Summary
Synopsis
Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) with strong analgesic activity. The analgesic efficacy of ketorolac has been extensively evaluated in the postoperative setting, in both hospital inpatients and outpatients, and in patients with various other acute pain states.
After major abdominal, orthopaedic or gynaecological surgery or ambulatory laparoscopic or gynaecological procedures, ketorolac provides relief from mild to severe pain in the majority of patients and has similar analgesic efficacy to that of standard dosages of morphine and pethidine (meperidine) as well as less frequently used opioids and other NSAIDs. The analgesic effect of ketorolac may be slightly delayed but often persists for longer than that of opioids. Combined therapy with ketorolac and an opioid results in a 25 to 50% reduction in opioid requirements, and in some patients this is accompanied by a concomitant decrease in opioid-induced adverse events, more rapid return to normal gastrointestinal function and shorter stay in hospital.
In children undergoing myringotomy, hernia repair, tonsillectomy, or other surgery associated with mild to moderate pain, ketorolac provides comparable analgesia to morphine, pethidine or paracetamol (acetaminophen).
In the emergency department, ketorolac attenuates moderate to severe pain in patients with renal colic, migraine headache, musculoskeletal pain or sickle cell crisis and is usually as effective as frequently used opioids, such as morphine and pethidine, and other NSAIDs and analgesics. Subcutaneous administration of ketorolac reduces pain in patients with cancer and seems particularly beneficial in pain resulting from bone metastases.
The acquisition cost of ketorolac is greater than that of morphine or pethidine; however, in a small number of studies, the higher cost of ketorolac was offset when treatment with ketorolac resulted in a reduced hospital stay compared with alternative opioid therapy.
The tolerability profile of ketorolac parallels that of other NSAIDs; most clinically important adverse events affect the gastrointestinal tract and/or renal or haematological function. The incidence of serious or fatal adverse events reported with ketorolac has decreased since revision of dosage guidelines. Results from a large retrospective postmarketing surveillance study in more than 20 000 patients demonstrated that the overall risk of gastrointestinal or operative site bleeding related to parenteral ketorolac therapy was only slightly higher than with opioids. However, the risk increased markedly when high dosages were used for more than 5 days, especially in the elderly. Acute renal failure may occur after treatment with ketorolac but is usually reversible on drug discontinuation. In common with other NSAIDs, ketorolac has also been implicated in allergic or hypersensitivity reactions.
In summary, ketorolac is a strong analgesic with a tolerability profile which resembles that of other NSAIDs. When used in accordance with current dosage guidelines, this drug provides a useful alternative, or adjuvant, to opioids in patients with moderate to severe pain.
Pharmacodynamic Properties
As a nonsteroidal anti-inflammatory drug (NSAID), ketorolac possesses analgesic, anti-inflammatory and antipyretic activity. The major mechanism by which ketorolac and other NSAIDs exert their pharmacological effects is inhibition of prostaglandin synthesis. NSAIDs are most active in the periphery but recent evidence suggests they may also act centrally.
In animal models of pain, ketorolac generally appears to have less analgesic activity than morphine; however, in single-dose clinical trials, it provided analgesia similar to that of morphine and other opioids. Ketorolac is significantly more effective than aspirin and paracetamol (acetaminophen), and at least as effective as pethidine (meperidine), ibuprofen or paracetamol combined with codeine or hydrocodone in the human dental pain model (extraction of third mandibular molars).
By virtue of its effect on prostaglandin synthesis, ketorolac may prolong bleeding times by inhibiting platelet aggregation. No significant differences in thromboelastographic parameters or prothrombin or partial thromboplastin times were evident between ketorolac and placebo recipients. This same mechanism of action may result in gastrointestinal (GI) ulceration or other adverse effects, either by a direct irritant effect or indirectly by decreasing prostaglandin-dependent gastric acid inhibition. However, the mucosal damage in the stomach of healthy volunteers induced by ketorolac 30mg intramuscularly is less than that seen with oral aspirin 650mg daily.
In patients with prostaglandin-dependent renal blood flow, the administration of ketorolac may adversely affect kidney function; this is minimal in patients without hypovolaemia or other risk factors for haemodynamic compromise. In one study in postoperative patients, no treatment-related changes in renal function occurred after treatment with ketorolac or placebo; however, significant differences between baseline and postoperative days 1 and 2 were seen in both treatment groups.
In contrast to opioid drugs, ketorolac does not alter gastric motility or haemodynamic variables or adversely affect respiration, nor is it associated with adverse CNS effects, abuse or addiction potential.
Pharmacokinetic Properties
The oral bioavailability of ketorolac is about 80 to 100%, and peak plasma concentrations (Cmax) are achieved within about 30 to 60 minutes after oral or parenteral administration. Food reduces the rate, but not the extent, of absorption. The bioavailability of the drug is similar after intramuscular or intravenous administration. The pharmacokinetic s of ketorolac are linear over the usual oral and parenteral dosage range. Steady-state plasma drug concentrations are about 50% higher than after single-dose administration.
As with other NSAIDs, ketorolac is almost entirely bound to plasma proteins (>99%), which results in a small apparent volume of distribution (Vd) [<0.3 L/kg]. It is extensively metabolised, primarily by conjugation with glucuronic acid, and excreted via the kidney. The metabolites have no significant analgesic activity. The mean terminal elimination half-life (t½β) of ketorolac in healthy volunteers is about 5 hours.
In the elderly, the absorption and plasma protein binding of ketorolac are unaffected; however, plasma drug clearance (CL) is reduced, which results in a moderate prolongation of t½β to about 6 to 7 hours. In paediatric patients, the Vd and CL of ketorolac appear to be greater than in adults and the t½β is similar; no correlation appears to exist between age (<1 to 18 years) and Vd, CL or t½β values.
As would be expected in patients with renal impairment, the plasma clearance of ketorolac is decreased, which results in an increased t½β (9 to 10 hours). Slight increases in t½β and time to Cmax are seen in patients with alcoholic cirrhosis.
Serum lithium concentrations increased, and resulted in toxic effects, in 2 patients after coadministration of lithium and ketorolac.
Therapeutic Use
The analgesic efficacy of ketorolac has been extensively evaluated in postoperative patients with moderate to severe pain after major abdominal, orthopaedic or gynaecological surgery. There is substantial interoperative and interpatient variation in patients’ response to therapy. Nevertheless, results indicate that single or multiple doses of intramuscular or intravenous ketorolac 10 to 30mg have similar analgesic efficacy to intramuscular morphine 10 to 12mg, pethidine 50 to 100mg, pentazocine 30mg or intravenous morphine 2 to 4mg, and greater efficacy than intramuscular diclofenac 75mg. The analgesic effect of ketorolac tends to be slower in onset than that of morphine or pethidine but persists for longer.
When administered via patient-controlled analgesia, ketorolac 5 mg/h provides similar pain relief to morphine 1 mg/h, dipyrone (metamisole, metamizole) 330 mg/h and lysine clonixinate (clonixin-lysinate) 15 mg/h in patients after major abdominal surgery, but may be less effective than tramadol 15 mg/h. Intermittent intramuscular administration of ketorolac results in analgesia which is much the same as that provided by nalbuphine, pethidine and a multi-ingredient product containing ketobemidone (Ketogan®) and slightly better than papaveretum.
Administration of a single oral dose of ketorolac 10mg to patients within 4 days after major surgery attenuates pain to the same extent as combination analgesic products containing paracetamol and ibuprofen, oxycodone (oxycone) or dextropropoxyphene (propoxyphene), or dextropropoxyphene, aspirin and phenazone (antipyrine). However, intramuscular morphine 10mg, but not 5mg, tends to provide greater pain relief than oral ketorolac 10mg in some patients after orthopaedic surgery.
Preoperative administration of ketorolac reduces pain in the immediate post-operative period. Combination therapy with ketorolac and opioids results in a significant 25 to 50% reduction in morphine and fentanyl requirements in the first 1 to 2 postoperative days and may be accompanied by a reduction in opioid-induced adverse events. In addition, some patients experience a more rapid return to normal GI function and shorter time in hospital.
In general, pre-, intra- or postoperative parenteral administration of a single dose of ketorolac 30 to 60mg appears to be an effective alternative to parenterally administered opioid agents such as fentanyl 50 to 100µg, pethidine 100mg, dezocine 6mg or other NSAIDs such as diclofenac 75 to 100mg (intramuscular or rectal), indomethacin 100mg (rectal) and piroxicam 40mg (oral) after various outpatient laparoscopic or orthopaedic procedures associated with mild to moderate pain. Intravenous or intra-articular administration of ketorolac combined with bupivacaine or lidocaine (lignocaine) provides better analgesia than either agent alone in patients after knee arthroscopy or hand surgery.
In paediatric patients, intramuscular or intravenous ketorolac 0.5 to 1.5 mg/kg provided similar analgesia to morphine 0.1 mg/kg, pethidine 1 mg/kg or paracetamol 35 mg/kg (rectal) after outpatient surgical procedures usually associated with mild to moderate pain, such as bilateral myringotomy, hernia repair and tonsillectomy.
