Infusion Of Ketorolac Research Articles

A Double-Blind Randomized Controlled Trial of Continuous Intravenous Ketorolac vs Placebo for Adjuvant Pain Control After Renal Surgery

ObjectiveTo evaluate the efficacy and safety of a novel, continuous intravenous infusion of ketorolac, a powerful nonopioid analgesic, for postoperative pain control. Patients and MethodsA prospective, double-blind, randomized, placebo-controlled trial of a continuous infusion of ketorolac tromethamine in 1 L of normal saline vs placebo was performed in 135 patients aged 18 to 75 years after laparoscopic donor nephrectomy or percutaneous nephrolithotomy completed from October 7, 2008, through July 21, 2010. Primary study end points were the 24-hour differences in visual analog pain scores and total narcotic consumption, whereas secondary end points were differences in urine output, serum creatinine level, and hemoglobin level. ResultsThe study was stopped after randomization of 135 patients (68 in the ketorolac group and 67 in the placebo group) when interim analysis indicated that the difference in mean pain scores between the 2 groups (difference, 0.6) was smaller than the 1-point threshold set forth in the power calculations. No statistically significant change was noted in hemoglobin levels from preoperative to postoperative values (P=.13) or in postoperative serum creatinine levels (P=.13). ConclusionAlthough continuous infusion of ketorolac produced only a modest decrease in the use of narcotics, it appears to offer a safe therapeutic option for nonnarcotic pain control. Trial Registrationclinicaltrials.gov Identifiers: NCT00765128 and NCT00765232

Low dose ketorolac infusion improves postoperative analgesia combined with patient controlled fentanyl analgesia after living donor hepatectomy – Randomized controlled trial

BackgroundHepatectomy elaborates significant post-operative pain. Opioids represent cornerstone for post-operative analgesia in such cases. This study examined the therapeutic effect and outcome of adding low dose ketorolac tromethamine infusion to PO intravenous patient controlled fentanyl analgesia IV-PCA.Patients and methodsSixty right lobe donors were randomized into either fentanyl or ketorolac groups (30 patients each). Patients in both groups received fentanyl (2 μg/ml) solution in normal saline as IV-PCA with background infusion in a rate adjusted to deliver 0.25 μg kg h−1 and boluses of 10 ml with a lock-out time of 20 min. They received 15 mg ketorolac IV bolus in ketorolac group and similar placebo injection in the control. Patients in both groups received a continuous intravenous infusion of 240 ml normal saline solution that is either free in the FENT group or containing 60 mg ketorolac in ketorolac group, adjusted to a rate of 0.2 ml kg h−1. Visual analogue score (VAS) and hemodynamic profile were recorded at 1, 6, 12, 24, 36 and 48 h while laboratory results were recorded after 48 h and 7 days post-operatively.ResultsVAS was significantly lower in ketorolac group compared to fentanyl group from 6 to 36 h post-operatively while sedation score was significantly higher in fentanyl group compared to fentanyl–ketorolac group between 12 and 36 h post-operatively. Fentanyl consumption was significantly lower in ketorolac group at 24 (318.7 ± 66 vs 468.3 ± 79) and 48 (211.5 ± 59 vs 369.1 ± 68) h. Hemodynamic data and laboratory parameters were comparable in both groups. Nausea had a significantly higher incidence in FENT compared to KETR groups while other complications (vomiting and blood loss) were homogenous in both groups.ConclusionAdding ketorolac to IV PCA fentanyl improved the analgesic state and reduced the dose of fentanyl used without adding any side effects or risks to donors subjected to right lobe hepatectomy.

Continuous Bupivacaine Infusion Post-Iliac Crest Bone Graft Harvesting in Pediatric Cleft Surgery: Role and Comparison with Ketorolac

