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Nonopioid analgesics commonly used for perioperative pain in adults

Drug	Suggested dosing	Timing of administration	Comments
Acetaminophen (paracetamol)	Oral: 325 to 1000 mg every 4 to 6 hours; maximum dose 4 g per day IV: Weight ≥50 kg: 650 mg every 4 hours or 1000 mg every 6 hours, maximum dose 4 g per day Weight <50 kg or with chronic alcoholism, malnutrition, or dehydration: 12.5 mg/kg every 4 hours or 15 mg/kg every 6 hours, maximum 750 mg/dose, maximum 3.75 g/day	Preoperative, intraoperative, and postoperative	Avoid regularly scheduled administration concomitantly with other medications that include acetaminophen (ie, combination drugs), to reduce risk of exceeding daily maximum dose No clinical advantage to IV form pre- and postoperatively in patients able to take oral form IV acetaminophen is contraindicated in patients with severe hepatic insufficiency or severe active liver disease Oral acetaminophen at a reduced dose of 2 g per day is used safely in most patients with cirrhosis or advanced chronic liver disease Avoid use in patients with alcoholic hepatitis or severe active liver disease
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Celecoxib	200 to 400 mg orally preoperatively; 200 mg orally every 12 to 24 hours postoperatively	Preoperative*, intraoperative, and postoperative until hospital discharge	Use with caution or avoid in patients with kidney dysfunction, cardiovascular disease, or peptic ulcer disease Use with caution in those at high bleeding risk, especially those taking concomitant anticoagulants All NSAIDs have US FDA boxed warning for risk of cardiovascular thrombotic events including MI and stroke; risk may be higher for COX-2-selective NSAIDs (eg, celecoxib) NSAIDs are contraindicated for patients having coronary artery bypass surgery
Diclofenac	50 mg orally every 6 to 12 hours, maximum 150 mg in 24 hours
Ibuprofen	600 to 800 mg orally or IV every 6 to 8 hours
Ketoprofen	50 to 75 mg orally every 6 to 8 hours
Naproxen (base)	500 mg orally every 12 hours
Ketorolac^¶	Weight ≥50 kg and age <65 years: 15 to 30 mg IV every 6 to 8 hours Weight <50 kg or age ≥65 years: 15 mg IV every 6 to 8 hours
Meloxicam^Δ	15 mg orally (conventional tablet) or 30 mg IV once per day
Gabapentinoids
Pregabalin	75 to 150 mg orally once (preoperatively); 75 mg orally every 12 hours (postoperatively)	Preoperative, postoperative until hospital discharge for patients with moderate to severe pain	Synergistic respiratory depression when administered with opioids Evidence of perioperative benefit versus risk is uncertain, particularly for gabapentin Use reduced dose in kidney impairment Dose-dependent ataxia and somnolence; use reduced dose or avoid in older adults
Gabapentin	300 to 600 mg orally every 8 hours
Ketamine	Intraoperative: Bolus 0.25 to 0.5 mg/kg IV (maximum 35 mg) followed by an infusion of 0.1 to 0.5 mg/kg/hour (2 to 8 mcg/kg/minute)	Intraoperative; postoperative should be considered if local policy allows	Reserve use for painful surgery in hospitalized patients Consider adding clonidine and low dose benzodiazepine as needed to mitigate adverse effects (eg, emergence reaction, hypertension) Reduce or discontinue 45 to 60 minutes before end of surgery to avoid prolonged emergence Reduce dose in patients with liver disease
Lidocaine	Bolus: 1 mg/kg IBW IV near time of induction Infusion: 1 to 2 mg/kg IBW/hour intraoperatively	Intraoperative; postoperative may be considered if local policy allows and surgery is associated with high degree of inflammation (ie, abdominal surgery, breast, or spine surgery)	Benefit likely limited to 24 hours postoperatively If titrating infusion outside of operating room patient should be in a monitored setting (eg, PACU or ICU) Not consistently shown to worsen cardiac conduction delays Reduce dose in patients with liver disease In underweight patients, use actual body weight to calculate dose
Dexamethasone	4 to 8 mg IV or orally every 8 hours	Preoperative, intraoperative, and postoperative	May improve analgesia and reduce PONV; dosing at higher end of range may be needed for analgesia May prolong duration of peripheral nerve blocks Causes transient hyperglycemia, not associated with increased surgical complications
Alpha-2-receptor agonists
Clonidine	IV: 1 to 4 mcg/kg once Oral: 200 to 300 mcg once Transdermal patch: 0.2 mg/24 hours for patients receiving ketamine infusions for multiple days	Preoperative and postoperative	Used to mitigate adverse effects of ketamine, particularly when ketamine is administered for two days or more or at high doses
Dexmedetomidine	Loading dose, if hemodynamically stable (may be omitted): ≤0.5 mcg/kg IV over 10 to 15 minutes Infusion: 0.3 to 0.7 mcg/kg/hour	Intraoperative and postoperative	Used for patients who undergo very painful surgery and who also have risk factors for emergence delirium (eg, prior history, alcohol abuse) Loading doses greater than 0.5 mcg/kg associated with bradycardia and/or hypotension Postoperative administration should be in a monitored setting (eg PACU); monitoring should continue for one hour after infusion stopped

For further information on management of acute pain, refer to UpToDate content on nonopioid pharmacotherapy for acute pain.

IBW: ideal body weight; IV: intravenous; US FDA: United States Food and Drug Administration; MI: myocardial infarction; COX-2: cyclooxygenase, isoform 2; PONV: postoperative nausea and vomiting; PACU: post anesthesia care unit; ICU: intensive care unit.

* For some surgical procedures, NSAIDs should not be administered until the surgeon confirms adequate intraoperative hemostasis.

¶ UpToDate contributors avoid ketorolac in patients with significant kidney impairment (ie, CrCl <60 mL/minutes) and those at increased risk for acute kidney injury.

Δ Due to its prolonged half-life (ie, ~24 hours) onset of full analgesic effect of meloxicam may be delayed relative to shorter-acting NSAIDs.

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