The effects of perineural dexmedetomidine on the pharmacodynamic profile of femoral nerve block: a dose-finding randomised, controlled, double-blind study.

This randomised, controlled, double-blind study investigated the effects of different doses of perineural dexmedetomidine on the pharmacodynamic profile of femoral nerve block in patients undergoing arthroscopic knee surgery. Ultrasound-guided femoral nerve block was performed before general anaesthesia using 25 ml of bupivacaine 0.5% combined with normal saline in the control group, and 25 µg, 50 µg or 75 µg of dexmedetomidine in three treatment groups (n = 15 for each group). All patients received a standard general anaesthetic and multimodal postoperative analgesic regimen. The use of the 50 µg and 75 µg dose levels of dexmedetomidine was associated with reduction of the onset time, extension of the duration of block, prolonged time to the first postoperative request for rescue analgesia, and reduced postoperative morphine requirements. The times to first request for postoperative analgesia were mean (SD) 10.8 (1.6) h in the control group and 11.0 (7.1), 21.8 (3.0) and 28.6 (10.0) in the 25 µg, 50 µg and 75 µg treatment groups, respectively. These times were significantly longer in the 50 µg and 75 µg treatment groups compared with the 25 µg (p < 0.0001) and control group (p < 0.0001). The total 24-h postoperative morphine consumption was 7.6 (5.1) mg in the control group, and 6.5 (3.5), 3.9 (3.4), 1.8 (2.6) in the 25 µg, 50 µg and 75 µg treatment groups, respectively. Postoperative morphine consumption was significantly higher in the control group compared with the 50 µg (p = 0.045) and the 75 µg (p = 0.001) treatment groups. The best analgesic profile was achieved at the 75 µg dose, but this was associated with increased risk of hypotension.

Pitfalls in reporting sample size calculation in randomized controlled trials published in leading anaesthesia journals: a systematic review.

We have evaluated the pitfalls in reporting sample size calculation in randomized controlled trials (RCTs) published in the 10 highest impact factor anaesthesia journals.Superiority RCTs published in 2013 were identified and checked for the basic components required for sample size calculation and replication. The difference between the reported and replicated sample size was estimated. The sources used for estimating the expected effect size (Δ) were identified, and the difference between the expected and observed effect sizes (Δ gap) was estimated.We enrolled 194 RCTs. Sample size calculation was reported in 91.7% of studies. Replication of sample size calculation was possible in 80.3% of studies. The original and replicated sample sizes were identical in 67.8% of studies. The difference between the replicated and reported sample sizes exceeded 10% in 28.7% of studies. The expected and observed effect sizes were comparable in RCTs with positive outcomes (P=0.1). Studies with negative outcome tended to overestimate the effect size (Δ gap 42%, 95% confidence interval 32-51%), P<0.001. Post hoc power of negative studies was 20.2% (95% confidence interval 13.4-27.1%). Studies using data derived from pilot studies for sample size calculation were associated with the smallest Δ gaps (P=0.008).Sample size calculation is frequently reported in anaesthesia journals, but the details of basic elements for calculation are not consistently provided. In almost one-third of RCTs, the reported and replicated sample sizes were not identical and the assumptions for the expected effect size and variance were not supported by relevant literature or pilot studies.

Feasibility and acceptability of HIV screening through the use of rapid tests by general practitioners in a Brussels area with a substantial African community.

OBJECTIVES: To assess:1) if HIV screening with rapid tests in neighbourhoods with a substantial African community is feasible and acceptable among GPs and patients; 2) HIV seroprevalence. METHODS: Multicenter prospective study with 10 trained physicians. Use of HIV standard test and INSTI Ultrarapid test. INCLUSION CRITERIA: MSM, sex worker, multiple sexual partners, having returned or coming from a country with high HIV prevalence, IVDU, Indicator conditions as defined by HIV Indicator Diseases across Europe Study, having an AIDS-defining illness, having had a recent pregnancy or abortion; or presenting other risks. RESULTS: From August 2010 to August 2011, 10 trained GPs offered an HIV test to 224 patients: 51% ♀, 48% ♂, 43% Caucasians, 45% Africans. INCLUSION CRITERIA: 32% "high risk group", 9% returning from an endemic country, 29% with an indicator condition; 12 patients (6%) refused the standard test. The INSTI was offered to 217(97%), 197 performed with 2 reactive rapid tests confirmed. The seroprevalence according to ethnic origin was 0% among Caucasians and 2.2% among Africans and was 1.5% among patients with an indicator condition. 1087 consecutive consultations of the same GPs were recorded: 42% patients had ≥ 1 inclusion criteria among which 41% of offered tests, that is to say 59% of "missed opportunities". The reasons for not offering the test as recorded for 55% of patients:"not indicated" 44.5%, "no time" 33%, "impossible to propose" 15%, test completed previously 11%, known HIV-positive 4%. CONCLUSIONS: Standard and rapid tests are well received by patients but were usually not offered by doctors who have been trained.