To investigate the use of intravenous ketorolac and iliac crest bupivacaine infusion in the management of iliac crest donor-site pain in the pediatric cleft population. The null hypothesis was there is no difference with respect to pain scores between ketorolac and iliac crest bupivacaine infusion as analgesic adjuncts to intravenous opioids. A total of 54 children and adolescents (27 boys, 27 girls) undergoing alveolar cleft repair or Le Fort I osteotomy were assigned randomly in a prospective, single-blinded fashion to one of three groups: intravenous ketorolac plus iliac crest normal saline infusion, intravenous ketorolac plus iliac crest bupivacaine infusion, or iliac crest bupivacaine infusion alone. Iliac crest infusions and ketorolac were administered for 48 hours or until discharge, whichever occurred first. All patients received morphine via a patient-controlled analgesia device. Primary outcome was pain score, and secondary outcomes were morphine consumption and satisfaction scores. Pain scores, morphine consumption, and satisfaction scores were not significantly different among groups. Estimated costs were significantly higher for bupivacaine infusion than intravenous ketorolac. Iliac crest donor-site pain is well managed in this patient population. Intravenous ketorolac and iliac crest bupivacaine infusion provide comparable analgesia for iliac crest bone graft donor-site pain in children and adolescents.

Mechanisms of ATP-mediated vasodilation in humans: modest role for nitric oxide and vasodilating prostaglandins

ATP is an endothelium-dependent vasodilator, and findings regarding the underlying signaling mechanisms are equivocal. We sought to determine the independent and interactive roles of nitric oxide (NO) and vasodilating prostaglandins (PGs) in ATP-mediated vasodilation in young, healthy humans and determine whether any potential role was dependent on ATP dose or the timing of inhibition. In protocol 1 (n = 18), a dose-response curve to intrabrachial infusion of ATP was performed before and after both single and combined inhibition of NO synthase [N(G)-monomethyl-L-arginine (L-NMMA)] and cyclooxygenase (ketorolac). Forearm blood flow (FBF) was measured via venous occlusion plethysmography and forearm vascular conductance (FVC) was calculated. In this protocol, neither individual nor combined NO/PG inhibition had any effect on the vasodilatory response (P = 0.22-0.99). In protocol 2 (n = 16), we determined whether any possible contribution of both NO and PGs to ATP vasodilation was greater at low vs. high doses of ATP and whether inhibition during steady-state infusion of the respective dose of ATP impacted the dilation. FBF in this protocol was measured via Doppler ultrasound. In protocol 2, infusion of low (n = 8)- and high-dose (n = 8) ATP for 5 min evoked a significant increase in FVC above baseline (low = 198 ± 24%; high = 706 ± 79%). Infusion of L-NMMA and ketorolac together reduced steady-state FVC during both low- and high-dose ATP (P < 0.05), and in a subsequent trial with continuous NO/PG blockade, the vasodilator response from baseline to 5 min of steady-state infusion was similarly reduced for both low (ΔFVC = -31 ± 11%)- and high-dose ATP (ΔFVC -25 ± 11%; P = 0.70 low vs. high dose). Collectively, our findings indicate a potential modest role for NO and PGs in the vasodilatory response to exogenous ATP in the human forearm that does not appear to be dose or timing dependent; however, this is dependent on the method for assessing forearm vascular responses. Importantly, the majority of ATP-mediated vasodilation is independent of these putative endothelium-dependent pathways in humans.

Combined inhibition of nitric oxide and vasodilating prostaglandins abolishes forearm vasodilatation to systemic hypoxia in healthy humans

