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%.     

Effect of succinylcholine on subsequently administered mivacurium in children

The interaction between mivacurium and succinylcholine when mivacurium was administered during the early recovery from succinylcholine block was studied in 30 children 2-12 years of age anaesthetized with propofolalfentanil-N₂O-O₂. Neuromuscular response was monitored by adductor pollicis EMG. Fifteen patients received 200 μg. kg^-1 of mivacurium (Group M), and another fifteen received 1500 μg. kg^-1 of succinylcholine followed by 200 μg. kg^-1 of mivacurium when the first EMG response recovered to 5% of calibration value (Group SchM). Plasma cholinesterase (pChE) activity was normal in each patient. The recovery times following mivacurium did not differ between the two groups. Times required for recovery of the first EMG response from 25 to 75% of full EMG recovery were 3.6±1.0 (mean±SD) and 4.0±0.7 min for the Groups M and SchM, respectively. The time from administration of mivacurium to the recovery of train-of-four ratio 0.70 was 13.2±3.3 min for the Group M and 13.6±3.1 min for the Group SchM (NS). Thus, in patients with normal pChE activity preceding administration of succinylcholine did not influence the recovery of neuromuscular function from subsequent mivacurium.     

Synergism between mivacurium and pancuronium in adults

Mivacurium could be a useful agent as a final dose of a muscle relaxant following pancuronium if only additivily exists between these agents. We examined the interaction between mivacurium and pancuronium in 70 patients (ASA I-II) during propofol-alfentanil-N₂O-C₂ anaesthesia. Neuromuscular function was monitored by adductor pollicis EMG.
Firstly we established dose-response curves for mivacurium and pancuronium. Thereafter, 20 patients received a combination of 0.5 times the ED₅₀ doses of mivacurium and pancuronium (cMP) determined in the first part of this study. Patients were randomized to receive the cMP to the same IV-line (n=10) or to two separate IV-lines in opposite hands (n=10).
ED₅₀ values for mivacurium and pancuronium were 57.7 and 37.1 μg kg^-1, respectively. Maximal neuromuscular block following the cMP was 91.8 ±5.0% (mean±SD). This was highly significantly different from the estimated 50% NMB if only additivity exists between mivacurium and pancuronium ( P =0.0001). After the cMP, the 25 75% recovery rime was 9.4± 1.3 min and the time to train-of-four ratio of 0.70 was 35.8±5.4 min. There was no statistical difference in any recorded neuromuscular parameter between the two subgroups receiving mivacurium and pancuronium to the same or to opposite hands ( P >040).
We conclude that a significant synergism exists between mivacurium and pancuronium which may indicate that mivacurium does not produce a short-acting NMB if given after pancuronium. We do not recommend using mivacurium together with pancuronium.     

Quantifying the interaction of vecuronium with enflurane using closed-loop feedback control of vecuronium infusion

The influence of different levels of enflurane anaesthesia on infusion requirements of vecuronium was studied in 40 adult surgical patients. Ninety percent neuromuscular block was maintained by computer controlled infusion of vecuronium. During the first 90 min study period all patients received fentanyl-nitrous oxide-oxygen (2:1) anaesthesia. For the following 90 min the patients were randomly assigned to receive enflurane at different end-tidal concentrations: group I, control, fentanyl-nitrous oxide anaesthesia; group II, enflurane 0.3%-nitrous oxide; group III, enflurane 0.6%-nitrous oxide; group IV, enflurane 0.9%-nitrous oxide. Every patient served as his/her own control and the changes of vecuronium infusion requirements were determined individually. When the administration of enflurane was started, vecuronium infusion requirements decreased progressively until 90 min. In group II the infusion rate lowered from 80±28 to 56±20 μg . kg^-1 . h ^-1, in group III from 61 ±29 to 34±17 μg . kg^-1 . h^-1 and in group IV from 65±20 to 30± 14 μg . kg^-1 . h^-1. In the control group the infusion rate decreased during the three hour study period from 69± 17 (first 90 min period) to 59± 16 μg . kg^-1 . h^-1 (second 90 min period). Enflurane reduces the dose requirements of vecuronium administered by continuous infusion in a dose- and time-dependent manner.     

