Ketorolac at Lower Doses for Analgesic Pain Control in ICU: A Pilot Feasibility Study

Exclusion Criteria28

• Serum Cr > 100 mmol/L for females, and >130 mmol/L for males
• Ongoing ACEi (angiotensin converting enzyme inhibitor)/ARB (angiotensin receptor blocker) use in ICU
• Known hyperkalemia > 5.5
• Pre-existing chronic kidney disease (CKD Stage > 3), defined by a serum Cr > 100 mmol/L for females, and >130 mmol/L for males (at the time of screening, based on pre-hospital stable outpatient baseline values)
• New acute kidney injury KDIGO Stage > 2 (increased more than > 2-to-3 times in serum creatinine above baseline AND/OR <0.5mL/kg/hour urine output for >12 hours)
• Pre-existing gastrointestinal bleeding (within 12 weeks of hospital admission, requiring hospitalization or medical evaluation), new peptic ulcer disease, esophagitis, esophageal varices within the last 3 months
• Active gastric / duodenal / peptic ulcer, active GI bleeding
• Prior contraindications/allergies to NSAIDS or stress ulcer prophylaxis, specifically if a participant has had an anaphylactic reaction (asthma or urticaria) or non-anaphylactic asthma reaction to NSAIDs or any stress ulcer prophylaxis, e.g. proton pump inhibitor, histamine-2-blockers, etc. (e.g. proton pump inhibitor, histamine-2-blockers, etc.)
• Complete or partial syndrome of ASA-intolerance (e.g. rhinosinusitis, urticaria/angioedema, nasal polyps, asthma)
• Participants who are not receiving stress ulcer prophylaxis (e.g. proton pump inhibitor, histamine-2-blockers, etc.) while in ICU
• Any active bleeding (requiring any blood products or adjunctive coagulation agents, any output of blood >100 mL/hr, e.g. chest tube drainage, abdominal cavity drain, etc.)
• Currently receiving NSAID(s) for another indication
• Inflammatory bowel disease (e.g. participants with prior diagnosis of Crohn's disease or ulcerative colitis)
• Receiving probenecid, oxpentifylline or pentoxifylline
• Active ischemic heart disease (acute myocardial infarction, acute coronary syndrome during current hospital admission)
• Moderate-severe uncontrolled heart failure (New York Heart Association: Class II-IV)
• Moderate to severe liver impairment or active liver disease (Operational definition: participants with prior history of Child-Pugh class B (moderate) or C (severe) liver cirrhosis, OR Model for End-Stage Liver Disease-Sodium (MELD-Na) score >25, OR active acute liver failure: severe acute liver injury with encephalopathy and impaired synthetic function International Normalized Ratio (INR) >1.5 with or without pre-existing liver disease)
• Active cerebrovascular bleeding or stroke (cerebrovascular accident, transient ischemic attacks and/or amaurosis fugax, e.g. participants with active stroke symptoms within current hospital admission)
• Cerebrovascular bleeding or other bleeding disorders
• Coagulation disorders, post-operative patients with high haemorrhagic risk or incomplete haemostasis in patients with suspected or confirmed cerebrovascular bleeding
• Neuraxial (epidural or intrathecal) administration of ketorolac tromethamine injection due to its alcohol content
• Rhabdomyolysis (creatinine kinase >5000 U/L)
• Recent transplant (during same hospital admission, e.g., heart, lung, kidney, liver, etc.)
• Known allergy to ketorolac or other NSAIDs
• Participants expected to stay in ICU < 48 hours
• In the opinion of the attending physician, expected death or withdrawal of life-sustaining treatments within 48 hours
• Participant is known to be pregnant and/or breastfeeding
• Most responsible physician, participant, or substitute decision maker declines study participation (and reason)