In the emergency room, parenteral administration of ketorolac 10 to 60mg provides effective pain relief in the majority of patients with acute pain resulting from various causes including renal colic, sickle cell crisis, migraine headache, fractures, strains, sprains and gout. As in the postoperative setting, no significant difference in response to therapy is seen between patients treated with ketorolac and standard doses of morphine, pethidine, pentazocine, ibuprofen, diclofenac or indomethacin.
Subcutaneous administration of ketorolac 60 to 120 mg/day was beneficial in the treatment of some patients with cancer pain, especially those with a component of pain resulting from bone metastases, and was accompanied by a concomitant reduction in opioid dosage. However, in other cancer patients, morphine was more effective than ketorolac but less well tolerated.
Pharmacoeconomic Considerations
The pharmacoeconomic consequences of using ketorolac in the treatment of acute pain have not been extensively investigated. The acquisition cost of ketorolac ($US5.76 to 5.85/30mg; currency year not stated) is markedly higher than that of the commonly used opioids morphine ($US0.42 to 0.49/10mg; currency year not stated) or pethidine ($US0.59 to 1.30/100mg; currency year not stated). Nevertheless, results from some retrospective cohort studies indicated that, from a hospital perspective, the cost of therapy with ketorolac was favourable compared with that of control groups (patients typically received morphine or pethidine). Sensitivity analyses were not conducted. Cost savings arose primarily as a result of reduced length of stay in hospital.
As expected, the mean cost of hospitalisation varied with operative procedure, and duration of stay was the largest cost determinant. Procedures such as cholecystectomy, abdominal hysterectomy, major limb surgery/limb reattachment and lumbar laminectomy were associated with lower costs per patient treated with ketorolac than control. However, the reverse cost scenario was seen in patients who underwent intestinal resection, back and neck procedures and lumbar fusion. In a paediatric hospital, about $US52 000 (currency year not stated) was saved over a 3-year period by repackaging unit dose ketorolac 60mg syringes into smaller 7.5 to 30mg increments.
Tolerability
The tolerability profile of ketorolac and other NSAIDs is well defined and relates directly to the pharmacological action of these drugs, particularly with respect to effects on the GI tract and on renal and haematological function. The number and severity of adverse events which occurred in ketorolac recipients in the 3 years after the drug was released prompted regulatory review of drug labelling and usage in several countries. This subsequently led to revised prescribing guidelines and dosage recommendations.
Most adverse events with ketorolac involve the GI tract and range from mild upset to serious ulceration and haemorrhage. Results from a large postmarketing surveillance study (n > 20 000) indicate that, overall, parenteral ketorolac is associated with only a slightly increased risk of GI or operative site bleeding compared with opioids [odds ratios (OR): 1.30 and 1.02, respectively]. The risk of bleeding with ketorolac is strongly linked to increasing age, high dosages and treatment for more than 5 days. For example, elderly patients (aged ≥65 years) who receive ketorolac >120 mg/day have a significantly higher risk of GI bleeding than if they receive a lower dosage of ketorolac 30 mg/day (OR: 6.69 vs 1.13). In children who underwent tonsillectomy, parenteral administration of ketorolac was associated with a similar incidence of bleeding episodes to placebo but with a greater incidence than morphine, paracetamol or codeine. Ketorolac usually causes less nausea and vomiting than opioids.
All NSAIDs have the potential to cause nephropathies, but these occur more frequently in patients with hypovolaemia or other medical conditions which predispose them to haemodynamic compromise. Ketorolac-mediated renal toxicity is associated with increasing levels of serum creatinine, blood urea nitrogen and potassium, and decreased urine output. Importantly, nephrotoxicity is usually reversible on discontinuation of drug therapy; however, it may occur rarely in low-risk patients after a single dose.
As with other NSAIDs, ketorolac has been implicated in allergic or hypersensitivity reactions, ranging from bronchospasm to anaphylaxis.
Many of the reports of serious toxicity with ketorolac predated the revised manufacturers’ dosage guidelines and occurred at high dosages and in patients in whom drug therapy would not currently be recommended. The increased risk of GI events compared with opioids appears to be decreased by appropriate patient selection and prescribing.
Dosage and Administration
Ketorolac is available for intramuscular, intravenous or oral administration and is indicated for the short term treatment of moderate to severe pain which requires analgesia at the opioid level. In the US, the maximum recommended intramuscular single-dose treatment of ketorolac is 60mg. In healthy adults, the usual parenteral dosage is 10 to 30mg every 4 to 6 hours. The total daily dosage should not exceed 90 (UK, Italy, Spain, Belgium, Switzerland) or 120 mg/day (US, Mexico, Canada, Finland and Sweden). Parenteral therapy should be limited to 2 (e.g. UK) or 5 days (e.g. US) and oral therapy should replace parenteral treatment as soon as possible. The usual oral dosage is ketorolac 10mg every 4 to 6 hours to a maximum of 40 mg/day. In the US, oral administration of ketorolac is indicated only as continuation therapy after parenteral administration and the maximum duration of combined therapy is 5 days. In the UK, treatment with oral ketorolac may be initiated without prior parenteral therapy and should not exceed 7 days.
The total daily dosage of parenteral ketorolac should not exceed 60mg in patients aged ≥65 years or those with renal impairment (creatinine clearance of 1.2 to 3 L/h in the UK; not defined in the US) or bodyweight <50kg. The use of ketorolac is not currently recommended in children.
Treatment with ketorolac is contraindicated in patients with congestive heart failure, hepatic impairment, hypertension or conditions that may lead to a reduction in blood volume and in those who are hypersensitive to aspirin or other NSAIDs. Ketorolac should not be coadministered with other NSAIDs, probenecid, pentoxifylline or lithium and should be administered cautiously to patients on anticoagulation therapy (including low dose heparin).
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Buckley MM-T, Brogden RN. Ketorolac: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. Drugs 1990 Jan; 39: 86–109
Brooks PM, Day RO. Nonsteroidal antiinflammatory drugs — differences and similarities. N Engl J Med 1991 June 13; 324(24): 1716–25
Insel PA. Analgesic-antipyretics and antiinflammatory agents; drugs employed in the treatment of rheumatoid arthritis and gout. In: Gilman AG, Rall TW, Nies AS, et al., editors. Goodman and Gilman’s the pharmacological basis of therapeutics. 8th ed. v. 1. Singapore: McGraw-Hill Inc, 1992: 638–81
Dahl JB, Kehlet H. Non-steroidal anti-inflammatory drugs: rationale for use in severe postoperative pain. Br J Apaesth 1991; 66: 703–12
Alon E, Niv D, Varrassi G, et al. Nonsteroidal anti-inflammatory drugs in the control of postoperative pain. Pain Digest 1996; 6: 145–52
Malmberg AB, Yaksh TL. Antinociceptive actions of spinal nonsteroidal anti-inflammatory agents on the formalin test in the rat. J Pharmacol Exp Ther 1992 Oct; 263: 136–46
McCormack K. Non-steroidal anti-inflammatory drugs and spinal nociceptive processing. Pain 1994; 59: 9–43
Brune K, Menzel-Soglowek S, Zeilhofer HU. Differential analgesic effects of aspirin-like drugs. Drugs 1992; 44 Suppl.5: 52–9
Granados-Soto V, Flores-Murrieta FJ, Castañeda-Hernández G, et al. Evidence against the participation of μ- and κ-opioid receptors in the analgesic activity of ketorolac in rats. J Pharm Pharmacol 1995 Jun; 47: 514–7
Negus SS, Butelman ER, Gatch MB, et al. Effects of morphine and ketorolac on thermal allodynia induced by prostaglandin E2 and bradykinin in rhesus monkeys. J Pharmacol Exp Ther 1995 Aug; 274: 805–14
Domer F. Characterization of the analgesic activity of ketoralac in mice. Eur J Pharmacol 1990 Feb; 177: 127–35
Tripathi A, Welch SP. Blockade of the antinociceptive activity of centrally administered ketorolac by nor-binaltorphimine. Eur J Pharmacol 1995 May 4; 278: 27–32
Maves TJ, Pechman PS, Meller ST, et al. Ketorolac potentiates morphine antinociception during visceral nociception in the rat. Anesthesiology 1994 May; 80: 1094–101
Vitale G, Sandrini M, Pini LA. Lack of activity of ketorolac in hot-plate test and serotonin binding capacity of brain membranes in rats. Agents Actions 1994 May; 41: 184–7
Granados-Soto V, Flores-Murrieta FJ, Castaneda-Hemandez G, et al. Evidence for the involvement of nitric oxide in the antinociceptive effect of ketolorac. Eur J Pharmacol 1995 Apr 24; 277: 281–4
Brocks DR, Jamali F. Clinical pharmacokinetics of ketorolac tromethamine. Clin Pharmacokinet 1992 Dec; 23: 415–27
Syntex Laboratories I. Ketorolac prescribing information.
