Effective dose of granisetron in the reduction of nausea and vomiting after breast surgery

Background: Prophylactic use of granisetron, a selective Shydroxytryptamine type 3 receptor antagonist, reduces the incidence of nausea and vomiting after breast surgery. This study was undertaken to determine the minimum effective dose of granisetron in the reduction of postoperative nausea and vomiting (PONV) in patients undergoing general anaesthesia for breast surgery.
Methods: In a randomized, double-blind manner, 120 female patients aged 42–66 years were assigned to receive either placebo (saline) or granisetron in a dose of 20 μg · kg^-1, 40 μg · kg^-1 and 80 μg · kg^-1 i.v. immediately before the induction of anaesthesia. A standard general anaesthetic technique was employed throughout. The POW and safety assessments were performed continuously during the first 24 h after anaesthesia.
Results: There were no significant differences among the groups with regard to patient demographics, surgical procedures, anaesthetics administered and analgesics given. The incidence of PONV was 47%, 43%, 17% and 17% after administration of placebo and granisetron 20 μg -kg^-1, 40 μg kg^-1 and 80 μg kg^-1, respectively. Granisetron 40 μg kg^-1 was as effective as 80 μ g - kg^-1 and both resulted in significant reductions of the incidence of PONV compared with placebo and granisetron 20 μg kg^-1 ( P < 0.05). No differences in the incidence of adverse events were observed among the groups.
Conclusion: Granisetron 40 μg · kg^-1 appears to be the minimum effective dose for reducing POW in patients undergoing general anaesthesia for breast surgery.     

Prophylactic antiemetic therapy with granisetron-dexamethasone combination in women undergoing breast surgery

Background: Dexamethasone decreases chemotherapy-induced emesis when added to an antiemetic regimen. This study was undertaken to evaluate the efficacy of granisetron-dexamethasone combination for the prevention of postoperative nausea and vomiting (PONV) in female patients undergoing general anaesthesia for breast surgery.
Methods: In a randomized, double-blind manner, 135 ASA I patients, aged 40–65 years, were assigned to receive placebo (saline), granisetron 40 μg · kg⁻¹ or granisetron 40 μg · kg⁻¹ plus dexamethasone 8 mg i.v. (n=45 of each) immediately before the induction of anaesthesia. A standard general anaesthetic technique and postoperative analgesia were used. The PONV and safety assessments were performed continuously during the first 3 h (0–3 h) and the next 21 h (3–24 h) after anaesthesia.
Results: A complete response, defined as no PONV and no administration of rescue antiemetic medication, during 0–3 h after anaesthesia was 51%, 82% and 96% in patients who had received placebo, granisetron and granisetron-dexamethasone combination, respectively; the corresponding incidence during 3–24 h after anaesthesia was 56%, 84% and 98% ( P <0.05; overall Fisher's exact probability test). No clinically important adverse events were observed in any of the groups.
Conclusion: Prophylactic use of granisetron-dexamethasone combination is more effective than granisetron alone for the prevention of PONV after breast surgery.     

Prevention of nausea and vomiting with granisetron, droperidol and metoclopramide during and after spinal anaesthesia for caesarean section: A randomized, double-blind, placebo-controlled trial

Background: Nausea and vomiting during and after spinal anaesthesia for caesarean section are distressing to the patient. This study was undertaken to evaluate the efficacy and safety of granisetron, droperidol and metoclopramide for the prevention of nausea and vomiting in parturients undergoing caesarean section under spinal anaesthesia.
Methods: In a randomized, double-blind, placebo-controlled trial, 120 patients received granisetron 3 mg, droperidol 1.25 mg, metoclopramide 10 mg or placebo (saline) ( n =30 of each) i. v. immediately after clamping of the foetal umbilical cord. Nausea, vomiting and safety assessments were performed during and after spinal anaesthesia for caesarean section.
Results: The incidence of intraoperative, post-delivery nausea and vomiting was 13%, 17%, 20% and 63% after administration of granisetron, droperidol, metoclopramide and placebo, respectively; the corresponding incidence during 0–3 h after surgery was 7%, 27%, 27% and 43%; the corresponding incidence during 3–24 h after surgery was 7%, 20%, 23% and 37% ( P <0.05; overall Fisher's exact probability test). No clinically important adverse events were observed in any of the groups.
Conclusion: Granisetron is highly effective for preventing nausea and vomiting during and after spinal anaesthesia for caesarean section. Droperidol and metoclopramide are effective for the prevention of intraoperative, post-delivery emesis, but are ineffective for the reduction of the incidence of postoperative emesis.     

