Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Low-molecular-weight heparins, when used in surgical patients for thromboprophylaxis, may be used concurrently with ketorolac, a non-steroidal anti-inflammatory drug that is used for analgesia. Because these two agents can influence the haemostatic system, it is important to identify any such effect. The haemostatic interaction between dalteparin and ketorolac was assessed in a double-blind, placebo-controlled, randomized, crossover study of healthy male volunteers each given all four combinations of ketorolac/placebo and dalteparin/placebo. The effect of ketorolac and dalteparin on haemostasis was assessed by measuring in-vitro platelet aggregation, anti-factor-Xa, activated partial thromboplastin times and skin bleeding time. The results were analysed for evidence of an interaction between ketorolac and dalteparin. Ketorolac inhibited platelet aggregation in whole blood and platelet-rich plasma. The administration of dalteparin led to a significant increase in levels of anti-factor-Xa and a significant prolongation in the activated partial thromboplastin time, although it remained within the range of the normal population. There was no evidence of any interaction between ketorolac and dalteparin with regard to platelet aggregation, anti-factor-Xa activity or activated partial thromboplastin time. The administration of ketorolac significantly prolonged the skin bleeding time. There was a significant interaction between ketorolac and dalteparin to prolong the bleeding time, although dalteparin alone had no effect on bleeding time. There was an interaction between ketorolac and dalteparin, which affected bleeding times. Such an interaction raises the possibility of haemorrhagic complications developing perioperatively when these agents are used concomitantly. Further studies are required to examine the clinical importance of this interaction.
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PMID:Effect of ketorolac and low-molecular-weight heparin individually and in combination on haemostasis. 1049 18

The management of severe pain may require "balanced analgesia," involving the use of analgesics with different modes of action. Clonidine, an alpha(2)-adrenoreceptor agonist produces analgesia by itself as well as when given with morphine and local anesthetics. Ketorolac is indicated for the management of moderately severe acute pain and causes analgesia equivalent to morphine. This study was designed to investigate whether the addition of ketorolac promotes antinociception produced by intrathecal administration of clonidine in male Sprague-Dawley rats. Intrathecal injection of clonidine (1-30 microg) induced a dose-dependent increase in antinociception as measured by the tail flick (TF) and hot plate tests. Ketorolac alone (150-600 microg) increased the antinociception by 50%-60% only in the TF test. Ketorolac (10 microg) decreased clonidine (10 microg)-induced antinociception from 69.1% +/- 7.8% to 23.5% +/- 1. 6% (P < 0.05) in the TF test and 35.7% +/- 4.7% to 4.5% +/- 0.1% (P < 0.05) maximum possible effect in the hot plate test. Ketorolac also antagonized the effect of 30 microg of clonidine. The opioid receptor antagonist naloxone antagonized the antinociceptive effect of clonidine and ketorolac, indicating the involvement of the opioid system in the antinociception produced by clonidine or ketorolac. However, neither clonidine nor ketorolac (10(-8) to 10(-3) M) inhibited the binding of specific ligands to mu-, delta-, and kappa-opioid receptors, indicating a lack of direct interaction of clonidine and ketorolac with opioid receptors. These results suggest that intrathecal injection of ketorolac antagonizes the antinociception produced by clonidine.
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PMID:Antagonism of antinociception produced by intrathecal clonidine by ketorolac in the rat: the role of the opioid system. 1078 70