Rodriguez R, Medina M, Rojas Y. Comparative efficacy and safety of intravenous non-steroidal anti-inflammatory drugs in two animal models of pain. Drug Dev Res 1995 Nov; 36: 136–40
Uphouse LA, Welch SP, Ward CR, et al. Antinociceptive activity of intrathecal ketorolac is blocked by the κ-opioid receptor antagonist, nor-binaltorphimine. Eur J Pharmacol 1993 Sep 21; 242: 53–8
Miranda HF, Sierralta F, Pinardi G. Previous administration of indomethacin or naloxone did not influence ketorolac antinociception in mice. Anesth Analg 1993 Oct; 77: 750–3
Bustamante D, Paeile C. Ketorolac tromethamine: an experimental study of its analgesic effects in the rat. Gen Pharmacol 1993 May; 24: 693–8
Sorkin LS. IT ketorolac blocks NMDA-evoked spinal release of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) [abstract no. A909]. Anesthesiology 1993 Sep; 79 Suppl.
Parris MCV, Janicki PK, Johnson B, et al. Ketorolac tromethamine produces analgesia after intrathecal administration in rat model of chronic neuropathic pain [abstract]. Reg Anesth 1994; 19(2) Suppl: 17
Malmberg AB, Yaksh TL. Pharmacology of the spinal action of ketorolac, morphine, ST-91, U50488H, and L-PIA on the formalin test and an isobolographic analysis of the NSAID interaction. Anesthesiology 1993 Aug; 79: 270–81
Cooper SA, Beaver WT. A model to evaluate mild analgesics in oral surgery outpatients. Clin Pharmacol Ther 1976; 20: 241–50
Forbes JA, Butterworth GA, Burchfield WH, et al. Evaluation of ketorolac, aspirin, and an acetaminophen-codeine combination in postoperative oral surgery pain. Pharmacotherapy 1990; 10(6): 77S–93S
Forbes JA, Kehm CJ, Grodin CD, et al. Evaluation of ketorolac, ibuprofen, acetaminophen, and an acetaminophen-codeine combination in postoperative oral surgery pain. Pharmacotherapy 1990; 10(6): 94S–105S
Fricke Jr J, Angelocci D, Fox K, et al. Comparison of the efficacy and safety of ketorolac and meperidine in the relief of dental pain. J Clin Pharmacol 1992 Apr; 32: 376–84
Fricke J, Halladay SC, Bynum L, et al. Pain relief after dental impaction surgery using ketorolac, hydrocodone plus acetaminophen, or placebo. Clin Ther 1993 May–Jun; 15: 500–9
Nhrholt SE, Sindet-Pedersen S, Bugge C, et al. A randomized, double-blind, placebo-controlled, dose-response study of the analgesic effect of lornoxicam after surgical removal of mandibular third molars. J Clin Pharmacol 1995 Jun; 35: 606–14
Chellman GJ, Lollini LO, Dorr AE, et al. Comparison of ketorolac tromethamine with other injectable nonsteroidal anti-inflammatory drugs for pain-on-injection and muscle damage in the rat. Hum Exp Toxicol 1994 Feb; 13: 111–7
Vargas R, Maneatis T, Bynum L. Evaluation of the antipyretic effect of ketorolac, acetaminophen, and placebo in endotoxin-induced fever. J Clin Pharmacol 1994 Aug; 34: 848–53
Greer IA. Effects of ketorolac tromethamine on hemostasis. Pharmacotherapy 1990; 10(6): 71S–6S
Kenny GNC. Potential renal, haematological and allergic adverse effects associated with nonsteroidal anti-inflammatory drugs. Drugs 1992; 44 Suppl. 5: 31–7
Dordoni PL, Ventura MD, Stefanelli A, et al. Effect of ketorolac, ketoprofen and nefopam on platelet function. Anaesthesia 1994 Dec; 49: 1046–9
Pallapies D, Peskar BA, Brune K, et al. Effects on platelet functions and pharmacokinetics of azapropazone and ketorolac tromethamine given as single parenteral doses. Br J Clin Pharmacol 1994 Apr; 37: 335–9
Thwaites BK, Nigus DB, Bouska GW, et al. Intravenous ketorolac tromethamine does not worsen platelet function during knee arthroscopy under general anesthesia. Anesth Analg 1995 Jul; 81: 119–24
Concannon MJ, Meng L, Welsh CF, et al. Inhibition of perioperative platelet aggregation using Toradol (ketorolac). Ann Plast Surg 1993 Mar; 30: 264–6
Aitken HA, Bums JW, McArdle CS, et al. Effects of ketorolac trometamol on renal function. Br J Anaesth 1992 May; 68: 481–5
Fragen RJ, Stulberg SD, Wixson R, et al. Effect of ketorolac tromethamine on bleeding and on requirements for analgesia after total knee arthroplasty. J Bone Joint Surg Am 1995 Jul; 77: 998–1002
Gibbs NM, Sear JW. Effect of ketorolac, bupivacaine and lowdose heparin on thrombelastographic variables in vitro. Br J Anaesth 1995 Jul; 75: 27–30
Reinhart DJ, Latson TW, Whitten CW, et al. Influence of ketorolac tromethamine on clot elastic strength in humans as assessed by thromboelastography. J Clin Anesth 1993 May–Jun; 5: 216–20
Koenig HM, Cunningham FE, Andrews C, et al. The effect of ketorolac vs placebo on thromboelastogram in patients undergoing surgery [abstract]. Anesth Analg 1994 Feb; 78 Suppl.: abstr. S10
Varrassi G, Panella L, Piroli A, et al. The effects of perioperative ketorolac infusion on postoperative pain and endocrine-metabolic response. Anesth Analg 1994 Mar; 78: 514–9
Jones SF, Ulyatt D. Ketorolac and renal impairment [letter]. Anaesth Intensive Care 1994 Feb; 22: 113–4
Rao TRK, Naidu MUR, Shobha JC, et al. Renal effects of oral ketorolac in patients with mild to moderate pain. Clin Drug Invest 1995 Feb; 9: 111–5
Perlmutter A, Miller L, Trimble LA, et al. Toradol, an NSAID used for renal colic, decreases renal perfusion and ureteral pressure in a canine model of unilateral ureteral obstruction. J Urol 1993 Apr; 149: 926–30
Kehlet H, Dahl JB. Are perioperative nonsteroidal anti-inflammatory drugs ulcerogenic in the short term?. Drugs 1992; 44 Suppl. 5: 38–41
Vane JR, Botting RM. The mode of action of anti-inflammatory drugs. Postgrad Med J 1990; 66 Suppl. 4: S2–S17
Lanza FL, Karlin DA, Yee JP. A double-blind placebo controlled endoscopic study comparing the mucosal injury with an orally and parenterally administered new nonsteroidal analgesic ketorolac tromethamine at therapeutic and supratherapeutic doses [abstract]. Am J Gastroenterol 1987; 82: 939
Petring OU, Dawson PJ, Blake DW, et al. Normal postoperative gastric emptying after orthopaedic surgery with spinal anaesthesia and i.m. ketorolac as the first postoperative analgesic. Br J Anaesth 1995 Mar; 74: 257–60
Yee MK, Evans WD, Facey PE, et al. Gastric emptying and small bowel transit in male volunteers after I.M. ketorolac and morphine. Br J Anaesth 1991 Oct; 67: 426–31
Krimmer H, Bullingham RES, Lloyd J, et al. Effects on biliary tract pressure in humans of intravenous ketorolac tromethamine compared with morphine and placebo. Anesth Analg 1992 Aug; 75: 204–7
Ferraz AAB, Cowles VE, Condon RE, et al. Opioid and nonopioid analgesic drug effects on colon contractions in monkeys. Dig Dis Sei 1995 Jul; 40: 1417–9
Camu F, Van Overberge L, Bullingham R, et al. Hemodynamic effects of two intravenous doses of ketorolac tromethamine compared with morphine. Pharmacotherapy 1990; 10 (6 Pt 2): 122S–6S
Schwenzer KJ, Vega H, McGory R. Intravenous ketorolac for patients in intensive care units. Anesthesiology Review 1994 Jul–Aug; 21(4): 125–8
Beattie WS, Etches R, CAPTIV Study Group, et al. PCA morphine and continuous infusion of ketorolac does not reduce postoperative myocardial ischaemia [abstract]. Anesth Analg 1994 Feb; 78 Suppl.: abstr. S4
Joseph J, Schieren H, Seltzer JL, et al. Prophylactic ketorolac tromethamine inhibits prostacyclin biosynthesis and hypotension associated with abdominal mesenteric traction [abstract]. Anesth Analg 1995 Feb; 80 Suppl.: abstr. S218
Beattie WS, Badner N, CAPTIV Study Group, et al. Postoperative oxygen requirements and desaturations are reduced by continuous infusion ketorolac [abstract]. Anesth Analg 1994 Feb; 78 Suppl.: abstr. S3
Liu J, Ding Y, White PF, et al. Effects of ketorolac on postoperative analgesia and ventilatory function after laparoscopic cholecystectomy. Anesth Analg 1993 May; 76: 1061–6
Campbell SC, Krumpe P, Shepard J. Ventilatory effects of ketorolac and morphine in chronic obstructive pulmonary disease. Drug Invest 1993; 5(1): 1–10
