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.     

Zona pellucida as physiological trigger for the induction of acrosome reaction

Summary.  To evaluate the kinetics of acrosome reaction, sperm samples from four fertile donors were prepared by swim-up and incubated with solutions of human zonae containing 0.1, 0.15, 0.3, 0.5 and 1.0 zonae μl^-1. After 20, 40 and 60 min of incubation at 37 °C, aliquots were taken for evaluation of the acrosomal status. The results showed a distinct time- and dose dependence of the acrosome reaction induced by solubilized zona proteins. After 60 min of incubation in 1.0 zonae μl^-1, about 80% of the spermatozoa showed signs of acrosomal loss; about 40% were completely acrosome-reacted. In addition, zona-bound sperm showed the same ratios of acrosome-reacted spermatozoa in control experiments. The velocity of acrosome reaction was calculated by means of a double-reciprocal plot being 2.0–2.5% min^-1 for completely reacted spermatozoa and those showing signs of acrosome reaction. However, both subgroups differed considerably in their constants of equilibrium (K = 2.0 ZP μl^-1 and K = 0.2 ZP μl^-1, respectively). In nonreacted and partly reacted spermatozoa results might indicate a disturbed course of acrosome reaction or possibly the existence of different subpopulations in respect of sperm competition.     

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)     

The Effect of pH on Ram Sperm Collective Motility Driven by Mitochondrial Respiration

Ram sperm cells treated with 0.02 M 2-deoxy-D-glucose exhibit collective motility which is driven only by mitochondrial respiration. This motility was measured, by means of multichannel optical objective technique, under various [H⁺] concentrations (pH range 5.6–7.2) buffered by 0.125 M phosphate buffers. Semen was divided into 8 aliquots and motility was monitored simultaneously for intensity and duration within 10 min of ejaculation until its complete cessation. The optimal pH range found for the two above-mentioned parameters was in the range of 6.0–6.5. A certain characteristic of the pattern of sperm motility intensity (an oscillations phenomenon) was similarly related to pH. It is suggested that the mechanisms underlying the relationship between pH and motility are rather metabolic. Concerning the results, some practical implications are introduced.     

Cadmium, lead, selenium, and zinc in semen of occupationally unexposed men

Summary. Concentrations of cadmium, lead, selenium, and zinc were determined in semen and seminal plasma of 22 volunteers by atomic absorption spectrometry. Additionally conventional semen parameters and, by means of computer videomicrography, motion parameters of spermatozoa were evaluated. Concentrations of Cd, Pb, and Zn determined in semen were not significantly different from those measured in seminal plasma. However, selenium levels were significantly higher in semen (53.8 ± 22.9 μg 1⁻¹) than in seminal plasma (40.4 ± 15.5 μg 1⁻¹, P <0.01). The investigated semen samples on average contained low levels of Cd (0.4 ± 0.23 μg 1⁻¹) and Pb (9.8 ± 6.5 μg 1⁻¹). Studies on the intra-individual variability revealed the following average coefficients of variation (%) for element concentrations: Pb (70), Cd (53), Se (27), and Zn (23); and for semen parameters: total sperm count (46), sperm concentration (37), motility (22), ejaculate volume (21), linearity (19), linear velocity (11), curvilinear velocity (10), and percentage of normally formed sperm (9). Significant positive correlations were detected between semen selenium levels and sperm concentration ( r =0.51, P <0.05), and percentage of normally formed sperm ( r =0.46, P <0.05), respectively. Sperm motility ( r =0.53, P <0.02), linear ( r = 0.76, P <0.001) and curvilinear velocity ( r = 0.64, P < 0.002) were significantly correlated with semen cadmium levels.     