The study objective was to assess the efficacy and patient acceptance of ketorolac as an alternative to meperidine for the treatment of severe musculoskeletal low back pain (LBP). A double blinded prospective trial in a convenience sample of patients >18 years of age presenting to an urban university hospital emergency department (ED) was conducted over a 19-month period. Patients were included if the pain was musculoskeletal in origin and was severe enough to warrant parenteral analgesics. Patients were randomized to receive 1 mg/kg meperidine intramuscularly (IM) or 60 mg ketorolac IM. Pain intensity was measured preadministration and at 60 minutes via a 100 mm Visual Analog Scale (VAS). Outcomes measured at 60 minutes were pain intensity decrease (PID), patient satisfaction, rescue analgesia requirement, sedation level, and adverse effects. Clinically significant pain reduction was defined as a PID of at least 13 mm or a reduction in pain of least 30%. One hundred fifty-five patients were enrolled (meperidine = 75, ketorolac = 80) and 153 patients completed the study. At 60 minutes the mean PID was 7 mm less in the ketorolac group (95% confidence interval [CI] - 15 mm to 2.6 mm). Pain reduction of at least 30% occurred in 63% of the ketorolac group versus 67% of the meperidine group (95% CI, odds ratio [OR] .43 to 1.61). Rescue analgesia was required in 35% of the ketorolac group versus 37% of the meperidine group (95% CI, OR .47 to 1.74). Patient satisfaction was less in the ketorolac group (ketorolac 68% satisfied versus meperidine 74% satisfied) however this was not significant (95% CI, OR .66 to 2.72). Sedation level and adverse effects were significantly greater in the meperidine group. Ketorolac shows comparable single dose analgesic efficacy to a single moderate dose of meperidine with less sedation and adverse effects in an ED population with severe musculoskeletal LBP. The trend for greater pain reduction and patient satisfaction with meperidine needs further investigation.
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PMID:Ketorolac versus meperidine: ED treatment of severe musculoskeletal low back pain. 1091 28

The success of out-patients laparoscopic surgery depends on a careful selection of patients and the ability of anesthetic technique to ensure a rapid emergence from anesthesia, with a satisfactory control of postoperative pain and the absence of side effects. This study was undertaken to investigate the influence of a total intravenous anesthetic management on the recovery process after laparoscopic varicocelectomy. Fifty-three ASA 1 patients aged 12-41 yrs (mean 26.02) scheduled to undergo laparoscopic varicocelectomy as day surgery procedure were included in this study. Propofol was used as inductor agent and in variable-rate infusion (170-100 mcg/Kg/min) to maintain anesthesia supplemented with Fentanyl (FNT) before endotracheal intubation, incision surgery and if the patient manifested clinical signs of inadequate analgesia. Local anesthesia was infiltrated into the skin before incision. Tramadol 100 mg and Ketorolac 30 mg were administered before the end of surgery to delay the onset of the postoperative pain. Pain was evaluated using a self-rating visual analoque scale (VAS) ranging from 0 to 10 at 0-0.5 hrs postoperatively and every 2 hrs until discharge. At the same time nausea was clinically evaluated using a scale ranging from 0 to 3. Postoperative pain and nausea (PONV) treatment were standardized. Patients were discharged by Post-Anesthesia Discharge Scoring System (PADS). Mean operating time was 34.2 min and mean estubation time was 11.6 min. At time 0 all patients had VAS pain score < 3, on the same time 2 of patients was treated for mild PONV; mean time to first request for postoperative analgesia treatment in 89% of patients was more than 6 hrs, 5 patients required pain treatment before discharge in a mean time 216' +/- 156'. Using the PADS system, 64% of patients were discharged at 4 hrs and 89% at 6 hrs after surgery. One patient was admitted to hospital for an overnight stay for walking dizziness; another was readmitted for surgical complications. This results suggest that the proposed anesthetic management provided adequate pain control with minimun postoperative nausea and a good recovery rate. This permitted a short postoperative hospital stay without compromising in safety, efficacy, or patient satisfaction.
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PMID:[Laparoscopic surgery of varicocele. Role of total endovenous anesthesia in same-day discharge]. 1112 41

Ketorolac is a nonsteroidal anti-inflammatory medication that is used widely for pain management. Its effects are mediated through the inhibition of prostaglandins, which makes it uniquely different from opioids in relieving pain. We conducted a randomized, prospective, double blind study of patients presenting to our Emergency Department (ED) with a diagnosis of acute biliary colic. Study patients were randomized into one of two treatment groups, meperidine 1.5 mg/kg with a maximum dose of 100 mg or ketorolac 60 mg given intramuscularly (i.m.). The patients rated their pain before and 30 min after medication on a scale of 1 to 10 using a Visual Analog Pain Scale. Overall pain relief was compared between the two groups using a two-sample t test. Thirty patients were enrolled in the study, 16 in the ketorolac group and 14 in the meperidine group. Patients ranged in age from 18 to 71 years and 6 (20%) were male. The average pain score at time 0 was 7.6 for the ketorolac group and 7.3 for the meperidine group. Pain relief at time 30 min was 3.8 in the ketorolac group and 3.9 in the meperidine group, which was not statistically different. The mean global pain score and need for an emergency cholecystectomy were similar in the two groups. Rescue medication for additional analgesia at 30 min was needed in 4 patients in the meperidine group and in 2 patients in the ketorolac group (28.6% versus 12.5%, respectively; NS). In this study of patients with acute biliary colic there was no significant difference in the pain relief achieved by using either ketorolac or meperidine.
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PMID:A prospective study comparing i.m. ketorolac with i.m. meperidine in the treatment of acute biliary colic. 1120 4

