A randomized, placebo-controlled study of rofecoxib with paracetamol in early post-tonsillectomy pain in adults.

BACKGROUND AND OBJECTIVE: Effective and early treatment of postoperative pain and nausea have become pivotal for the early discharge of patients after tonsillectomy. Opioid-based analgesia is standard practice but the use of non-steroidal anti-inflammatory drugs is discouraged due to their platelet inhibiting properties. The cyclo-oxygenase-2 selective non-steroidal anti-inflammatory drugs are effective analgesics and do not affect platelet function. We hypothesized that premedication with cyclo-oxygenase-2 selective non-steroidal anti-inflammatory drug in addition to paracetamol would provide effective analgesia and decrease opioid consumption during early recovery from tonsillectomy. METHODS: In a randomized, placebo-controlled study of adult tonsillectomy patients (n=40) one group (R-group; n=20) was premedicated with paracetamol 1.5 g and rofecoxib 50 mg and a control group (P-group; n=20) was premedicated with paracetamol 1.5 g and placebo. Morphine was used as rescue medication. Postoperative (24 h) pain scores (0--10), morphine consumption as well as intraoperative blood loss were recorded. RESULTS: We found no overall difference in pain scores between the groups but significantly more patients in the placebo group had pain scores >5 within the first 8 h. The rofecoxib group consumed less morphine during the first 12 h. A lower intraoperative blood loss was observed in the rofecoxib group. CONCLUSION: Our results suggest an early although clinically minor analgesic benefit of the addition of a cyclo-oxygenase-2 selective non-steroidal anti-inflammatory drug to paracetamol as premedication for adult tonsillectomy.

Decreased reuptake of serotonin in human platelets after surgery.

We have documented earlier a decrease in platelet serotonin and a concurrent increase in plasma serotonin, 5-hydroxytryptamin (5-HT) after various forms of stress, suggesting a disturbed platelet 5-HT reuptake mechanism following stress. In order to further elucidate these findings, we have studied platelet 5-HT reuptake kinetics (Vmax and Km) in nine patients before and 4 days after major, uncomplicated abdominal surgery. We found a significant decrease in the maximal 5-HT reuptake velocity (Vmax) after surgery and changes in Km, verifying alterations in the affinity of the platelet 5-HT transport system. The present results thus confirm the hypothesis that 5-HT reuptake kinetics are altered following adrenergic hyperactivity. A decrease in platelet 5-HT reuptake may bear implications for our understanding of poststress adaptive changes in the cardiovascular system as well as in the central nervous system (CNS) serotonergic neurones following stressful stimulation.

No evident neuronal damage after electroconvulsive therapy.

Electroconvulsive therapy (ECT) is regarded as one of the most effective treatments for major depressive disorder but has also been associated with cognitive deficits possibly reflecting brain damage. The aim of this study was therefore to evaluate whether ECT induces cerebral damage as reflected by different biochemical measures. The concentrations in the cerebrospinal fluid (CSF) of three established markers of neuronal/glial degeneration, tau protein (tau), neurofilament (NFL) and S-100 beta protein, were determined in nine patients who fulfilled DSM-IV criteria for major depression. CSF samples were collected before and after a course of six ECT sessions. The CSF/serum (S) albumin ratio reflecting potential blood-brain barrier (BBB) dysfunction was also determined at these time points. The treatment was clinically successful with a significant decline of depressive symptoms in all patients as assessed by the Montgomery-Asberg Rating Scale for Depression. Several patients had signs of BBB dysfunction and/or neuronal damage before the start of treatment. Levels of CSF-tau, CSF-NFL and CSF-S-100 beta levels were not significantly changed by ECT. Also the CSF/S albumin ratio was found to be unchanged after the course of ECT. In conclusion, no biochemical evidence of neuronal/glial damage or BBB dysfunction could be demonstrated following a therapeutic course of ECT.

Changes in cross-sectional area of psoas major muscle in unilateral sciatica caused by disc herniation.

