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MMR

MMR. PRESENTER: NAJMI MODERATOR: DR ROHAIDAH. OUTLINE. Case presentation Methadone therapy Effect Analgesic option. MR X, 43 yo Malay Male admitted to HSNZ on 9/11/13 Underlying hepatitis B

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MMR

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  1. MMR PRESENTER: NAJMI MODERATOR: DR ROHAIDAH

  2. OUTLINE • Case presentation • Methadone therapy • Effect • Analgesic option

  3. MR X, 43 yo Malay Male admitted to HSNZ on 9/11/13 • Underlying hepatitis B • Ex IVDU, RVD +ve since 1990 on HAART and PCP prophylaxis, CD4 count on oct 200, under ID visiting f/up, next TCA 10/11/13, on methadone therapy 60mg BD • Smoker, work as lorry driver • ADL independent • Referred from Hospital Hulu Terengganu for acute intestinal obstruction in sepsis. • Presented with generalised persistant abdominal pain for 1 week, described as cramping in nature, non radiating, pain score 10/10, a/w abominal distention and worsening on the day of admmision.

  4. NBO and not passing flatus for 1 week, claimed had constipation for 2/52, a/w nausea, vomiting, LOA, LOW. Low grade fever for 2 days, no chill and rigor • No chest pain/ SOB/altered bowel habit / PR bleed • O/E: alert, concious, not tachypnoeic, dehydrated, febrile temp 38.4 • BP:102/77, PR 90 • Lung : clear, cvs: drnm, • P/A: soft, distended, generalised tenderness, BS sluggish, no palpable mass • PR: No malena, RT- greesnish fluid • FBC: Hb 13/TWC 17.4/plt 234 • BUSEC: urea 19.3/Na 128/K4.1/creat172 Amylase 75

  5. AXR: dilated large bowel, CXR erect: no air under diaphragm • U/S bedside: normal, no free fluid • Admitted to 2EF treated as acute intestinal obstruction ? cause, renal impairment sec to dehydration. • Hydration and started with cefobid and flagyl, iv tramal as analgesic. Referred to PSY team regarding methadone. • In ward, pt was treated conservatively, methadone withold. • Restarted on HAART after d/w medical team-T.stavudine 300mg bd, T. lamivudine 150mg bd, T. nevirapine 200mg bd • Abdominal pain still persist but pain score reducing 6/10, passing flatus and BO after given ravin enema. • On 8/11/13, pt complaint severe abdominal pain,worsening abdominal distention

  6. 8/10/13: Underwent Emergency exploratory laparotomy KIV proceed, done under combined GA + thoracic epidural. • Intraop finding: grossly dilated small bowel till 70cm from ileocaecal junction, noted localised 200cc pus at right side, grossly inflamed appendix but no obvious perforation (possible microperforation), 2 parts of small bowel kinked due to adhesion with slough tissue. Decompression of the bowel done through apendix stump. • No ascites, liver smooth surface, large bowel normal • Postoperatively, thoracic epidural catheter dislodge hence pt started on PCA fentanyl as post op analgesia • Pt complaint untolerable pain at surgical site, pain score 6-8/10, unable to sleep despite on PCA fentanyl

  7. D3 post op, pt started on IVI ketamine 0.1mg/kg/h (dilution 250mg in 50cc), then increased to 0.5mg/kg/h overnight since his pain score still the same and persistant abdominal pain. • On 15/11/13, pt complaint severe abdominal pain, abdomen distended, treated as ileus induced by opiod. PCA fentanyl stopped by surgical team. • Pt started on t.celebrex 200mg bd as analgesic with intermintent bolus of IV tramal on PRN basis as analgesic. • On 17/11/13, pt had severe abdominal pain and BP in lowish side, no urine output and persistant temp spike. Pt devlelope sepsis with required inotropes, started on IVI Noradrenalin d/s 10cc/h • TWC increasing in trend, already completed cefobid and flagyl for 1 week.