We tested the hypothesis that nitric oxide (NO) and vasodilating prostaglandins (PGs) contribute independently to hypoxic vasodilatation, and that combined inhibition would reveal a synergistic role for these two pathways in the regulation of peripheral vascular tone. In 20 healthy adults, we measured forearm blood flow (Doppler ultrasound) and calculated forearm vascular conductance (FVC) responses to steady-state (SS) isocapnic hypoxia (O₂ saturation ~85%). All trials were performed during local α- and β-adrenoceptor blockade (via a brachial artery catheter) to eliminate sympathoadrenal influences on vascular tone and thus isolate local vasodilatory mechanisms. The individual and combined effects of NO synthase (NOS) and cyclooxygenase (COX) inhibition were determined by quantifying the vasodilatation from rest to SS hypoxia, as well as by quantifying how each inhibitor reduced vascular tone during hypoxia. Three hypoxia trials were performed in each subject. In group 1 (n = 10), trial 1, 5 min of SS hypoxia increased FVC from baseline (21 ± 3%; P < 0.05). Infusion of N(G)-nitro-L-arginine methyl ester (L-NAME) for 5 min to inhibit NOS during continuous SS hypoxia reduced FVC by -33 ± 3% (P < 0.05). In Trial 2 with continuous NOS inhibition, the increase in FVC from baseline to SS hypoxia was similar to control conditions (20 ± 3%), and infusion of ketorolac for 5 min to inhibit COX during continuous SS hypoxia reduced FVC by -15 ± 3% (P < 0.05). In Trial 3 with combined NOS and COX inhibition, the increase in FVC from baseline to SS hypoxia was abolished (~3%; NS vs. zero). In group 2 (n = 10), the order of NOS and COX inhibition was reversed. In trial 1, five minutes of SS hypoxia increased FVC from baseline (by 24 ± 5%; P < 0.05), and infusion of ketorolac during SS hypoxia had minimal impact on FVC (-4 ± 3%; NS). In Trial 2 with continuous COX inhibition, the increase in FVC from baseline to SS hypoxia was similar to control conditions (27 ± 4%), and infusion of L-NAME during continuous SS hypoxia reduced FVC by -36 ± 7% (P < 0.05). In Trial 3 with combined NOS and COX inhibition, the increase in FVC from baseline to SS hypoxia was abolished (~3%; NS vs. zero). Our collective findings indicate that (1) neither NO nor PGs are obligatory to observe the normal local vasodilatory response from rest to SS hypoxia; (2) NO regulates vascular tone during hypoxia independent of the COX pathway, whereas PGs only regulate vascular tone during hypoxia when NOS is inhibited; and (3) combined inhibition of NO and PGs abolishes local hypoxic vasodilatation (from rest to SS hypoxia) in the forearm circulation of healthy humans during systemic hypoxia.

Ketorolac or fentanyl continuous infusion for post-operative analgesia in children undergoing ureteroneocystostomy

children undergoing ureteroneocystostomy suffer from post-operative pain due to the surgical incision and bladder spasm. A single-shot caudal block is a common technique for paediatric analgesia, but a disadvantage is the limitation of a short duration in spite of the additives co-administered. A few clinical trials have shown that ketorolac provides an effective post-operative analgesia and reduces the bladder spasms after ureteral implantation in children. We compared the efficacy of a continuous infusion of ketorolac and fentanyl in post-operative analgesia and bladder spasm in children who underwent ureteroneocystostomy. fifty-two children were allocated to the ketorolac group (Group K, n=26) and fentanyl group (Group F, n=26). After general anaesthesia, a caudal block was performed with 1.5 ml/kg of 0.15% ropivacaine. At the beginning of surgery, an infusion was started after the bolus injection of ketorolac 0.5 mg/kg or fentanyl 1 microg/kg. An infusion device was programmed to deliver ketorolac 83.3 microg/kg/h or fentanyl 0.17 microg/kg/h for 48 h. two of Group F and three of Group K were excluded from the study. Post-operative pain scores were similar between the two groups. One of Group K (4%) and seven of Group F (30.4%) experienced bladder spasms. The rescue analgesic requirements were significantly less in Group K. a Continuous infusion of ketorolac provided effective analgesia after operation in children who underwent ureteroneocystostomy as well as a low dosage of fentanyl. Ketorolac was more effective in reducing the frequency of bladder spasms and rescue analgesic requirements.

Roles of nitric oxide synthase and cyclooxygenase in leg vasodilation and oxygen consumption during prolonged low-intensity exercise in untrained humans