The effect of magnesium sulphate infusion on the incidence and severity of emergence agitation in children undergoing adenotonsillectomy using sevoflurane anaesthesia.

This randomised, controlled, double-blind study investigated the effects of intra-operative magnesium sulphate administration on the incidence of emergence agitation in children undergoing adenotonsillectomy using sevoflurane anaesthesia. Seventy children were randomly allocated to receive a 30 mg.kg(-1) bolus of intravenous magnesium sulphate after induction of anaesthesia followed by a continuous infusion of 10 mg.kg(-1).h(-1) or an equal volume of saline 0.9%. All children received titrated sevoflurane anaesthesia adjusted to maintain haemodynamic stability. The Pediatric Anesthesia Emergence Delirium scale and the Children's Hospital of Eastern Ontario Score were used for the assessment of postoperative emergence agitation and pain, respectively. Emergence agitation was more common in the control group than in the magnesium group (23 (72%) and 12 (36%), respectively (p = 0.004)), with a relative risk of 0.51 (95% CI 0.31-0.84), an absolute risk reduction of 0.35 (95% CI 0.10-0.54), and number needed to treat of 3 (95% CI 2-9). Postoperative pain scores were comparable in the two groups. Magnesium sulphate reduces the incidence and severity of emergence agitation in children undergoing adenotonsillectomy using sevoflurane anaesthesia and is not associated with increased postoperative side-effects or delayed recovery.

Edrophonium antagonism of cisatracurium-induced neuromuscular block: dose requirements in children and adults.

This randomized, controlled study compared edrophonium dose requirements to antagonize cisatracurium-induced neuromuscular block in children and adults. Sixty children, aged two to 10 years, and 60 adults aged 20 to 60 years, all subjects ASA physical status 1 or 2, having propofol, fentanyl and isoflurane-N2O anaesthesia, were studied. Cisatracurium 0.1 mg x kg(-1) was given for muscle relaxation. Neuromuscular block was monitored with accelerometry. Edrophonium 0.1, 0.2, 0.4 or 1 mg x kg(-1) or no anticholinesterase (controls) was given by random allocation to antagonize 90% neuromuscular block in each of the study groups (n=12). Atropine 5 to 10 microg x kg(-1) was given according to edrophonium dose. Onset time of cisatracurium-induced block in children was mean (SD) 2.4 (0.8) versus 4.1 (2.3) minutes in adults, P<0.01. The times to 10% spontaneous recovery of the first twitch (T1) were respectively, 28.4 (5.2) and 41.8 (6.1) minutes in children and adults, P<0.01. Spontaneous and antagonist assisted neuromuscular recovery was more rapid in children. Adequate neuromuscular recovery (train of four (TOF) ratio 80%) was achieved in children at 3 and 10 minutes after edrophonium 1.0 mg kg(-1) and 0.4 mg x kg(-1), respectively. A TOF ratio of 80% was not achieved, within 10 minutes, with any of the four dose levels of edrophonium in adults. The dose of edrophonium to achieve a TOF ratio of 80% (ED(TOF-80)) after 5 and 10 minutes in children were, respectively, mean (SD) 0.85 (0.38) and 0.38 (0.19) mg x kg(-1). The equivalent ED(TOF-80) in adults was outside the edrophonium dose range studied.

Epidural ketamine reduces post-operative epidural PCA consumption of fentanyl/bupivacaine.