Seminal fibronectin-like antigen and transferrin concentrations in infertile and fertile men

Summary.  Fibronectin like antigen (Fn) and transferrin (Trs) levels were measured in the seminal plasma of 40 fertile and 102 infertile men. The concentrations of both proteins were significantly ( P <0.001) higher in the fertile controls compared to the infertile groups. The levels of Fn and Trs (mean value ± SEM) in the fertile men were 857.9 ± 9.8 μg ml^-1 and 164.0 ± 6.5 μg ml^-1, respectively; in the azoospermic men ( n = 17) 552.7 ± 24.65 μg ml^-1 and 20.7 ± 2.19 μg ml^-1, respectively; in the group of severe oligozoospermia ( n = 35) 568.34 ± 25.7 μg ml^-1 and 31.1 ± 4.18 μg ml^-1, respectively; in the moderate oligozoospermic group ( n = 8) 572.50 ± 47.9 μg ml^-1 and 43.4 ± 15.4 μg ml^-1 respectively, and in the asthenozoospermic group ( n = 26) 512.76 ± 40.4 μg ml^-1 and 47.0 ± 7.9 μg ml^-1, respectively. Of special interest was the finding from a group of 16 normospermic men (partners of couples with unexplained infertility) who showed significantly lower levels of Fn like antigen, 632.5 ± 26.9 μg ml^-1 ( P <0.001) and Trs 41.8 ± 6.94 μg ml^-1 ( P <0.0001) compared to normals. No correlation was found between Fn levels with either Trs or FSH levels or sperm count. In conclusion, our results indicate that male infertility is associated with changes in seminal plasma Fn like antigen concentrations and that it can be possibly used as an index of sperm fertilizing capacity.     

Scavenging effect of N-acetyl-L-cysteine against reactive oxygen species in human semen: a possible therapeutic modality for male factor infertility?

Summary. A new approach to reduce the level of reactive oxygen species (ROS) in human semen by using N-acetyl-L-cysteine (NAG) was evaluated. Semen samples were incubated with or without NAC (1.0 nig ml⁻¹) at room temperature. The chemiluminescent signal of the oxidation of luminol was detected by means of an MTP reader after 0, 20, 40, 60 and 120 min, respectively, using 200 μM luminol. In addition, the dose-dependent action of NAC (0.1, 1.0 and 5.0 mg ml⁻¹) and the influence of NAC on functional sperm parameters (motility and acrosome reaction) were studied.
ROS levels decreased significantly after 20 min incubation with NAG. This reduction was greater in the high ROS group (>30 000 counts/10⁷ viable sperm at t = 0) than in the low ROS group (<30 000). In addition, a marked dose-dependence of NAC was observed. Concerning sperm function, total sperm motility improved after incubation with NAC, but no significant change was observed with respect to the acrosome reaction.
NAC (at concentrations of 1.0 mg ml⁻¹) significantly reduced ROS in human semen and showed the possibility of improving impaired sperm function. After further testing NAC might be useful for the treatment of male infertility patients.     

The optimum bolus dose of remifentanil to facilitate laryngeal mask airway insertion with a single standard dose of propofol at induction in children

The purpose of this study was to determine the optimal bolus dose of remifentanil required for the successful insertion of the laryngeal mask airway during propofol induction in children without a neuromuscular blocking agent. Twenty-six paediatric patients, aged 3–10 years, requiring anaesthesia for short ambulatory surgery were recruited. A predetermined bolus dose of remifentanil was injected over 30 s, followed by propofol 2.5 mg.kg⁻¹ over 10 s. The bolus dose of remifentanil was determined by a modified Dixon's up-and-down method, starting from 0.5 μg.kg⁻¹ (0.1 μg.kg⁻¹ as a step size). Laryngeal mask insertion was attempted 90 s after the end of remifentanil injection and the response of patients was classified as either 'movement' or 'no movement'. The bolus dose of remifentanil at which there was a 50% probability of successful laryngeal mask insertion (ED₅₀) during induction with 2.5 mg.kg⁻¹ propofol was 0.56 (0.07) μg.kg⁻¹ in children without a neuromuscular blocking agent. From probit analysis, the ED₅₀ and ED₉₅ of remifentanil were 0.52 μg.kg⁻¹ (95% confidence limits, 0.42–0.62 μg.kg⁻¹) and 0.71 μg.kg⁻¹ (95% confidence limits, 0.61–1.40 μg.kg⁻¹), respectively.     