  8. Then treated as sepsis sec to HAP, started with IV Augmentin . Referred anaest team for close observation. • Unfortunately , on abdominal pain did not resolve, pain score persistnaly 10/10 and restart PCA fentanyl and given bolus 50mcg. Pain reducing after bolus fentanyl. • 19/11/13 @ 1240H- noted pt gasping and unresponsive, BP unrecordable, ulse not palpable. CPR commmenced immediately for 3 cycle then ROSC which sustained for 5 min. pt asystole again CPR commence another 2 cycle, ROSC but developed PEA and CPR again. • DIL issued and family members not keen for active resuscitation. • Cause of death: sepsis sec to HAP

  9. PERIOPERATIVE PAIN MANAGEMENT IN CHRONIC OPIOD USER

  10. METHADONE • Potent synthetic opiod agonist which well absorbed orally, has long but variable plasma half life. Effect of methadone are qualitatively similar to morphine and other opiod • Fat soluble, bind to a range of body tissues including lung, kidney, liver and spleen such that the conc. Of methadone is much higher in these organ than in blood, there is slow transfer of methadone these store and the blood. • Because of it good oral bioavailability and long half life, methadone is taken in orally daily dose. • Primarily metabolized by liver, 10% administered orally excreted unchanged. The rest is metabolised and inactive metabolite eliminated in urine and faeces, saliva and sweat. • Onset -30min, peak ~3h, half life ~24h, reach stabilisation 3-10d

  11. METHADONE MAINTAINACE THERAPY • INDICATION: to those who dependent on opiod or who had extended period of regular opiod use • CONTRAINDICATION: severe hepatic impairment, severe respiratory depression, acute asthma, acute alcoholism, head injury and raised ICP, ulcerative colitis, biliary & renal tract spasm, pt on MAO • CAUTION: high risk polydrug use, co-occuring alcohol dependence, psychiatric illness, concomitant medical illness • Consist of 4 phases: 1) induction 2)stabilisation 3)maintainence 4) cessation

  12. INDUCTION • Assessment of severity of dependence and level tolerance of opiod • A dose of less or equal to 20mg is safe for 70kg man, even in opiod naïve user as this is the lowest dose at which toxicity has been observed • Observed for 3-4h, if pt is experiencing withdrawal sx at 4h, a supplementary of 5mg can beconsidered • Caution if starting dose of 30mg, specialist consultation needed if starting dose more than 40mg

  13. STABILISATION • Aim to stabilize during 1st 2 weeks of MMT so that pt not oscillating between intoxication and withdrawal • It is desirable if pt reviewed at least once, or preferably twice by experience clinician in the 1st week to assess intoxication from methadone. Increased dose should be considered after assessment. • Do not increase the dose in the 1st 3 days of treatment unless there are sign of withdrawal at the time of peak effect (3-4 h) • Consider increment 5-10mg every 3 days prior to assessment. Total weekly increment should not exceed 20mg. Maximum dose at the end of the week should not more than 40mg.

  14. MAINTAINENCE • Dose should be determined for individual pt but generally higher dose is required for maintenance than is required for initial stabilization. Usually effective maintenance dose are greater than 60mg/day. (60-100mg/day) • Methadone dose in excess of 60mg/day a/w higher retention rates and less heroin used as demonstrated in randomised controlled trial and cohort studies.

  15. CESSATION • Voluntary withdrawal- recommended reducing 10mg/week to level 40mg/day, then 5mg/week • Usually it takes 3months to 2 years after observed pt remained in the treatment with significant reduction in heroin use and criminality. • Dose reduction should be made in consultation with pt and aim to ensure that withdrawal process is completed with safety and comfort. • Regime reducing dose is used to manage withdrawal sx, typically withdrawal will begin to rise as methadone dose fall below 20mg/day. Peak sx within 2-3days after cessation.

  16. EFFECT • TOLERANCE(DSM IV)- it relates to addict as “ the need for markedly increased amount of substance to achieve intoxication or desired effect, and markedly diminished effect with continued use of the same amount of substance • It is due to desensitization, in which the uncoupling of G protien result in receptor that are still expressed on the suface of cell but less responsive to opiate and down regulation, in which internalization of activated opiod receptor through endocytosis actually reduces the number of receptors expressed on the cell surface.

  17. EFFECT • HYPERALGESIA- dramatically increased sensitivity to painful stimuli in chronic opiod abusing pt. it is thought to develop through spinal sensitization to glutamate and substance P • It is also postulated the reaction may result from NMDA receptor agonist action. Therefore, NMDA antagonist have been shown to be effective in reduction of opiod hyperalgesia. Agent such as ketamine is useful in refractory case.