PURPOSE: To study the analgesic effect of epidural ketamine on postoperative pain and epidural PCA consumption after total abdominal hysterectomy. METHODS: Sixty-one ASA I-II patients, 34-60 yr were randomly assigned into three groups. Epidural catheters were inserted before induction of anaesthesia. Patients in group I and II received 30 mg ketamine epidurally before induction of anaesthesia or 20 min after skin incision: group III received placebo. Postoperatively, on first analgesia request, sedation score, Visual Analogue Scale (VAS), Prince Henry Score (PHS) and Bromage motor weakness score were taken and followed by an epidural bolus of 9 ml bupivacaine 0.25% + 50 micrograms fentanyl. Analgesia was maintained by PCA with a mixture of bupivacaine 0.1% + fentanyl 0.001% epidurally. Measurements were repeated at 1, 2, 4, 8, 12 and 24 hr. RESULTS: First analgesia request was 17 +/- 6.8 min in the control group compared with 31.4 +/- 23.8 and 44 +/- 23.1 min for groups I and II respectively. The differences between group III and group I (P < 0.05) and between group III and group II (P < 0.01) were statistically significant. Twenty four hour PCA consumption was 101.2 +/- 47.2, 87 +/- 27 and 162 +/- 38 ml for groups I, II and III respectively. The differences between group III and group I and that between group III and group II were statistically significant (P < 0.001). CONCLUSION: Epidural ketamine 30 mg reduces post hysterectomy pain as evidenced by prolongation of time to first analgesia request and reduction in postoperative epidural PCA consumption. This effect is manifest whether ketamine is given before induction or 20 min after skin incision.

Blood flow and mivacurium-induced neuromuscular block at the orbicularis oculi and adductor pollicis muscles.

We have studied the pattern of blood flow and pharmacodynamic profile of mivacurium-induced block at the adductor pollicis and orbicularis oculi muscles. We studied 30 adult patients anaesthetized with fentanyl, thiopentone, nitrous oxide-isoflurane, and mivacurium 0.2 mg kg-1. Neuromuscular transmission was monitored with accelerometry (TOF Guard, Biometer, Denmark). Blood flow was measured at the two muscles with the use of a laser Doppler flowmeter (Laserflo BPM2, Vasamedics, USA). All patients developed 100% neuromuscular block at the adductor pollicis muscle. Mean maximum neuromuscular block at the orbicularis oculi was 96.4 (SD 3.5)% (ns). Onset time, time required for 25% and 75% recovery of the first twitch in the train-of-four (T1), and a train-of-four ratio (T4/T1) of 90% at the orbicularis oculi were respectively, mean 130.4 (SD 28.5) s, 9.1 (3.2) min, 16.2 (3.9) min and 20.2 (4.3) min and were significantly shorter than the corresponding values at the adductor pollicis: 202.7 (37.2) s, 12.9 (3.9) min, 21.1 (5.1) min and 30.8 (7.4) min. For a given T1, there was significantly less train-of-four fade (T4/T1) at the orbicularis oculi than at the adductor pollicis muscle during recovery. Blood flow was comparable at the two muscles before induction of anaesthesia. Thiopentone significantly increased thenar muscle blood flow from 2.9 (1.5) to 12.3 (6.8) ml 100 g-1 min-1, with a further increase to 22.7 (8.0) ml 100 g-1 min-1 after isoflurane (P < 0.001). Blood flow at the orbicularis oculi was not altered by thiopentone or isoflurane and was consistently lower than that at the adductor pollicis muscle. We conclude that the different pharmacodynamic profiles of mivacurium-induced block at the orbicularis oculi and adductor pollicis muscles were not related primarily to a difference in blood flows.

Dose-response relationships for neostigmine antagonism of rocuronium-induced neuromuscular block in children and adults.

Dose-response relationships for the antagonism of intermediate-acting neuromuscular blocking agents have not been evaluated previously in children. We have examined the dose-response relationships for neostigmine antagonism of 90% rocuronium-induced neuromuscular block in children and adults, during nitrous oxide-1 MAC of isoflurane anaesthesia. We studied 40 children, aged 2-10 yr, and 50 adults, aged 18-60 yr; all received a single bolus dose of rocuronium 0.6 mg kg-1 and accelerometry was used to monitor neuromuscular transmission. When the first twitch of the train-of-four (TOF) response (T1) recovered to 10% of its control (T0), one of five doses of neostigmine 0, 5, 10, 20 or 50 micrograms kg-1 was given by random allocation to each of the study groups (n = 8 children and n = 10 adults). Recovery of T1 and TOF ratio (T4/T1%) was recorded for 10 min after initial administration of neostigmine. Onset time of rocuronium-induced block was faster in children than in adults (mean 64.6 (95% confidence intervals 57.7-71.5) s vs 83.7 (70.7-96.6) s; P < 0.05). The time to 10% recovery of T1/T0 was shorter in children than in adults (25.4 (22.9-27.9) min vs 38.8 (36.1-41.4) min; P < 0.001). Spontaneous and antagonist-assisted recovery were more rapid in children than in adults. Adequate recovery (T4/T1 of 80%) occurred in children at 4, 5 and 8 min after neostigmine 50, 20 and 10 micrograms kg-1, respectively. Adequate recovery was not produced in adults by any dose of neostigmine within 10 min. The effective doses of neostigmine required to achieve a TOF ratio of 80% (ED80) after 10 min in children and adults were, respectively, 7.10 (5.2-9.8) micrograms kg-1 and 56.56 (45.5-71.9) micrograms kg-1 (P < 0.001). There was no advantage in administering doses of neostigmine greater than 20 micrograms kg-1 to antagonize 90% rocuronium-induced neuromuscular block in children. In contrast, it appeared prudent to use neostigmine 50 micrograms kg-1 or more for adequate antagonism of a similar degree of block in adults.