Hamunen K, Maunuksela E-L. Ketorolac does not depress ventilation in children [letter]. Paediatr Anaesth 1996; 6: 79
Krimmer H, Bruch HP, Hoffman G, et al. Comparison of the respiratory effects of ketorolac and morphine in postoperative analgesia. Curr Ther Res 1994 Nov; 55(11): 1293–303
Van Lersberghe C, Lauwers M, Camu F. Ventilatory effects of morphine and ketorolac infusions for postoperative pain [abstract no. A.455]. Br J Anaesth 1995 May; 74 Suppl. 1: 138
Murray AW, Brockway MS, Kenny GNC. Comparison of the cardiorespiratory effects of ketorolac and alfentanil during propofol anaesthesia. Br J Anaesth 1989 Nov; 63: 601–3
Gonzalez CA, Martinez JL, Esparza V, et al. Comparison of intravenous ketorolac and butorphanol on ventilatory function and analgesia of pain after surgery. Proc West Pharmacol Soc 1994; 37: 147–8
Singh H, Bossard RF, White PF. Epidural PCA: effect of ketorolac vs bupivacaine supplementation on pulmonary functions after thoracotomy [abstract no. A874]. Anesthesiology 1995 Sept; 83 (3A)
Lucker P, Bullingham R, Hooftman L, et al. Tolerability, central effects and pharmacokinetics of intravenous ketorolac tromethamine in volunteers. Int J Clin Pharmacol Ther 1994 Aug; 32: 409–14
Pritchett J. Ketorolac prophylaxis against heterotopic ossification after hip replacement. Clin Orthop Relat Res 1995 May: 162–5
Hayball PJ, Tamblyn JG, Holden Y, et al. Stereoselective analysis of ketorolac in human plasma by high-performance liquid chromatography. Chirality 1993; 5(1): 31–5
Jones DJ, Bjorksten AR. Detection of ketorolac enantiomers in human plasma using enantioselective liquid chromatography. J Chromatogr B Biomed Appl 1994 Nov 4; 661: 165–7
Kamath BV, Shivram K, Shah AC. Determination of diclofenac sodium, famotidine and ketorolac tromethamine by flow injection analysis using dichloronitrophenol. J Pharm Biomed Anal 1994 Mar; 12: 343–6
Mills MH, Mather LE, Gu XS, et al. Determination of ketorolac enantiomers in plasma using enantioselective liquid chromatography on an α1-acid glycoprotein chiral stationary phase and ultraviolet detection. J Chromatogr B Biomed Appl 1994 Aug 5; 658: 177–82
Vakily M, Corrigan B, Jamali F. The problem of racemization in the stereospecific assay and pharmacokinetic evaluation of ketorolac in human and rats. Pharm Res 1995 Nov; 12: 1652–7
Chaudhary RS, Gangwal SS, Jindal KC, et al. Reversed-phase high-performance liquid chromatography of ketorolac and its application to bioequivalence studies in human serum. J Chromatogr B Biomed Appl 1993 Apr 21; 614: 180–4
Flores-Murrieta FJ, Granados-Soto V, Castañeda-Hernández G, et al. Comparative bioavailability of two oral formulations of ketorolac tromethamine: Dolac (Rm) and Exodol (Rm). Biopharm Drug Dispos 1994 Mar; 15: 129–36
Gordon MS, Ling TL, Yee JP. Ketorolac tromethamine bioavailability via tablet, capsule, and oral solution dosage forms. Drug Dev Ind Pharm 1995; 21(10): 1143–55
Jallad NS, Garg DC, Martinez JJ, et al. Pharmacokinetics of single-dose oral and intramuscular ketorolac tromethamine in the young and elderly. J Clin Pharmacol 1990 Jan; 30: 76–81
Sane RT, Desai AJ, Tirodkar VB, et al. Comparison of standard and test formulations of ketorolac: a pharmacokinetic and bioequivalence study in Indian volunteers. Curr Ther Res 1993 Oct; 54: 425–9
Shobha JC, Sekhar KR, Sekhar EC, et al. Bioequivalence of ketorolac tablet in healthy volunteers. Indian Journal of Pharmaceutical Sciences 1993 May–Jun; 55(3): 105–7
Martinez JJ, Garg DC, Pages LJ, et al. Single dose pharmacokinetics of ketorolac in healthy young and renal impaired subjects [abstract no. 72]. J Clin Pharmacol 1987; 27: 722
Pages LJ, Martinez JJ, Garg DC, et al. Pharmacokinetics of ketorolac tromethamine in hepatically impaired vs. young healthy subjects [abstract no. 78]. J Clin Pharmacol 1987; 27: 724
Noren RL, Hord AH, Denson DD. Pharmacokinetics of ketorolac tromethamine following subcutaneous administration [abstract]. Reg Anesth 1993 Mar–Apr; 18(2S) Suppl.: 28
Cohen DE, Siegal S, Davis L, et al. Pharmacokinetics of intravenous ketorolac in infants less than 1 year of age [abstract]. Anesthesiology 1994 Sep; 81 Suppl.: abstr. 1334
Kauffman RE, Lieh-Lai MW, Uv H, et al. Ketorolac pharmacokinetics and metabolism in children [abstract no. 433]. Pediatr Res 1996 Apr; 39 (4 Pt 2): 75A
Gerna M, Tajana A, Wool C, et al. Pharmacokinetics of ketorolac tromethamine following oral and rectal administration [abstract]. Eur J Pharmacol 1990 Jul 2; 183: 398
Hayball PJ, Wrobel J, Tamblyn JG, et al. The pharmacokinetics of ketorolac enantiomers following intramuscular administration of the racemate. Br J Clin Pharmacol 1994 Jan; 37: 75–8
Olkkola KT, Maunuksela E-L. The pharmacokinetics of postoperative intravenous ketorolac tromethamine in children. Br J Clin Pharmacol 1991 Feb; 31: 182–4
Brown CR, Moodie JE, Phillips E, et al. Pharmacokinetics and pharmacodynamics (PK/PD) of ketorolac tromethamine (KT) IM and IV following major orthopedic surgery [abstract]. Clin Pharmacol Ther 1993 Feb; 53: 222
Garg DC, Mroszczak E, Combs D, et al. Ketorolac pharmacokinetics (PK) following continuous infusion and repeated bolus injection [abstract]. Clin Pharmacol Ther 1993 Feb; 53: 209
Rice ASC, Lloyd J, Bullingham RES, et al. Ketorolac penetration into the cerebrospinal fluid of humans. J Clin Anesth 1993 Nov–Dec; 5: 459–62
Mroszczak E, Combs D, Chaplin M, et al. Chiral kinetics and dynamics of ketorolac. J Clin Pharmacol 1996; 36: 521–39
Mroszczak EJ, Solish SB, Combs DL, et al. Pharmacokinetics and interconversion of ketorolac enantiomers in humans [abstract]. 95th Annu Meet Am Soc Clin Pharm, New Orleans 1994: 164
Kerr KA, Banner Jr W, Pappas J, et al. A pharmacokinetic study comparing intermittent vs continuous infusion ketorolac in a pediatric intensive care unit [abstract]. Crit Care Med 1994 Jan; 22: A182
Toon S, Holt BL, Mullins FGP, et al. Investigations into the potential effects of multiple dose ketorolac on the pharmacokinetics and pharmacodynamics of racemic warfarin. Br J Clin Pharmacol 1990 Nov; 30: 743–50
Weale AE, Warwick DJ, Durant N, et al. Is there a clinical interaction between low molecular weight heparin and nonsteroidal analgesics after total hip replacement? Ann R Coll Surg Engl 1995 Jan; 77: 35–7
Langlois R, Paquette D. Increased serum lithium levels due to ketorolac therapy. Can Med Assoc J 1994 May 1; 150: 1455–6
Iyer V. Ketorolac (Toradol [Rm]) induced lithium toxicity. Headache 1994 Jul–Aug; 34: 442–4
Shah J, Bullingham R, Jonkman J, et al. PK-PD interaction of ketorolac and furosemide in healthy volunteers in a normovolemic state [abstract]. 95th Annu Meet Am Soc Clin Pharm, New Orleans 1994: 198
Souter AJ, Fredman B, White PF. Controversies in the perioperative use of nonsteroidal antiinflammatory drugs. Anesth Analg 1994; 79: 1178–90
Woolf CJ. Recent advances in the pathophysiology of acute pain. BrJ Anaesth 1989; 63: 139–46
Dahl JB, Kehlet H. The value of pre-emptive analgesia in the treatment of postoperative pain. Br J Anaesth 1993; 70: 434–9
Brown CR, Moodie JE, Wild VM, et al. Comparison of intravenous ketorolac tromethamine and morphine sulfate in the treatment of postoperative pain. Pharmacotherapy 1990; 10(6): 116S–21S
Maslanka MA, de Andrade JR, Maneatis T, et al. Comparison of oral ketorolac, intramuscular morphine, and placebo for treatment of pain after orthopedic surgery. South Med J 1994 Apr; 87: 506–13
Peirce RJ, Fragen RJ, Pemberton DM. Intravenous ketorolac tromethamine versus morphine sulfate in the treatment of immediate postoperative pain. Pharmacotherapy 1990; 10(6): 111S–5S
Stouten EM, Armbruster S, Houmes RJ, et al. Comparison of ketorolac and morphine for postoperative pain after major surgery. Acta Anaesthesiol Scand 1992 Oct; 36: 716–21
