Impact of combined NO and PG blockade on rapid vasodilation in a forearm mild-to-moderate exercise transition in humans.
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We tested the hypothesis that nitric oxide (NO) and prostaglandins (PGs) contribute to the rapid vasodilation that accompanies a transition from mild to moderate exercise. Nine healthy volunteers (2 women and 7 men) lay supine with forearm at heart level. Subjects were instrumented for continuous brachial artery infusion of saline (control condition) or combined infusion of N(G)-nitro-L-arginine methyl ester (L-NAME) and ketorolac (drug condition) to inhibit NO synthase and cyclooxygenase, respectively. A step increase from 5 min of steady-state mild (5.4 kg) rhythmic, dynamic forearm handgrip exercise (1 s of contraction followed by 2 s of relaxation) to moderate (10.9 kg) exercise for 30 s was performed. Steady-state forearm blood flow (FBF; Doppler ultrasound) and forearm vascular conductance (FVC) were attenuated in drug compared with saline (control) treatment: FBF = 196.8 +/- 30.8 vs. 281.4 +/- 34.3 ml/min and FVC = 179.3 +/- 29.4 vs. 277.8 +/- 34.8 ml.min(-1).100 mmHg(-1) (both P < 0.01). FBF and FVC increased from steady state after release of the initial contraction at the higher workload in saline and drug conditions: DeltaFBF = 72.4 +/- 8.7 and 52.9 +/- 7.8 ml/min, respectively, and DeltaFVC = 66.3 +/- 7.3 and 44.1 +/- 7.0 ml.min(-1).100 mmHg(-1), respectively (all P < 0.05). The percent DeltaFBF and DeltaFVC were not different during saline infusion or combined inhibition of NO and PGs: DeltaFBF = 27.2 +/- 3.1 and 28.1 +/- 3.8%, respectively (P = 0.78) and DeltaFVC = 25.7 +/- 3.2 and 26.0 +/- 4.0%, respectively (P = 0.94). The data suggest that NO and vasodilatory PGs are not obligatory for rapid vasodilation at the onset of a step increase from mild- to moderate-intensity forearm exercise. Additional vasodilatory mechanisms not dependent on NO and PG release contribute to the immediate and early increase in blood flow in an exercise-to-exercise transition. (+info)
Comparison of ketorolac and morphine as adjuvants during pediatric surgery.
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The intraoperative use of opioid analgesics decreases the volatile anesthetic requirement and provides for pain relief in the early postoperative period. In a randomized double-blind, placebo-controlled study involving 95 ASA physical status 1 or 2 children (ages 5-15 yr) undergoing general anesthesia for elective operations, we compared postoperative analgesia following the intraoperative intravenous (iv) administration of ketorolac, a nonsteroidal antiinflammatory drug or morphine, an opioid analgesic. After induction of general anesthesia and before the start of the surgical procedure, children received equal volumes of saline, morphine (0.1 mg.kg-1, iv) or ketorolac (0.9 mg.kg-1, iv). Postoperative pain was evaluated by the child using a 10-cm linear visual analog scale (VAS) and by a blinded observer using both a VAS and an objective pain scale (OPS) in the postanesthesia care unit (PACU). There were no statistically significant differences in the VAS and OPS scores in the PACU or in the postoperative analgesic requirements in children receiving morphine or ketorolac. The placebo group had a significantly higher VAS and OPS score and required earlier and more frequent analgesic therapy in the PACU compared to the two analgesic groups. Patients receiving ketorolac had less postoperative emesis than those receiving morphine. We conclude that ketorolac (0.9 mg.kg-1) is an effective alternative to morphine (0.1 mg.kg-1) as an iv adjuvant during general anesthesia, and in the dose used in this study, is associated with less postoperative nausea and vomiting in children. (+info)
Quantitative assessment of the transport of elastic and rigid vesicle components and a model drug from these vesicle formulations into human skin in vivo.