The vasodilator signals regulating muscle blood flow during exercise are unclear. We tested the hypothesis that in young adults leg muscle vasodilation during steady-state exercise would be reduced independently by sequential pharmacological inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX) with NG-nitro-L-arginine methyl ester (L-NAME) and ketorolac, respectively. We tested a second hypothesis that NOS and COX inhibition would increase leg oxygen consumption (VO2) based on the reported inhibition of mitochondrial respiration by nitric oxide. In 13 young adults, we measured heart rate (ECG), blood pressure (femoral venous and arterial catheters), blood gases, and venous oxygen saturation (indwelling femoral venous oximeter) during prolonged (25 min) steady-state dynamic knee extension exercise (60 kick/min, 19 W). Leg blood flow (LBF) was determined by Doppler ultrasound of the femoral artery. Whole body VO2 was measured, and leg VO2 was calculated from blood gases and LBF. Resting intra-arterial infusions of acetylcholine (ACh) and nitroprusside (NTP) tested inhibitor efficacy. Leg vascular conductance (LVC) to ACh was reduced up to 53±4% by L-NAME+ketorolac infusion, and the LVC responses to NTP were unaltered. Exercise increased LVC from 4±1 to 33.1±2 ml.min(-1).mmHg(-1) and tended to decrease after L-NAME infusion (31±2 ml.min(-1).mmHg(-1), P=0.09). With subsequent administration of ketorolac LVC decreased to 29.6±2 ml.min(-1).mmHg(-1) (P=0.02; n=9). While exercise continued, LVC returned to control values (33±2 ml.min(-1).mmHg(-1)) within 3 min, suggesting involvement of additional vasodilator mechanisms. In four additional subjects, LVC tended to decrease with L-NAME infusion alone (P=0.08) but did not demonstrate the transient recovery. Whole body and leg VO2 increased with exercise but were not altered by L-NAME or L-NAME+ketorolac. These data indicate a modest role for NOS- and COX-mediated vasodilation in the leg of exercising humans during prolonged steady-state exercise, which can be restored acutely. Furthermore, NOS and COX do not appear to influence muscle VO2 in untrained healthy young adults.

Is Intravenous Patient Controlled Analgesia Enough for Pain Control in Patients Who Underwent Thoracoscopy?

This prospective randomized study was conducted to evaluate the efficacy of two common analgesic techniques, thoracic epidural patient-controlled analgesia (Epidural PCA), and intravenous patient-controlled analgesia (IV PCA), in patients undergoing lobectomy by the video-assisted thoracic surgical (VATS) approach. Fifty-two patients scheduled for VATS lobectomy were randomly allocated into two groups: an Epidural PCA group receiving an epidural infusion of ropivacaine 0.2%+fentanyl 5 µg/mL combination at a rate of 4 mL/hr, and an IV PCA group receiving an intravenous infusion of ketorolac 0.2 mg/kg+fentanyl 15 µg/mL combination at a rate of 1 mL/hr. Pain scores were then recorded using the visual analogue scale at rest and during motion (VAS-R and VAS-M, 0-10) for five days following surgery. In addition, we measured the daily morphine consumption, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), satisfaction score, and the incidence of side effects. Thirty-seven patients out of 52 completed the study (18 in the Epidural PCA group, 19 in the IV PCA group). There were no differences in the pain scores, analgesic requirements, pulmonary function, satisfaction score, and the incidence of side effects between groups. This indicates that IV PCA and Epidural PCA are equally effective to control the postoperative pain after VATS lobectomy, which suggests that IV PCA may be used instead of Epidural PCA.

Leg exercise hyperemia: role of nitric oxide synthase and cyclooxygenase

The key vascular signals regulating muscle blood flow during exercise are unclear. We tested the hypothesis that in young adults, leg blood flow (LBF) during exercise would be reduced independently by pharmacological inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX). In 13 young adults, we measured heart rate (ECG), blood pressure (femoral artery and vein), blood gases, and venous oxygen saturation (indwelling oximeter) during steady‐state dynamic (60/min) knee extension exercise. LBF was determined by Doppler ultrasound of the femoral artery. Exercise (20W) increased leg vascular conductance (LVC) from 4± 1 to 33± 3 ml/min/100mmHg. The NOS inhibitor L‐NAME reduced LVC by ∼10% to 30± 1. Infusion of the COX inhibitor, ketoralac (n=9), increased LVC from 30± 1 to 34± 2. L‐NAME infusion reduced venous oxygen saturation from 48 to 38%, suggesting greater extraction to maintain oxygen consumption. Control intra‐arterial infusions of acetylcholine (ACH) and nitroprusside (NTP) tested inhibitor efficacy. The change in LVC to two doses of ACh was blunted 53 and 15%, by L‐NAME+ketorolac infusion. In contrast, the LVC responses to NTP were unaltered. These data implicate a modest role for NO‐mediated leg exercise hyperemia in adults and a potentially modest LBF restraint by vasoconstrictor prostaglandins. Funded by the NIH HL‐46493 and the Minnesota Obesity Center.

