Investigating the TNP-OVA and direct popliteal lymph node assays for the detection of immunostimulation by drugs associated with anaphylaxis in humans.

Using current animal models, it is not possible to identify low-molecular-weight compounds (LMWCs) that are likely to be associated with anaphylaxis. It is generally accepted that the ultimate effector mechanism involves drug-induced IgE antibody. The objective of the present study was to determine if diclofenac, zomepirac and glafenine, which are associated with anaphylaxis in humans, have immunostimulating potential in the murine TNP-OVA (trinitrophenyl-ovalbumin) popliteal lymph node assay (PLNA), and more specifically to determine if the immunostimulation caused by these LMWCs results in IgE antibody production. These LMWCs were chosen because both zomepirac and glafenine were removed from the market due to high association with anaphylaxis, and diclofenac, which remains on the market, is frequently associated with anaphylaxis. In addition to conducting a TNP-OVA PLNA, the immunostimulating potential of these compounds was examined in the direct PLNA. When co-administered with TNP-OVA, all three LMWCs caused dose-dependent (0.25, 0.50, 1.00 and 1.25 mg) increases in popliteal lymph node (PLN) weight and cellularity that were observed beginning with the 0.25-mg dose. In addition, beginning with the 0.25-mg dose, all three compounds caused dose-dependent increases in TNP-OVA specific IgM and IgG(1) antibody-forming cells (AFCs). Diclofenac induced an isotype switch and caused a dose-dependent increase in the number of IgE AFCs with no detectable IgG(2a) AFCs and minimal high-dose-only IgG(2b) AFCs. Zomepirac induced IgE, IgG(2a) and IgG(2b) AFCs following the injection of 0.50 mg only, and glafenine induced IgE, IgG(2a) and IgG(2b) AFCs following the injection of 0.50-1.00 mg. In the direct PLNA, diclofenac caused dose-dependent increases in PLN weight and cellularity that were observed beginning with dose of 0.50 mg, whereas zomepirac failed to increase any PLN parameter and glafenine only increased the PLN weight. These results suggest that diclofenac, zomepirac and glafenine are immunostimulating LMWCs in the TNP-OVA PLNA with the potential to induce IgE antibody against a co-administered hapten-conjugate. Furthermore, these results suggest that the TNP-OVA PLNA offered significant advantages over the direct PLNA. Although it is not realistic to suggest that a single assay, based on a low number of test compounds, can identify all LMWCs with the potential to cause anaphylaxis in humans, these observations do demonstrate the potential utility of the PLNAs in examining LMWC-induced immunomodulation and support further development and investigation of the assays.

Postoperative pain following knee arthroscopy: the effects of intra-articular ketorolac and/or morphine.

BACKGROUND AND OBJECTIVES: Morphine and nonsteroidal antiinflammatory drugs (NSAID) have been found to be effective in relieving postoperative pain. The goal of this study was to determine whether ketorolac alone or in combination with morphine provides superior pain relief following arthroscopy performed with local anesthesia (LA). METHODS: This was a randomized, double-blind, prospective, study in 100 healthy patients from 15 to 60 years of age. Knee arthroscopy was performed with LA using 40 mL prilocaine (5 mg/mL) with adrenaline (4 microg/mL). At the end of the operation, a catheter was inserted intra-articularly, and one of the following solutions diluted to a total volume of 40 mL was injected: group P (40 mL normal saline), group M (3 mg morphine), group K30 (30 mg ketorolac), group K60 (60 mg ketorolac), and group KM (3 mg morphine + 30 mg ketorolac). Visual analog scale (VAS) pain scores (0-100 mm) were measured preoperative and at 30, 60, 90, 120 minutes postoperative and thereafter 4, 8, 24, and 48 hours at rest and on movement of the knee. The total number of distalgesic tablets (325 mg paracetamol + 32.5 mg dextropropoxyphene) consumed during the 48 hours postoperative was recorded. RESULTS: Significant differences in VAS pain scores were seen between group P and group KM at 4, 8, and 24 hours (P < .05) and between group M and group KM at 4, 8, 24, and 48 hours (P < .01) after the operation at rest. During mobilization of the knee, a significant difference in VAS pain score was found between group P and group KM at 8, 24, and 48 hours (P < .05) and between group P and group K60 at 24 and 48 hours (P < .05). The total consumption of distalgesic tablets did not differ among the groups. CONCLUSIONS: The combination of 3 mg morphine plus 30 mg ketorolac provided significantly better analgesia than either placebo alone or morphine alone. This result could be a synergistic effect.