Folsland B, Skulberg A, Halvorsen P, et al. Placebo-controlled comparison of single intramuscular doses of ketorolac tromethamine and pethidine for post-operative analgesia. J Int Med Res 1990 Jul–Aug; 18: 305–14
Stanski DR, Cherry C, Bradley R, et al. Efficacy and safety of single doses of intramuscular ketorolac tromethamine compared with meperidine for postoperative pain. Pharmacotherapy 1990; 10(6): 40S–4S
Johansson S, Josefsson G, Malstam J, et al. Analgesic efficacy and safety comparison of ketorolac tromethamine and doleron for the alleviation of orthopaedic post-operative pain. J Int Med Res 1989 Jul–Aug; 17: 324–32
Kumar TR, Naidu MUR, Shobha JC, et al. A comparison of intramuscular ketorolac, pentazocine and diclofenac sodium in postoperative pain. Asia Pac J Pharmacol 1993 Sep; 8: 115–9
Naidu MUR, Kumar TR, Jagdishchandra US, et al. Evaluation of ketorolac, ibuprofen-paracetamol, and dextropropoxyphene-paracetamol in postoperative pain. Pharmacotherapy 1994 Mar–Apr; 14: 173–7
Reines HD, Adams D, Hawkes T, et al. Evaluation of oral ketorolac, oxycodone plus acetaminophen, and placebo for pain relief after orthopedic surgery. Curr Ther Res 1994 June; 55(6): 615–24
Bosek V, Miguel R. Comparison of morphine and ketorolac for intravenous patient-controlled analgesia in postoperative cancer patients. Clin J Pain 1994 Dec; 10: 314–8
Brown CR, Mazzulla JP, Mok MS, et al. Comparison of repeat doses of intramuscular ketorolac tromethamine and morphine sulfate for analgesia after major surgery. Pharmacotherapy 1990; 10(6): 45S–50S
Cepeda MS, Vargas L, Ortegon G, et al. Comparative analgesic efficacy of patient-controlled analgesia with ketorolac versus morphine after elective intraabdominal operations. Anesth Analg 1995 Jun; 80: 1150–3
Powell H, Smallman JM, Morgan M. Comparison of intramuscular ketorolac and morphine in pain control after laparotomy. Anaesthesia 1990 Jul; 45: 538–42
Power I, Noble DW, Douglas E, et al. Comparison of I.M. ketorolac trometamol and morphine sulphate for pain relief after cholecystectomy. Br J Anaesth 1990 Oct; 65: 448–55
DeAndrade JR, Maslanka M, Reines HD, et al. Ketorolac versus meperidine for pain relief after orthopaedic surgery. Clin Orthop Relat Res 1996 Apr; 325: 302–12
Gebuhr PH, Soelberg M, Strauss W. A multiple-dose, doubleblind comparison of intramuscularly and orally administered ketorolac tromethamine and Ketogan (Rm) in patients with pain following orthopaedic surgery. J Int Med Res 1994 Jul–Aug; 22: 202–17
Munguía-Fajardo Y, González-García CA, Zamora-López G. Comparative study of intramuscularly administered ketorolac and nalbuphine in patients with pain following orthopedic surgery. Proc West Pharmacol Soc 1992; 35: 195–9
Rodriguez MJ, De La Torre MR, Perez-Iraola P, et al. Comparative study of tramadol versus NSAIDs as intravenous continuous infusion for managing postoperative pain. Curr Ther Res 1993 Oct; 54: 375–83
Smallman JMB, Powell H, Ewart MC, et al. Ketorolac for postoperative analgesia in elderly patients. Anaesthesia 1992 Feb; 47: 149–52
Stahlgren LR, Trierweiler M, Tommeraasen M, et al. Comparison of ketorolac and meperidine in patients with postoperative pain — mpact on health care utilization. Clin Ther 1993 May–Jun; 15: 571–80
Fletcher D, Zetlaoui P, Monin S, et al. Influence of timing on the analgesic effect of intravenous ketorolac after orthopedic surgery. Pain 1995 May; 61: 291–7
Parke TJ, Lowson SM, Uncles DR, et al. Pre-emptive versus post-surgical administration of ketorolac for hysterectomy. Eur J Anaesthesiol 1995; 12: 549–53
Blackburn A, Stevens JD, Wheatley RG, et al. Balanced analgesia with intravenous ketorolac and patient-controlled morphine following lower abdominal surgery. J Clin Anesth 1995 Mar; 7: 103–8
Bums JW, Aitken HA, Bullingham RES, et al. Double-blind comparison of the morphine sparing effect of continuous and intermittent I.M. administration of ketorolac. Br J Anaesth 1991 Sep; 67: 235–8
Etches RC, Warriner CB, Badner N, et al. Continuous intravenous administration of ketorolac reduces pain and morphine consumption after total hip or knee arthroplasty. Anesth Analg 1995 Dec; 81: 1175–80
Fogarty DJ, O’Hanlon JJ, Milligan KR. Intramuscular ketorolac following total hip replacement with spinal anaesthesia and intrathecal morphine. Acta Anaesthesiol Scand 1995 Feb; 39: 191–4
Parker RK, Holtmann B, Smith I, et al. Use of ketorolac after lower abdominal surgery. Effect on analgesic requirement and surgical outcome. Anesthesiology 1994 Jan; 80: 6–12
Power I, Bowler GMR, Pugh GC, et al. Ketorolac as a component of balanced analgesia after thoracotomy. Br J Anaesth 1994 Feb; 72: 224–6
Ready LB, Brown CR, Stahlgren LH, et al. Evaluation of intravenous ketorolac administered by bolus or infusion for treatment of postoperative pain: a double-blind, placebo-controlled, multicenter study. Anesthesiology 1994 Jun; 80: 1277–86
Sevarino FB, Sinatra RS, Paige D, et al. The efficacy of intramuscular ketorolac in combination with intravenous PCA morphine for postoperative pain relief. J Clin Anesth 1992 Jul–Aug; 4: 285–8
Sevarino FB, Sinatra RS, Paige D. Intravenous ketorolac as an adjunct to patient-controlled analgesia (PCA) for management of postgynecologic surgical pain. J Clin Anesth 1994 Jan–Feb; 6: 23–7
Valdrighi JB, Hanowell LH, Loeb RG, et al. Effect of intraoperative ketorolac on postanesthesia care unit comfort. J Pain Symptom Manage 1994 Apr; 9: 171–4
Vetter TR, Heiner EJ. Intravenous ketorolac as an adjuvant to pediatric patient-controlled analgesia with morphine. J Clin Anesth 1994 Mar–Apr; 6: 110–3
Grass JA, Sakima NT, Valley M, et al. Assessment of ketorolac as an adjuvant to fentanyl patient-controlled epidural analgesia after radical retropubic prostatectomy. Anesthesiology 1993 Apr; 78: 642–8
Gwirtz KH, Helvie JE, Young JV, et al. Ketorolac enhances intrathecal analgesia after major surgery. Anesthesiology Review 1993; 20(6): 222–8
Rogers JEG, Fleming BG, Macintosh KC, et al. Effect of timing of ketorolac administration on patient-controlled opioid use. Br J Anaesth 1995 Jul; 75: 15–8
See WA, Fuller JR, Toner ML. An outcome study of patient-controlled morphine analgesia, with or without ketorolac, following radical retropubic prostatectomy. J Urol 1995 Oct; 154: 1429–32
Fredman B, Olsfanger D, Flor P, et al. Ketorolac does not decrease postoperative pain in elderly men after transvesical prostatectomy. Can J Anaesth 1996; 43(5): 438–41
Cade L, Kakulas P. Ketorolac or pethidine for analgesia after elective laparoscopic sterilization. Anaesth Intensive Care 1995 Apr; 23: 158–61
Chui PT, Gin T. A comparison between ketorolac and diclofenac in laparoscopic sterilization. Eur J Anaesthesiol 1995; 12: 597–601
Ding Y, White PF. Comparative effects of ketorolac, dezocine, and fentanyl as adjuvants during outpatient anesthesia. Anesth Analg 1992 Oct; 75: 566–71
Forse A, El-Beheiry H, Butler PO, et al. Indomethacin and ketorolac given preoperatively are equally effective in reducing early postoperative pain after laparoscopic cholecystectomy. Can J Surg 1996; 39(1): 26–30
Higgins MS, Givogre JL, Marco AP, et al. Recovery from outpatient laparoscopic tubal ligation is not improved by preoperative administration of ketorolac or ibuprofen. Anesth Analg 1994 Aug; 79: 274–80
Lysak SZ, Anderson PT, Carithers RA, et al. Postoperative effects of fentanyl, ketorolac, and piroxicam as analgesics for outpatient laparoscopic procedures. Obstet Gynecol 1994 Feb; 83: 270–5
Murrell GC, Leake T, Hughes PJ. A comparison of the efficacy of ketorolac and indomethacin for postoperative analgesia following laparoscopic surgery in day patients. Anaesth Intensive Care 1996; 24: 237–40