Plasma bupivacaine levels after fascia iliaca compartment block with and without adrenaline

Twenty children undergoing unilateral surgery on the thigh received a fascia iliaca compartment block using 2 mg·kg⁻¹ of bupivacaine with (Group A) or without (Group P) adrenaline 1/200 000. Venous blood samples were taken as 5, 10, 15, 20, 25, 30, 40, 50 and 60 min after injection and assayed for concentrations of bupivacaine. In all subjects an adequate block was produced. Plasma concentrations of bupivacaine in Group P were significantly higher than those in Group A ( P <0.05). The median maximum plasma concentration (C_max) was 1.1 μg·ml⁻¹ (range 0.54–1.29 μg·ml⁻¹) in Group P and 0.35 μg·ml⁻¹ (range 0.17–0.96 μg·ml⁻¹) in Group A. The median time taken to attain C_max (T_max) was 20 min (range 10–25 min) in Group P and 45 min (range 5–50 min) in Group A. The median time to first analgesia was 9.75 h (range 3–15 h) in Group P and 10.5 h (range 2.5–21 h) in Group A. The study confirmed the efficacy of the fascia iliaca compartment block in children and showed that when performed with 2 mg·kg⁻¹ of bupivacaine it is associated with plasma concentrations of bupivacaine well within acceptable limits. The addition of adrenaline 1/200 000 to the local anaesthetic solution reduces the maximum plasma concentration reached.     

Effects of five amino–amide local anaesthetic agents on human polymorphonuclear leukocytes measured by chemiluminescence

The aim of this study was to assess the influence of five amino–amide local anaesthetic agents on the production of oxygen metabolites in the human polymorphonuclear leukocyte (PMNL), both intra– and extracellularly.
Ropivacaine, a new long–acting amino–amide local anaesthetic agent, bupivacaine, lidocaine, mepivacaine and prilocaine in concentrations 1–5 μg–ml^-1 up to 500–1000 μg–ml^-1 were compared to an untreated control. PMNLs were isolated from heparinized blood (healthy adult volunteers). Cells were incubated with the various local anaesthetics (37C, 30 min), then placed in a Biolumat (luminol–amplified chemiluminescence) and stimulated by formyl–methionyl–leucyl–phenylalanine (FMLP), phorbol myristate acetate (PMA) or ionomycin. Horseradish peroxidase (HRP) was added to discriminate between an intra– or extracellular response.
In general, a decrease in chemiluminescence–response was seen with higher concentrations (500–1000 μg–ml^-1) of the various local anaesthetics. Lidocaine showed a decrease even at lower concentrations. A marked increase in intracellular response for prilocaine 1000 μg–ml^-1 (3894 μmol–1^-1) accompanied by a reduction in extracellular response, using FMLP HRP as a stimuli, was noted. Ropivacaine 1000 μg ml^-1 (3216 umol–1^-1) showed a decrease both intra– and extracellularly that was similar to, and even somewhat more pronounced than lidocaine 1000 μg–ml^-1 (3692 μmol'l^-1), when using PMA with or without HRP as the stimuli.     

Attenuation of arterial baroreflex control of renal sympathetic nerve activity during lidocaine infusion in alpha–chloralose–anesthetized dogso