Neuromuscular interaction between cisatracurium and mivacurium, atracurium, vecuronium or rocuronium administered in combination

We compared the dose–response relationships of cisatracurium, mivacurium, atracurium, vecuronium and rocuronium and examined the interactions of cisatracurium with mivacurium, atracurium, vecuronium and rocuronium in humans by isobolographic and fractional analyses. We studied 180 adult patients during nitrous oxide–fentanyl–propofol anaesthesia. Neuromuscular block was monitored using mechanomyography to detect the twitch response of the ulnar nerve at the wrist. The dose–response curves were determined by probit analysis. The calculated ED₅₀ values and their 95% confidence intervals were 40.9 (38.1–43.7), 49.8 (47.0–52.6), 187.2 (175.1–199.3), 36.6 (34.7–38.5) and 136.4 (129.2–143.6) μg.kg⁻¹ for cisatracurium, mivacurium, atracurium, vecuronium and rocuronium, respectively. Corresponding ED₉₅ values were 57.6 (53.5–61.7), 91.8 (88.1–95.5), 253.1 (238.9–267.3), 52.9 (49.1–56.7) and 288.7 (276.2–301.2) μg.kg⁻¹, respectively. The interaction between cisatracurium and mivacurium, vecuronium or rocuronium was found to be synergistic, but the interaction between cisatracurium and atracurium was found to be additive. Synergy between cisatracurium and vecuronium or rocuronium was greater than between cisatracurium and mivacurium.     

Mivacurium chloride—a comparative profile

Mivacurium is a new nondepolarizing muscle relaxant of the benzylisoquinoline type. Its short duration of action is due to rapid breakdown by plasma cholinesterase. The dose of mivacurium which produces 95% inhibition of twitch response (ED₉₅) is between 60 and 80 μg/kg. Thus, mivacurium is 0.8 times and four times as potent as vecuronium and atracurium, respectively. With 2–3×ED₉₅, tracheal intubation can be accomplished within 2.5 min of intravenous injection. The ensuing DUR25% (time from injection to 25% recovery of control twitch tension) is twice as long as with suxamethonium and about half as long as with equipotent doses of atracurium or vecuronium. For muscle relaxation during long surgical procedures, mivacurium has been used as a continuous infusion. The average 6-min recovery index after infusion of mivacurium is particularly favourable for flexible control of muscle paralysis, whereas the recovery indices after infusion of atracurium or vecuronium are 15–30 min. In conclusion, mivacurium will close the pharmacodynamic gap between suxamethonium and the nondepolarizing muscle relaxants of intermediate duration of action. It will probably also be a suitable alternative to suxamethonium in elective cases.     

The effect of epidural bupivacaine on vecuronium–induced neuromuscular blockade in children

The efTect of epidural bupivacaine on potency and duration of action of vecuronium–induced neuromuscular blockade (NMB) was evaluated in 30 general surgical paediatric patients (ASA I–II) of three to ten years of age. Premedication was midazolam 0.5 μg kg^-1 orally (max 15 mg). In addition to general anaesthesia, 15 of the children received a lumbar epidural block with 0.5% bupivacaine 2.5 mg kg^-1. Anaesthesia was induced and maintained with N₂O:o₂ (2:1), propofol and alfentanil. NMB was monitored by adductor pollicis EMG with the train–of–four stimulus every 20 sec. Thirty minutes following the epidural bupivacaine injection (mean plasma concentration 0.86 μg ml^-1) or induction of anaesthesia a cumulative dose–response curve of vecuronium was established to achieve a 95% depression of the twitch response. Thereafter, NMB was allowed to recover spontaneously. ED doses of vecuronium were 19–22% greater in the control group than in the epidural group. ED^ doses were 33.8 (s.e.mean 1.3) μg kg"¹ and 28.4 (2.2) μg kg"', respectively ( P <0.05). There were no differences in recovery times from NMB between control and epidural group, the recovery index (time of twitch height to recover from 25 to 75%) being 6.4 (0.4) min and 7.0 (0.9) min, respectively. However, a negative correlation was found between bupivacaine plasma concentration and an ED₅₀ dose of vecuronium ( P =0.01). Our results indicate that vecuronium is slightly more potent in children with bupivacaine epidural block than in children without it.     