Terminating Migraine With Allodynia and Ongoing Central Sensitization Using Parenteral Administration of COX1/COX2 Inhibitors

To determine whether delayed infusion of COX1/COX2 inhibitors (ketorolac, indomethacin) will stop migraine in allodynic patients, and suppress ongoing sensitization in central trigeminovascular neurons in the rat. The majority of migraineurs seeking secondary or tertiary medical care develop cutaneous allodynia during the course of migraine, a sensory abnormality mediated by sensitization of central trigeminovascular neurons in the spinal trigeminal nucleus. Triptan therapy can render allodynic migraineurs pain free within a narrow window of time (20 to 120 minutes) that opens with the onset of pain and closes with the establishment of central sensitization. Can drugs that tackle ongoing central sensitization render allodynic migraineurs pain free after the window for triptan therapy has expired? Patients exhibiting migraine with allodynia were divided in two groups (n=14, each): group 1 received delayed sumatriptan injection (6 mg) 4 hours after onset of attack--which failed to render them pain free-and ketorolac infusion (two 15-mg boluses) 2 hours later; group 2 received delayed ketorolac monotherapy 4 hours after onset of attack. Pain intensity (visual analog scale) and skin sensitivity (quantitative sensory testing) were measured when the patients were migraine free (baseline); 4 hours after onset of migraine (just before treatment); 2 hours after sumatriptan; 1 hour after ketorolac. In the rat, we tested whether infusion of ketorolac (0.4 mg/kg) or indomethacin (1 mg/kg) will block ongoing sensitization in peripheral and central trigeminovascular neurons. The induction of sensitization (using topical application of inflammatory soup on the dura) and its suppression by COX1/COX2 inhibitors were assessed by monitoring changes in spontaneous activity and responses to mechanical and thermal stimuli. Patients had normal skin sensitivity in the absence of migraine, and presented cutaneous allodynia 4 hours after onset of migraine. In group 1, all patients continued to exhibit allodynia 2 hours after sumatriptan treatment, and none of them became pain free. However, 71% and 64% of the patients in groups 1 and 2, respectively, were rendered free of pain and allodynia within 60 minutes of ketorolac infusion. Nonresponders from both groups, in contrast to the responders, had had a history of opioid treatment. In the rat, infusion of COX1/COX2 inhibitors blocked sensitization in meningeal nociceptors and suppressed ongoing sensitization in spinal trigeminovascular neurons. This inhibitory action was reflected by normalization of neuronal firing rate and attenuation of neuronal responsiveness to mechanical stimulation of the dura, as well as mechanical and thermal stimulation of the skin. The termination of migraine with ongoing allodynia using COX1/COX2 inhibitors is achieved through the suppression of central sensitization. Although parenteral administration of COX1/COX2 inhibitors is impractical as routine migraine therapy, it should be the rescue therapy of choice for patients seeking emergency care for migraine. These patients should never be treated with opioids, particularly if they had no prior opioid exposure.

The Effects of Perioperative Ketorolac Infusion on Platelet Function and Blood Loss: Comparison of Anesthesia Methods

Background: The purposes of this study were to investigate the effects of perioperative continuous infusion of ketorolac on platelet function and blood loss under either general or spinal anesthesia. Methods: The patients under general anesthesia received saline 1 ml (C group) or ketorolac 30 mg (GK group) intravenously 10 min before skin incision, followed, respectively, by a continuous infusion of saline (4 ml/h) or ketorolac (2.5 mg/h) for 24 h. The patients under spinal anesthesia (SK group) received the same amount of ketorolac as that of the GK group. Blood loss was collected and measured at 3 h, 6 h, 12 h and 24 h postincision. Platelet count, hemoglobin, platelet aggregometry (PA) with adenosine diphosphate (ADP) and collagen, and bleeding time (BT) were measured at 30 min before skin incision and at 3 h and 24 h postincision. Blood coagulation status was analysed using thromboelastography (TEG) at 30 min before skin incision and at 3 h postincision. Results: BT in the SK group at postincision increased significantly compared to preoperative value and were significantly higher than those of the GK and C group. PA with collagen at 3 h after skin incision was lower in the SK group than in the C group. There were no significant differences in any of the TEG variables among the three groups. No significant differences were observed in blood loss among the three groups. Conclusions: Blood loss was not increased by ketorolac under either general or spinal anesthesia, although platelet function was impaired under spinal anesthesia.