  18. CLINICAL MANAGEMENT • Chronic opiod-abusing pt should be treated in much the same way a chronic pain pt who has become tolerant to opiods. An attempt to calculate 24 h dose and convert to an oral or iv equivalent dose for maintenance should be made. Divide by 24 for estimate pt hourly requirement. • Assume 20-30% increase in acute opiod requirement. • Resumption of the opiate postoperatively is indicated

  19. OPTION

  20. OPIOD • PREOPERATIVELY • Opiod dependent pt scheduled for surgery should instructed to take their usual dose of oral opiod (include methadone) on the morning of surgery. • Fentanyl patch also can be given prior pre operatively. • If pt did not take an opiod at baseline – can administered preoperative equivalent loading dose of morphine or hydromorphine as oral or i.v , either at induction or during operation.

  21. INTRAOPERATIVELY • if pt on fentanyl patch, it should be kept on during surgery. If it is remove <12h before surgery completion, i.v fentanyl infusion is indicated. • if new patch applied intraop, bridging with an agent that having a more rapid onset of action is necessary because of slow onset of transdermal fentanyl patch. • Fentanyl infusion rate can be tapered during patch’s onset of action

  22. POSTOPERATIVELY • Intravenous PCA opiod should be considered with the suggestive dose: • Morphine 2-5mg (bolus ) in 5-15 min interval • Hydromorphine 0.1-0.5mg (bolus) in 5-15 min interval • Fentanyl 10-20 mcg in 5-10 min interval • Epidural route alone is not advisable as post op analgesia because of withdrawal sx will develop owing to lack of systemic opiod. • There is documented use of epidural sulfentanil that succesfully managed pain and prevent withdrawal sx in methadone-dependent pt with cancer.

  23. NON-OPIOD • NSAID – either oral or I.V, primarily useful for somatic pain mild to moderate intensity but usually not effective for neuropathic pain. • Ketorolac -30mg IV every 6h as needed • celecoxib- - 400mg initially, followed by additional 200mg dose if needed on the 1st day. On subsequent days, the recommended dose is 200mg OD. • Acetaminophen (tylenol) – orally 650mg every 4-6h as needed. Reduced dose if acetaminophen containing opiod analgesic also administered.

  24. ANTICONVULSANT • Can be used as adjuvant. Anticonvulsant are effective in treating neuropathic pain even though their exact mecahnism are not fully understood. • Phenytoin: can administered as 1g loading dose for acute pain and maintenance dosage 300mg/day • Carbamazepine: (usu. In chronic pain) can be initiated 100mg/day and increment of 100mg every 3-7days to minimize dizziness. • Gabapentin: can be initited 100mg ON, and 100-300mg increment every 3-5days. (max 3.6g/day). • Pregablin (Lyrica ): orally 75mg BD or 50-100mg TDS. Note that it can cause dizziness, wt gain, somnolence, thrombocytopenia

  25. Most anticonvulsant stated above cause somnolence (more prominent with gabapentin) which may lessen over times as patient acclimate or develop tolerance toward therapy • It is unfavorable to use carbamazepine and phenytoin in HIV pt due its effect on blood count. • Pt on MMT are very sensitive to small changes in the serum conc. of methadone, so it is advisable to avoid use of phenytoin because of its drug interaction profile.

  26. Alpha 2 agonist also useful as adjuvant for pain managemnt • Clonidine: 0.3 mcg/kg I.V bolus preincision followed by 0.3mcg/kg infusion. Also can be added to local anaesthesia for epidural or peripheral nerve block 1mcg/ml. • Ketamine : 0.1-0.5 mg/kg bolus pre incision and followed by 0.1-0.5 mg/kg/h infusion • Lidocaine infusion : 5mg/kg for 30 min resulting pain relief for several day. It inhibit spontaneous C fiber activity a/w inflammation. • Mexiletine : initiate with oral mexiletine 150mg/day, then increase dosage 150mg every 3-5 days up to dosage 300mg three times/day. SE: sedation, dizziness, nausea, tremor. hematological reaction is rare, useful for pt with blood dyscrasias.

  27. REGIONAL • RA target the site of surgery and allow for the administration of lower dose of opiods. • Peripheral nerve block and central neuraxial blockade using LA with or without opiods inhibit conduction of pain and avoid central sensitization and remodelling (neuroplastic changes )in the dorsal horn of the spinal cord, • Have immidiate effect as they result in less perioperative pain, long term analgesia as it decrease risk of develop chronic pain state.

  28. PHYSICAL THERAPIES • TENS (transcutaneous electrical nerve stimulation) – is non drug option for pt with addiction and joint, neck and acute pain but less effective for back pain • Acupuncture - its modulate nerve fiber firing and stimulate release of endorphine. There is more evidence to support the use of acupunture for somatic pain than neuropathic pain. It is safe and viable treatment option for pt with addiction.

  29. THANK YOU

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