Reversal of atracurium-induced neuromuscular block in paediatric patients

We studied the efficacy of neostigmine and edrophonium to reverse an atracurium-induced 90% neuromuscular block in 80 paediatric patients anaesthetized with thiopentone, fentanyl and nitrous oxide. The patients were divided into five age groups: 0–2 months, 3–11 months, 2–5 years, 6–10 years, and 11–15 years. At the end of surgery, the neuromuscular block was randomly antagonized with either neostigmine 50 μg kg^-1 with atropine 20 μg kg^-1 or with edrophonium 1 mg kg^-1 with atropine 10 μg kg^-1. In general, the first EMG response and train-of-four (TOF) ratio recovered fastest in the youngest age groups following either reversal agent ( P <0.05). However, in each age group edrophonium had a faster onset of effect than neostigmine ( P <0.05) even though a greater TOF-ratio was finally reached with neostigmine. The effects of neostigmine were less variable and more predictable than those of edrophonium. Therefore, we recommend the use of neostigmine for routine paediatric practice.     

The influence of the duration of isoflurane anaesthesia on neuromuscular effects of mivacurium

Background: The pharmacodynamic profile of muscle relax-ants is usually changed by volatile anaesthetics. These changes seem to be time-dependent, even though few data are available to substantiate this.
Methods: We studied neuromuscular effects of a single dose of mivacurium (0.2 mg·kg^-1) during short and intermediate duration of isoflurane anaesthesia. Forty-five children 1–10 years of age were randomized to receive 1.5% end-tidal concentration of isoflurane in N₂O/O₂ for 10 or 30 min (groups Iso-10 and Iso-30, respectively) or to receive nitrous oxide in oxygen for 10 min (Group N₂O) before 0.2 mg · kg^-1 of mivacurium was given. Neuromuscular response was recorded by adductor pollicis electromyogram.
Results: The onset time of mivacurium was shorter in Group Iso-30, 1.7 (1.0–2.3) min than in Group Iso-10, 2.3 (1.7-3.3) rnin or Group N₂O, 2.3 (1.7-3.3) min (median with 10–90% percen-tiles) ( P <0.05). In Group Iso-30 the recovery time of the first EMG response was significantly longer than in groups Iso-10 and N₂O ( P <0.0001). Groups Iso-10 and N₂O did not differ from each other.
Conclusions: Our results indicate that the duration of a constant concentration of isoflurane anaesthesia influences significantly the pharmacodynamics of mivacurium. The duration of a volatile anaesthesia is critical when potentiation of NMB is evaluated or compared in neuromuscular studies.     

Comparison of the effects of neostigmine and edrophonium on the duration of action of suxamethonium

Rapid sequence induction of anaesthesia necessitating the use of suxamethonium may occasionally be needed soon after antagonism of neuromuscular block with anticholinesterase agents. The onset and duration of action of 1 mg kg^-1 of suxamethonium was recorded in groups of 10 patients each, 5 or 10 min after the administration of edrophonium 1 mg kg^-1 or neostigmine 40 μg kg^-1 given for the antagonism of atracurium-induced neuromuscular block. Plasma cholinesterase activity was measured before, and 5 and 10 min after the administration of the anticholinesterases. A further 10 patients received suxamethonium 1 mg kg^-1 without prior atracurium or anticholinesterase administration to serve as controls. The onset of action of suxamethonium was significantly prolonged when administered 5 min after both anticholinesterases, compared to the control group ( P <0.01). Recovery of suxamethonium block was delayed significantly after neostigmine, compared to both the edrophonium and the control groups ( P <0.05–0.001). Plasma cholinesterase activity was significantly reduced with the use of neostigmine but not with edrophonium ( P <0.001).     