Sampson IH, Dimich I, Shamsi A. The effect of ketorolac on recovery after outpatient gynecologic laparoscopy. Curr Ther Res 1996 Aug; 57(8): 606–13
Twersky RS, Lebovits A, Williams C. Ketorolac versus fentanyl for postoperative pain management in outpatients. Clin J Pain 1995 Jun; 11: 127–33
Dennis AR, Leeson-Payne CG, Hobbs GJ. A comparison of diclofenac with ketorolac for pain relief after knee arthroscopy. Anaesthesia 1995 Oct; 50: 904–6
Reuben SS, Connelly NR. Postoperative analgesia for outpatient arthroscopic knee surgery with intraarticular bupivacaine and ketorolac. Anesth Analg 1995 Jun; 80: 1154–7
Reuben SS, Connelly NR. Postarthroscopic meniscus repair analgesia with intraarticular ketorolac or morphine. Anesth Analg 1996; 82: 1036–9
Smith I, Shively RA, White PF. Effects of ketorolac and bupivacaine on recovery after outpatient arthroscopy. Anesth Analg 1992 Aug; 75: 208–12
Ben-David B, Baune-Goldstein U, Goldik Z, et al. Is preoperative ketorolac a useful adjunct to regional anesthesia for inguinal herniorrhaphy?. Acta Anaesthesiol Scand 1996; 40: 358–63
Bosek V, Smith DB, Cox C. Ketorolac or fentanyl to supplement local anesthesia? J Clin Anesth 1992 Nov–Dec; 4: 480–3
Bosek V, Cox CE. Comparison of analgesic effect of locally and systemically administered ketorolac in mastectomy patients. Ann Surg Oncol 1996; 3(1): 62–6
Ding Y, Fredman B, White PF. Use of ketorolac and fentanyl during outpatient gynecologic surgery. Anesth Analg 1993 Aug; 77: 205–10
Morley-Forster P, Newton PT, Cook M-J. Ketorolac and indomethacin are equally efficacious for the relief of minor postoperative pain. Can J Anaesth 1993 Dec; 40: 1126–30
Morrison NA, Repka MX. Ketorolac versus acetaminophen or ibuprofen in controlling postoperative pain in patients with strabismus. Ophthalmology 1994 May; 101: 915–8
Reuben SS, Steinberg RB, Kreitzer JM, et al. Intravenous regional anesthesia using lidocaine and ketorolac. Anesth Analg 1995 Jul; 81: 110–3
Tarkkila P, Tuominen M, Rosenberg PH. Intravenous ketorolac vs diclofenac for analgesia after maxillofacial surgery. Can J Anaesth 1996; 43(3): 216–20
Wong HY, Carpenter RL, Kopacz DJ, et al. A randomized, double-blind evaluation of ketorolac tromethamine for postoperative analgesia in ambulatory surgery patients. Anesthesiology 1993 Jan; 78: 6–14
Bean-Lijewski JD, Hunt RD. Effect of ketorolac on bleeding time and postoperative pain in children: a double-blind, placebo-controlled comparison with meperidine. J Clin Anesth 1996; 8: 25–30
Graham SG, Wandless JG. The effect of ketorolac as an adjuvant to local anaesthetic infiltration for analgesia in paediatric umbilical hernia surgery. Paediatr Anaesth 1995; 5(3): 161–3
Maunuksela E-L, Kokki H, Bullingham RES. Comparison of intravenous ketorolac with morphine for postoperative pain in children. Clin Pharmacol Ther 1992 Oct; 52: 436–43
Munro HM, Riegger LQ, Reynolds PI, et al. Comparison of the analgesic and emetic properties of ketorolac and morphine for paediatric outpatient strabismus surgery. Br J Anaesth 1994 Jun; 72: 624–8
Purday JP, Reichert CC, Merrick PM. Comparative effects of three doses of intravenous ketorolac or morphine on emesis and analgesia for restorative dental surgery in children. Can J Anaesth 1996; 43(3): 221–5
Rusy LM, Houck CS, Sullivan LJ, et al. A double-blind evaluation of ketorolac tromethamine versus acetaminophen in pediatric tonsillectomy: analgesia and bleeding. Anesth Analg 1995 Feb; 80: 226–9
Sutters KA, Levine JD, Dibble S, et al. Analgesic efficacy and safety of single-dose intramuscular ketorolac for postoperative pain management in children following tonsillectomy. Pain 1995 Apr; 61: 145–53
Watcha MF, Jones MB, Lagueruela RG, et al. Comparison of ketorolac and morphine as adjuvants during pediatric surgery. Anesthesiology 1992 Mar; 76: 368–72
Watcha MF, Ramirez-Ruiz M, White PF, et al. Perioperative effects of oral ketorolac and acetaminophen in children undergoing bilateral myringotomy. Can J Anaesth 1992 Sep; 39: 649–54
Green CR, Pandit SK, Levy L, et al. Intraoperative ketorolac has an opioid-sparing effect in women after diagnostic laparoscopy but not after laparoscopic tubal ligation. Anesth Analg 1996; 82: 732–7
Buck ML. Clinical experience with ketorolac in children. Ann Pharmacother 1994 Sep; 28: 1009–13
Larsen LS, Miller A, Allegra JR. The use of intravenous ketorolac for the treatment of renal colic in the emergency department. Am J Emerg Med 1993 May; 11: 197–9
Oosterlinck W, Philp NH, Charig C, et al. A double-blind single dose comparison of intramuscular ketorolac tromethamine and pethidine in the treatment of renal colic. J Clin Pharmacol 1990 Apr; 30: 336–41
Sandhu DPS, Iacovou JW, Fletcher MS, et al. A comparison of intramuscular keterolac and pethidine in the alleviation of renal colic. Br J Urol 1994 Dec; 74: 690–3
Larkin GL, Pearl SM, Blair GA, et al. A randomized, doubleblind, comparative study of the efficacy of ketorolac tromethamine versus meperidine in the treatment of acute renal colic [abstract]. Ann Emerg Med 1994 Apr; 23: 924
Cordell WH, Wright SW, Wolfson AB, et al. Comparison of intravenous ketorolac, meperidine, and both (balanced analgesia) for renal colic. Ann Intern Med 1996 Aug; 28: 151–8
Timerding BL, Hite P, Gin-Shaw S, et al. Comparison of IV metoclopramide, ketorolac, and morphine for the acute relief of renal colic [abstract]. Ann Emerg Med 1992 May; 21: 630
Stein A, Ben Dov D, Finkel B, et al. Single-dose intramuscular ketorolac versus diclofenac for pain management in renal colic. Am J Emerg Med 1996; 14: 385–7
Bunn HF. Disorders of hemoglobin. In: Wilson JD, Braunwald E, Isselbacher KJ, et al., editors. Harrison’s principles of internal medicine. 12th ed. v. 2. New York: McGraw-Hill, Inc., 1991: 1543–52
Sanders DY, Severance HW, Pollack Jr CV. Sickle cell vaso-oc-clusive pain crisis in adults: alternative strategies for management in the emergency department. South Med J 1992 Aug; 85: 808–11
Wright SW, Norris RL, Mitchell TR. Ketorolac for sickle cell vaso-occlusive crisis pain in the emergency department: lack of a narcotic-sparing effect. Ann Emerg Med 1992 Aug; 21: 925–8
Udeani G, Mock J, Eilbert W, et al. A prospective randomized double-blind study comparing the efficacy of intramuscular ketorolac and meperidine in sickle cell painful episodes [abstract]. J Clin Pharmacol 1995 Sep; 35: 937
Perlin E, Finke H, Castro O, et al. Enhancement of pain control with ketorolac tromethamine in patients with sickle cell vasoocclusive crisis. Am J Hematol 1994 May; 46: 43–7
Pollack Jr CV, Sanders DY, Severance Jr HW. Emergency department analgesia without narcotics for adults with acute sickle cell pain crisis: case reports and review of crisis management. J Emerg Med 1991; 9: 445–52
Turturro MA, Paris PM, Seaberg DC. Intramuscular ketorolac versus oral ibuprofen in acute musculoskeletal pain. Ann Emerg Med 1995 Aug; 26: 117–20
Shrestha M, Morgan DL, Moreden JM, et al. Randomized double-blind comparison of the analgesic efficacy of intramuscular ketorolac and oral indomethacin in the treatment of acute gouty arthritis. Ann Emerg Med 1995 Dec; 26: 682–6
Koenig KL, Hodgson L, Kozak R, et al. Ketorolac vs meperidine for the management of pain in the emergency department. Acad Emerg Med 1994 Nov–Dec; 1: 544–9
Andujar EG. Analgesia with ketorolac (Toradol(Rm)) or pentazocine (Fortral(Rm)) in patients with post-traumatic orthopaedic pain. A double-blind study. Clin Trials J 1990; 27(3): 211–8
Wright JM, Price SD, Watson WA. NSAID use and efficacy in the emergency department: single doses of oral ibuprofen versus intramuscular ketorolac. Ann Pharmacother 1994 Mar; 28: 309–12
Bartfield JM, Kern AM, Raccio-Robak N, et al. Ketorolac tromethamine use in a university-based emergency department. Acad Emerg Med 1994 Nov–Dec; 1: 532–8