The purpose of this study was to identify the relationship between sensitivity of arterial baroreflex and plasma concentrations of lidocaine. Using twelve mongrel dogs anesthetized with alpha–chloralose, the left kidney was exposed retroperitoneally, and renal sympathetic nerve activity was recorded continuously. Lidocaine was infused in four different doses: 2 mg– kg BW^-1 bolus + 100 μg– BW^-1. min; 3 mg– kg BW^-1 bolus+ 200 μg–kg BW^-1min; 6 mg–kg BW^-1 bolus+ 400 μg–kg BW^-1min; and 12 mg–kg BW^-1+ 800 μg–kg BW^-1min. Baroreflex depressor and pressor tests using sodium nitroprusside (5–10 μg–kg^-1) and phenylephrine (2–4 μg–kg^-1) were performed before and at 10 min after beginning lidocaine infusion. Plasma lidocaine concentrations determined by high performance liquid chromatography revealed that the steady–state levels were maintained during the baroreflex tests. Baroreflex sensitivity was preserved at plasma concentrations of lidocaine below 5 μg. ml^-1. However, cardiac and sympathetic baroreflex sensitivity were significantly attenuated ( P < 0.01) when plasma lidocaine concentrations were well above human convulsion levels (10μg–ml^-1). The results indicate that hemodynamic derangement observed in the lidocaine–induced central nervous system toxicity is, at least in part, due to the attenuated arterial baroreflex.     

Effects on skeletal muscle oxygenation and capillary blood flow by adenosine-, sodium nitroprusside- and acetylcholine-induced hypotension

Background: Adenosine (ADO)-induced hypotension during diethyl ether anesthesia has been shown to increase skeletal muscle oxygenation. Whether this beneficial effect of ADO hypotension is present also during another anesthetic technique was tested in the present study using ketamine-xylazine anesthesia, and its actions were compared with sodium nitroprusside (SNP) and acetylcholine (ACh) induced hypotension in rabbits.
Methods: Local oxygen pressure and capillary blood flow were measured with a multiwire microelectrode which was placed on the surface of the left vastus medialis muscle. The experiments were performed in three groups, in which either ADO, SNP or ACh was infused into a central vein in a dose that produced a reduction of the mean arterial pressure by 20–25%, to approximately 60 mmHg.
Results: In the ADO group (60–170 μg kg^-1 min^-1) the tissue oxygen pressures increased by 23% while capillary blood flow decreased by 38%. During SNP administration (1–3 μg kg^-1 min^-1) the oxygen pressures decreased by 21% and an increase of 31% in capillary flows was seen. When ACh was infused (1–4 μg kg^-1 min^-1) the oxygen pressures decreased by 21% and, in parallel, capillary blood flow decreased by 50%. During hypotension no low tissue oxygen pressure values (<1.5 kPa) were found in the ADO group, whereas they were present in both the SNP and ACh group.
Conclusion: Compared to sodium nitroprusside and acetylcholine, adenosine appears to have an oxygen-sparing effect in the skeletal muscle during pharmacologically induced hypotension.     

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.     

PGE1 and hCG Responsive Adenylyl Cyclases in Interstitial Cells from Rat Testis: Biphasic Effects of Calcium

The effects of PGE₁ (10 μg/ml), hCG (10 mIU/ml) and Ca²⁺ (0–10 mM) on rat interstitial cell adenylyl cyclase (AC) activity have been investigated. Like hCG, PGE₁ also stimulated membrane bound AC, and both hormonal effects proved to be influenced by Ca²⁺. Low concentrations of Ca²⁺ (0.3 mM) enhanced hormonal stimulation, while high concentrations (up to 10 mM) suppressed AC activity. Relative stimulations caused by PGE₁ and hCG were maximal in the presence of 0.6 mM Ca²⁺. Ovine FSH (NIH-S12), at concentrations causing maximal activation of AC in seminiferous tubules (12.5 μg/ml), had no effect on AC in interstitial cells. Germinal cell membranes displayed insignificant AC activity. We therefore conclude that the AC activity stimulable by PGE₁ is located on Leydig cell membranes and that both PGE₁ and hCG activities are susceptible to regulation by Ca²⁺.     