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The aim of this study was to quantitatively assess the distribution profiles of elastic and rigid vesicle material in human skin in vivo. Furthermore, the distribution profiles of the model drug ketorolac applied in these vesicle formulations was investigated. A deuterium-labelled phospholipid was incorporated into these vesicles to serve as a marker for the vesicle material. The vesicles were loaded with ketorolac at saturated concentrations. Vesicle solutions were applied non-occlusively onto the skin and the treated site was sequentially tape-stripped. Tape-strips were analyzed for vesicle material using attenuated total reflectance-Fourier transform infrared spectroscopy and for ketorolac by extraction of the tape-strips followed by high pressure liquid chromatography. Distribution profiles in the stratum corneum (SC) were obtained for the elastic and rigid vesicle material and for the ketorolac. These profiles have suggested that elastic vesicle material can rapidly enter the deeper layers of the SC and can reach almost the SC-viable epidermal junction. Rigid vesicle material, however, did not penetrate deep into the SC. Furthermore, the elastic vesicles were better than the rigid vesicles in the enhancement of ketorolac transport into human SC. The distribution profile of ketorolac in the deeper SC layers was, however, different from that of the vesicle material. This suggests that once the elastic vesicles partition into the SC, the ketorolac is released from the vesicles. The elastic vesicles are superior to the rigid vesicles both in terms of vesicular transport into the SC and in terms of therapeutic potential as a skin delivery vehicle. (+info)
Cyclooxygenase inhibition and baroreflex sensitivity in humans.
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Animal studies suggest that prostanoids (i.e., such as prostacyclin) may sensitize or impair baroreceptor and/or baroreflex responsiveness depending on the site of administration and/or inhibition. We tested the hypothesis that acute inhibition of cyclooxygenase (COX), the rate-limiting enzyme in prostanoid synthesis, impairs baroreflex regulation of cardiac period (R-R interval) and muscle sympathetic nerve activity (MSNA) in humans and augments pressor reactivity. Baroreflex sensitivity (BRS) was determined at baseline (preinfusion) and 60 min after (postinfusion) intravenous infusion of a COX antagonist (ketorolac; 45 mg) (24 +/- 1 yr; n = 12) or saline (25 +/- 1 yr; n = 12). BRS was assessed by using the modified Oxford technique (bolus intravenous infusion of nitroprusside followed by phenylephrine). BRS was quantified as the slope of the linear portion of the 1) R-R interval-systolic blood pressure relation (cardiovagal BRS) and 2) MSNA-diastolic blood pressure relation (sympathetic BRS) during pharmacological changes in arterial blood pressure. Ketorolac did not alter cardiovagal (19.4 +/- 2.1 vs. 18.4 +/- 2.4 ms/mmHg preinfusion and postinfusion, respectively) or sympathetic BRS (-2.9 +/- 0.7 vs. -2.6 +/- 0.4 arbitrary units.beat(-1).mmHg(-1)) but significantly decreased a plasma biomarker of prostanoid generation (plasma thromboxane B2) by 53 +/- 11%. Cardiovagal BRS (21.3 +/- 3.8 vs. 21.2 +/- 3.0 ms/mmHg), sympathetic BRS (-3.4 +/- 0.3 vs. -3.2 +/- 0.2 arbitrary units.beat(-1).mmHg(-1)), and thromboxane B2 (change in -1 +/- 12%) were unchanged in the control (saline infusion) group. Pressor responses to steady-state incremental (0.5, 1.0, and 1.5 microg.kg(-1).min(-1)) infusion (5 min/dose) of phenylephrine were not altered by ketorolac (n = 8). Collectively, these data indicate that acute pharmacological antagonism of the COX enzyme does not impair BRS (cardiovagal or sympathetic) or augment pressor reactivity in healthy young adults. (+info)
A pilot study on the efficacy of ketorolac plus tramadol infusion combined with erythrocytapheresis in the management of acute severe vaso-occlusive crises and sickle cell pain.
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One of the major causes of hospitalization for patients with sickle cell disease (SCD) are vaso-occlusive crises (VOC), which are characterized by acute pain and organ damage related to the presence of dense red cells. Here we report a pilot study which combined balanced analgesia with tramadol plus ketorolac and erythrocytapheresis. Key words: sickle cell disease, therapeutic erythrocytapheresis, HbS, visual analog scale, vaso-occlusive crisis. (+info)
The effects of ketorolac injected via patient controlled analgesia postoperatively on spinal fusion.
