Observations on the zinc protoporphyrin/heme ratio in whole blood

The aim of this study was to examine whether severity of preoperative pain intensity is related to postoperative pain and morphine consumption. Sixty consecutive patients scheduled for total hip surgery during intrathecal anesthesia were studied. Preoperative visual analog scale (VAS) scores and analgesic intake was assessed 1 day before surgery. Three groups of patients were identified: those with mild pain (n = 12, VAS score 0-4), moderate pain (n = 18, VAS score 4-7), and severe pain (n = 28, VAS score 7-10). Postoperative pain scores were recorded in the first 24 h, as was the amount of morphine delivered by the patient-controlled analgesia pump. There were no differences among the groups in VAS scores at any time. Severe preoperative pain levels correlated with significantly greater postoperative morphine intake. The mean morphine intake during the first 24 h postoperatively was 19.2 mg in the mild pain group, 21.2 mg in the moderate pain group, and 29.5 mg in the severe pain group (P < 0.05 compared with both other groups). We conclude that patients with severe preoperative pain self-medicate to achieve postoperative pain scores equivalent to those of patients with mild and moderate pain and require a greater postoperative morphine intake for adequate analgesia than patients with mild or moderate preoperative pain. IMPLICATIONS: In this study, we showed that severity of preoperative pain intensity relates to postoperative pain levels and morphine consumption. Patients scheduled for total hip surgery with severe preoperative pain require more postoperative morphine in the first 24 h.     

Postoperative pain and fatigue after laparoscopic or conventional colorectal resections. A prospective randomized trial

BACKGROUND: Conventional colorectal resections are associated with severe postoperative pain and prolonged fatigue. The laparoscopic approach to colorectal tumors may result in less pain as well as less fatigue, and may improve postoperative recovery after colorectal resections. METHODS: Sixty patients were included into a prospective randomized trial to determine the influence of laparoscopic (n = 30) or conventional (n = 30) resection of colorectal tumors on postoperative pain and fatigue. Major endpoints of the study were dose of morphine sulfate during patient-controlled analgesia (PCA), visual analog scale for pain while coughing (VASC), and visual analogue scale for fatigue (VASF). Efficacy of pain medication was assessed by visual analogue score at rest (VASR). RESULTS: Preoperative age, sex, stage, and localization of tumors were comparable in both groups. The PCA dose of morphine given immediately after surgery until postoperative day 4 was higher in the conventional group (median, 1.37 mg/kg; 5-95 percentile 0.71-2. 46 mg/kg) than the laparoscopic group (0.78 mg/kg; 0.24-2.38 mg/kg, p < 0.01). Postoperative VASR was comparable between both groups, but VASC was higher from the first to the seventh postoperative day (p < 0.01). Postoperative fatigue was higher after conventional than after laparoscopic surgery from the second to the seventh day (p < 0. 05). CONCLUSIONS: This study confirms that analgetic requirements are lower and pain is less intense after laparoscopic than after conventional colorectal resection. Patients also experience less fatigue after minimal invasive surgery. Because of these differences, the duration of recovery is shortened, and the postoperative quality of life is improved after laparoscopic colorectal resections.     

Multicomponent intravenous and epidural anesthesia in aorto-coronary bypass surgery

The influence of epidural anesthesia (CEA) on clinical manifestations, cortisole and adrenocorticotropic hormone (ACTH) level, central hemodynamic values during aorto-coronary bypass surgery (ACBS) in 56 patients aged 42-68 years with preserved functional capacity of the myocardium was studied. Catheterisation of the epidural space was carried out in the evening before the operation according to the standard method at the level of T4-T5 with the use of disposable epidural set. During the procedure before perfusion 2% solution of lidocaine 3.8 +/- 0.2 mg/kg was introduced in epidural space (taking into account test-dose) as a bolus in 3-4 motions. The dose of local anesthetics for infusion was selected separately for each individual case with due regard for hemodynamic values. During artificial circulation additionally local anesthetic was introduced as a bolus, the dose being 4.7 +/- 0.8 mg/kg. At the end of the operation morphine (0.061 +/- 0.001 mg/kg) was introduced. It was established that combined application of intravenous and epidural anesthesia represents highly effective method of anesthesia in aorto-coronary bypass surgery. According to clinical course data, cortisone and ACTH blood contents and hemodynamic parameters, EA provides adequate anesthesia, promotes stabilization of hemodynamic values and creates functionally more advantageous conditions for the myocardium in patients with CHD during aorto-coronary bypass operation. Anesthesiologic aid with the use of EA promotes reduction of intravenous anesthetics expenditure, earlier waking up of the patients in postoperative period and decrease in duration of postoperative artificial lung ventilation.     

