, arrhythmia, hyperventilation, tremor, sweating; rarely seizures; very rarely ventricular fibrillation, cardiac arrest, pulmonary oedema, erythema multiforme, and hypersensitivity reactions including anaphylaxis; also reported agitation. Version no.: 1.0 Page 10 of 14
Appendix 1: Additional drug information Morphine First line oral opioid analgesic Metabolised to two metabolites - M3 & M6 glucuronides M6G has analgesic properties as a mu opioid receptor agonist. It crosses the blood/brain barrier more slowly than morphine M3G has no analgesic activity but is primarily responsible for neurotoxic side effects of morphine including hyperalgesia, allodynia & myoclonus Morphine and its metabolites are renally excreted so accumulate in renal failure leading to toxicity. Oral dose is 1-3 times higher than intravenous dose due to low bioavailability Pharmacokinetics: Bioavailability 35% PO Onset of action 30-60 min IM 5-90 min SC Time to peak plasma conc. 15-60 min PO 10-20 min IM/SC Plasma half life 1.5-4.5 hrs PO 1.5 hrs IV Duration of action 3-6 hours Codeine Weak opioid Weak mu agonist Primary action is by metabolism by CYP2D6 by de-methylation - approximately 10% is metabolised to morphine Large variability in metabolism so hypermetabolisers (~5%) get excessive effects and are at risk of narcosis Hypometabolisers (~7.5%) get little benefit from drug but may still get side effects As a result of this highly varied metabolism leading to potential toxicity or lack of effect codeine is no longer recommended for breast feeding mothers or for children as per NPSA warnings. We would recommend that it is not used as first line analgesia for in hospital acute pain. Dose = 30-60mg qds Pharmacokinetics: Bioavailability 40% po Onset of action 30-60 min Time to peak plasma conc. 1-2 hours Plasma half life 2.5-3.5 hours Duration of action 4-6 hours Version no.: 1.0 Page 11 of 14
Tramadol Synthetic centrally-acting analgesic with opioid and non-opioid properties Opioid agonist, serotonin and NA reuptake inhibitor Can be effective treatment for neuropathic pain Can potentiate serotonin syndrome - theoretical risk of precipitating serotonin syndrome if used with other drugs which increase serotonin levels, (SSRIs, TCAs, Pethidine). Presents with tachycardia, mycoclonus, dilated pupils, sweating, shivering & hyper-reflexia. Pro-convulsant: caution with epilepsy, particularly with tramadol IV Can led to hyponatraemia Dose = 50-100mg up to QDS Pharmacokinetics: Bioavailability 65-75% po Onset of action 30 min - 1 hour Time to peak plasma conc. 2 hours Plasma half life 6 hours (doubles in cirrhosis & severe renal failure) Duration of action 4-9 hours Oxycodone Potent opioid agonist By mouth, oxycodone is approximately twice as potent as morphine, (so dose needs to be halved when converting from morphine to oxycodone) Consider switch from morphine to oxycodone if neurotoxic side effects of morphine occur. Oxycodone is renally excreted but has no active metabolites. The dose is unchanged in renal impairment until GFR is <10ml/min Pharmacokinetics: Bioavailability 75% po Onset of action 20-60 min po Time to peak plasma conc. 1-1.5 hours Plasma half life 3.5 hours (4.5 hrs in renal failure) Duration of action 4-6 hours Version no.: 1.0 Page 12 of 14
Buprenorphine Partial mu agonist and kappa antagonist Consider use where oral route to be avoided or for patients in renal failure (second line after oxycodone) No analgesic ceiling effect but respiratory depression ceiling effect 2/3 excreted unchanged, 1/3 hepatically metabolised Not renally excreted so safe to use in renal failure In severe renal impairment (creatinine clearance <10 reduce dose by 25%) Strong receptor affinity so increased doses of naloxone needed to reverse effect Highly lipid soluble making it suitable for transdermal delivery in the form of BuTrans and Transtec patches. These take >48 hours to reach steady state so are unsuitable for use in acute pain It may take 30 hours for levels to drop by 50% after patch removal Sub lingual tablet dose: 200-400 micrograms 6-8 hourly Pharmacokinetics (Sublingual): Bioavailability 30-50% Onset of action 15-45 min Time to peak plasma conc. 30 min - 3.5 hours Plasma half life 24-68 hours Duration of action 6-8 hours Fentanyl Highly potent semi-synthetic opioid Minimally renally excreted (<7%) so safe to use in renal failure Lipid soluble making it suitable for transdermal delivery in form of patches Highly lipid soluble making it suitable for transdermal delivery in form of patches These take >48 hours to reach steady state so are unsuitable for use in acute pain It may take 30 hours for levels to drop by 50% after patch removal Fentanyl can precipitate Serotonin syndrome - theoretical risk of precipitating serotonin syndrome if used with other drugs which increase serotonin levels, (SSRIs, TCAs, Pethidine). Presents with tachycardia, mycoclonus, dilated pupils, sweating, shivering & hyper-reflexia. Version no.: 1.0 Page 13 of 14
Sublingual preparations: Abstral - sublingual fentanyl tablet Can be used when oral route is to be avoided or for patients in renal failure Very rarely required except in palliative care Please seek advice before use from either palliative care or acute pain team Licensed for breakthrough pain (predominantly cancer) for patients on 60mg morphine equivalent/day Dosage needs to be titrated to individual, independently of other opioid analgesia (see flow chart below Figure 3: Sub-Lingual Fentanyl Tablet flowchart Starting dose 100 micrograms Adequate pain relief within 15-30 minutes? Yes No Take a second tablet* Use this dose for further breakthrough episodes * Dose of second tablet if first tablet unsuccessful Increase first tablet to next higher strength for next breakthrough pain episode. 2 tablets total per pain episode First Tablet Second Tablet 100 micrograms 100 micrograms 200 micrograms 100 micrograms 300 micrograms 100 micrograms 400 micrograms 200 micrograms 600 micrograms 200 micrograms 800 micrograms - Version no.: 1.0 Page 14 of 14