Immunomodulation with interleukin-10 and interleukin-4 compared with ketorolac tromethamine for prevention of postoperative adhesions in a murine model.

OBJECTIVE: To assess the effects of two macrophage down-regulating cytokines (interleukin [IL]-10 and IL-4) and the nonsteroidal anti-inflammatory drug ketorolac tromethamine on postoperative adhesion formation. DESIGN: Randomized controlled trial. SETTING: Research center vivarium. ANIMAL(S): Six-week-old Swiss Webster mice. INTERVENTION(S): One hundred eighty animals were randomized to serve as nonsurgical controls or to undergo a standardized adhesion-inducing procedure. Subsequently, animals were randomized to nine different treatment groups to receive no injections, phosphate-buffered saline (PBS) only, IL-10, IL-4, ketorolac, IL-10 plus IL-4, IL-10 plus ketorolac, IL-4 plus ketorolac, or all three agents. MAIN OUTCOME MEASURE: Adhesion scores on postoperative day 10. RESULT(S): Postoperative adhesion scores were significantly reduced in all groups of animals treated with IL-10 or ketorolac. Animals treated with IL-4 showed a nonsignificant trend toward reduction of adhesions. There were significantly more animals with adhesion scores of < or = 3 in the IL-10 and ketorolac treatment groups than in the control groups receiving no treatment or PBS only. CONCLUSION(S): Although treatment with IL-10 and ketorolac did not completely prevent adhesion formation, treatment with these drugs did lead to a significant reduction in adhesion formation. Adhesions also tended to be thin and filmy rather than thick and vascular. Addition of IL-4 did not augment these effects.

Ketorolac, diclofenac and ketoprofen are equally efficacious for pain relief after total hip replacement surgery.

We have compared the efficacy of ketorolac 30 mg i.v. followed by infusion at a rate of 90 mg/15.5 h, with that of diclofenac 75 mg followed by infusion of 75 mg/15.5 h or ketoprofen 100 mg followed by infusion of 100 mg/15.5 h, on postoperative pain in 85 patients after hip replacement surgery under spinal anaesthesia in a prospective, double-blind, randomized study. Supplementary analgesia was administered during the 16-h postoperative period with bolus doses of fentanyl delivered by a patient-controlled analgesia system. Mean total consumption of PCA-administered fentanyl was 890 (SD 400) micrograms in the ketorolac group, 920 (550) micrograms in the diclofenac group and 850 (350) micrograms in the ketoprofen group (ns). Median VAS scores were low over the entire study in each group and there was no significant difference between groups. No serious adverse events were recorded.

A comparison of ketorolac tromethamine/oxycodone versus patient-controlled analgesia with morphine in anterior cruciate ligament reconstruction patients.

Effective postoperative analgesia with minimal side effects remains an important goal in enabling increasingly complex surgical procedures to be performed on an outpatient basis. In this study, we examined the efficacy of postoperative analgesia in 90 patients undergoing anterior cruciate ligament reconstruction using a patellar tendon autograft, with a 24-hour hospital stay. Patients were randomized to receive either intramuscular ketorolac supplemented by oral oxycodone, or intravenous morphine via patient-controlled analgesia (PCA) device, for postoperative analgesia. Patients were monitored for 2 hours in the recovery room, then every 4 hours until discharge, for the presence of complications of nausea, vomiting, urinary retention, pruritus, and dizziness. Pain was assessed using a visual analog scale (VAS) on the morning of postoperative day one. All patients were discharged by 24 hours after surgery. Ten (20%) of the patients receiving ketorolac/oxycodone versus 31 (79%) of those receiving PCA morphine experienced postoperative complications (P < .05). Postoperative nausea, vomiting, and urinary retention were each significantly more common in the PCA morphine group (P < .05). The incidence of pruritus and dizziness was low overall. There was no significant difference between groups in the severity of postoperative pain as assessed using a VAS. We conclude that ketorolac/oxycodone may provide comparable analgesia with fewer undesirable side effects than PCA morphine in patients undergoing anterior cruciate ligament reconstruction. Patients receiving ketorolac/oxymorphone may have a better quality recovery and more rapid discharge.