Rocuronium priming of atracurium-induced neuromuscular blockade: the use of short priming intervals.

STUDY OBJECTIVE: To evaluate the effects of priming doses of rocuronium on the duration of priming interval and on the outcome of priming sequence using rocuronium-atracurium combination. DESIGN: Three phase, randomized, controlled study. SETTING: Inpatient anesthesia in a university hospital. PATIENTS: 144 ASA physical status I and II patients, 19 to 57 years of age, weighing 50 to 90 kg, and undergoing low-risk elective surgery. INTERVENTIONS: Phase I, two equal groups (n = 12) of adult patients anesthetized with propofol, fentanyl, and nitrous oxide (N2O), received a priming dose of rocuronium 0.1 mg/kg or vecuronium 0.015 mg/kg. Phase II included six equal groups (n = 12): Groups 1, 2, and 3 received a priming dose of rocuronium 0.1 mg/kg and atracurium 0.42 mg/kg for intubation. The priming intervals were, respectively, 1, 1.5, or 2 minutes in Groups 1, 2, and 3. Groups 4, 5, and 6 received, respectively, a bolus dose of rocuronium 0.6 mg/kg, atracurium 0.5 mg/kg, or succinylcholine 1 mg/kg. Intubation was performed at maximum block. Phase III included four equal groups (n = 12). A priming dose of rocuronium 0.1 mg/kg (Group 1) or a placebo (Groups 2, 3, and 4) was given to awake patients. Anesthesia was induced during the one-minute priming interval. Intubating doses of atracurium 0.42 mg/kg, rocuronium 0.6 mg/kg, atracurium 0.5 mg/kg, or succinylcholine 1 mg/kg were given to Groups 1, 2, 3, and 4, respectively. Intubation was attempted 1 minute after intubating doses were administered. MEASUREMENTS AND MAIN RESULTS: Adductor pollicis response to train-of-four stimulation was recorded mechanically in Phases I and II only. The priming interval after rocuronium 0.1 mg/kg was in the range of 1 to 2 minutes. Priming doses of rocuronium resulted in significant acceleration in the onset time of intubating doses of atracurium, irrespective of the duration of the priming interval. The onset times [mean (SD)] following rocuronium-atracurium sequence in Groups 1, 2, and 3 were, respectively, 67 (17), 73 (14), and 66 (18) seconds and were comparable with the onset of bolus doses of rocuronium and succinylcholine. In Phase II, good to excellent intubating conditions were obtained in 41% to 58% of patients included in Groups 1 through 5. Excellent to good intubating conditions were obtained in all patients (100%) who received succinylcholine. In Phase III, good to excellent intubating conditions were obtained in 91% of patients who received recuronium-atracurium sequence. Symptoms of muscle weakness were not reported. CONCLUSIONS: Priming doses of recuroniums 0.1 mg/kg reduce the priming interval to 1 minute, allow early induction of anesthesia, eliminate patient discomfort, and accelerate the onset time of altracurium with intubating conditions comparable with succinylcholine and rocuronium.

Edrophonium antagonism of intense mivacurium-induced neuromuscular block in children.