Local inhibition of nitric oxide and prostaglandins independently reduces forearm exercise hyperaemia in humans.

We tested the hypothesis that inhibition of synthesis of either nitric oxide (NO) or vasodilating prostaglandins (PGs) would not alter exercise hyperaemia significantly, but combined inhibition would synergistically reduce the hyperaemia. Fourteen subjects performed 20 min of moderate rhythmic forearm exercise (10% maximal voluntary contraction). Forearm blood flow (FBF) was measured by Doppler ultrasound. Saline or study drugs were infused (2 ml x min(-1)) into the forearm via a brachial artery catheter to locally inhibit synthesis of NO and PGs during steady state exercise (N(G)-nitro-L-arginine methyl ester (L-NAME), 25 mg over 5 min to inhibit NO synthase (NOS); and ketorolac, 3 mg over 5 min to inhibit cyclooxygenase (COX)). After achieving steady state exercise over 5 min (control), L-NAME was infused for 5 min, followed by 2 min saline, then by a 5 min infusion of ketorolac, and finally by 3 min of saline (n= 7). Drug order was reversed in seven additional subjects, such that single inhibition of NOS or COX was followed by combined inhibition. FBF during exercise decreased to 83 +/- 2% of control exercise (100%) with NOS inhibition, followed by a transient decrease to 68 +/- 2% of control during COX inhibition. However, FBF returned to levels similar to those achieved during NOS inhibition within 2 min (80 +/- 3% of control) and remained stable through the final 3 min of exercise. When COX inhibition was performed first, FBF decreased transiently to 88 +/- 4% of control (P < 0.01), and returned to control saline levels by the end of ketorolac infusion. Addition of L-NAME reduced FBF to 83 +/- 3% of control, and it remained stable through to the end of exercise. Regardless of drug order, FBF was approximately 80% of steady state control exercise (P < 0.01) during the last 30 s of exercise. We conclude that (1). NO provides a significant, consistent contribution to hyperaemia, (2). PGs contribute modestly and transiently, suggesting a redundant signal compensates for the loss of vasodilating PGs, and (3). NO and PG signals appear to contribute independently to forearm exercise hyperaemia.

Intrathecal Ketorolac in Dogs and Rats

This study was conducted to assess spinal safety of the cyclo-oxygenase inhibitor ketorolac in dogs and rats. Beagle dogs were prepared with lumbar intrathecal catheters and received continuous spinal infusions of 5 mg/ml ketorolac (N = 6), 0.5 mg/ml ketorolac (N = 8), or saline vehicle (N = 6) at 50 microl/h (1.2 ml/day) for 28 days. No systematic drug or dose-related changes were observed in motor function, heart rate, or blood pressure. Histological examination revealed a mild pericatheter reaction in all groups with no drug or dose related effect upon spinal pathology at the lumbar site of highest drug concentration. Cisternal CSF protein was elevated for all treatment groups at necropsy, and cisternal glucose was within normal range for all treatment groups, though three dogs displayed decreases in cisternal glucose. Significant reductions in hematocrit were noted, and increased incidence of gastric bleeding at necropsy was observed in animals receiving ketorolac. Intrathecal ketorolac kinetics revealed a biphasic clearance: t1/2 s = 10.3 and 53 min, respectively. After initiation of infusion (0.5 mg and 5 mg/ml/50 microl/h), lumbar CSF concentrations of ketorolac were 3.8 and 52.7 microg/ml, respectively. Bolus and continuous infusion of intrathecal ketorolac resulted in significant reduction of lumbar CSF PGE2 concentrations. In rats, with intrathecal catheters, four daily bolus deliveries of saline or ketorolac (5 mg/ml/10 microl) had no effect upon spinal histology or upon spinal cord blood flow. These data indicate that intrathecal ketorolac in two species at the dose/concentrations employed does not induce evident spinal pathology but diminishes spinal prostaglandin release.