Prevention of nausea and vomiting in female patients undergoing breast surgery: A comparison with granisetron, droperidol, metoclopramide and placebo

Background : Breast surgery is associated with a relatively high incidence of postoperative nausea and vomiting (PONV). This study was undertaken to evaluate the efficacy of granisetron, droperidol and metoclopramide for preventing PONV after breast surgery.
Methods : In a randomized, double-blind, placebo-controlled trial, 120 female patients received granisetron 40μg.kg^-1, droperidol 1.25 mg, metoclopramide 10 mg or placebo (saline) (n=30 for each) intravenously immediately before the induction of anaesthesia. A standard general anaesthetic technique was employed throughout. Postoperatively, during the first 24 h after anaesthesia, the incidence of PONV and adverse events was recorded.
Results : The incidence of PONV was 17% with granisetron, 37% with droperidol, 43% with metoclopramide and 50% with placebo ( P <0.05; overall Fisher's exact probability test). The incidence of adverse events was not different among the groups.
Conclusion : Granisetron is highly effective for reducing the incidence of PONV in female patients undergoing breast surgery. Droperidol and metoclopramide are ineffective in this population.     

Desflurane versus propofol maintenance for outpatient laparoscopic cholecystectomy

Background : The aims of the study were to evaluate costs and clinical characteristics of desflurane-based anaesthetic maintenance versus propofol for outpatient cholecystectomy.
Methods : All 60 patients received ketamine 0.2 mg kg^-1, fentanyl 2 μg kg^-1 and propofol 2 mg kg^-1 for induction. Ketorolac 0.4 mg kg^-1 and ondansetron 0.05 mg kg^-1 +droperidol 20 μg Kg^-1 was given as prophylaxis for postoperative pain and emesis, respectively. The patients were randomly assigned into Group P with propofol maintenance and opioid supplements, or Group D with desflurane in a low-flow circuit system.
Results : All the patients were successfully discharged within 8 h without any serious complications. Emergence from anaesthesia was more rapid after desflurane; they opened their eyes and stated date of birth at mean 6.4 and 8.4 min respectively, compared with 9.6 and 12 min in the propofol group (P<0.05). Nausea and pain were more frequent in Group D, 40% and 80% respectively; versus 17% and 50% in Group P (P<0.05). By telephone interview at 24 h and 7 d after the procedure, there was no major difference between the groups. With desflurane, drug costs per case were 10 $ lower than with propofol.
Conclusion : We conclude that desflurane is cheaper and has a more rapid emergence than propofol for outpatient cholecystectomy. However, propofol results in less pain and nausea in the recovery unit. Despite ondansetron and droperidol prophylaxis, there was still a substantial amount of nausea and vomiting after desflurane.     