Intrathecal NSAIDS attenuate inflammation-induced neuropeptide release from rat spinal cord slices.

Inflammation enhances release of neuropeptides from sensory nerve terminals in the spinal cord, and this may contribute to the development of hyperalgesia. In a similar manner, proinflammatory prostaglandins also augment peptide release from sensory neurons. To ascertain whether the inflammation-induced increase in peptide release from spinal cord slices is mediated by production of these eicosanoids, we examined whether intrathecal administration of nonsteroidal antiinflammatory drugs (NSAIDS) could attenuate the effects of inflammation. Unilateral injection of 150 microl of complete Freund's adjuvant (CFA) into the hindpaw of adult Sprague-Dawley rats resulted in a lower threshold for paw withdrawal (hyperalgesia) on 1, 4, and 5 days after injection. Five days after the induction of inflammation, capsaicin-evoked release of immunoreactive substance P (iSP) and immunoreactive calcitonin gene-related peptide (iCGRP) was increased approximately 2-fold in slices of cord tissue from the side ipsilateral to CFA injection, compared to spinal cord slices from the non-inflamed side. Intrathecal administration of 1 microl/h of 10 nmol/microl solution of the NSAID, ketorolac, for 1 day prior to and throughout the inflammation significantly attenuated the inflammation-induced increase in capsaicin-evoked release of both peptides without altering release in cord tissue from the non-inflamed side. Systemic administration of the same amount of ketorolac did not attenuate the effect of inflammation on peptide release. Intrathecal administration of 16 nmol/h (S)-ibuprofen, before and throughout the inflammation, also significantly attenuated the increase in evoked neuropeptide release associated with inflammation, whereas (R)-ibuprofen was ineffective. These results suggest that inhibition of cyclooxygenase at the level of the spinal cord attenuates the augmentation of neuropeptide release induced by peripheral inflammation, and provide further evidence for an action of prostaglandins at central terminals of sensory neurons during inflammation.

Effect of intra-articular versus systemic anti-inflammatory drugs in a rabbit model of temporomandibular joint inflammation.

PURPOSE: In an attempt to better understand the time course of inflammatory mediator production or release in inflammatory joint disease, a rabbit model of acute temporomandibular joint (TMJ) inflammation was established. This model was used to evaluate the effects of specific anti-inflammatory agents administered either systemically (intraperitoneal, IP) or locally (intra-articular, IA) on the modulation of in vivo tissue levels of two prototypic inflammatory mediators, prostaglandin E2 (PGE2) and bradykinin (BK). MATERIALS AND METHODS: An experimental model of inflammation was created by administering carrageenan (carra) into one joint and an equivalent volume of saline (control) into the contralateral joint of 42 male New Zealand White rabbits. The development of hyperthermia was assessed by placement of a microthermister probe into the joint space. The inflammatory mediators, immunoreactive PGE2 (iPGE2) and BK (iBK), were recovered with microdialysis probes, and samples were assayed in conjunction with specific pharmacologic interventions. In the first part of the study, the time course for the release or production of iBK and iPGE2 was determined. In the second part, the effects of IP versus IA administration of dexamethasone and a nonsteroidal anti-inflammatory drug, ketorolac tromethamine, were compared. Dexamethasone and ketorolac were administered at 3 hours and 1 hour, respectively, before the peak release of the inflammatory mediators. RESULTS: The onset of IA hyperthermia, an index of inflammation, was evident by 90 minutes post-carra and reached a maximum of 1.2 degrees C above core temperature by 150 minutes post-carra. Intra-articular levels of iPGE2 and iBK peaked at 240 minutes (3.35+/-1.9 nmol/L) and 270 minutes (0.45+/-0.29 nmol/L), respectively, after the induction of inflammation in the superior joint space. iBK levels within the superior joint space were significantly decreased by dexamethasone and ketorolac. Ketorolac (50 microg) decreased iBK and iPGE2 levels when given IA or IP. With dexamethasone (3 mg), the levels of iBK were significantly reduced, and iPGE2 levels were not changed. CONCLUSIONS: This study shows that the rabbit model of TMJ inflammation, with concurrent collection of iBK and iPGE2 via microdialysis, is a reproducible and reliable method to investigate the time course of inflammatory mediator release and their modulation by either the local or systemic administration of anti-inflammatory medications.