Pharmacokinetics and efficacy of ropivacaine continuous wound instillation after joint replacement surgery

As continuous wound instillation with local anaesthetic has not been evaluated after hip/knee arthroplasties, our study was designed to determine whether this technique could enhance analgesia and improve patient outcome after joint replacement surgery. Thirty-seven patients undergoing elective hip/knee arthroplasties under spinal block were randomly assigned to two analgesia groups. Group M received continuous i.v. infusion of morphine plus ketorolac for 24 h. Then, a multi-hole 16 G catheter was placed subcutaneously and infusion of saline was maintained for 55 h. Group R received i.v. saline. Thereafter the wound was infiltrated with a solution of ropivacaine 0.5% 40 ml, then a multi-hole 16 G catheter was placed subcutaneously and an infusion of ropivacaine 0.2% 5 ml h(-1) was maintained for 55 h. Visual analogue scale scores were assessed at rest and on passive mobilization by nurses blinded to analgesic treatment. Total plasma ropivacaine concentration was measured. Group R showed a significant reduction in postoperative pain at rest and on mobilization, while rescue medication requirements were greater in Group M. Total ropivacaine plasma concentration remained below toxic concentrations and no adverse effects occurred. Length of hospital stay was shorter in Group R. Infiltration and wound instillation with ropivacaine 0.2% is more effective in controlling postoperative pain than systemic analgesia after major joint replacement surgery.

Ketoprofen, Diclofenac or Ketorolac for Pain After Tonsillectomy in Adults?

We have compared the analgesic and opioid sparing effect of three i.v. non-steroidal anti-inflammatory drugs with placebo in a randomized, double-blind, placebo-controlled study in 80 adult patients after elective tonsillectomy. A standard anaesthetic was used. After induction of anaesthesia, patients received ketoprofen 100 mg, diclofenac 75 mg or ketorolac 30 mg by i.v. infusion over 30 min. Patients in the placebo group received saline. Ketoprofen and diclofenac infusions were repeated after 12 h and ketorolac infusion at 6 h and 12 h. Oxycodone was used as rescue analgesic. Patients in the ketoprofen group requested 32% less opioid and patients in the diclofenac and ketorolac groups 42% less opioid than those in the placebo group (P < 0.05). There were one, two and six patients in the placebo, diclofenac and ketorolac groups, respectively, but none in the ketoprofen group, who did not request opioid analgesia during the study (P < 0.05, ketorolac vs placebo and ketoprofen). Visual analogue pain scores were similar in all groups. Visual analogue satisfaction scores were significantly higher in the diclofenac group compared with the placebo group. The incidence of nausea was 44-54%. There were no differences in the incidence of other adverse reactions. We conclude that all three non-steroidal anti-inflammatory drugs were superior to placebo after tonsillectomy.

I.v. diclofenac and ketorolac for pain after thoracoscopic surgery

We studied intensity of pain, cumulative morphine consumption, ventilatory and renal function, and haemostasis in patients undergoing video-assisted thoracoscopic surgery and receiving a 2-day i.v. infusion of diclofenac, ketorolac or saline. Plasma concentrations of the two NSAID were also measured. The study was randomized, double-blind and placebo-controlled, with 10 patients in each group. Patients experienced mainly moderate pain. Mean consumption of i.v. morphine during the first day after operation was 57 (SEM 11) mg in the placebo group. Diclofenac and ketorolac were equally effective in reducing total morphine consumption (61% and 52%, respectively). Adverse events were similar and minor. Greater variability in plasma concentrations of ketorolac were detected compared with diclofenac.

Ketoprofen, diclofenac or ketorolac for pain after tonsillectomy in adults?

We have compared the analgesic and opioid sparing effect of three i.v. non-steroidal anti-inflammatory drugs with placebo in a randomized, double-blind, placebo-controlled study in 80 adult patients after elective tonsillectomy. A standard anaesthetic was used. After induction of anaesthesia, patients received ketoprofen 100 mg, diclofenac 75 mg or ketorolac 30 mg by i.v. infusion over 30 min. Patients in the placebo group received saline. Ketoprofen and diclofenac infusions were repeated after 12 h and ketorolac infusion at 6 h and 12 h. Oxycodone was used as rescue analgesic. Patients in the ketoprofen group requested 32% less opioid and patients in the diclofenac and ketorolac groups 42% less opioid than those in the placebo group (P < 0.05). There were one, two and six patients in the placebo, diclofenac and ketorolac groups, respectively, but none in the ketoprofen group, who did not request opioid analgesia during the study (P < 0.05, ketorolac vs placebo and ketoprofen). Visual analogue pain scores were similar in all groups. Visual analogue satisfaction scores were significantly higher in the diclofenac group compared with the placebo group. The incidence of nausea was 44-54%. There were no differences in the incidence of other adverse reactions. We conclude that all three non-steroidal anti-inflammatory drugs were superior to placebo after tonsillectomy.