Effects of propofol on ipecacuanha-induced nausea and vomiting

Background : The purpose of this study was to evaluate if propofol has 5-HT₃ antagonistic effects. Ipecacuanha is known to release serotonin (5-HT) in the gastrointestinal tract and therefore ipecacuanha syrup was used to induce nausea and vomiting. The 5-HT₃ antagonist ondansetron was used as a control substance.
Results : During the first 150 min after ingestion of ipecacuanha there were no retchings during the ondansetron infusion ( P = 0.01 vs placebo, P =0.02 vs propofol) and significantly fewer retchings during propofol infusion compared to placebo ( P <0.02). There was no nausea during the ondansetron infusion ( P <0.01 vs placebo and propofol) but the volunteers experienced nausea both during the placebo and propofol infusion (NS).
Conclusion : This study in volunteers has shown that propofol reduces the intensity of retching after oral intake of ipecacuanha syrup. As ipecacuanha releases 5-hydroxytryptamine, it can be concluded that propofol may have a weak 5-HT₃ antagonistic effect.
Method : Ten healthy male volunteers (20–37 years) were studied on three occasions and were randomly allocated to receive a concomitant infusion of propofol (initial bolus 0.1 mg kg^-1 then 1 mg kg^-1h^-1), ondansetron (initial bolus 0.11 mg kg^-1 then 14 μg kg^-1 h^-1) and placebo on either occasion. The infusions started 30 min before oral ingestion of 30 ml of ipecacuanha and continued until 150 min after the intake. The number of retchings was recorded and the intensity of nausea was estimated by the subjects on a visual analog scale.     

Comparison of subhypnotic doses of thiopentone vs propofol on the incidence of postoperative nausea and vomiting following middle ear surgery

Background : Middle ear surgery is associated with a high incidence of emetic sequelae and propofol has been reported to have antiemetic activity in subhypnotic doses.
Methods : In a double-blind, randomized study, the patients received either thiopentone 1.0 mg.kg^-1 (n=26) or 0.5 mg.kg^-1 propofol (n=26) at the end of middle ear surgery under isoflurane-N₂O-fentanyl-vecuronium anaesthesia. Trained nurses, unaware of the group assignment, assessed postoperative nausea, retching and vomiting up to 24 h after the end of anaesthesia. Droperidol 10μg.kg^-1 was used as a "rescue" antiemetic.
Results : The main result was that the patients in the propofol group did not suffer from retching and vomiting (R&V) during the first 6 h, whereas these symptoms occurred in 46% ( P <0.001) of the patients in the thiopentone group. The patients in the propofol group needed significantly less droperidol during the first 24 h (mean number of doses 0.39 ± 0.57 (SD)) than the patients in the thiopentone group (1.35 ± 1.47, P <0.005). Treatment with propofol was a predictor for lowered incidence of R&V, as well as male gender and negative history of motion sickness.
Conclusion : Propofol at a subhypnotic dose of 0.5 mg.kg^-1 provides prophylaxis against retching and vomiting for the first 6 h postoperatively after middle ear surgery. The incidence of nausea was not reduced by propofol.     

Granisetron reduces incidence of nausea and vomiting after breast surgery

Background: Postoperative nausea and vomiting (PONV) remains a troublesome problem. This study was performed to evaluate the antiemetic efficacy of prophylactic granisetron, a selective 5-hydroxytryptamine type 3 receptor antagonist, on the incidence of PONV in patients undergoing general anaesthesia for breast surgery.
Methods: In a randomized, placebo-controlled, double-blind study, 50 female patients, 45–68 years, were given a single dose of either placebo (saline, n=25) or granisetron (40 ug kg^-1, n= 25) intravenously over 2–5 min immediately before the induction of anaesthesia. Postoperatively, during the first 24 hours after anaesthesia, the incidence of PONV and adverse events was recorded.
Results: The treatment groups were similar for patient demographics, types of surgery, anaesthetic and postoperative management. Postoperatively, the incidence of PONV was 48% and 16% after administration of placebo and granisetron, respectively ( P < 0.05). No differences in the incidence of other adverse events were observed between the two groups.
Conclusion: Granisetron is an effective antiemetic for preventing PONV in patients undergoing general anaesthesia for breast surgery.     