Preemptive pain control in patients having laparoscopic hernia repair: a comparison of ketorolac and ibuprofen.

OBJECTIVES: To determine if nonsteroidal anti-inflammatory drugs provide adequate pain control for patients having laparoscopic hernia repair and to compare the effectiveness of ketorolac tromethamine with ibuprofen in reducing postoperative laparoscopic hernia pain. DESIGN AND SETTING: Prospective double-blind randomized study at a 100-bed community hospital. PATIENTS: Seventy patients ranging in age from 16 to 83 years scheduled for elective laparoscopic inguinal hernia repair. INTERVENTIONS: Patients undergoing laparoscopic hernia repair were enrolled in a double-blind randomized study to compare the 2 treatments. Group 1 received a placebo capsule 1 hour before surgery and ketorolac tromethamine, 60 mg intravenously, at the time of trocar insertion. Group 2 received ibuprofen, 800 mg an hour before surgery, and isotonic sodium chloride solution, 2 mL intravenously, at the time of trocar insertion. In addition, all patients received local infiltration of 30 mL of bupivacaine hydrochloride into their trocar sites. All patients were discharged within 5 hours of the operation and were instructed to take 400 mg of ibuprofen orally every 4 hours for 24 hours whether or not they were experiencing pain. A 24-hour supply of ibuprofen was provided to all study patients. Pain was assessed using the Visual Analog Pain Scale with a maximum pain rating of 100. Assessments were done at the time of and 18 hours after discharge. MAIN OUTCOME MEASURE: Postoperative pain 18 and 24 hours after discharge was assessed using a standardized questionnaire in a telephone interview by a registered nurse from the Outpatient Surgical Unit. RESULTS: There was no significant difference in the level of pain experienced by 35 patients who received ketorolac intravenously and 35 who received ibuprofen orally. There was no significant difference between the 2 treatment groups in the amount of pain experienced at discharge and 18 hours after discharge. CONCLUSIONS: Pain relief from ibuprofen, 800 mg, administered orally an hour before laparoscopic hernia repair was not statistically different from that obtained with intravenous ketorolac, 60 mg, administered intraoperatively when comparing the hospital discharge pain score and the mean and highest pain scores 18 hours after discharge. Ibuprofen offers equivalent pain control at a lower cost and reduced potential for adverse drug events compared with intravenous ketorolac in patients having laparoscopic hernia repair. No patient required narcotic supplementation, and pain control was judged satisfactory by all the patients.

Factors influencing ketorolac-associated perioperative renal dysfunction.

UNLABELLED: Nonsteroidal antiinflammatory drugs (NSAIDs) are useful for the treatment of postoperative pain, but there is continuing concern about adverse effects on renal function. We studied the renal effects of ketorolac in an animal model using Fischer 344 rats undergoing isoflurane anesthesia and laparotomy. Treatment groups--control (C), ketorolac (5 mg x kg(-1) x d(-1)) (K), large-dose ketorolac (15 mg x kg(-1) x d(-1)) (KH), dehydration-ketorolac (5 mg x kg(-1) x d(-1)) (DK), gentamicin (20 mg x kg(-1) x d(-1)) (G), and gentamicin (20 mg x kg(-1) x d(-1)) with ketorolac (5 mg x kg(-1) x d(-1)) (GK)--each comprised 10 animals. Renal function was assessed before laparotomy and after 3 treatment days using concurrent paraaminohippurate and iothalamate clearances, respectively, to estimate renal plasma flow and glomerular filtration rate, and by measuring serum and urine electrolytes, osmolality, urea, and creatinine. A significant increase in serum potassium was found in the GK and DK groups. There were no major changes in renal function in the C, K, KH, and DK groups. Mild renal dysfunction was found in the G group. We found severe and consistent changes in renal function, accompanied by severe, widespread histological changes of acute tubular necrosis, in the GK group. In this postoperative rat model, the combination of ketorolac and gentamicin was deleterious to renal function. IMPLICATIONS: We examined the renal effects of the nonsteroidal antiinflammatory drug ketorolac. Renal function was measured in rats before and after surgery and 3 days' drug administration; the kidneys studied by using microscopy. Only ketorolac plus the antibiotic gentamicin produced marked changes in kidney function and structure.

Prolonged central intravenous ketorolac continuous infusion in a cancer patient with intractable bone pain.

