What is the recommended dosing regimen, contraindications, and precautions for ketorolac injection in an adult with acute moderate-to-severe pain?

Ketorolac Injection for Acute Moderate-to-Severe Pain

For adults under 65 years with acute moderate-to-severe pain requiring opioid-level analgesia, administer ketorolac 30 mg IV over at least 15 seconds or 60 mg IM, followed by 30 mg IV/IM every 6 hours (maximum 120 mg/day) for no more than 5 days total. 1, 2

Dosing Regimen

Single-Dose Administration

• Adults <65 years: 30 mg IV (over ≥15 seconds) or 60 mg IM 2
• Adults ≥65 years, renally impaired, or <50 kg: 15 mg IV or 30 mg IM 2

Multiple-Dose Administration

• Adults <65 years: 30 mg IV/IM every 6 hours, maximum 120 mg/day 1, 2
• Adults ≥65 years, renally impaired, or <50 kg: 15 mg IV/IM every 6 hours, maximum 60 mg/day 1, 2

Critical timing note: Analgesic effect begins in approximately 30 minutes with maximum effect at 1-2 hours, lasting 4-6 hours 2, 3. The delayed onset compared to opioids means patients may initially report inadequate relief—wait the full 30-60 minutes before considering rescue analgesia 4.

Maximum Duration

• Never exceed 5 days of total ketorolac therapy (IV/IM plus oral combined) 1, 2
• Switch to alternative analgesics as soon as clinically appropriate 2

Dosing Equivalence

Recent evidence demonstrates that 10 mg IV ketorolac provides equivalent analgesia to 30 mg IV, suggesting the analgesic ceiling is reached at 10 mg 5. However, FDA labeling and current guidelines continue to recommend 30 mg dosing 2. In practice, consider 15-30 mg as the standard dose range for adults under 65 years 1.

Absolute Contraindications

Ketorolac is strictly contraindicated in the following situations 2:

• Active peptic ulcer disease or GI bleeding
• History of peptic ulcer disease or GI bleeding
• Advanced renal impairment or patients at risk for renal failure due to volume depletion
• Suspected or confirmed cerebrovascular bleeding
• Hemorrhagic diathesis, incomplete hemostasis, or high bleeding risk
• Aspirin or NSAID-induced asthma or allergic reactions
• Pregnancy, labor, or delivery (inhibits uterine contractions and affects fetal circulation)
• Coronary artery bypass graft (CABG) surgery setting
• Concurrent use with aspirin or other NSAIDs (additive toxicity without additional benefit)
• Prophylactic use before major surgery
• Intrathecal or epidural administration

High-Risk Populations Requiring Extreme Caution

Elderly Patients (≥60-65 years)

• Use reduced dosing: 15 mg IV/IM every 6 hours, maximum 60 mg/day 1, 2
• Elderly patients have markedly increased risk of serious GI bleeding, especially when high doses are used beyond 5 days 1, 4

Renal Impairment

• Use reduced dosing: 15 mg IV/IM every 6 hours, maximum 60 mg/day 2
• Correct hypovolemia before administering ketorolac 2
• Patients with compromised fluid status, dehydration, or on concurrent nephrotoxic drugs are at increased risk for acute renal failure 1, 2

Cardiovascular Risk

• NSAIDs including ketorolac increase risk of serious cardiovascular thrombotic events, MI, and stroke 2
• Risk may occur early in treatment and increases with duration 2

Bleeding Risk

• Ketorolac inhibits platelet function reversibly 3, 6
• Contraindicated with concurrent anticoagulant/antiplatelet therapy 7
• Monitor for operative site bleeding, particularly in postoperative patients 4

Required Monitoring

Baseline Assessment

Before initiating ketorolac, obtain 1, 7:

• Blood pressure
• BUN and creatinine
• Liver function tests
• Complete blood count
• Fecal occult blood (if indicated)

Ongoing Monitoring

Discontinue ketorolac immediately if 7:

• BUN or creatinine doubles from baseline
• Hypertension develops or worsens
• Liver function tests increase >3× upper limit of normal
• Any signs of GI bleeding appear

For prolonged therapy (approaching 5-day maximum), repeat monitoring every 3 months 1.

Common Adverse Effects

The most frequent adverse effects (occurring in approximately 39% of patients) include 3:

• Edema
• Drowsiness and dizziness
• Gastrointestinal upset (nausea)
• Increased diaphoresis

Ketorolac demonstrates a slightly higher total adverse event rate (74%) compared to placebo (65%), with a number needed to harm of 16.7 8. However, serious adverse events are rare when used according to dosing guidelines 4, 8.

Clinical Efficacy Context

Comparison to Opioids

• Ketorolac provides analgesia comparable to morphine 4 mg IV, meperidine, and pentazocine for moderate-to-severe postoperative pain 1, 3, 4
• For acute low back pain, oral ketorolac was superior to acetaminophen/codeine with fewer adverse events (34% vs 64%) 9, 7
• Unlike opioids, ketorolac does not cause respiratory depression, tolerance, or physical dependence 3

Opioid-Sparing Effects

When combined with opioids, ketorolac reduces opioid requirements by 25-50%, potentially decreasing opioid-related adverse events and facilitating faster return to normal GI function 4, 8

Response Variability

Important caveat: More than 25% of patients exhibit little or no response to ketorolac 7. For breakthrough pain, do not increase dose or frequency—instead, supplement with low-dose opioids unless contraindicated 2.

Multimodal Analgesia Strategy

Ketorolac works optimally as part of multimodal analgesia 1:

• Can be safely combined with acetaminophen (paracetamol) 1 gram IV every 6-8 hours 10
• May be given with opioids (morphine, fentanyl) without adverse interactions 1, 3
• Never combine with other NSAIDs (including ibuprofen)—toxicities are additive without additional analgesic benefit 7

Critical Safety Warning

The risk of serious GI bleeding and renal failure increases dramatically when ketorolac is used at high doses (>120 mg/day in adults <65 years) for more than 5 days, particularly in elderly patients 4. Strict adherence to dosing limits and duration restrictions is essential to minimize these life-threatening complications 2.