Survival after massive ecstasy overdose

This study was designed to evaluate the potential advantages of combined epidural and light general anesthesia over the commonly employed general anesthesia during open heart surgery. Twenty-four patients undergoing mitral valve replacement were thus studied. General anesthesia was maintained with an isoflurane-nitrous oxide-oxygen was mixture and morphine sulfate (0.4 mg/kg i.v. initially) followed by postoperative pain control with morphine in 12 patients (group GA). The remaining 12 patients (group EAA) received continuous epidural bupivacaine (0.125%)-morphine (50 micrograms/ml) supplemented with the same gas mixture as group GA. Epidural infusion was continued until the third postoperative day. Changes in the serum cortisol and beta-endorphin levels together with postoperative pain relief defined as good (scale 0-2), fair (3-4), or poor (5-10) were observed serially. Lower cortisol levels were observed in group EAA than in group GA (P < 0.05) just before skin closure, on the second and the third postoperative day. The beta-endorphin levels were substantially lower in group EAA than in group GA throughout the observation. The pain scores were good in 2 patients (17%), fair in 6 (50%), and poor in 4 (33%) for group GA, and good in 8 (67%), fair in 3 (25%), and poor in 1 (8%) for group EAA. We thus conclude that a combined epidural and light general anesthesia is considered to attenuate the stress response and thereby provides a better quality of postoperative pain control.     

Indicators of postoperative pain in cats and correlation with clinical criteria

OBJECTIVE: To identify clinical indicators that may help identity postoperative pain in cats after ovariohysterectomy. ANIMALS: Healthy, laboratory animal source cats. PROCEDURE: Clinical indicators of pain were identified, and relief from pain in response to butorphanol was studied in 5 groups of cats. 10 cats had 1 hour of general anesthesia only, followed by recovery without additional medication. 10 cats had general anesthesia and ovariohysterectomy, followed by recovery without additional medication. 10 cats had general anesthesia, ovariohysterectomy, and postoperative administration of 0.1 mg of butorphanol/kg of body weight. Another 10 cats had general anesthesia, ovariohysterectomy, and postoperative administration of 0.3 mg butorphanol/kg. 10 cats received 0.1 mg of butorphanol/kg, IM, only. Samples and recorded data were obtained before, during, and after the anesthesia period. Clinical variables measured included heart rate, blood pressure, respiratory rate, rectal temperature, PCV, and blood glucose concentration. Results were compared with changes in norepinephrine, epinephrine, and cortisol concentrations. RESULTS: Cats that did not receive analgesics had higher cortisol concentration than did cats without surgery and cats that received butorphanol after surgery. Systolic blood pressure measured by ultrasonic Doppler was found to be predictive of cortisol concentration, using a multiple linear regression model. CONCLUSIONS: Cortisol concentration increased in response to surgical stress and pain, and this increase was diminished by use of butorphanol. CLINICAL RELEVANCE: Systolic blood pressure was the best clinical predictor of postoperative pain.     