OBJECTIVE: To report the case of a prolonged intravenous ketorolac continuous infusion given via a central line in a cancer patient with intractable bone pain. CASE SUMMARY: 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. DISCUSSION: 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. CONCLUSIONS: 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.

Postoperative pain relief following laparoscopic tubal sterilization with silastic bands.

OBJECTIVE: To evaluate postoperative pain relief of intramuscular ketorolac, topical bupivacaine, and placebo in patients undergoing laparoscopic tubal sterilization with silastic bands. METHODS: One hundred five women undergoing laparoscopic tubal sterilization with silastic bands were randomized to one of three groups: one received intramuscular ketorolac and topical placebo applied to the fallopian tubes, the second received intramuscular placebo and topical bupivacaine, and the third received intramuscular placebo and topical placebo. Surgical procedures, anesthesia, and recovery were conducted with standardized protocols. Postoperative pain perception was graded using the modified McGill pain intensity scale at 30 minutes postoperatively, at discharge from the recovery room, and the next morning by telephone interview. Other measured variables included postoperative vomiting, additional analgesia requirement, and length of time spent in the recovery room. RESULTS: Only topical bupivacaine was found to decrease postoperative pain scores significantly over those with placebo, at 30 minutes postoperatively (median score 2 compared with 4, P = .002) and at discharge from the recovery room (median score 2 compared with 3, P = .03). There was no significant decrease in pain scores with intramuscular ketorolac compared with placebo. No differences in pain scores were found between the three groups at the next morning phone call. There were no significant differences between the three groups with respect to requirements for supplemental pain medications in the recovery room, incidence of postoperative vomiting, or length of time spent in the recovery room. CONCLUSION: Topical bupivacaine decreases postoperative pain scores significantly compared with placebo in women undergoing laparoscopic tubal sterilization with silastic bands.

Reducing pain after inguinal hernia repair in children: caudal anesthesia versus ketorolac tromethamine.

BACKGROUND: The optimal method to achieve analgesia after inguinal hernia repair in children is unknown. This study compared the analgesic efficacy, adverse events, and the costs associated with supplementation of local anesthesia (infiltration of the wound) with either intravenous ketorolac or caudal analgesia in children having inguinal hernia repair. METHODS: With parental consent and institutional review board approval, children aged 2-6 yr having elective, outpatient inguinal hernia repair were studied in this randomized, single-blinded investigation. Anesthesia was induced by inhalation with nitrous oxide and halothane or intravenously with propofol. Anesthesia was maintained with nitrous oxide and halothane. Patients were randomly assigned to receive caudal analgesia (1 ml/kg 0.20% bupivacaine with 1/200,000 epinephrine) or intravenous ketorolac (1 mg/kg) immediately after induction of anesthesia. Both groups received field blocks with 0.25% bupivacaine administered by the surgeon under direct vision during operation. Patients were assessed for 24 h. In-hospital pain was assessed using a behavior-based pain score. Parents assessed pain with a visual linear analog pain scale with anchors of 0 (no pain) and 100 (worst pain imaginable). RESULTS: The authors studied 164 children, with 84 patients in the ketorolac group. The groups had similar demographic data. In-hospital analgesic requirements and pain scores were almost identical in both groups. Pain at home was significantly less in the ketorolac group, with visual linear analog pain scale scores of 10 (0-80) compared with 20 (0-80) (median [range]) for ketorolac versus caudal (P = 0.002 by the Mann-Whitney U test). The ketorolac group also had a lower incidence of vomiting, ambulated more rapidly, and micturated earlier (P < 0.05). CONCLUSION: The use of intravenous ketorolac to supplement local anesthesia infiltrated by the surgeon during pediatric inguinal hernia repair is superior to supplementation with caudal analgesia.

Transurethral microwave thermotherapy: strategies to ensure successful outcomes with Prostasoft 2.0.

Transurethral microwave thermotherapy (TUMT) is a unique and promising method of treating benign prostatic hyperplasia. Clinical outcomes are related to thermal dose delivered. In 359 consecutive patients, strategies to increase thermal dose using the FDA-approved Prostasoft 2.0 delivered a mean of 148 kJ, which was almost 50 kJ more than the U.S. FDA trials. These strategies include careful preoperative patient teaching, exclusion of very small prostates, ketorolac, prewarming of the prostaprobe, antitorque of the rectal probe, use of urethral cooling adjustment during power ramping, and no manual power interruptions. Clinical outcomes improved without any significant adverse events. Peak urinary flow increased in 4 months by 5.5 mL/sec.