STUDY DESIGN: A clinical prospective cohort study of 15 healthy volunteers and 25 patients with unilateral sciatica from single-level disc herniation. OBJECTIVES: To detect any changes in the cross-sectional area of the psoas major muscle in patients with single-level (lateral to mediolateral) disc herniation causing unilateral sciatica. SUMMARY OF BACKGROUND DATA: The exact role of the psoas major muscle in the origin of low back pain and sciatica has not been clarified. METHODS: Fifteen healthy volunteers and 25 patients with unilateral sciatica from single-level disc herniation were subjected to magnetic resonance imaging of the lumbar spine. The cross-section area of the psoas major muscle on either side was recorded, and differences were noted. In patients, the cross-section area of either side was compared with and duration of sciatica was related to changes in the cross-section area. RESULTS: Insignificant variation in the cross-section area of the psoas major was observed in volunteers. In the patient group, significant reduction in the cross-section area of the psoas major was observed at the level and the site of the disc herniation. A significant correlation between cross-section area of the psoas major and ipsilateral continuous sciatica was found. There was no relation between the reduction of the cross-section area and the amount of disc herniation. CONCLUSION: The cross-section area of the psoas major is ipsilaterally decreased in unilateral lumbar disc herniation. The reduction in cross-section area is positively correlated with the duration of continuous sciatica.

Subarachnoid bupivacaine increases human cerebrospinal fluid concentration of serotonin.

BACKGROUND AND OBJECTIVES: Serotonin (5-hydroxytryptamine [5-HT]) has antinociceptive properties at the spinal level. Activation of descending serotonergic neurons or topically applied 5-HT at the spinal cord inhibits rostral spread of sensory information. Epidural anesthesia has been shown to increase 5-HT in plasma, and local anesthetics may interfere with 5-HT reuptake and metabolism. For these reasons, the action of subarachnoid local anesthetics on cerebrospinal fluid (CSF) 5-HT concentrations has been studied. METHODS: Six volunteers received lumbar spinal anesthesia with 0.5% bupivacaine through subarachnoid catheters, and CSF and plasma 5-HT concentrations were determined radioenzymatically before and after anesthesia. RESULTS: Plasma 5-HT was unchanged, but CSF 5-HT increased by 300% after bupivacaine administration (P < .02). CONCLUSION: Subarachnoid bupivacaine increases local 5-HT concentration. This may have implications for nociceptive gating as well as for local vasoregulation.

Purine metabolite washout and platelet aggregation at reflow after tourniquet ischemia: effect of intravenous regional lidocaine.

Tourniquet ischemia will influence the biochemical milieu of tissue cells and affect the metabolism of purines in skeletal muscle distal to the occlusion. At reperfusion, generation of oxygen radicals by the hypoxanthine-xanthine oxidase system may ensue, influencing white blood cell and thrombocyte aggregation, causing damage to the endothelial cell barrier and inducing non-reflow type phenomena. Amide-type local anaesthetics are known to affect local vasotone, leukocyte adherence and platelet function but the influence of lidocaine on purine metabolite washout and platelet aggregation following tourniquet ischemia for lower limb surgery is not known in detail. Therefore, the effects of regional intravenous lidocaine during tourniquet ischemia for knee surgery on purine catabolite washout and platelet function following reflow were assessed. Eight patients served as control (C-group) and 8 (L-group) received 100 ml of lidocaine (2.5 mg/ml) in the emptied venous bed of the leg to be operated. All patients had spinal anaesthesia (0.5% bupivacaine). Effluent venous blood from the leg and radial arterial blood was collected and analysed for xanthine (X), hypoxanthine (HX), base excess (BE), pH and potassium before and after reperfusion. Platelet ADP-induced aggregation (ADP-agg.) and secretion of beta-thromboglobulin (beta-TG) were measured in the effluent blood as well as systemically. After tourniquet release (TR), X and HX were significantly increased in effluent venous blood but the washout was enhanced in the L-group during the initial reperfusion phase. BE was significantly higher in the L-group both before and after TR whereas pH and potassium washout was comparable between the groups. No systemic effects on platelets were detected after tourniquet release but ADP-agg. in effluent venous blood was attenuated in 6 out of 8 patients in the L-group (NS). It is concluded that HX and X are generated during leg ischemia. Regional intravenous lidocaine, most probably through a vasodilatory mechanism and inhibition of white blood cell activation, may attenuate non-reflow phenomena and thereby exert beneficial effects on post-ischemic recovery by enhancing post-ischemic tissue reperfusion.

Platelet activation in major surgical stress: influence of combined epidural and general anaesthesia.