Ketamine for pediatric cardiac anesthesia

Eighty-five patients ranging from 12 h to 7 years of age were included in this study. In the first group 35 cases received ketamine, gallamine and oxygen for surgery on the great vessels. Ketamine provided satisfactory analgesia and amnesia. Heart rate did not change significantly. Gallamine gave additional safety in the prevention of bradycardia. One hundred per cent oxygen increased oxygen saturation and made more oxygen available for the tissues. The combination secured favorable conditions even in cases of sevre right to left shunt. Seven patients developed some degree of bradycardia, requiring treatment. All but one responded to epinephrime infusion. The one who did not improve died on the table. There were 6 additional deaths during the first 48 postoperative hours. Fifty infants and children received pentobarbital and morphine premedication and ketamine, pancuronium, nitrous-oxide oxygen anesthesia for open heart surgery. Cardiovascular stability with good operating conditions characterized the course of anesthesia. The increase in systolic and diastolic blood pressures and heart rate was small after induction. Further changes in these parameters during anesthesia were statistically insignificant. Perfusion pressure during cardio-pulmonary bypass was well maintained. The addition of 50 per cent nitrous oxide to inhaled oxygen significantly potentiated the duration of hypnosis and analgesia proved by ketamine. Mechanical ventilation was facilitated in both groups by the analgesia extending well into the postoperative period. There were 6 deaths in the first 48 postoperative hours in this group. The state of consciousness at the end of anesthesia and postoperative conditions of all 85 patients were comparable with that found with other agents. The techniques described provided suitable alternatives to the anesthetic management pediatric cardiac surgery.     

Evaluation of the safety and efficacy of ketorolac versus morphine by patient-controlled analgesia for postoperative pain

STUDY OBJECTIVE: To compare ketorolac tromethamine with morphine for pain management after major abdominal surgery. DESIGN: Double-blind, randomized study. SETTING: Hospital recovery room and postoperative surgical unit. PATIENTS: One hundred ninety-one patients with at least moderate pain after major abdominal surgery. INTERVENTIONS: Patients received ketorolac by patient-controlled analgesia (PCA) bolus alone (Ket B), ketorolac by bolus plus infusion (Ket I), or morphine by PCA bolus (morphine), with injectable morphine available for supplementation. MEASUREMENTS AND MAIN RESULTS: Levels of sedation, pain intensity, pain relief, and adverse events were recorded at baseline, at 2, 4, and 6 hours, and at termination. Supplemental morphine was required by 71% of Ket B patients, 67% of Ket I patients, and 38% of morphine patients (p < or = 0.001 for Ket B vs morphine). Although patients receiving ketorolac required more supplemental morphine than the morphine group (6.0 mg Ket I, 6.2 mg Ket B, 4.0 mg morphine), there was a large morphine-sparing effect in both ketorolac groups (total morphine 6.0 mg Ket I, 6.2 mg Ket B, 33.3 mg morphine). Overall pain relief scores were similar for morphine and Ket I groups, and were lower for Ket B than for morphine (p = 0.002). There were no differences among groups in numbers of patients with adverse events. CONCLUSION: Ketorolac may be effective when administered by PCA device, and has a clear morphine-sparing effect.     

Comparative study of preemptive and postincisional lumbar epidural morphine in pulmonary resection. Preliminary report

OBJECTIVES: To evaluate the efficacy and incidence of side effects of two types of lumbar epidural analgesia with morphine, preemptive or postincisional, combined with total intravenous anesthesia in chest surgery. PATIENTS AND METHODS: This double-blind prospective study enrolled 20 patients (ASA I-IV) undergoing lobectomy or pneumonectomy. Anesthetic induction and maintenance was provided with propofol, atracurium and alfentanil. Lumbar epidural analgesia (L2-L3) with morphine was provided for group A patients with 2 to 4 mg upon excision of tissue and for group B with 2 to 4 mg during anesthetic induction. The following variables were recorded: arterial blood gas concentrations, heart rate, SpO2, EtCO2, postanesthetic recovery, arterial gases, side effects and pain on a visual analogue scale. Top-up analgesia was provided by intravenous metamizole and/or epidural morphine. For statistical analysis we used ANOVA, chi-square tests and Student-Newman-Keuls tests. RESULTS: The need for propofol and alfentanil during anesthesia, and for morphine and metamizole after surgery were statistically greater in group A. Pain 18 hours after surgery was also greater in group A. No significant differences between groups for other variables was observed. CONCLUSIONS: Preemptive analgesia with lumbar epidural morphine in addition to the general anesthesia described here seems to provide higher-quality analgesia with few side effects, reducing the need for propofol and alfentanil during surgery and for postoperative morphine and metamizole.     