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.     

Cisatracurium during halothane and balanced anaesthesia in children

Cisatracurium, 51W89, is one of the ten stereoisomers of Tracrium^® which, unlike atracurium, has been reported to have a lack of histamine mediated cardiovascular effects at doses as high as 8×ED₉₅ in adults. We compared the time-course of neuromuscular effects of 80 μg·kg⁻¹ or 100 μg·kg⁻¹ cisatracurium during N₂O-O₂-halothane or N₂O-O₂-opioid anaesthesia, respectively, in 32 children 2–12 years old. Neuromuscular function was monitored by evoked adductor pollicis EMG. Even-numbered patients ( n =16) were allowed to obtain full spontaneous recovery of neuromuscular function and odd-numbered patients ( n =16) received neostigmine 45 μg·kg⁻¹ together with glycopyrrolate at the time of 25% EMG recovery. Data are expressed as median with 10th to 90th percentile range. Cisatracurium had an onset time (time from administration to maximal effect) of 2.2 (1.7–3.8) or 2.3 (1.8–4.9) min, a clinical duration (time to 25% EMG recovery) of 34 (22–40) or 27 (24–33) min, and a spontaneous 25–75% recovery time (time from 25 to 75% EMG recovery) of 11 (9–13) or 11 (7–12) min during halothane or balanced anaesthesia, respectively (NS). Train-of-four ratio recovered to 0.70 in 2.5 (1.8–3.0) or 3.2 (2.1–4.3) min following neostigmine during halothane or balanced anaesthesia, respectively (NS). Changes in blood pressure or heart rate following cisatracurium were negligible. We regard cisatracurium as a safe and promising intermediate duration muscle relaxant the effects of which can easily be reversed with neostigmine.     

Mivacurium chloride in infants and children

Mivacurium has been little studied in infants and children without a volatile anaesthetic agent. We analysed onset time and maximal neuromuscular response after mivacurium 0.1 mg/kg, and the infusion requirement of mivacurium to maintain a 50, 90, or 95% neuromuscular block in 76 infants and children under N₂O-O₂ alfentanil anaesthesia. Furthermore, we assessed the time course of potentiation of 1 MAC end-tidal halothane or isoflurane on the infusion requirement of mivacurium. Neuromuscular response was recorded by adductor pollicis electromyogram. The onset time of mivacurium was shorter in infants than in children (2.1 ± 0.6 and 3.2 ± 0.9 min (mean±SD); P =0.0001). The dose potency of mivacurium did not depend on the age of a paediatric patient. The estimated ED₉₅ of mivacurium was 136±46 μg/kg. The mivacurium requirement to maintain a 50, 90, or 95% neuromuscular block averaged 340, 730, and 900 μg/kg/h, respectively. Halothane and isoflurane decreased this hourly requirement by 35 and 70%, respectively. The decrease in the mivacurium infusion requirement was fastest in the youngest children. In conclusion, mivacurium is easy to administer as bolus doses or continuous infusion in paediatric patients because its potency is similar in all patients from 1 month to 15 years of age. Halothane and isoflurane produce their maximal potentiation of neuromuscular block only after 30–60 min of administration. This potentiation is similar in magnitude in all patients, but takes place fastest in the youngest children.     