Platelets are activated in surgery releasing vasoactive substances such as serotonin and thromboxane. Platelets become temporarily hypoaggregable during surgery followed by a postoperative hyperaggregability. Local anaesthetics are known to inhibit platelet function but earlier reports are conflicting. In order to study the impact of the combined use of general and regional anaesthesia on platelet function during major surgery 16 otherwise healthy patients were randomised to either general anaesthesia (GA) (n = 8) or GA combined with epidural anaesthesia (GA+EPI) (n = 8) for elective upper abdominal surgery. Cyclic 3',5' adenosine monophosphate, plasma glucose, plasma cortisol and the rate pressure product (RPP) were markers of the stress response. ADP-induced platelet aggregation and the release products beta-thromboglobulin, serotonin and thromboxane 2 were measured in plasma before and during as well as for 3 days after surgery. A marked stress response was noted in both groups and epidural anaesthesia (EPI) only reduced the rate pressure product (RPP). Platelet aggregation was reduced during surgery, a little more so in the GA+EPI group. Postoperatively both groups showed significant hyperaggregability. The release products were not significantly influenced by regional anaesthesia. In conclusion epidural as combined with general anaesthesia affects platelet responses to major abdominal surgery only to a minor extent, although it may attenuate the haemodynamic response.

Epidural anaesthesia prolonged into the postoperative period prevents stress response and platelet hyperaggregability after peripheral vascular surgery.

The occlusion rate of peripheral vascular grafts depends on technical as well as endogenous factors. Platelets play an integral part in graft failure and it has been suggested that anaesthesia may influence platelet function. In order to evaluate the influence of anaesthesia on stress response and platelet function in peripheral vascular surgery, patients (n = 18) were allocated to either general anaesthesia (GA; n = 9) followed by alleviation of postoperative pain with intramuscular analgesics or to lumbar epidural anaesthesia (EPI; n = 9) which was continued for 24 hours postoperatively. Before, during, as well as after vascular surgery of the lower extremity plasma levels of cortisol, glucose, serotonin (p-5HT), and urinary 5-hydroxyindole-3-acetic acid (5-HIAA) were analysed and platelet aggregability was determined. In the GA group surgery was accompanied by a significant stress response while in the EPI group this stress response was almost completely abolished. Platelet aggregability was reduced intraoperatively in both groups but in the postoperative period there was a marked hyperaggregability only in the GA group. P-5HT was increased preoperatively in both groups but was not affected by surgery. It is concluded that epidural anaesthesia, due to its effects on platelet aggregability, may be advantageous for peripheral vascular surgery.

General versus regional anaesthesia and platelet aggregation in minor surgery.

In order to evaluate the impact of minor surgery on platelet aggregability and the effect of anaesthesia on this parameter, we allocated 14 otherwise healthy men for inguinal herniotomy to either general anaesthesia (n = 7) or lumbar epidural anaesthesia (n = 7). Platelet aggregation threshold to adenosine diphosphate (ADP-threshold) was measured before and after anaesthesia, prior to surgery, at the end of surgery and during the following hours as well as on the first post-operative morning. General anaesthesia did not affect ADP-threshold while epidural analgesia itself induced a significant increase. During and soon after surgery the ADP-threshold increased in those receiving general anaesthesia while in those receiving epidural analgesia the ADP-threshold returned to pre-operative levels. On the first post-operative morning both groups showed a significantly lower ADP-threshold as compared to the pre-operative level. Surgery induced an increase in 3'5' cyclic-adenosine monophosphate (cAMP). This adrenergic response was attenuated by epidural analgesia.

Effect of nitrous oxide and volatile anaesthetics on platelet function in man.

Twelve otherwise healthy male volunteers scheduled for arthroscopy of the knee were studied. The influence in vivo of nitrous oxide (N2O) per se and the addition of a halogenated volatile anaesthetic (halothane or isoflurane) on ADP-induced platelet aggregation and release of beta-thromboglobulin into plasma was evaluated. All measurements were made before surgery. We found that N2O increased platelet aggregation. Adding a halogenated anaesthetic reversed the relative hyperaggregation induced by N2O. The concentrations in plasma of the platelet release product beta thromboglobulin were not influenced by the anaesthetics.

Platelet activation in mental stress.