A single dose of morphine sulfate increases the incidence of vomiting after outpatient inguinal surgery in children

BACKGROUND: In children, opioids are valuable both for their analgesic properties and for their salutary effect on emergence delirium. Although intraoperative administration of opioids is often cited as the cause of postoperative emesis, few data quantitating the magnitude of this effect exist. METHODS: Patients undergoing inguinal surgery as outpatients were randomly assigned to one of two groups. One group received a single intravenous dose of morphine 0.1 mg/kg (morphine group), and the other (control) group had the identical anesthetic but instead received saline. Intravenous ketorolac was administered in response to verbal complaints of pain or a Children's Hospital of Eastern Ontario Pain Score greater than 9 on two successive evaluations performed at 5-min intervals. The authors compared the incidence of postoperative emesis and emergence, behavior, and pain scores between the two groups. RESULTS: Patients in the morphine group (n = 48) were 5.6 +/- 2.8 yr old and weighed 20.8 +/- 7.8 kg, and those in the control group (n = 49) were 4.5 +/- 2.9 yr old and weighed 18.9 +/- 9.2 kg. More patients in the morphine group were cooperative and deeply asleep both on arrival and through the first 30 min of their stay in the postanesthesia care unit (PACU) (P < 0.05). Sixty-three percent of the children in the control group received ketorolac in the PACU compared with 20% of the morphine group (P < 0.01). The incidence of emesis for the 24 h after arrival in the PACU was 56% for those who received morphine compared with 25% in the control group (P < 0.01). CONCLUSIONS: For children undergoing inguinal surgery, the administration of a single dose of intravenous morphine after the induction of anesthesia smooths emergence from anesthesia as assessed by improved cooperation and sedation in the PACU, decreases the need for postoperative analgesics, but increases the incidence of vomiting in the first 24 h after surgery.     

Extent and severity of periodontal destruction based on partial clinical assessments

OBJECTIVES: To evaluate the postoperative analgesic efficacy, side effects and acceptance by patients and nurses of intravenous "patient-controlled analgesia" (PCA) with morphine, metamizole and buprenorphine. MATERIAL AND METHODS: In this randomized double blind prospective study of 150 patients in three groups receiving morphine (group A), metamizole (group B) or buprenorphine (group C), the patients had undergone low abdominal surgery with the same anesthetic protocol. Pain was recorded during the first 48 h after surgery on an orally-communicated scale of none or slight = 0, moderate = 1 and severe = 2. Upon the first report of moderate pain, patients were administered an intravenous bolus containing 5 mg morphine, 1 g metamizole or 0.15 mg buprenorphine. A perfusion pump was then connected and set with one bolus of 1.2 mg morphine, one of 333 mg metamizole or one of 0.04 buprenorphine. The maximum dose allowed in 24 h was 40 mg morphine, 8 g metamizole or 1.2 mg buprenorphine. The minimum interval between doses was 30 min for all three groups. Side effects reported were respiratory depression, sedation, nausea, vomiting, pruritus, perspiration and pain upon administration. Patients and nurses were asked to evaluate the system when the pump was disconnected and the results were then analyzed statistically. RESULTS: The analgesic effect was satisfactory in all three groups, with no significant differences among them. The percentages of patients reaching the maximum allowed dose on the first day were 2% with morphine, 18% (p < 0.05) with metamizole and 8% with buprenorphine. No respiratory depression was observed. Sedation was greater with morphine and buprenorphine than with metamizole (p = 0.0001). Pruritus was also greater with morphine and buprenorphine than with metamizole (p = 0.02) and pain upon infusion was greater with metamizole (p = 0.0002). CONCLUSIONS: Intravenous postoperative PCA was effective with all three drugs studied. Patient and nurse acceptance was good and side effects were few in the three groups. The lower rate of side effects for metamizole makes it the drug of choice.     