Effect of prior administration of succinylcholine on duration of action of vecuronium during enflurane anaesthesia

The effects of succinylcholine, which was given to facilitate tracheal intubation on the duration of action of subsequently administered vecuronium bromide, were evaluated in 54 adult patients who underwent abdominal surgeries under enflurane anaesthesia. The electromyographic response to train–of–four ulnar nerve stimulation was measured. Twenty–seven patients received 1 mg–kg^-1 of succinylcholine, followed by 0.15 mg kg^-1 of vecuronium when the electromyographic response recovered to 50% of control after succinylcholine–induced neuromuscular blockade. The other 27 patients served as the control group, receiving 0.15 mg kg^-1 of vecuronium without prior administration of succinylcholine. In both groups, administration of supplemental 0.04 mg kg^-1 of vecuronium was repeated whenever the electromyographic response recovered to 25% of control during surgical procedures. The duration of blockade induced by the initial 0.15 mg kg^-1 of vecuronium was 56.5 ± 12.8 (mean ± s.d.) min for the group with succinylcholine, and 58.5 ± 21.5 min for the control group. In both groups, the average duration of four consecutive supplemental doses of vecuronium was approximately 35 min. No significant differences between groups were found in the duration of neuromuscular blockade induced by initial and supplemental doses of vecuronium.     

Vecuronium and Atracurium in the Elderly: A Clinical Comparison with Pancuronium

The intubating conditions, time to complete block and duration of clinical relaxation were observed in a group of 101 elderly patients (aged over 65 years) following pancuronium 0.1 mg kg^-1, vecuronium 0.1 mg kg^-1 or atracurium 0.5 mg kg^-1. The intubating conditions in the three groups were similar when assessed at 2 min following relaxant administration. The time to complete block was shortest with vecuronium (4.3 min) in comparison to atracurium (5.0 min) and pancuronium (6.0 min), but the differences were not statistically significant. The duration of clinical relaxation, however, was significantly shorter with vecuronium (37 min) and atracurium (35 min) in comparison to pancuronium (99 min).     

Quantification of train-of-four responses during recovery of block from non-depolarising muscle relaxants

Train-of-four (TOF) responses were assessed in 70 patients (seven groups of ten patients each) during recovery of neuromuscular block from atracurium (226 or 452 μg/kg), vecuronium (40 or 80 μg/kg), pancuronium (60 or 120 μg/kg) and tubocurarine (450 μg/kg) in order to quantify the height of T₁ (first response in the TOF sequence) at which T₂, T₃ and T₄ (2nd, 3rd and 4th response in TOF sequence) reappear. Patients were anaesthetised with thiopentone, nitrous oxide in oxygen and fentanyl. There were small but significant differences between relaxants. The clinically useful parameter, i.e. the 4th response in the TOF sequence, appeared at approximately 30% height of the first response (T₁) rather than at 25% as generally believed. It is suggested that the third response in the TOF sequence, which reappeared at an average height of T₁ of about 25%, be used for administration of further supplements of muscle relaxants since abdominal muscle relaxation becomes inadequate at this stage.     

Succinylcholine-induced fasciculations in denevated rat muscles as measured using 31P-NMR spectroscopy

Background : We have previously demonstrated by ³¹P nuclear magnetic resonance (NMR) that succinylcholine (SCh) induces metabolic changes in denervated muscle. To specify those changes, we attempted to inhibit them using two different kinds of drugs, dantrolene and vecuronium.
Methods : Three weeks after unilateral sciatic nerve section, 75 male Wistar rats were randomly assigned to one of the following 5 groups: (1) non-pretreated normal muscle group; (2) non-pretreated denervated muscle group; (3) denervated muscle group pretreated with a low dose of vecuronium (0.02 mg · kg^-1); (4) denervated muscle group pretreated with a high dose of vecuronium (0.2 mg · kg^-1); (5) denervated muscle group pretreated with dantrolene (2 mg · kg^-1). The change of the inorganic phosphate/phosphocreatine (Pi/PCr) ratio of each muscle was measured by ³¹P-NMR before and after SCh (1 mg · kg^-1) administration and the corresponding peak amplitude of the electromyograms (EMG) was determined.
Results : The high dose of vecuronium totally inhibited SCh-induced fasciculation on EMG (100%2%). In this group, though the Pi/PCr ratio significantly increased 10 min after SCh, the peak after 5 min disappeared. The inhibition with dantrolene was about the same order of magnitude as with the low dose of vecuronium (35%:21%). However, the increase in the Pi/PCr only lasted about 10 min, in contrast to the other drugs.
Conclusion : Our findings indicate that the Pi/PCr increases 5 and 10 min after SCh, respectively, as a result of two different processes. The first peak is caused by an excessive energy consumption in response to excessive muscle contraction. This in turn triggers the second peak, caused by breakdown of glycogen, initiated by an increased Ca²⁺ concentration.     