Platelets are known to become activated in vivo by different stressful stimuli such as surgery and dynamic exercise. Mental stress has been shown to increase platelet aggregability. Platelet activation is thought to be of major importance in atherogenesis and cardiac fatalities. In order to clarify further stress-induced platelet activation with special reference to the period after the stress, we studied eight young, healthy volunteers during and for 1 h after a mental stress test (Stroops Colour Word Conflict Test). Using highly standardized techniques, we have measured platelet aggregability ex vivo and the platelet release products beta-thromboglobulin, platelet factor 4 and serotonin in plasma. As markers of the stress response we measured cyclic-AMP in plasma, heart rate, cardiac output and blood pressure. The stress test induced a significant cardiovascular response with increases in heart rate, blood pressure, and cardiac output and as a measure of adrenergic activity an increase in cyclic AMP in plasma during the test. Platelet aggregability was unaffected during the test but decreased following the stress. During the first hour following the test and release products beta-thromboglobulin and serotonin increased significantly in plasma. We conclude that platelets are activated during mental stress and that this activation involves a post-stress release of vasoactive compounds from platelets.

Serotonin concentrations in plasma and variations during the menstrual cycle.

We used a specific and sensitive radioenzymatic method to establish a reference interval for the concentration of serotonin in platelet-poor plasma in 98 healthy volunteers (49 men, 49 women). The interval was 0-11 nmol/L with a median of 2.8 nmol/L. No difference in concentration in relation to sex or age was observed. In a group of eight very old volunteers (ages 86-92 years), however, concentrations were increased. In addition, we monitored the plasma concentrations of serotonin in 20 healthy women (ages 26-45 years) through two menstrual cycles. Periovulatory and premenstrual concentrations were greater than the serotonin concentration at the start of menstruation.

Platelet responses to intravenous infusion of Intralipid in healthy volunteers.

Platelet function and morphology were studied in eight healthy male volunteers before, immediately after, and 1 d after the infusion of 250 mL of 10% Intralipid. The plasma concentrations of the platelet-release products beta-thromboglobulin (beta-TG), serotonin (5-HT), and platelet factor 4 (PF4) and the threshold to ADP- and adrenaline-induced aggregation were determined ex vivo. In addition the platelets were examined by electron microscopy. Although platelets released beta-TG, PF4, and 5-HT after the infusion, there was no significant change in ex vivo aggregability. About 3% of the platelets had internalized small-sized lipid particles (0.1-0.2 micron) whereas no other morphological changes were detected. The release products may negatively affect the hemorheological properties of the microcirculation in critically ill patients. The release of PF4 may explain the antiheparin effect of parenteral lipid therapy.

Post-exercise platelet activation--aggregation and release in relation to dynamic exercise.

Relatively scarce information is found on the period immediately following physical stress, with special reference to human platelet activity. This, in connection with earlier observations of an increase in platelet release products and hyperaggregability following surgical stress, has initiated the present study. We studied platelet function in eight healthy non-mediated volunteers during and 1 h after cycle exercise of submaximal intensity. ADP-induced platelet aggregability was enhanced in the last minute of exercise followed by a decreased aggregability 1 h after. Adrenaline-induced platelet aggregation showed the same attenuation after exercise but no change during work. The release products beta-thromboglobulin and serotonin in plasma showed significant increases after exercise. This is taken as evidence of an enhanced platelet activity following exercise. A normal stress-response, measured as increase in cyclic AMP in plasma, was observed. In conclusion, platelets are activated following moderate exercise and it seems valid to include the post-exercise period in future studies.

Effect of doxapram on postoperative pulmonary complications after upper abdominal surgery in high-risk patients.

In a double-blind randomised trial an infusion of doxapram, 2 mg per min for 6 h immediately after surgery and repeated on the first postoperative day, or the same volume of saline, was given to 39 patients who underwent upper abdominal surgery and who were at high risk of postoperative day, or the same volume of saline, was given to 39 patients who underwent upper abdominal surgery and who were at high risk of postoperative pulmonary complications. The patients were assessed pre-operatively and during the first 5 postoperative days by physical examination, spirometry, blood-gas analysis, and chest radiography. Postoperative pulmonary complications were defined as temperature over 38 degrees C for 2 days, abnormal auscultation, pathological radiography, and/or productive cough. Data from 16 patients per group were analysed. Significantly more patients in the placebo group had three criteria of postoperative pulmonary complication compared with the doxapram group (63% vs 19%). The doxapram group also had higher PaO2 postoperatively.