Ketorolac is frequently used as an adjunct for postoperative pain relief, especially by anesthesiologists during the immediate postoperative period. It can be used alone as an analgesic but is more often used to potentiate the actions of narcotics such as morphine or meperidine in an attempt to reduce the total dose and side effects of those drugs. The manufacturer of ketorolac cautions against its use in patients who have a high risk of postoperative bleeding, for fear of increasing the risk of hematoma, but the risk in transverse rectus abdominis musculocutaneous (TRAM) flap patients has never been reported. In a study of 215 patients who had undergone TRAM flap breast reconstruction, it was determined that patients who received intravenous ketorolac (n = 65) as an adjunct to their treatment with morphine administered by use of a patient-controlled analgesia device required less morphine (mean cumulative dose, 1.39 mg/kg) than did patients who did not receive ketorolac (n = 150; mean cumulative dose, 1.75 mg/kg; p = 0.02). There was no increase in the incidence of hematoma in patients who were treated with ketorolac. The data presented in this study suggest that the use of intravenous ketorolac does reduce the need for narcotics administration in patients undergoing TRAM flap breast reconstruction, without significantly increasing the risk of hematoma.
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PMID:Incidence of hematoma associated with ketorolac after TRAM flap breast reconstruction. 1121 49

While non-steroidal anti-inflammatory drugs (NSAIDs) are the mainstay of therapy for the management of acute pain and rheumatoid arthritis, toxicity associated with chronic administration limits their benefit-to-risk relationship in many patients. A series of studies is reviewed that assesses the relationship between cytokines released at the site of tissue injury and NSAID analgesia, and the in vivo selectivity of a selective cyclooxygenase (COX)-2 inhibitor (celecoxib) in comparison to a dual COX-1/COX-2 inhibitor (ketorolac). Three replicate studies in the oral surgery model of acute pain used submucosal microdialysis sample collection for the measurement of prostaglandin E2 (PGE2; a product of both COX-1 and COX-2) and thromboxane B2 (as a biomarker for COX-1 activity) with parallel assessments of pain. The time course of PGE2 production was consistent with early release due to COX-1 activity followed by increased production 2-3 hours after surgery, consistent with COX-2 expression. Ketorolac 30 mg at pain onset suppressed both pain and peripheral PGE2 levels. Ketorolac 1 mg either at the site of injury or intramuscularly also produced analgesia but without any effect on peripheral PGE2 levels. Celecoxib selectively suppressed PGE2 but not TxB2 at time points consistent with COX-2 activity, while producing analgesia. These studies demonstrate the ability to assess the time course and selective effects of COX-2 inhibitors in vivo and suggest that suppression of COX-2 mediated PGE2 is temporally related to NSAID analgesia.
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PMID:Analgesia and COX-2 inhibition. 1169 55