Restricted expression of Fc gammaRIII (CD16) in synovium and dermis: implications for tissue targeting in rheumatoid arthritis (RA)

The authors conducted a prospective randomised double-blind comparison of patient-controlled analgesia (PCA), with a combination of morphine and ketorolac versus morphine alone and ketorolac alone in the management of postoperative pain after orthopaedic surgery. Forty-two patients were randomly assigned to three groups. Group 1 was given 1 mg/ml morphine, group 2 was given 3 mg/ml ketorolac and group 3 half-doses of each. After a loading dose of 0.07 ml/kg, PCA was started at an initial setting of 1 ml per demand, with a 10-min lock-out interval and no background infusion. Pain was measured at rest and during movements for 48 h. The combination of morphine and ketorolac was more effective than morphine or ketorolac alone in relieving rest pain throughout the study. The combination was also more effective during movement than either drug alone, but only for the first 24 h. The consumption of morphine and ketorolac was significantly lower when the two drugs were administered together. The incidence of urinary retention was highest in the group given morphine alone. The combination of half-doses of morphine and ketorolac is more effective in controlling postoperative pain than either drug alone. This combination also reduces analgesic consumption and morphine-related adverse events.     

Is there any clinical advantage of increasing the pre-emptive dose of morphine or combining pre-incisional with postoperative morphine administration?

Pre-emptive treatment with an i.v. infusion of morphine 10 mg at induction reduces postoperative analgesic requirement and wound hypersensitivity compared with the same dose administered at the end of operation. Increasing the dose of preemptive morphine may potentially reduce postoperative pain further, while administering morphine at the end of operation, in addition to the beginning, may reduce pain generated by the sensory activity elicited from the wound in the immediate postoperative period. To examine this we have conducted a randomized, double-blind study in patients undergoing abdominal hysterectomy to compare the effect of morphine 20 mg administered before operation with 10 mg at induction and 10 mg on closure of the peritoneum. Postoperative pain was assessed by visual analogue score (VAS) at rest and on movement and by total morphine consumption administered by patient-controlled analgesia (PCA). Wound sensitivity was assessed by von Frey pain thresholds. Both groups had similar morphine consumption, VAS scores and touch and pain thresholds, and in both, secondary hyperalgesia was prevented. Nausea and vomiting scores were higher in the 20-mg group. There was no significant difference between the two groups and neither regimen appeared to offer obvious clinical advantages compared with a lower dose (10 mg) morphine analgesic strategy. Therefore, there may be a ceiling effect to the production of pre-emptive analgesia by morphine.     

Postoperative analgesia after co-administration of clonidine and morphine by the intrathecal route in patients undergoing hip replacement

Postoperative analgesia after intrathecal co-administration of clonidine hydrochloride (75 micrograms) and morphine sulfate (0.5 mg) was compared with analgesia produced after either intrathecal morphine (0.5 mg) or 0.9% sodium chloride in 90 patients undergoing total hip replacement under bupivacaine spinal anesthesia. Patient-controlled morphine requirements were significantly reduced (P < 0.001) postoperation by both clonidine/morphine (median 5 mg/24 h) and morphine (median 7 mg/24 h) compared with control (saline) (median 28 mg/24 h). However, no significant additional reduction in postoperative analgesic requirements was shown with the clonidine/morphine combination compared with morphine alone. Visual analog pain scores, although good in all groups at all times, were significantly poorer in the control group at 2 h (P < 0.04) and 4 h (P < 0.001) after operation compared with both treatment groups, and significantly poorer than the clonidine/morphine group at 6 h (P < 0.002) and 24 h (P < 0.009) postoperation. Mean arterial blood pressure was significantly lower in the clonidine/morphine group than in the two other groups (P < 0.001) between 2 and 5 h after operation. The incidence of emesis was similar in the clonidine/morphine and morphine groups and was significantly more than in the control group.     

