Ketorolac

Ketorolac: A Detailed Clinical Review

Ketorolac tromethamine is a high-potency non-steroidal anti-inflammatory drug (NSAID) indicated for the short-term management of moderate to severe acute pain. It achieves analgesia through potent inhibition of cyclooxygenase enzymes (COX-1 and COX-2), thereby suppressing prostaglandin synthesis involved in nociception and inflammation. It is non-narcotic, does not induce respiratory depression, and lacks addictive potential—qualities that make it an opioid-sparing alternative in many surgical and emergency settings.

Clinically, it offers opioid-comparable efficacy but with a different side effect profile and without the risks of sedation or dependency. Available in oral, intramuscular, intravenous, and ophthalmic formulations, Ketorolac is adaptable across multiple care environments.

Image source Google

Indications and Therapeutic Use

Ketorolac is reserved for short-term use due to its high gastrointestinal and renal toxicity profile. Common clinical indications include:

• Postoperative pain: Especially following orthopaedic, abdominal, or gynaecological procedures

• Musculoskeletal injuries: Acute sprains, dislocations, and fractures

• Renal colic: Due to its rapid onset and ability to reduce prostaglandin-mediated renal vasodilation

• Dental pain: Management post-extraction or oral surgery

• Ophthalmic use: Control of inflammation post-cataract surgery or allergic conjunctivitis

It is increasingly integrated into Enhanced Recovery After Surgery (ERAS) protocols for its opioid-sparing benefits and contribution to faster patient mobilisation.

Image source Google

Dosing Regimens and Administration

Proper dosing of Ketorolac is essential to minimise adverse effects:

• IV/IM (Adults): 30 mg every 6 hours; max 120 mg/day

• Elderly or <50 kg: 15 mg every 6 hours; max 60 mg/day

• Oral: 10 mg every 4–6 hours; not to exceed 40 mg/day; to be used after parenteral initiation

• Ophthalmic: 0.4%–0.5%, 1 drop 2–4 times/day

Duration of therapy should not exceed 5 days in any case due to cumulative toxicity.

Dose Adjustments in Special Populations

• Renal impairment: Avoid in moderate-to-severe renal dysfunction. In mild impairment, initiate at reduced doses and monitor serum creatinine.

• Hepatic dysfunction: Cautious use in mild liver disease. Contraindicated in advanced hepatic failure due to bleeding risks and impaired drug metabolism.

• Pregnancy: Avoid in third trimester due to risks of foetal renal dysfunction and premature ductus arteriosus closure.

• Lactation: Though low levels appear in breast milk, short-term use may be permissible under medical supervision.

Adverse Effects

Common reactions:

• Gastrointestinal disturbances (nausea, dyspepsia)

• CNS symptoms (dizziness, somnolence)

• Headache

Serious risks:

• GI ulceration and bleeding

• Nephrotoxicity (including acute tubular necrosis)

• Elevations in hepatic transaminases

• Cardiovascular events (hypertension, fluid retention)

• Bronchospasm in NSAID-sensitive asthma patients

Routine monitoring of renal and hepatic function is advisable with repeated use.

Pharmacological Profile

• Bioavailability: IM – 100%; Oral – ~80–85%

• Distribution: High protein binding (>99%)

• Metabolism: Hepatic via hydroxylation and conjugation

• Excretion: Primarily renal (91%)

• Half-life: 4–6 hours (prolonged in renal impairment)

• Onset: Within 30–60 minutes

While Ketorolac has no antimicrobial activity, its analgesic action supports improved patient comfort during infection treatment.

Drug Combinations and Infusion Practices

Common co-therapies:

• Paracetamol: Enhances analgesia via multimodal mechanism

• Opioids: Reduces opioid requirement and related side effects

• PPIs: For gastroprotection in high-risk patients

• Antibiotics: Used concomitantly for symptomatic relief in infective conditions

Infusion considerations:

• Administer in a dedicated line or flush adequately if mixed

• Avoid combination with promethazine or opioids in same syringe

• Maintain adequate hydration

• Monitor renal function, bleeding risk, and blood pressure if prolonged use is necessary

Formulations and Standard Dosing

Formulation	Strength	Route	Dose	Remarks
Tablet	10 mg	Oral	10 mg every 4–6 hours	Use after parenteral form
Injection	30 mg/mL	IV/IM	15–30 mg every 6 hours	Max 5 days of therapy
Eye Drops	0.4%–0.5%	Ophthalmic	1 drop 2–4 times daily	Post-operative ocular use

Drug Interactions

Caution is required when Ketorolac is administered with:

• Other NSAIDs/aspirin: Increased GI and renal toxicity

• Anticoagulants: Enhanced bleeding risk

• Diuretics/ACE inhibitors: Potentiation of nephrotoxicity

• Corticosteroids: Increased risk of GI ulceration

• SSRIs: Potential for platelet dysfunction and GI bleeding

Therapeutic drug monitoring and renal panels are recommended with polypharmacy.

Comparison with Other NSAIDs

Drug	Analgesic Potency	Max Duration	GI Risk	Renal Risk	Formulations
Ketorolac	Very High	≤5 days	High	High	Oral, IM, IV, Ophthalmic
Diclofenac	Moderate	7–10 days	Moderate	Moderate	Oral, IM, Topical, Suppository
Ibuprofen	Mild	Long-term safe	Low	Low	Oral, Suspension, IV
Naproxen	Moderate	Long-term safe	Moderate	Moderate	Oral, Delayed-release tablets

Contraindications and Precautions

• Active GI ulcers or history of GI bleeding

• Renal insufficiency or volume depletion

• Known hypersensitivity to NSAIDs

• Uncontrolled hypertension or heart failure

• Concomitant anticoagulant therapy

• Avoid in paediatrics without specialist guidance

Toxicology and Overdose Management

Symptoms of overdose:

• Gastrointestinal bleeding

• Somnolence, nausea

• Seizures (rare)

Management:

• Gastric decontamination with activated charcoal (early presentation)

• Supportive therapy (IV fluids, PPI administration)

• No specific antidote; haemodialysis ineffective due to protein binding

Clinical Guidelines and Recent Developments

Recent NICE and WHO guidance reaffirm the short-term use of Ketorolac in perioperative care:

• Maximum use: 5 consecutive days

• Preferred as adjunct in ERAS protocols

• New trial data support its role in opioid reduction by 30–40% postoperatively

Summary Highlights

• High-potency NSAID with rapid analgesic onset

• Opioid-sparing option for acute pain

• Strict limitation on duration to minimise toxicity

• High-risk in renal impairment and elderly

• Optimal in post-op and emergency settings when monitored properly

Did You Know?

Ketorolac played a critical role during military conflicts for non-opioid pain relief in field hospitals. Its parenteral availability and effectiveness in trauma made it a strategic analgesic in combat medicine.

References

1. British National Formulary (BNF) 2025

2. NICE Guidelines on Acute Pain Management (2025)

3. WHO Analgesic Ladder Update (2024)

4. FDA Drug Monograph – Ketorolac Tromethamine

5. PubMed – “Systematic Review on Ketorolac Efficacy in Surgery” (2024)

6. ERAS Society Position Statement (2025)

7. Journal of Clinical Pharmacology (2024)