Spinal prostaglandin synthesis has been implicated in acute pain processes and in generation and maintenance of central sensitization, and intrathecal injection of cyclo-oxygenase (COX) inhibitors produce antinociception and reduce hypersensitivity in animals. We herein report a Phase I safety assessment of intrathecal injection of the COX inhibitor, ketorolac, in healthy volunteers, and demonstrate no serious side effects. Preclinical studies suggest a major site of action of COX inhibitors for analgesia lies in the central nervous system, especially the spinal cord. For example, COX isoenzymes are expressed in the spinal cord, acute noxious stimuli and inflammation increase spinal prostaglandin production, and spinally administered prostaglandins excite dorsal horn projection neurons, induce release of excitatory neurotransmitters, and cause nociceptive behavior. Intrathecal injection of COX inhibitors increases thermal and mechanical withdrawal threshold in animals with inflammation or nerve injury at doses several 100-fold less than those required systemically. Following pre-clinical neurotoxicity screening and regulatory agency approval, we examined the safety of intrathecal injection of a preservative-free formulation of the COX inhibitor, ketorolac. In an open label, dose-escalating design, 20 healthy volunteers received intrathecal ketorolac, 0.25, 0.5, 1, or 2mg (n=5 per group). Ketorolac did not alter blood pressure, although there was small (10-12%), dose-independent reduction in heart rate for the first hour after injection when data from all subjects were pooled. Ketorolac did not affect sensory or motor function or deep tendon reflexes, and there were no subjective sensations, neurologic or otherwise, reported by the volunteers. Ketorolac did not reduce pain report to heat stimuli applied to the lateral calf. One subject had a mild headache 24h after study, resolving the next day. There were no long-term side effects 6 months after study. These data suggest that intrathecal ketorolac does not produce a high incidence of serious adverse events, and they support further investigation for analgesia.
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PMID:Phase I safety assessment of intrathecal ketorolac. 1240 36

Pain after surgery results in significant morbidity, and systemic opioids often fail to provide adequate analgesia without marked sedation and respiratory depression. Intrathecal morphine provides better analgesia, but is limited by delayed respiratory depression. Intrathecal injection of the cyclooxygenase inhibitor, ketorolac, has recently entered clinical trials, and the current study examined the interaction between intrathecal morphine and ketorolac to treat postoperative pain. We also sought to compare these treatments on a commonly used assessment of withdrawal threshold and a new assessment of spontaneous behavior after surgery. Male Sprague Dawley rats and underwent hind paw incision or subcostal laparotomy surgery. Intrathecal morphine, ketorolac, or their combination were injected on the first postoperative day, with outcome measure being return to pre-surgery withdrawal threshold with von Frey filament testing of the paw after paw incision, or return to pre-surgery exploratory activity after laparotomy. Intrathecal morphine completely reversed the effects of surgery in both models, but intrathecal ketorolac only partially reversed them. Ketorolac enhanced the potency of morphine several fold in both models, and did so synergistically after paw incision. In all cases drug potency was greater for spontaneous than elicited responses. These data confirm that spinal opioid receptor and cyclooxygenase enzyme inhibition diminish elicited tactile hypersensitivity after surgery, and that they similarly return spontaneous behavior to normal. Differences in drug potency could reflect fundamental differences in outcome measures or in the surgical procedures themselves. These data support combination study of intrathecal morphine and ketorolac for postoperative pain.
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PMID:Intrathecal morphine and ketorolac analgesia after surgery: comparison of spontaneous and elicited responses in rats. 1566 47

Surgical stress causes changes in the composition of white blood cells (WBCs). Ketorolac is believed to have analgesic effects and to reduce the stress response and may therefore improve postoperative outcomes. The aim of this study was to assess the effect of preoperative ketorolac on the WBC subsets in patients who had laparoscopic surgery for endometriosis. Fifty patients who had laparoscopic surgery for endometriosis were randomly assigned to one of two groups: the ketorolac group (n = 25) received ketorolac 0.5 mg/kg before the induction of anesthesia, and the control group (n = 25) received saline. White cell count, differential, and pathology studies were done immediately after surgery, on postoperative day 1, and on postoperative day 3. We compared the baseline values within and between the two groups. We also assessed postoperative pain and side effects. The time that elapsed before the first patient request for analgesia, total meperidine dose and VAS (Visual Analog Scale) for postoperative pain were significantly lower in the ketorolac group than in the control group. Compared to the pre- surgical values, there was an increase in total WBC count and percentage of neutrophils, but a decrease in percentages of lymphocytes, monocytes, eosinophils, basophils, and leucocytes. Total WBC count, neutrophils, monocytes, eosinophils and leucocytes showed significant differences between the two groups. The incidences of postoperative side effects, such as nausea, dizziness, headache, and shoulder pain were not different between the groups. Preoperative ketorolac reduced postoperative pain and influenced the WBC response in laparoscopic surgery for endometriosis.
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PMID:The effect of preoperative ketorolac on WBC response and pain in laparoscopic surgery for endometriosis. 1638 58


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