Antiemetic activity of propofol after sevoflurane and desflurane anesthesia for outpatient laparoscopic cholecystectomy

BACKGROUND: Controversy exists regarding the effectiveness of propofol to prevent postoperative nausea and vomiting. This prospective, randomized, single-blinded study was designed to evaluate the antiemetic effectiveness of 0.5 mg/kg propofol when administered intravenously after sevoflurane- compared with desflurane-based anesthesia. METHODS: Two hundred fifty female outpatients undergoing laparoscopic cholecystectomy were assigned randomly to one of four treatment groups. All patients were induced with intravenous doses of 2 mg midazolam, 2 microg/kg fentanyl, and 2 mg/kg propofol and maintained with either 1-4% sevoflurane (groups 1 and 2) or 2-8% desflurane (groups 3 and 4) in combination with 65% nitrous oxide in oxygen. At skin closure, patients in groups 1 and 3 were administered 5 ml intravenous saline, and patients in groups 2 and 4 were administered 0.5 mg/kg propofol intravenously. Recovery times were recorded from discontinuation of anesthesia to awakening, orientation, and readiness to be released home. Postoperative nausea and vomiting and requests for antiemetic rescue medication were evaluated during the first 24 h after surgery. RESULTS: Propofol, in an intravenous dose of 0.5 mg/kg, administered at the end of a sevoflurane-nitrous oxide or desflurane-nitrous oxide anesthetic prolonged the times to awakening and orientation by 40-80% and 25-30%, respectively. In group 2 (compared with groups 1, 3, and 4), the incidences of emesis (22% compared with 47%, 53%, and 47%) and requests for antiemetic rescue medication (19% compared with 42%, 50%, and 47%) within the first 6 h after surgery were significantly lower, and the time to home-readiness was significantly shorter in duration (216 +/- 50 min vs. 249 +/- 49 min, 260 +/- 88 min, and 254 +/- 72 min, respectively). CONCLUSIONS: A subhypnotic intravenous dose of propofol (0.5 mg/kg) administered at the end of outpatient laparoscopic cholecystectomy procedures was more effective in preventing postoperative nausea and vomiting after a sevoflurane-based (compared with a desflurane-based) anesthetic.     

Clearance of morphine in postoperative infants during intravenous infusion: the influence of age and surgery

We analyzed morphine clearance values in infants receiving the drug by continuous i.v. infusion for analgesia after surgery, because we found lower steady-state morphine concentrations than we expected from our previous studies. Infants received morphine after a loading dose of 0.05 mg/kg and continuous infusion calculated to reach a steady-state concentration of 20 ng/mL. Blood was sampled twice on Postoperative Day 1 at times separated by at least 2 h, and morphine and morphine-6-glucuronide (M-6-G) concentrations were determined by high-performance liquid chromatography. Clearance of morphine was calculated as infusion rate divided by the steady-state morphine concentration. Morphine given to 26 infants by continuous i.v. infusion after major noncardiac surgery has rapidly increasing clearance values, from a median value of 9.2 mL x min(-1) x kg(-1) in infants 1-7 days old, 25.3 in infants 31-90 days old, and 31.0 in infants 91-180 days old to 48.9 in infants 180-380 days old. Adult clearance values are reached by 1 mo of age, more quickly than in infants of the same age previously studied who received morphine after cardiac surgeries. M-6-G was measured in all infants. The ratio of M-6-G to morphine concentrations was 1.9-2.1 in these infants, which is lower than ratios reported in older infants or adults by others, but higher than those reported in newborns. Infants with normal cardiovascular systems undergoing surgery clear morphine more efficiently than infants of the same age undergoing cardiac surgery. Implications: Morphine removal from the body is slow in newborns but increases to reach adult values in the first months of life. Calculating the clearance of morphine from blood samples drawn during continuous i.v. infusions after surgery shows that this maturation occurs more quickly in infants undergoing noncardiac surgery (by 1-3 mo of age) than in those receiving morphine after cardiac surgery (by 6-12 mo of age).     

