Pain difficult to control, we often do an inadequate job o In burn patients is often severe, and maybe more important than

n other pts o These patients experience pain with burn itself, any procedures, dressing changes, PT o Primary Hyperalgesia at site of burn o Secondary Hyperalgesia inflammation and pain of surrounding intact tissue o Opioid Induced Hyperalgesia talk more about later Pain of burn pt can evolve over time o Covering with grafts or dressing reduces pain o Skin DONOR HARVEST SITES usually associated with MORE PAIN than injury site itself o NEUROPATHIC PAIN as neurons regenerate in deeper burns Approximately 50% of burn patients have LONG TERM OR CHRONIC PAIN WHY DO WE CARE? o Risk poor compliance with rehab, and decreased cooperation with the burn team o Uncontrolled pain associated w/ development of chronic pain, depression, suicidal ideation, and PTSD HOW DO WE TREAT? Main method of combating opioids good relief, but can also induce pain (hyperalg) Others NMDA antagonists ketamine/gabapentin opioid sparing Tylenol-antipyretic, analgesic Methadone technically an opioid, but is synthetic and has different properties Before starting important to think about what changes are taking place in a burn pt o First 48H decrease in organ bloodflow reduced drug clearance o 48h+ - HYPERMETABOLIC state will lead to increased levels of drug clearance, also Vd can change Opioids main method of dealing with pain good relief, but can also induce additional pain o Morphine is the gold standard, drug of choice for background & breakthru pain o Shown to reduce PTSD in burn pts o Opioid tolerance rapidly develops, especially with shorter acting IV forms o Opioid induced hyperalgesia increased pain sensitivitiy throughout entire body after opioid exposure o This is due to increased central sensitization to pain STUDY - pain score and opioid requirements higher in postop pts who received fentanyl intraop occurs thru activation of the NMDA receptors lowers the bodies pain threshold NMDA receptors play a key role in Opioid Induced Hyperalgesia o Ketamine and Gabapentin (antagonists) shown to decrease the incidence of OIH o Another drug with these properties is methadone Methadone o Becoming more commonly used it is a potent and useful analgesic o Can be given in multiple forms oral, IV, subQ as well as spinally and rectally o Well absorbed 80% bioavailability vs 26 for morphine (roughly 3x the bioavailability) o Metabolized in the liver no adjustment needed for renal insufficiency Unlike morphine does NOT have any active metabolites o One of the downsides metabolism and response to methadone can vary significantly between patients Transition to methadone must occur slowly and over several days systemic tox in 3-5d (t=22h) o When is methadone best? Suggested that with opioid tolerance switch to methadone Superior analgesia @ 10-20% of morphine equivalent dose study of cancer pts w uncontrolled pain or intolerable side effects w Op 80% improved w/ metha o Why can we use methadone in morphine tolerant patient? key is that there is incomplete cross tolerance Methadone is a racemic mixture (D/L types) D analgesic properties (mu1, mu2, delta) 10x higher than S Methadone has higher intrinsic activity than morphine at mu receptor Its chemical structure is unrelated to morphine contributes to inhibition of MOA reuptake (5HT and NE) enhances analgesic properties ALSO NMDA antag prevents lowering of CNS pain thresholds and development of tolerance

Dose start with 2.5mg q8 in opioid nave, 2.5 q24h in frail/elderly For opioid tolerant no single ratio can be used to convert morphine methadone, many charts single dose o Approximately 3:1 for <100mg morphine, but up to 20:1 if you are near 1,000 mg morphine o In hospital pts safe to increase dose 20-30% daily, must keep rescue meds nearby Sides like all opioids pruritis, nausea, constipation, confusion, sedation, and respiratory depression o Oral form more commonly associated with DIAPHORESIS and FLUSHING o QT prolongation at high doses can cause lethal cardiac arrhythmia (worsened if hypoK) Cost Savings o Available in tablets and oral solutions o Unlike extended release morphine or oxycodone can be split o Pt on equivalent doses methadone (5mg tid = $8/m), vs ER Opioids (100-176 for morphine, oxy, fentanyl) Concerns o Negative stigma associated with drug use o Variable pharmKinetics, must monitor for side effects (respiratory depression, QT prolongation) Metabolized by the liver altered metabolism in pts with CYP variations, liver disease o Methadone for the patient with a long anticipated recovery, and prolonged ventilator wean