We have studied the time course of recovery after administration of edrophonium during intense mivacurium block in children aged 2-10 yr, using thumb acceleration in response to train-of-four (TOF) stimulation. Forty-three children receiving alfentanil, propofol, nitrous oxide, isoflurane anaesthesia and mivacurium 0.2 mg kg-1 were allocated randomly to one of three groups. Patients in group 1 (n = 15) received edrophonium 1 mg kg-1, 2 min after maximum block (intense block group). At the time of administration of edrophonium in this group, there was no response to TOF stimulation (100% block) and the post-tetanic count was 10.7 (range 0-20). Patients in group 2 received the same dose of edrophonium after 10% recovery of the first twitch (T1) in the TOF (conventional reversal). Patients in group 3 (n = 13) recovered spontaneously. All patients developed complete suppression of twitch height in response to the bolus dose of mivacurium. All recovery times were measured from the point of maximum block after mivacurium. Mean time for 25% recovery of T1 (clinical duration) was 3.8 (SD 1.1) min in the intense block group. This was significantly shorter than the conventional reversal (8.3 (2.4) min) and spontaneous recovery (9.2 (3.5) min) groups (P < 0.001). The times for 75% and 90% recovery of T1 were shorter in the intense block group (9.4 (2.8), 12.3 (4.2) min) compared with the conventional (13.1 (3.8), 17.3 (4.8) min) and spontaneous recovery (14.9 (4.5), 17.9 (5.2) min) groups (P < 0.01). Total recovery time required for 70% recovery of the TOF ratio (T4/T1) was 8.8 (2.4) min in the intense block group. This was significantly shorter than the conventional reversal (11.9 (3.2) min) (P < 0.05) and spontaneous recovery (17.1 (4.0) min) groups (P < 0.001). Conventional reversal was associated with a shorter total recovery time compared with spontaneous recovery (P < 0.01). The recovery index (time interval between T1 25% and 75%) was comparable in groups 1-3 (5.5 (2.0), 4.8 (2.1) and 5.7 (1.4) min respectively). Ten minutes after development of maximum block, the numbers of patients who recovered adequately (TOF ratio 70% or more) were, respectively, 12 (80%), 8 (53%) and 1 (8%) in groups 1-3. We conclude that edrophonium antagonized intense (no response to TOF stimulation) mivacurium-induced block in children, with significant reduction in the recovery times of T1 and TOF ratio compared with conventional reversal and spontaneous recovery.

Can pre-emptive interpleural block reduce perioperative anesthetic and analgesic requirements?

BACKGROUND AND OBJECTIVES: The hypothesis that preoperative interpleural block might reduce intraoperative anesthetic and analgesic requirements and modify the intensity of postoperative pain was examined in this double-blind, randomized, saline-controlled study. METHODS: Thirty women undergoing cholecystectomy with subcostal incision were included. All patients received a background isoflurane anesthetic in 40% O2 and air. Interpleural catheters were inserted after induction of anesthesia and 20-25 minutes before surgical incision. Patients were randomly allocated to one of two groups. Group 1 received a bolus of 0.5% plain bupivacaine followed by a continuous infusion of 7 mL/h 0.25% bupivacaine. Group 2 received similar bolus volume and infusion of 0.9% saline. The attending anesthesiologist was blinded to patient groups. Intraoperative analgesia was assessed by the hemodynamic responses to surgery and by the anesthetic and analgesic requirements. Postoperative analgesia was accomplished by 20 mL bupivacaine 0.5% in group 2 patients followed by an infusion of bupivacaine 0.25% in the two groups. Postoperative analgesia was assessed by visual analog scale (0-10), hourly bupivacaine requirements, peak expiratory flow rate, and the request for additional intramuscular morphine. RESULTS: Preoperative interpleural block produced a significant decrease in mean arterial pressure and heart rate. These hemodynamic changes were partly corrected by surgical incision and reduction of isoflurane concentration. The mean intraoperative isoflurane requirements in group 1 and 2 were, respectively, 0.59 +/- 0.02% and 1.2 +/- 0.12% (P < .001). Preoperative instillation of bupivacaine in the pleural space resulted in about 50% reduction in isoflurane requirements. Intraoperative alfentanil requirements were 13.6 +/- 6 and 29.2 +/- 11 micrograms/kg in the bupivacaine and saline groups, respectively (P < .001). After the operation, both study groups had comparable visual analog scale peak expiratory flow rate, bupivacaine infusion rate, and intramuscular morphine supplements. CONCLUSIONS: Preoperative interpleural block, during a background isoflurane anesthetic, reduces the hemodynamic response to surgery and the intraoperative anesthetic and analgesic requirements. Preoperative interpleural block with plain bupivacaine results in significant reductions in mean arterial pressure and heart rate, probably related to unilateral sympathetic block and the concomitant use of isoflurane. The timing of interpleural block, that is, pre-emptive versus postoperative, does affect the intensity of postoperative pain or the request for supplementary analgesia.

Surgeon-controlled mivacurium administration during elective caesarean section.