Lack of effect of flumazenil on the reversal of propofol anaesthesia

Propofol, like the benzodiazepines, activates the GABA_A receptor-chloride ionophore complex; they potentiate one another. Since neither pharmacodynamic nor pharmacokinetic data concerning drug interaction between flumazenil and propofol is available, and especially considering the relationship of binding sites, flumazenil, the antagonist of benzodiazepines, was investigated to determine its effect upon recovery from propofol anaesthesia. Forty women receiving dilatation and curettage procedures were included in this double-blind test. After 50 μg fentanyl, propofol 2 mg · kg^-1 was injected for induction and followed by infusion at the rate of 15 mg · kg^-1 · hr^-1. After the operation, patients were given normal saline (Group A) or flumazenil 10 μg · kg^-1 (Group B) randomly.
Recovery time in Group A was 15.2±5.1 min and Group B 15.8±4.8 min. Propofol concentrations at the end of infusion were 4.17±1.33 μg ·ml^-1 (Group A) and 4.03±1.45 μg · ml^-1 (Group B); these then declined to 1.22±0.17 μg · ml^-1 (Group A) and 1.18±0.15 μg · ml^-1 (Group B) when patients were able to open their eyes on command. No significant differences were found between the groups based on propofol concentrations and recovery time, nor did haemodynamic changes differ between them after administration of reversal agents. It was concluded that flumazenil 10 μg · ml^-1 does not influence recovery from propofol anaesthesia.     

Contradictory effects of dopamine at 32°C in pigs anesthetized with ketamine

Background: In critically ill patients who were surface cooled to 332C, we have observed that dopamine sometimes causes a substantial decrease in blood pressure. The present study was designed to compare the effects of dopamine in normothermia to those seen after surface cooling to 32C.
Methods: Seven pigs with a mean body weight of 21 kg were anesthetized with ketamine and muscle relaxation was induced with pancuronium. They were mechanically ventilated and given dopamine infusions (5 and 12 μg · kg^-1 min^-1) in normothermia and after surface cooling by cold water immersion to a central blood temperature of 320C (range 31.6–32.6C).
Results: In normothermia, dopamine at a dose of 5 μg · kg^-1 min^-1 increased mean arterial blood pressure (MAP) by 16% ( P < 0.01) and cardiac output (CO) by 9% ( P =0.051); at 12 μg kg^-1 min^-1 dopamine increased MAP by 26% ( P < 0.01) and CO by 18% ( P < 0.01). In hypothermia, MAP and CO did not change at an administration rate of 5 μg kg^-l · min^-1; at 12 μg · kg^-1 min^-1 CO was unchanged but MAP was significantly reduced by 15% ( P < 0.01).
Conclusion: Dopamine increased CO and MAP in normothermia but not at 32C, where there was even a significant reduction of MAP in this porcine model.     

Potency and maintenance requirement of atracurium and vecuronium given alone or together

A synergism exists between some competitive muscle relaxants. However, maintenance requirement of a combination of muscle relaxants has been evaluated only in paediatric patients. We studied 45 elective adult surgical patients (ASA I-II) during propofol-alfentanyl-N₂O-O₂-anaesthesia. The first 30 patients were randomized to receive either atracurium or vecuronium to create individual dose-response curves for these muscle relaxants. ED₉₅-values for atracurium and vecuronium were 260±9 and 59±3 μg · kg^-1, respectively (mean±s.e.mean). Requirements of atracurium and vecuronium to maintain an 85–95% neuromuscular blockade were 301 and 83 μg kg^-1 h^-1, respectively. An additional 15 patients received a combination of atracurium and vecuronium (cAV) in an equipotent dose ratio. An ED₉₅ of a cAV was 94± 7 μg · kg^-1 of atracurium together with 21±2 μg · kg^-1 of vecuronium, or 72±6% of one ED₉₅ dose of a parent agent. Potentiation was significant ( P =0.0001). A maintenance requirement of a cAV was 120 μg kg^-1 h^-1 of atracurium together with 27 μg kg^-1 h^-1 of vecuronium. Thus, a significant potentiation was maintained also during the course of anaesthesia. A cAV had an effect like one intermediate-acting agent. If a cAV is used instead of using atracurium or vecuronium alone, the maximal reduction of drug consumption would be approximately 30%.     