Penniston SG, Hargreaves KM. Evaluation of periapical injection of ketorolac for management of endodontic pain. J Endodont 1996; 22(2): 55–9
Vanos DN, Ramamurthy S, Hoffman J. Intravenous regional block using ketorolac: preliminary results in the treatment of reflex sympathetic dystrophy. Anesth Analg 1992 Jan; 74: 139–41
Connelly NR, Reuben S, Brull SJ. Intravenous regional anesthesia with ketorolac-lidocaine for the management of sympathetically-mediated pain. Yale J Biol Med 1995; 68: 95–9
Arunasalam S, Siegel RJ. Rapid resolution of symptomatic acute pericarditis with ketorolac tromethamine: a parenteral nonsteroidal antiinflammatory agent. Am Heart J 1993 May; 125 (P 1): 1455–8
Shrestha M, Singh R, Moreden J, et al. Ketorolac vs chlorprom-azine in the treatment of acute migraine without aura. A prospective randomized double-blind trial. Arch Intern Med 1996 Aug 12; 156: 1725–8
Davis CP, Torre PR, Williams C, et al. Ketorolac versus meperidine-plus-promethazine treatment of migraine headache: evaluations by patients. Am J Emerg Med 1995 Mar; 13: 146–50
Duarte C, Dunaway F, Turner L, et al. Ketorolac versus meperidine and hydroxyzine in the treatment of acute migraine headache: a randomized, prospective, double-blind trial. Ann Emerg Med 1992 Sep; 21: 1116–21
Harden RN, Carter TD, Gilman CS, et al. Ketorolac in acute headache management. Headache 1991 Jul; 31: 463–4
Davis CP, Torre PR, Schafer NC. Ketorolac as a rapid and effective treatment of migraine headache: evaluations by patients. Am J Emerg Med 1993 Nov; 11: 573–5
Klapper JA, Stanton JS. Ketorolac versus DHE and metoclopramide in the treatment of migraine headaches. Headache 1991 Sep; 31: 523–4
Harden RN, Gracely RH, Carter T, et al. The placebo effect in acute headache management: ketorolac, meperidine, and saline in the emergency department. Headache 1996; 36: 352–6
Larkin GL, Prescott JE. A randomized, double-blind, comparative study of the efficacy of ketorolac tromethamine versus meperidine in the treatment of severe migraine. Ann Emerg Med 1992 Aug; 21: 919–24
Myers KG, Trotman IF. Use of ketorolac by continuous subcutaneous infusion for the control of cancer-related pain. Postgrad Med J 1994 May; 70: 359–62
DeConno F, Zecca E, Martini C, et al. Tolerability of ketorolac administered via continuous subcutaneous infusion for cancer pain: a preliminary report. J Pain Symptom Manage 1994 Feb; 9: 119–21
Blackwell N, Bangham L, Hughes M, et al. Treatment of resistant pain in hypertrophic pulmonary arthropathy with ketorolac. Thorax 1993 Apr; 48: 401
Middleton RK, Lyle JA, Berger DL. Ketorolac continuous infusion: a case report and review of the literature. J Pain Symptom Manage 1996 Sep; 12(3): 190–4
Miller LJ, Kramer MA. Pain management with intravenous ketorolac. Ann Pharmacother 1993 Mar; 27: 307–8
Jameel A, Stein RC, Rawson NSB, et al. Comparative study of intramuscular ketorolac tromethamine and morphine in patients experiencing cancer pain (clinical study). Int J Oncol 1995 Jun; 6: 1307–11
Toscani F, Piva L, Corli O, et al. Ketorolac versus diclofenac sodium in cancer pain. Arzneimittel Forschung 1994 Apr; 44: 550–4
Estapé J, Viñolas N, González B, et al. Ketorolac, a new nonopioid analgesic: a double-blind trial versus pentazocine in cancer pain. J Int Med Res 1990 Jul–Aug; 18: 298–304
Carlson RW, Borrison RA, Sher HB, et al. A multiinstitutional evaluation of the analgesic efficacy and safety of ketorolac tromethamine, actaminophen plus codeine, and placebo in cancer pain. Pharmacotherapy 1990; 10(3): 211–6
Burke JP, Pestotnik SL, Classen DC, et al. Evaluation of the financial impact of ketorolac tromethamine therapy in hospitalized patients. Clin Ther 1996 Jan–Feb; 18: 197–211
Reinhart SP, Trotter JP, Larson LR. A pharmacoeconomic comparison of narcotic and nonnarcotic analgesics in abdominal surgery. Pharmacy & Therapeutics 1995 Oct: 639–49
Trotter JP, Reinhart SP, Katz RM, et al. Economic assessment of ketorolac versus narcotic analgesics in postoperative pain management. Clin Ther 1993 Sep–Oct; 15: 938–48
Turner DM, Warson JS, Wirt TC, et al. The use of ketorolac in lumbar spine surgery: a cost-benefit analysis. J Spinal Disord 1995 Jun; 8: 206–12
Houck CS, Wilder RT, McDermott JS, et al. Safety of intravenous ketorolac therapy in children and cost savings with a unit dosing system. J Pediatr 1996; 129(2): 292–6
Balevi B. Ketorolac versus ibuprofen: a simple cost-efficacy comparison for dental use. J Can Dent Assoc 1994 Jan; 60: 31–2
Cashman J, McAnulty G. Nonsteroidal anti-inflammatory drugs in perisurgical pain management. Mechanisms of action and rationale for optimum use. Drugs 1995; 49(1): 51–70
Skeith KJ, Wright M, Davis P. Differences in NSAID tolerability profiles: fact or fiction?. Drug Saf 1994; 10(3): 183–95
Strom BL, Berlin JA, Kinman JL, et al. Parenteral ketorolac and risk of gastrointestinal and operative site bleeding: a postmarketing surveillance study. JAMA 1996 Feb 7; 275: 376–82
Syntex Toradol labeling changes reported in ‘dear doctor’ letter. FDC Rep Pink Sheet 1993 Nov 1: 9–10
Ketorolac: new restrictions on dose and duration of treatment. Curr Probl Pharmacovig 1993 Jun; 19: 5–6
Choo V, Lewis S. Ketorolac doses reduced. Lancet 1993 Jul 10; 342: 109
New ketorolac dosage recommendations. Pharm J 1993 Jul 10; 251: 49
Ketorolac: restrictions on parenteral dosage. WHO Drug Info 1993; 7(2): 64
Summers K, Wilson R. The management of drug safety in the new Europe: ketorolac, a case study. Pharm Med 1994 Dec; 8: 135–43
Reduction in adverse effect reports for ketorolac. Pharm J 1994 Apr 9; 252: 498
Bushnell TG, Justins DM. Choosing the right analgesic: a guide to selection. Drugs 1993; 46(3): 394–408
Stalnikowicz R, Rachmilewitz D. NSAID-induced gastroduodenal damage: is prevention needed? A review and metaanalysis. J Clin Gastroenterol 1993; 17(3): 238–43
Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. Ann Intern Med 1991; 115: 787–96
Roth SH, Bennett RE. Nonsteroidal anti-inflammatory drug gastropathy. Arch Intern Med 1987 Dec; 147: 2093–100
Mendel HG, Guamieri KM, Sundt LM, et al. The effects of ketorolac and fentanyl on postoperative vomiting and analgesic requirements in children undergoing strabismus surgery. Anesth Analg 1995 Jun; 80: 1129–33
Maliekal J, Elboim CM. Gastrointestinal complications associated with intramuscular ketorolac tromethamine therapy in the elderly. Ann Pharmacother 1995 Jul–Aug; 29: 698–701
Traversa G, Walker AM, Ippolito FM, et al. Gastroduodenal toxicity of different nonsteroidal antiinflammatory drugs. Epidemiology 1995 Jan; 6: 49–54
Buchman AL, Schwartz MR. Colonic ulceration associated with the systemic use of nonsteroidal antiinflammatory medication. J Clin Gastroenterol 1996; 22(4): 224–6
Fuller DK, Kalekas PJ. Ketorolac and gastrointestinal ulceration. Ann Pharmacother 1993 Jul–Aug; 27: 978–9
Wolfe PA, Polhamus CD, Kubik C, et al. Giant duodenal ulcers associated with postoperative use of ketorolac: report of three cases. Am J Gastroenterol 1994 Jul; 89: 1110–1
Quigley EMM, Donovan JP, Livingston WC. Ketorolac-related giant gastric ulcers. Am J Gastroenterol 1994 Apr; 89: 631–2
Estes LL, Fuhs DW, Heaton AH, et al. Gastric ulcer perforation associated with the use of injectable ketorolac. Ann Pharmacother 1993 Jan; 27: 42–3
Quigley EMM, Ruh P. Ketorolac-associated upper gastrointestinal hemorrhage [letter]. Am J Gastroenterol 1994 Feb; 89: 287–9
O’Leary M, Martin P, McLean AS. Oliguria and haemorrhage after intramuscular injection of ketorolac trometamol. Med J Aust 1993 May 17; 158: 719–20
McCann KJ, Irish J. Postoperative gastrointestinal bleeding: a case report involving a non-steroidal anti-inflammatory drug. J Can Dent Assoc 1994 Feb; 60: 124–8