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Lumbar spinal fusions have been performed for spinal stability, pain relief and improved function in spinal stenosis, scoliosis, spinal fractures, infectious conditions and other lumbar spinal problems. The success of lumbar spinal fusion depends on multifactors, such as types of bone graft materials, levels and numbers of fusion, spinal instrumentation, electrical stimulation, smoking and some drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs). From January 2000 to December 2001, 88 consecutive patients, who were diagnosed with spinal stenosis or spondylolisthesis, were retrospectively enrolled in this study. One surgeon performed all 88 posterolateral spinal fusions with instrumentation and autoiliac bone graft. The patients were divided into two groups. The first group (n=30) was infused with ketorolac and fentanyl intravenously via patient controlled analgesia (PCA) postoperatively and the second group (n=58) was infused only with fentanyl. The spinal fusion rates and clinical outcomes of the two groups were compared. The incidence of incomplete union or nonunion was much higher in the ketorolac group, and the relative risk was approximately 6 times higher than control group (odds ratio: 5.64). The clinical outcomes, which were checked at least 1 year after surgery, showed strong correlations with the spinal fusion status. The control group (93.1%) showed significantly better clinical results than the ketorolac group (77.6%). Smoking had no effect on the spinal fusion outcome in this study. Even though the use of ketorolac after spinal fusion can reduce the need for morphine, thereby decreasing morphine related complications, ketorolac used via PCA at the immediate postoperative state inhibits spinal fusion resulting in a poorer clinical outcome. Therefore, NSAIDs such as ketorolac, should be avoided after posterolateral spinal fusion. (+info)
Tramadol does not modify the Bispectral Index during anaesthesia with sevoflurane and remifentanil.
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BACKGROUND: The aim of this study was to investigate the effects of tramadol administered with ketorolac on the Bispectral Index (BIS) during anaesthesia with sevoflurane and remifentanil. METHODS: Forty-six adult patients, ASA I-III, scheduled for elective minor surgical procedures were studied. Patients were premedicated with remifentanil infusion 0.4 microg kg(-1) min(-1) and anaesthesia was induced 4-5 min later with propofol 1.5 mg kg(-1) and maintained with air-oxygen (FI(O(2)) 0.4), remifentanil 0.1-0.15 microg kg(-1) min(-1) and sevoflurane, adjusted to keep the BIS between 40 and 50. After 20 min of stable anaesthesia, the subjects were allocated randomly to receive i.v. tramadol 1.5 mg kg(-1) and i.v. ketorolac 0.3 mg kg(-1) (tramadol group) or saline (control group). BIS values, mean arterial pressure, heart rate and end-tidal carbon dioxide were recorded every 5 min for 20 min. RESULTS: Mean BIS values after tramadol administration were not significantly different from those recorded in patients receiving saline throughout the period of observation. There were no patients who presented explicit recall of events under anaesthesia. No significant changes in mean arterial pressure, heart rate and end-tidal carbon dioxide were noted after tramadol injection. CONCLUSION: Tramadol, given with ketorolac to prevent postoperative pain, during anaesthesia maintained with sevoflurane and remifentanil at BIS between 40 and 50, does not modify the BIS value. (+info)
Comparison of morphine, ketorolac, and their combination for postoperative pain: results from a large, randomized, double-blind trial.
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BACKGROUND: Meta-analyses report similar numbers needed to treat for nonsteroidal antiinflammatory drugs (NSAIDs) and opioids. Differences in baseline pain intensity among the studies from which these numbers needed to treat were derived may have confounded the results. NSAIDs have an opioid-sparing effect, but the importance of this effect is unclear. Therefore, the authors sought to compare the proportions of subjects who obtain pain relief with ketorolac versus morphine after surgery and to determine whether the opioid-sparing effect of an NSAID reduces the magnitude of opioid side effects. METHODS: The study was a double-blind, randomized controlled trial. The authors randomly assigned 1,003 adult patients to receive 30 mg ketorolac or 0.1 mg/kg morphine intravenously. They calculated the proportion of subjects who achieved at least 50% reduction in pain intensity 30 min after analgesic administration. Further, so long as pain intensity 30 min after analgesic administration was 5 or more out of 10, patients received 2.5 mg morphine every 10 min until pain intensity was 4 or less out of 10. The authors assessed the presence of opioid-related side effects. RESULTS: Five hundred patients received morphine and 503 received ketorolac. Fifty percent of patients in the morphine group achieved pain relief, compared with 31% in the ketorolac group (difference, 19%; 95% confidence interval, 13-25%). The ketorolac-morphine group required less morphine (difference, 6.5 mg; 95% confidence interval, -5.8 to -7.2) and had a lower incidence of side effects (difference, 11%; 95% confidence interval, 5-16%) than the morphine group. CONCLUSIONS: Opioids are more efficacious analgesics than NSAIDs, although historic data for these two drugs yield similar numbers needed to treat. Adding NSAIDs to the opioid treatment reduces morphine requirements and opioid-related side effects in the early postoperative period. (+info)