Comparison of the recovery characteristics of midazolam, alone or antagonised with flumazenil, and thiopental in ASA III-IV patients

Sixty non-premedicated male patients, physically ASA III-IV, 50–80 years of age, undergoing translumbar aor-thography, were randomly allocated into three groups. Group A received midazolam (0.13 mg·kg^-1), group B received thiopental (4 mg · kg^-1), and group C midazolam (0.13 mg · kg^-1) combined with flumazenil (6 μg · kg^-1) at the end of the operation. Three minutes before the anaesthesia began, fentanyl (1.5 μg · kg^-1) was administered to all the patients. An evaluation was made of the time they took to open their eyes spontaneously, of time-space orientation, comprehension-collaboration, hypnosedation, psychomotor performance and memory. In groups "C" and "B" spontaneous opening of the eyes took place before that of group "A". The recovery of orientation, comprehension and hypnosedation was fastest with thiopental, next with midazolam combined with flumazenil, and later with midazolam. Psychomotor performance in Trieger test was impaired for a shorter period with thiopental than in the other two groups. Recovery in group "C" was incomplete within the time, with the result that resedation was detected in 20% of the subjects.     

Differential effects of pre-treatment with intrathecal or intravenous morphine on the prevention of spinal cord hyperexcitability following sciatic nerve section in the rat

The effect of intrathecal (i.t.) and intravenous (i.v.) morphine on spinal hyperexcitability following unilateral section of the sciatic nerve was studied in decerebrate, spinalized, unanesthetized rats. Sciatic nerve section evoked a biphasic, prolonged hyperexcitability of the flexor reflex. Either i.v. (0.2, 1 or 10 mg · kg^-1) or i.t. (3 or 10 μg) morphine was administered prior to sciatic nerve section. All doses of morphine significantly depressed the baseline flexor reflex and abolished the less intense prolonged second component of reflex hyperexcitability. One and 10, but not 02, mg · kg^-1 i.v. morphine significantly depressed the first phase of spinal cord sensitization. However, both 3 μg and 10 μg i.t. morphine were significantly more effective than i.v. morphine in suppressing spinal cord hyperexcitability. The present results suggest that moderate doses of i.t. morphine decrease spinal hyperexcitability following nerve transection more than even extremely large i.v. doses. The poorer effect of i.v. morphine on preventing spinal hyperexcitability may be due to low spinal concentration after systemic administration.     

Intravenous propofol vs thiamylal-isoflurane for caesarean section, comparative maternal and neonatal effects

Several studies on propofol (Diprivan) for induction of anaesthesia during caesarean section have demonstrated its safety, however, its safely during maintenance of anaesthesia is not yet fully evaluated.
The present study was undertaken to compare the maternal and neonatal effects of propofol or isoflurane in 74 term parturients undergoing primary or repeat caesarean section. Patients were randomly assigned to two groups, propofol group (n = 37) received propofol 1.5–2.5 mg·kg^-1 for induction followed by a continuous infusion of propofol of 0.05–0.2 mg 4mD kg^-1 · min^-1. The isoflurane group (n=37) received thiamylal 3–4 mg · kg^-1 for induction followed by isollurane 0.25–0.75% for maintenance. All patients had rapid sequence induction using suceinyl-choline and endotracheal intubation, 50% N₂O and O₂ were used in all patients until delivery. After delivery N₂O concentration was increased to 67% and intravenous butorphanol (Stadol) was given as needed. Patients in the propofol group had less hypertension after intubation ( P <0.05) and this was also of shorter duration compared to patients in the isoflurane group (5 min vs 10 min respectively). Maternal blood loss as well as intraoperative awareness and recovery time did not differ significantly between the two groups. Neonatal status as ascertained by Apgar scores, cord acid base status and the neurological and adaptive capacity scores (NACS) was equally good in both groups. It is concluded that propofol used for induction and maintenance of anaesthesia is a safe alternative to thiamylal/isoflurane for patients undergoing caesarean section and is associated with less hypertensive response during laryngoscopy and intubation.     