Postoperative hypoxaemia: continuous extradural infusion of bupivacaine and morphine vs patient-controlled analgesia with intravenous morphine

We carried out a randomized prospective study in 60 patients who had undergone major abdominal surgery for cancer. For postoperative pain control, 30 patients received continuous extradural infusion of 0.125% bupivacaine 12.5 mg h-1 and morphine 0.25 mg h-1 (EXI group) and 30 received patient-controlled analgesia (PCA) with intravenous morphine (1 mg bolus, 5-min lock-out and maximum dose 20 mg 4h-1). Both groups had general anaesthesia. The two groups were compared for postoperative pain scores, satisfaction, sedation and oxygen saturation. Oxygen saturation was recorded continuously the night before surgery and for two consecutive postoperative nights. Episodes of moderate desaturation (90% > SpO2 85%) were more frequent in the EXI group than in the PCA group (P < 0.05). Pain scores were lower in the EXI group compared with the PCA group at rest and while coughing (P < 0.05). No significant difference was found for patient sedation and satisfaction.     

Controlled trial of preperitoneal local anaesthetic for reducing pain following laparoscopic hernia repair

BACKGROUND: A prospective randomized trial was performed to determine whether local anaesthetic solutions injected into the preperitoneal space may provide additional pain relief following transabdominal preperitoneal laparoscopic hernia repair. METHODS: One hundred patients undergoing transabdominal preperitoneal laparoscopic hernia repair were allocated randomly to receive (1) bupivacaine 1.5 mg/kg, (2) bupivacaine 1.5 mg/kg with 1 in 200000 adrenaline, (3) bupivacaine 3 mg/kg or (4) saline instilled into the preperitoneal space at the end of the operation. An independent clinical assessor determined the level of pain using a visual analogue pain score and noted the parenteral and oral analgesia requirements at 4, 8, 12 and 24 h after operation. Results: At each of the time intervals, there was no significant difference between the groups for pain scores (at 24 h, P = 0.71) or the number of doses of either morphine (at 24 h, P = 0.73) or oral analgesia (at 24 h, P = 0.89). There was also no significant difference in the time to return to normal activity or work between the groups. CONCLUSION: This study suggests that instilling local anaesthetic into the preperitoneal space has no significant effect on postoperative pain relief requirement following laparoscopic hernia repair. Other methods of reducing postoperative pain should be sought that may facilitate day-case laparoscopic hernia surgery.     

Adrenaline markedly improves thoracic epidural analgesia produced by a low-dose infusion of bupivacaine, fentanyl and adrenaline after major surgery. A randomised, double-blind, cross-over study with and without adrenaline

BACKGROUND: Basic pharmacological research indicates that there are synergistic antinociceptive effects at the spinal cord level between adrenaline, fentanyl and bupivacaine. Our clinical experience with such a mixture in a thoracic epidural infusion after major surgery confirms this. The objectives of the present study were to evaluate the effects on postoperative pain intensity, pain relief and side effects when removing adrenaline from this triple epidural mixture. METHODS: A prospective, randomised, double-blind, cross-over study was carried out in 24 patients after major thoracic or abdominal surgery. Patients with only mild pain when coughing during a titrated thoracic epidural infusion of about 10 ml.h-1 of bupivacaine 1 mg.ml-1, fentanyl 2 micrograms.ml-1, and adrenaline 2 micrograms.ml-1 were included. On the 1st and 2nd postoperative days each patient was given a double-blind epidural infusion, at the same rate, with or without adrenaline. The effect was observed for 4 h or until pain when coughing became unacceptable in spite of a rescue analgesic procedure. Rescue analgesia consisted of up to two epidural bolus injections per hour and i.v. morphine if necessary. All patients received rectal paracetamol 1 g, every 8 h. Fentanyl serum concentrations were measured with a radioimmunoassay technique at the start and end of each study period. Main outcome measures were extent of sensory blockade and pain intensity at rest and when coughing, evaluated by a visual analogue scale, a verbal categorical rating scale, the Prince Henry Hospital pain score, and an overall quality of pain relief score. RESULTS: The number of hypaesthetic dermatomal segments decreased (P < 0.001) and pain intensity at rest and when coughing increased (P < 0.001) when adrenaline was omitted from the triple epidural mixture. This change started within the first hour after removing adrenaline. After 3 h pain intensity when coughing had increased to unacceptable levels in spite of rescue analgesia (epidural bolus injections and i.v. morphine). Within 15-20 min after restarting the triple epidural mixture with adrenaline, pain intensity was again reduced to mild pain when coughing. Serum concentration of fentanyl doubled from 0.22 to 0.45 ng.ml-1 (P < 0.01), and there was more sedation during the period without adrenaline. CONCLUSIONS: Adrenaline increases sensory block and improves the pain-relieving effect of a mixture of bupivacaine and fentanyl infused epidurally at a thoracic level after major thoracic or abdominal surgery. Serum fentanyl concentrations doubled and sedation increased when adrenaline was removed from the epidural infusion, indicating more rapid vascular absorption and systemic effects of fentanyl.     

