PRN acetaminophen Scheduled acetaminophen (e.g. 1 gram q6 - q8) PRN opioid Pain - dose ketamine infusion (0.1 - 0.3 mg/kg/ hr ) +/ - clonidine (0.2 - 0.3 mg q8 - 12hr PO ) or dexmedetomidine PRN opioid Opioid infusion Analgesic ladder for acute non - neuropathic pain in critical illness Persistent moderate - severe pain Resolution of pain Step 1 Step 2a Step 3 Step 4 Step 2b Strategy for designing balanced analgesic regimens. Most patients with pain refractory to PRN acetaminophen will receive PRN opioids (Step 2a), motivated largely by convenience. However, some patients with increased risk of opioid side - effects (e.g. hypercapnia with tenuous respiratory drive) may benefit instead from a combination of acetaminophen plus ketamine infusion instead (Step 2b). Clonidine or dexmedetomidine may be used to amplify the efficacy of ketamine while simultaneously avoiding side - effects (KetaDex). Although not shown here, gabapentin can also play a role as an adjunctive agent within a multi - modal strategy. The Internet Book of Critical Care, by @PulmCrit