Nausea and vomiting after major arthroplasty with spinal anaesthesia including morphine: a randomised trial of subhypnotic propofol infusion as prophylaxis

Background : Postoperative nausea and vomiting (PONV) following major arthroplasty with spinal anaesthesia and intrathecal morphine is reported in 45–74% of patients. This randomised, double-blind, placebo-controlled trial was undertaken to determine whether a subhypnotic infusion of propofol has a prophylactic antiemetic effect in this patient population.
Methods : 82 patients undergoing hip or knee replacement under subarachnoid bupivacaine anaesthesia plus morphine 0.25 mg were randomised at the end of surgery to receive either propofol 30 mg · h^-1 or fat emulsion (Intralipid®) 3 ml · h^-1 for 20 h postoperatively. Blinded observers recorded episodes of nausea, vorniting and pruritus.
Results : PONV in the intervention group was 40% vs 59% in the controls (P=0.1, not significant). Pruritus occurred in 34%, with a similar rate in both groups.
Conclusion : These results suggest that routine use of postoperative, subhypnotic propofol infusion as PONV prophylaxis is not justified in this patient population.     

Oculocardiac reflex and postoperative vomiting in paediatric strabismus surgery. A randomised controlled trial comparing four anaesthetic techniques

Background : Oculocardiac reflex (OCR) and postoperative vomiting are major complications of paediatric strabismus surgery.
Methods : Children (3–16 yr) undergoing elective strabismus surgery as inpatients were randomly allocated to four anaesthetic techniques: (A) thiopentone induction and isoflurane maintenance; (B) as (A) plus ondansetron 5 mg · m^-2 iv; (C) propofol induction and maintenance; (D) as (C) plus lignocaine 2 mg · kg^-1 iv. All children received prophylactic atropine 0.02 mg · kg^-1 and alfentanil. Nitrous oxide was omitted.
Results : Data on 157 children were analysed. The cumulative incidence of vomiting within 6 and 24 h after surgery with thio-pentone-isoflurane was 26% and 46%, respectively. Adding ondansetron decreased the incidence to 8% and 33%, respectively. This improvement was significant within 6 h only; the number-needed-to-treat was 5.5 (95% CI 2.9–46). Propofol was not different from thiopentone-isoflurane. The addition of lignocaine to propofol was of no benefit. The risk of an OCR was significantly increased with propofol (incidence 40%) compared with isoflurane (14%); the number-needed-to-harm was 3.9 (95% CI 2.6–8).
Conclusions : Thiopental-isoflurane-air/O₂-alfentanil resulted in a moderate risk of vomiting. Adding ondansetron significantly decreased this risk, but 6 children have to be treated for one to benefit in the early postoperative period. Propofol and propofol-lignocaine showed no benefit on vomiting but significantly increased the risk of an OCR despite high-dose prophylactic atropine.     

Intramuscular dexmedetomidine premedication—an alternative to midazolam-fentanyl-combination in elective hysterectomy?

Sedation, anxiolysis, intubation responses and fentanyl anaesthetic requirements were investigated in a double-blind, randomized study in twenty ASA I-II elective hysterectomy patients. Ten patients received dexmedetomidine 2.5 μg kg^-1 i.m. 60 min before induction and saline placebo i.v. 2 min prior to induction (= DP group). Ten patients received midazolam 0.08 mg kg^-1 i.m. 60 min and fentanyl 1.5 μg kg^-1 i.v. (= MF group) 2 min before induction of anaesthesia with thiopentone 4 mg kg^-1. Anaesthesia was maintained with 70% nitrous oxide in oxygen and with fentanyl 2 μg kg^-1 i.v. increments according to predetermined criteria. Both premedications induced sedation ( P < 0.01 in both groups) and anxiolysis ( P < 0.01 in DP vs <0.05 in MF group) without any differences between the groups. Haemodynamic changes following tracheal intubation did not significantly differ between the groups. Intraoperatively systolic and diastolic arterial pressure were 15% and 13% lower in DP group ( P < 0.01 and P < 0.05 for drug effect), the mean heart rate was approximately 9 beats min^-1 lower in DP group (n.s.). Fentanyl was required more often in MF group: median 3.5 (QD 1.5) vs. 2.5 (QD 0.5) times in DP group ( P < 0.05), the total amount being 57% smaller in DP group: 0.03 (QD 0.01) vs. 0.07 (QD 0.02) μg kg^-1 min^-1 ( P < 0.05). Postoperative course and analgesic requirements were similar in both groups. Dexmedetomidine premedication may offer an alternative to current anaesthesia practice in elective hysterectomy.     