Comparison of wound infiltration with ketorolac versus intravenous regional anesthesia with ketorolac for postoperative analgesia following ambulatory hand surgery.

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess the analgesic effectiveness of ketorolac administered with lidocaine via intravenous regional asesthesia (IVRA) or via wound infiltration following ambulatory hand surgery. METHODS: The patient population in this double-blind study consisted of 60 patients scheduled for elective ambulatory hand surgery, who were divided into three groups of 20 each. All patients received IVRA with 40 mL 0.5% lidocaine and 5 mL 1% lidocaine infiltrated into the surgical site. Group 1, the control group, received no additional medications; group 2 had 60 mg ketorolac added to the lidocaine used for IVRA; and group 3 had 60 mg ketorolac added to the lidocaine used for wound infiltration. Postoperative pain was assessed by a 10-cm visual analog scale. VAS) 1 hour and 2 hours after tourniquet deflation. In the postanesthesia care unit analgesia was provided with fentanyl until the VAS score reached 3 or lower. Patients were instructed to take one Tylenol No. 3 (acetaminophen with codeine) tablet every 4 hours as needed at home. They were contacted the next day, and the time to first additional narcotics and the total number of tablets taken were recoded. RESULTS: No differences in demographic variables or in operative, tourniquet, or discharge times were noted among the groups. The VAS scores were significantly lower in the two groups who received ketorolac than in the control group (P < .05); the mean time from tourniquet release to first medication was 109 +/- 73 minutes for group 1, 467 +/- 431 for group 2, and 393 +/- 312 for group 3 (P < .05); and the number of tablets taken was 4.1 +/- 1.3 for group 1, 1.8 +/- 1.2 for group 2, and 2.0 +/- 1.3 for group 3 (P < .05). CONCLUSION: Ketorolac provides similar postoperative analgesia after ambulatory hand surgery when administered with lidocaine either by IVRA or by wound infiltration.

Postarthroscopic meniscus repair analgesia with intraarticular ketorolac or morphine.

Both ketorolac, a nonsteroidal antiinflammatory drug, and morphine, an opioid agonist, provide enhanced patient analgesia after arthroscopic knee surgery when administered via the intraarticular route. This study was designed to determine whether ketorolac or morphine results in better patient analgesia and whether their combination would provide superior analgesia to either drug alone. Patients undergoing arthroscopic knee meniscus repair under local anesthesia with sedation were evaluated. Each of the study groups evaluated received ketorolac (either via the parenteral or intraarticular route) and morphine (via either the parenteral or intraarticular route). This study revealed a significant benefit from the individual intraarticular administration of both morphine and ketorolac. The combination of these drugs did not result in decreased postoperative pain or need for postoperative analgesics, and it did not result in an increased analgesic duration. We conclude that the use of either intraarticular ketorolac or intraarticular morphine improves the comfort in patients undergoing arthroscopic meniscus repair and that their combination offers no advantage over either drug alone.

Nonopioid analgesics shorten the duration of postoperative ileus.

Morphine inhibits propagating and stimulates nonpropagating colon contractions in monkeys and humans. The use of morphine or other opioids that inhibit propulsive contractions prolongs postoperative ileus. In contrast, ketorolac tromethamine, a nonsteroidal analgesic, has no effect on colon contractions in monkeys. In 14 patients having elective abdominal operations, bipolar electrodes were implanted on the right (n = 13) and left (n = 10) colon. Group A (n = 8) received ketorolac, 30 mg IM q6h, for pain relief. Group B (n = 6) needed supplemental morphine, 2-10 mg IV or IM, plus ketorolac to control their pain. Myoelectric activity was recorded from each subject on postop Days 1-5 and analyzed by computer for electrical control activity (ECA), short and long electrical response activity (ERA), and propagation of long ERA. There was a difference between the two groups in return of propagated long ERA bursts that correlated with clinical recovery from postoperative ileus. Postoperative analgesia with ketorolac resulted in faster resolution of ileus compared to morphine plus ketorolac because opioid-induced motor abnormalities in the colon were avoided.

Use of analgesics during propofol sedation: a comparison of ketorolac, dezocine, and fentanyl.