Hsu R, Kaur M, Prindiville T, et al. Prevalence of NSAID gastroduodenopathy in hospitalized patients with upper gastrointestinal bleeding after intramuscular ketorolac [abstract]. Am J Gastroenterol 1993 Sep; 88: 1509
Steinberg RB, Tessier EG. Gastrointestinal bleeding after administration of ketorolac. Anesthesiology 1993 Nov; 79: 1146
McDonald E, Marino C, Schwartz E. Toradol and the risk of gastrointestinal complications in the elderly. J Am Geriatr Soc 1993 Jan; 41: 90–1
Narayani RI, Takata JA, Polhamus CD. Ketorolac (Toradol)-induced upper gastrointestinal bleeding: the Wilford Hall experience [abstract no. 428]. Am J Gastroenterol 1996; 91: 1993
Wiedrick JED, Friesen EG, Garton AM, et al. Upper gastrointestinal bleeding associated with oral ketorolac therapy. Ann Pharmacother 1994 Sep; 28: 1109
Rosen DMB, Houghton CRS. Ketorolac. Med J Aust 1993 Oct 4; 159: 490
Read JRM, Bainton R. Operative haemorrhage in association with ketorolac. Anaesthesia 1994 Jan; 49: 73–4
Gales BJ, Gales MA. Death associated with inappropriate ketorolac dosing [letter]. Ann Pharmacother 1995 Dec; 29: 1299
Garcia Rodriguez LA, Agostinis L, Cattaruzzi C, et al. Outpatient use of ketorolac and other NSAIDs and risk of upper gastrointestinal bleeding or perforation [abstract no. 007]. Pharmacoepidemiol Drug Saf 1996; 5 Suppl. 1: S3
Splinter WM, Rhine EJ, Roberts DW, et al. Preoperative ketorolac increases bleeding after tonsillectomy in children. Can J Anaesth 1996 Jun; 43: 560–3
Gunter JB, Varughese AM, Harrington JF, et al. Recovery and complications after tonsillectomy in children: a comparison of ketorolac and morphine. Anesth Analg 1995 Dec; 81: 1136–41
Gallagher JE, Blauth J, Fornadley JA. Perioperative ketorolac tromethamine and postoperative hemorrhage in cases of tonsillectomy and adenoidectomy. Laryngoscope 1995 Jun; 105: 606–9
Judkins JH, Dray TG, Hubbell RN. Intraoperative ketorolac and posttonsillectomy bleeding. Arch Otolaryngol Head Neck Surg 1996 Sep; 122: 937–40
Garcha IS, Bostwick J. Postoperative hematomas associated with Toradol [letter] [see comments]. Plast Reconstr Surg 1991 Nov; 88: 919–20
Murray MD, Brater DC. Adverse effects of nonsteroidal antiinflammatory drugs on renal function. Ann Intern Med 1990; 112(8): 559–60
Abraham PA, Matzke GR. Drug-induced renal disease. In: DiPiro JT, Talbert RL, Hayes PE, et al., editors. Pharmacotherapy: a physiologic approach. New York: Elsevier, 1989: 543–58
Henrich WL, Agodoa LE, Barrett B, et al. National Kidney Foundation Position Paper: Analgesics and the Kidney: summary and recommendations to the Scientific Advisory Board of the National Kidney Foundation from an Ad Hoc Committee of the National Kidney Foundation. Am J Kidney Dis 1996 Jan; 27: 162–5
DuBose Jr TD, Molony DA, Verani R, et al. Nephrotoxicity of non-steroidal anti-inflammatory drugs. Lancet 1994 Aug 20; 344: 515–8
Murray RP, Watson RC. Acute renal failure and gastrointestinal bleed associated with postoperative Toradol and vancomycin. Orthopedics 1993 Dec; 16: 1361–3
Corelli RL, Gericke KR. Renal insufficiency associated with intramuscular administration of ketorolac tromethamine. Ann Pharmacother 1993 Sep; 27: 1055–7
Ketorolac and renal failure. Med J Aust 1993 Oct 4; 159: 488
Boras-Uber LA, Brackett JNC. Ketorolac-induced acute renal failure. Am J Med 1992 Apr; 92: 450–2
Fong J, Gora ML. Reversible renal insufficiency following ketorolac therapy. Ann Pharmacother 1993 Apr; 27: 510–2
Schoch PH, Ranno A, North DS. Acute renal failure in an elderly woman following intramuscular ketorolac administration. Ann Pharmacother 1992 Oct; 26: 1233–6
Perazella MA, Buller GK. NSAID nephrotoxicity revisited: acute renal failure due to parenteral ketorolac. South Med J 1993 Dec; 86: 1421–4
Haragsim L, Dalai R, Bagga H, et al. Ketorolac-induced acute renal failure and hyperkalemia: report of three cases. Am J Kidney Dis 1994; 24(4): 578–80
Smith K, Halliwell RMT, Lawrence S, et al. Acute renal failure associated with intramuscular ketorolac. Anaesth Intensive Care 1993 Oct; 21: 700–2
Pearce CJ, Gonzalez FM, Wallin JD. Renal failure and hyperkalemia associated with ketorolac tromethamine. Arch Intern Med 1993 Apr 26; 153: 1000–2
Kelley M, Bastani B. Ketorolac-induced acute renal failure and hyperkalemia [letter]. Clin Nephrol 1995 Oct; 44: 276–7
Ketorolac and renal failure. Aust Adv Drug React Bull 1994 Feb; 13: 3
Buck ML, Norwood VF. Ketorolac-induced acute renal failure in a previously healthy adolescent. Pediatrics 1996 Aug; 98 (Pt 1): 294–6
Randi ML, Tison T, Luzzatto G. Haemolytic uraemic syndrome during treatment with ketorolac trometamol. BMJ 1993 Jan 16; 306: 186
Sitz KV, Engler RJM, Carpenter GB. Ketorolac tromethamine (Toradol) induced asthma: a case report. Ann Allergy 1992 Jan; 68: 115
Alamar R, Arrufat R, Castellô JV, et al. Ketorolac (Kc) idiosyncrasy. Allergy 1993; 48 Suppl. 16: 144
Fournier DC, Linehan AT, Hilman BC. A case of ketorolac induced asthma in an adult with aspirin sensitivity. J Allergy Clin Immunol 1991 Jan; 87: 275
Gijsbers AJ, Clarke BG. Ketorolac. Med J Aust 1993 May 17; 158: 720
Zikowski D, Hord AH, Haddox JD. Ketorolac-induced bronchospasm. Anesth Analg 1993 Feb; 76: 417–9
Haddow GR, Riley E, Isaacs R, et al. Ketorolac, nasal polyposis, and bronchial asthma: a cause for concern. Anesth Analg 1993 Feb; 76: 420–2
Hebert WG, Scopelitis E. Ketorolac-precipitated asthma. South Med J 1994 Feb; 87: 282–3
Goetz CM, Sterchele JA, Harchelroad FR. Anaphylactoid reaction following ketorolac tromethamine administration. Ann Pharmacother 1992 Oct; 26: 1237–8
Hare RM. Reaction to ketorolac. Anaesth Intensive Care 1993 Aug; 21: 477
Shapiro N. Acute angioedema after ketorolac ingestion: report of case. J Oral Maxillofac Surg 1994 Jun; 52: 626–7
Schaab KC, Dickinson ET, Setzen G. Acute sensorineural hearing loss following intravenous ketorolac administration. J Emerg Med 1995; 13(4): 509–13
British National Formulary Number 31 ed. British Medical Society and Royal Pharmaceutical Society of Great Britian, London:, 1996
Acute pain management in adults: operative procedures. Am Fam Physician 1992 July; 46(1): 128–38
Acute pain management in infants, children and adolescents: operative and medical procedures. Am Fam Physician 1992 August; 46: 469–79
White PF. Management of postoperative pain and emesis. Can J Anaesth 1995 Nov; 42: 1053–5
Postoperative pain relief and non-opioid analgesics [editorial]. Lancet 1991 Mar 2; 337: 524–6
Author information
Authors and Affiliations
Corresponding author
Additional information
Various sections of the manuscript reviewed by: E. Alon, Department of Anesthesiology, Zurich University Hospital, Zurich, Switzerland; B. Bastani, Department of Internal Medicine, Health Sciences Center School of Medicine, St Louis University, St Louis, Missouri, USA; A.L. Buchman, Division of Gastroenterology Baylor College of Medicine, Houston, Texas, USA; D.B. Carr, Department of Anesthesia, New England Medical Center, Boston, Massachusetts, USA; J.N. Cashman, Department of Anaesthesia, St George’s Hospital, London, England; D. Fletcher, Département d’Anesthésie-Réanimation Chirurgicale, Hôpital de Bicêtre, Paris, France; P.J. Hughes, Anaesthetist, Central Anaesthetic Group, Melbourne, Victoria, Australia; F. Jamali, Faculty of Pharmacy, University of Alberta, Edmonton, Alberta, Canada; S.H. Roth, Arthritis Center Limited, Phoenix, Arizona, USA; A. Stein, Department of Urology, The Lady Davis Carmel Medical Center, Haifa, Israel.
Rights and permissions
About this article
Cite this article
Gillis, J.C., Brogden, R.N. Ketorolac. Drugs 53, 139–188 (1997). https://doi.org/10.2165/00003495-199753010-00012
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-199753010-00012