The influence of sperm/zona pellucida collision rates on zona binding

Summary. The satisfying success rates reported with intra-cytoplasmic sperm injection (ICSI) urged clinicians and scientists to re-address the emphasis in the management of the male factor patient towards gamete manipulation in order to circumvent the underlying problem causing fertilization failure. We have designed a study to (i) calculate the collision rate of a sperm population with the human zona pellucida, using a mathematical hypothesis and (ii) use the calculated collision rate to evaluate subsequent zona binding results obtained under hemizona assay conditions. Microdroplets were used to co-incubate sperm and human oocytes in order to evaluate zona binding. Using microvolumes, the track followed by sperm, as well as the maximum distance travelled were employed to calculate the collision rate of sperm and zona pellucida. The sperm concentrations of swim up samples were adjusted to 4 × 10⁶ and 0.8 × 10⁶ sperm ml⁻¹. Five separate droplets each of 20 μl containing 4 × 10⁶ sperm ml⁻¹ (80000 motile sperm) and 200 μl containing 0.8 × 10⁶ sperm ml⁻¹ (160000 motile sperm), respectively, were prepared. Both volumes were incubated for 18 h at 37°C. The mean (±SD) number of spermatozoa tightly bound to hemizona, incubated in 20 μl and 200 μl sperm droplets, was 2444±612 and 548±315, respectively ( P = 0.0001). The results can be used as a guideline to calculate the optimum insemination concentration needed for a specific sperm population to ensure the maximum collision rates with the oocyte.     

Use of a novel non-steroidal anti-inflammatory drug, nimesulide, in the treatment of abacterial prostatovesiculitis

Summary. Nimesulide, a novel non-steroidal anti-inflammatory drug, was used in cases of abacterial prostato-vesiculitis. Thirty patients with a mean age of 33.7 years (range 18–58) were studied. Nimesulide was administered orally 100 mg b.i.d. for three cycles of 10 d each. Dysuric symptoms, semen analysis, and transrectal ultrasound were examined during the study. The concentration-time curves of nimesulide (NIM) and its metabolite, hydroxynimesulide (OH-NIM) in seminal fluid were also evaluated after single oral administration (100 mg) using an HPLC technique. Following administration of the drug, the Cmax was reached in seminal fluid at the second hour for NIM (with a mean value ± SD of 0.58 ± 0.13 μg ml⁻¹) and at the fourth hour for OH-NIM (2.98 ± 0.38 μg ml⁻¹). Maximal seminal fluid concentrations compared to blood plasma levels were observed at the fourth hour for both substances (31.73 ± 2.34% for NIM; 31.87 ± 8.66% for OH-NIM.
Dysurie symptoms were relieved in 20 (66%) patients. A clear amelioration of inflammatory signs were observed at transrectal ultrasound evaluation in 16 (54%) patients. No statistically significant changes of sperm count and motility in the whole sample were observed, while a significant reduction in the number of abnormal forms occurred. From these results, nimesulide appears to be an effective anti-inflammatory drug with a good diffusion into the genital apparatus and low side-effects.     

Is testosterone essential for maintenance of normal morphology in immature rat Leydig cells?

Selective deprivation of gonadotrophins in prepubertal rats by administration of a GnRH antagonist (Ac-D2Nal¹, D4ClPhe², DTrp³, DArg⁶, DA1a¹⁰-GnRH; GnRH code: 103–289–10, National Institutes of Health, USA) for 3 weeks, initiated at 20–22 days of age, induced morphological changes in the Leydig cells, including thickening and indentation of the nuclear margin, pyknosis and elongation of the nuclei. Mean nuclear diameter was reduced to 22% of that in the controls. Under the electron microscope the cells exhibited reduced volume of the nucleus and cytoplasm and the plasma membrane was irregular. This abnormal appearance of the Leydig cells improved marginally in 20–30% of the Leydig cells and their mean nuclear diameter increased to 39% of the control level after FSH supplementation (20 μg ovine FSH/day). Normal morphological integrity of the Leydig cells consisting of round or oval nuclei, a smooth nuclear and cellular margin and the original mean nuclear diameter was restored completely when testosterone (30 μg/day) was administered to GnRH antagonist-treated rats, with or without simultaneous administration of FSH; in these rats testosterone levels in blood were also restored to normal. These findings indicate that testosterone may be important for the maintenance of normal Leydig cell morphology in the rat.     

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%.     

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.