Cardiovascular Effects of High-Dose Fentanyl Anaesthesia

An anaesthetic technique using high-dose fentanyl for coronary artery surgery is described. Fentanyl 160 or 70 μg kg^-1 was used as the sole anaesthetic agent, and patients were ventilated with air/O₂ (fentanyl 70 μg kg^-1) or N₂O/O₂ (fentanyl 60 μg kg^-1). Cardiovascular data from 30 patients are presented. Fentanyl caused no significant cardiovascular depression. The only statistically significant changes in cardiovascular parameters were seen in the patients who received fentanyl 60 μg kg^-1. Five minutes after skin incision there was an increase in peripheral resistance. Diastolic pressure was increased following sternotomy. Problems associated with this technique of anaesthesia are a 50% incidence of hypertension following sternotomy (requiring treatment with sodium nitroprusside) and prolonged respiratory depression. The lack of cardiovascular depression produced by fentanyl and the ability of fentanyl to reduce hormonal and metabolic responses to surgery make it a satisfactory technique for cardiac anaesthesia.     

Adenosine increases the cutaneous heat pain threshold in healthy volunteers

Adenosine is an endogenously produced substance which in animal experiments exerts anti-nociceptive effects. In humans, algcsic effects have been presented following exogenous adenosine administration. A recent study on anaesthetized patients, however, suggested an anti-nociceptive effect during i.v. adenosine. We have studied the pain-reducing effect in healthy volunteers using adenosine 50–80 μg · kg^-1 · min^-1 (n = 10), morphine 0.1 mg · kg^-1 (n = 5), adenosine 50 μg · kg ^-1 · min^-1 + morphine 0.1 mg · kg^-1 (n=6), and ketamine 0.1 mg · kg^-1 (n=5); all drugs given i.v., single-blind. Quantitative sensory tests (QST) revealed a significantly increased cutaneous heat pain threshold following adenosine. No effect was seen following ketamine or morphine. Suprathreshold heat pain perception was unchanged in all subjects. Furthermore, warm and cold perception thresholds were not influenced significantly by any drug. Adenosine, morphine and kctamine produced well-known side-effects but of a mild intensity not necessitating any treatment.
The present results show that i.v. adenosine can provide a modest but selective increase of cutaneous heat pain thresholds, suggesting a pain-reducing capacity of adenosine in humans.     

Retinyl palmitate injections reduce serum levels and effects of endotoxin on systemic haemodynamics and oxygen transport in the pig

Background : Retinyl palmitate [(RP) 230 IU · kg^-1] modulates the circulatory and respiratory responses of a subsequent infusion of endotoxin in the pig. The aims of this study were: I. To determine if RP (2300 IU · kg^-1) affects the serum endotoxin levels in this model. II. To evaluate the effect of this dose of RP on circulatory and respiratory variables in our porcine model. III. To investigate the levels of RP and neutrophil count in porcine endotoxaemia.
Methods : Ten anaesthetized pigs were randomly given 2300 IU · kg^-1 of RP or the solvent i.m. prior to the continuous i.v. infusion of E. coli endotoxin (10 μg · kg^-1 · h^-1). Another 4 sham animals were given either i.m. RP (n=2) or i.m. solvent (n=2) followed by an infusion of saline. Haemodynamics and oxygen extraction were monitored and samples taken for analysis of endotoxin, RP and blood cells.
Results : I. Endotoxin levels in serum were lower ( P <0.001) in the RP-pretreated pigs. II. These animals had higher cardiac index ( P <0.05), mean arterial pressure and left ventricular stroke work index (both P <0.001), and lower oxygen extraction ( P <0.01). III. RP-Pre=pretreatmert caused a paradoxical decrease in serum retinyl ( P <0.001) and a more rapid restitution of neutrophil count ( P <0.05).
Conclusion : Pretreatment with RP (2300 IU · kg^-1) counteracts the progressive increase in serum endotoxin levels in porcine endotoxaemia.