Prolonged Central Intravenous Ketorolac Continuous Infusion in a Cancer Patient with Intractable Bone Pain

To report the case of a prolonged intravenous ketorolac continuous infusion given via a central line in a cancer patient with intractable bone pain. A 56-year-old Hispanic man with stage IV non-small-cell lung cancer and multiple bone metastases was admitted to the hospital for intractable pain inadequately controlled at home by conventional therapy. He was treated with an intravenous continuous infusion of ketorolac 120 mg in 250 mL of NaCl 0.9% infused over 24 hours. The ketorolac was given via a central line for 14 days in addition to fentanyl patient-controlled analgesia. Over this time period the patient reported his pain to be well controlled. His requests for bolus doses of fentanyl decreased dramatically and the dose of the continuous intravenous fentanyl was reduced by 22%. In addition, the total daily dose of ketorolac was reduced following a change from intermittent bolus dosing to a continuous infusion. The management of cancer pain secondary to bone metastasis is a difficult and challenging problem frequently encountered by the healthcare team. The use of nonsteroidal antiinflammatory drugs (NSAIDs) as adjuvant therapy is a common practice. However, many terminally ill patients are unable to take oral medications, thus limiting NSAID treatment options. Ketorolac tromethamine is approved by the Food and Drug Administration (FDA) as a parenteral NSAID. As with other NSAIDs, the risk of adverse drug reactions must be considered when using this class of medication. The FDA has approved ketorolac for the short-term (< or = 5 d) management of moderately severe acute pain that requires analgesia at the opioid level, usually in the postoperative setting. However, certain patients may benefit from long-term use exceeding the FDA-recommended guidelines of 5 days of maximum therapy. A prolonged central intravenous ketorolac continuous infusion was successful in treating a cancer patient with intractable bone pain secondary to widely metastatic non-small-cell lung cancer.

The Addition of Continuous Intravenous Infusion of Ketorolac to a Patient-Controlled Analgetic Morphine Regime Reduced Postoperative Myocardial Ischemia in Patients Undergoing Elective Total Hip or Knee Arthroplasty

This double-blind randomized trial assessed the effect of adding an intravenous continuous infusion of ketorolac to a patient-controlled analgesia (PCA) morphine regimen on analgesia, heart rate, arterial blood pressure, and postoperative myocardial ischemia. Patients having elective total hip or knee replacement were randomized to receive ketorolac 30 mg bolus, followed by an infusion of 5 mg/h for 24 h or placebo. All patients had access to PCA morphine (20 micro g/kg bolus, with a lockout of 6 min). Patients were monitored for pain visual analog scale, blood pressure, heart rate, and ST segment depression via a continuous Holter monitor. ST depression of 1 mm 60 ms after the J point was considered significant if it lasted more than 1 min. There was no difference in demographics, risk factors, or cardiac medications between the groups. Ketorolac-treated patients had significantly better pain control at 2, 6, and 24 h. There was significant morphine sparing at all times after 3 h. There was no difference in the number of ischemic events between the groups. The ischemic episodes of the patients who received ketorolac occurred at slower heart rates (97 +/- 15 vs 114 +/- 16 bpm, P = 0.001) than those of patients in the placebo group. The duration of ST depression was shorter in ketorolac-treated patients (24 +/- 35 vs 76 +/- 95 min, P < 0.05). All ST depressions were clinically silent. Logistic regression of factors predicting ischemia included the use of calcium channel blockers and low pain score. These results suggest that analgesia with ketorolac reduces the duration of ischemic episodes in the first 24 h postoperatively. (Anesth Analg 1997;84:715-22)

Ketorolac continuous infusion: A case report and review of the literature

We report a case of intractable pain due to metastatic carcinoma that was effectively managed with a continuous intravenous (IV) infusion of ketorolac. Unlike previous reports of short-term continuous IV ketorolac for postoperative analgesia, this case is unique because of the etiology of the pain and the duration of treatment. The published literature on continuous administration of ketorolac by the intravenous, intramuscular, and subcutaneous routes is also reviewed.