Granisetron prevents nausea and vomiting during spinal anaesthesia for caesarean section

Background: Nausea and vomiting during spinal anaesthesia for caesarean section are common and unpleasant complications. This study was undertaken to evaluate the efficacy of granisetron, a selective 5-hydroxytryptamine type 3 receptor antagonist, for prophylactic treatment of nausea and vomiting in parturients undergoing nonemergent caesarean section under spinal anaesthesia.
Methods: In a randomized, double-blind, placebo-controlled trial, 100 patients, 21–38 years, received either placebo (saline) or granisetron at 3 different doses (20 μg · kg^-1, 40 μg · kg^-1 or 80 μg · kg^-1) (n=25 for each) intravenously immediately after clamping of the foetal umbilical cord. Nausea, vomiting and safety assessments were performed during spinal anaesthesia for caesarean section.
Results: The treatment groups were similar with regard to maternal characteristics and operative management. The incidence of nausea and vomiting was 64%, 52%, 14% and 12% after administration of placebo and granisetron in a dose of 20 μg · kg^-1, 40 μg · kg^-1 and 80 μg · kg^-1, respectively ( P <0.05; overall Fisher's exact probability test). No clinically important adverse effects were observed in any group.
Conclusions: Prophylactic use of granisetron in a minimum dose of 40 μg · kg^-1 is effective for preventing nausea and vomiting during spinal anaesthesia for caesarean section.
© Acta Anaesthesiologiat Scandinavica 42 (1998)     

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.     

A comparison of the effects of fentanyl and propofol on left ventricular contractility during myocardial stunning

Background : The intravenous anaesthetic propofol has been shown to possess free radical scavenging activity and calcium channel blocking effects in a number of in vitro models. We decided to compare the effects of propofol with those of fentanyl on myocardial contractility during and after ischaemia to determine whether propofol could protect the heart and improve recovery of ventricular contractile function in open-chested dogs.
Methods : Twenty adult beagles were acutely instrumented, under halothane anaesthesia, to measure ECG; aortic, left ventricular pressures; cardiac output; coronary flow; and segmental lengths in the regions perfused by the left anterior and left circumflex coronary arteries. After surgery and a stabilisation period halothane anaesthesia was terminated and fentanyl (100 μg. kg^-1 bolus followed by 2 μ.kg^-1·min^-1 infusion; n=10) or propofol (5 mg. kg^-1 bolus followed by 0.3 mg· kg^-1 min^-1 infusion; n=10) anaesthesia commenced. After a stabilisation period the LAD coronary artery was occluded for 10 min and then reperfused for 3 h. Measurements were taken throughout the protocol.
Results : We found no significant difference in recovery of contractile function between propofol and fentanyl as assessed by normalised preload recruitable work area (50±10 vs 47±16%), normalised systolic shortening (36±12 vs 48±14%) and peak left ventricular dP/dt (1665±276 vs 1846±151 mmHg.s^-1) at the end of reperfusion.
Conclusion : We conclude that at the concentration used in this study propofol shows no improvement in contractility during "stunning" when compared to fentanyl.