STUDY OBJECTIVE: To evaluate the comparative efficacy and side effect profile of ketorolac 60 mg, dezocine 6 mg, and fentanyl 100 micrograms when used as analgesic supplements to a propofol infusion during monitored anesthesia care (MAC). DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Ambulatory surgery facility at a university medical center. PATIENTS: 80 outpatients undergoing breast biopsy or inguinal herniorraphy procedures under MAC. INTERVENTIONS: All patients received midazolam 2 mg intravenously (IV) followed by 1 ml of the study medication containing either dezocine 3 mg IV, ketorolac 30 mg IV, fentanyl 50 micrograms IV, or normal saline. A propofol infusion was initiated at 75 micrograms/kg/min and then varied to maintain a stable level of sedation (i.e., Observer Assessment of Alertness/Sedation scale score of 3). An additional 1 ml of the same study medication was administered IV 2 to 3 minutes prior to infiltration of the local anesthetic solution. During the operation, supplemental (rescue) medication consisted of fentanyl 25 micrograms IV, bolus injections in all four treatment groups. MEASUREMENTS AND MAIN RESULTS: Propofol infusion and supplemental fentanyl dosage requirements, oxygen saturation values, respiratory rates, recovery times, and postoperative side effects were recorded. Visual analog scales were used to assess sedation, anxiety, pain, and nausea preoperatively (baseline), upon entry into the postanesthesia care unit, and at 30-minute intervals until discharge. The fentanyl and dezocine groups required lower average infusion rates of propofol to maintain a stable level of sedation than the control (saline) group. The saline and ketorolac groups required rescue analgesic medication more frequently and/or larger supplemental dosages of fentanyl than the two opioid analgesic treatment groups. Compared with the three analgesic treatment groups, postoperative pain scores were only marginally higher in the control group. Ketorolac-treated patients had consistently (but not significantly) shorter recovery times to oral intake, ambulation, and discharge than those in the dezocine or fentanyl groups. No postoperative nausea, vomiting, or pruritus was reported in the ketorolac group. CONCLUSION: Compared with ketorolac 60 mg, fentanyl 100 micrograms and dezocine 6 mg produced a greater decrease in the propofol sedation requirement during MAC. However, the use of ketorolac in combination with propofol for MAC was associated with an improved recovery profile.

Ketorolac (Toradol) and acute random-pattern skin flap survival in rat.

OBJECTIVE: To assess the efficacy of sustained postoperative intramuscular ketorolac tromethamine (Toradol) at analgesic levels in the augmentation of acute, random-pattern skin flaps in rat. DESIGN: Prospective, randomized, placebo-controlled, animal trial. SETTING: Animal research laboratory, School of Medicine, Oregon Health Sciences University, Portland. SUBJECTS: Forty-four adult male Sprague-Dawley rats (260 to 280 g). INTERVENTIONS: Twenty-two treatment animals underwent modified McFarlane random-pattern skin flaps followed immediately by intramuscular loading doses of ketorolac. Treatment animals were then maintained on a regimen of intramuscular ketorolac using a three times a day dosing schedule for 14 days postoperatively. Twenty-two control animals underwent identical modified McFarlane random-pattern skin flaps and were given equivalent volumes of intramuscular saline on the same dosing schedule for the 14-day treatment period. MAIN OUTCOME MEASURES: Postmortem measurements of skin flap ischemia (expressed as a percentage of total flap surface area) were performed for both treatment and control animals by three independent, non-blinded observers using the acetate tracing technique. Both pooled and individual data were statistically analyzed using personal computer software. RESULTS: Forty-three of the 44 animals successfully completed the experimental trial. One animal in the treatment group died on postoperative day 3 of unknown causes. During the study period, one postoperative hematoma was detected in both the treatment and control groups. The mean percentage of skin flap ischemic necrosis observed in control animals (35.4%) was consistently less than that measured in the treatment group (36.4%). However, the difference in ischemic flap necrosis between control and treatment groups was not statistically significant (P = .6919). CONCLUSIONS: Comparatively high-dose intramuscular ketorolac failed to augment acute, random-pattern skin flap survival in rat when initiated in the immediate postoperative period. Complications of prolonged, intramuscular ketorolac were not observed in this trial. Further studies using preoperative initiation of drug therapy may help to clarify the true efficacy of ketorolac in flap augmentation.