Diagnosis of trypanosomiasis in experimental mice and field-infected camels by detection of antibody to trypanosome tyrosine aminotransferase

We designed this double-blind study to evaluate the effect of adding small-dose ketamine in a multimodal regimen of postoperative patient-controlled epidural analgesia (PCEA). Ninety-one patients, ASA physical status I-III, undergoing major surgery, received a standardized general anesthesia and epidural catheterization in an appropriate intervertebral space after surgery. A PCEA device was programmed to deliver a regimen of morphine 0.02 mg/mL, bupivacaine 0.8 mg/mL, and epinephrine 4 microg/mL, with the addition of ketamine 0.4 mg/mL (ketamine, n = 45) or without (control, n = 46). The mean visual analog pain scale (VAS) scores during cough or movement for the first 3 days after surgery were higher in the control group than in the ketamine group (P < 0.05), whereas the mean VAS score at rest for the first 2 days were higher in the control group than in the ketamine group (P < 0.05). Furthermore, patients in the control group consumed more multimodal analgesics than patients in the ketamine group for the first 2 days (P < 0.05). The sedation scores and the incidence of side effects (pruritus, nausea, emesis, sleep deprivation, motor block, and respiration depression) were similar between the two groups. We conclude that adding ketamine 0.4 mg/mL in a multimodal PCEA regimen provides better postoperative pain relief and decreases consumption of analgesics. Implications: Many studies have evaluated one or a combination of two analgesics for postoperative pain control, but few have examined a multimodal approach using three or four different epidural analgesics. This study demonstrates an additive analgesic effect when ketamine is added to a multimodal analgesic treatment.     

Effect of 7-nitroindazole on tolerance to morphine, U-50,488H and [D-Pen2, D-Pen5] enkephalin in mice

The effects of 7-nitroindazole (7-NI), an inhibitor of the neuronal nitric oxide synthase (nNOS) which does not increase blood pressure, on tolerance to the antinociceptive activity of mu-(morphine), kappa-(U-50,488H) and delta-([D-Pen2, D-Pen5]enkephalin, DPDPE) opioid receptor agonists were determined in mice. Male Swiss-Webster mice were made tolerant by twice daily injections of morphine (20 mg/kg, s.c.), U-50,488H (25 mg/kg, i.p.) or DPDPE (20 micrograms/mouse, i.c.v.) for 4 days. When tested on day 5, tolerance to their antinociceptive activity was evidenced by decreased response in chronic drug treated mice in comparison to vehicle-injected mice. Concurrent administration of 7-NI (20, 40 or 80 mg/kg, i.p.) with DPDPE did not modify the development of tolerance to the antinociceptive action of DPDPE. However, 7-NI (40 or 80 mg/kg, i.p.) inhibited the development of tolerance to the antinociceptive activity of morphine and U-50,488H but the lower dose of 7-NI (20 mg/kg, i.p.) was not effective. Chronic administration of 7-NI by itself did not modify the acute response to morphine, U-50,488H or DPDPE. It is concluded that a specific inhibitor of nNOS can inhibit tolerance to the antinociceptive activity of mu- and kappa- but not of delta-opioid receptor agonists in mice.