We have compared the dose requirements and recovery characteristics of a continuous mivacurium infusion given by the anaesthetist to maintain 95-100% block at the hand muscles with that of a surgeon-controlled, on-demand dosing technique based on the direct assessment of abdominal muscle tone during elective Caesarean section. Twenty-four full term pregnant patients were included. A rapid-sequence induction using thiopentone 3-5 mg.kg-1 and succinylcholine 1 mg.kg-1 was used. Anaesthesia was maintained with fentanyl, N2O and isoflurane 0.5%. The mechanomyographic response of the adductor pollicis muscle to supramaximal train-of-four (TOF) ulnar nerve stimulation was recorded. Muscle relaxation was achieved initially with mivacurium 0.1 mg.kg-1 followed either by a continuous infusion of mivacurium to maintain 95-100% block at the adductor pollicis muscle (n = 12) or by surgeon-controlled relaxation (SCR) technique using a syringe pump for patient-controlled analgesia to administer on-demand doses of mivacurium 0.05 mg.kg-1 (n = 12). The lockout interval was three minutes and the maximum hourly dose of mivacurium allowed was 0.6 mg.kg-1. The total doses of mivacurium (mean +/- SD) were 23.2 +/- 10.4 and 12.4 +/- 3.5 mg in the infusion and SCR groups, P < 0.01. On-demand, surgeon-controlled doses of mivacurium were injected at a mean of T1 42.3 +/- 36%. At the end of surgery, T1 and TOF ratio were respectively 16.7 +/- 13%, 5 +/- 10% and 48 +/- 37%, 30 +/- 24% in the infusion and SCR groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Recovery characteristics after early administration of anticholinesterases during intense mivacurium-induced neuromuscular block.

The time course of recovery after early administration of anticholinesterases during intense mivacurium-induced block was evaluated by recording the mechanomyographic response of the adductor pollicis to post-tetanic count (PTC) and train-of-four (TOF) ulnar nerve stimulation. Seventy-two adult patients receiving thiopentone, fentanyl, nitrous oxide, isoflurane anaesthesia and mivacurium 0.15 mg kg-1 were allocated randomly to one of six equal groups according to the type of anticholinesterase and intensity of block at which antagonism was attempted. Groups 1, 3 and 5 received neostigmine 0.07 mg kg-1, while groups 2, 4 and 6 received edrophonium 1 mg kg-1. At the time of administration of antagonist there was no response to PTC in groups 1 and 2, a PTC of 1 or more was detectable in groups 3 and 4 and the first twitch of the TOF (T1) had recovered to 10% in the conventional antagonism groups (5 and 6). The longest clinical duration (CD) values (time from administration of mivacurium to T1 25%) were encountered in groups 1, 5 and 6 and were 17.4 (7.9), 19.7 (3.4) and 21.4 (4.8) min, respectively. CD was reduced significantly in groups 2, 3 and 4 and values were 13.9 (3.5), 13.7 (3.5) and 13.8 (3.3) min, respectively. Recovery indices (RI) (time interval between T1 25% and 75%) were 13.8 (7.3), 6.3 (1.4), 4.6 (1.8), 6.0 (2.1), 3.7 (2.2) and 4.8 (3.1) min in groups 1-6, respectively and was prolonged with neostigmine antagonism at PTC 0 (group 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-response studies of the interaction between mivacurium and suxamethonium.

We have determined the effect of pretreatment with mivacurium on the potency of suxamethonium and the effect of prior administration of suxamethonium on the potency of mivacurium. We studied 100 ASA I or II patients during thiopentone-fentanyl-nitrous oxide-isoflurane anaesthesia. Neuromuscular block was recorded as the evoked thenar mechanomyographic response to train-of-four stimulation of the ulnar nerve (2 Hz at 12-s intervals). Single dose-response curves were determined by probit analysis. Pretreatment with mivacurium had a marked antagonistic effect on the development of subsequent depolarizing block produced by suxamethonium. The dose-response curves for suxamethonium alone and after pretreatment with mivacurium did not deviate from parallelism, but those constructed after mivacurium were shifted significantly to the right (P < 0.0001). The calculated doses producing 50% depression of T1 (ED50) were 86 (95% confidence intervals 83-88) and 217 (208-225) micrograms kg-1 for suxamethonium alone and after mivacurium, respectively. This study also demonstrated that prior administration of suxamethonium did not appear to influence either the slope of the regression lines or the potency of mivacurium. Combining the results of this study with a previous study (mivacurium ED50 = 20.8 (20.3-21.3) micrograms kg-1 during isoflurane-nitrous oxide anaesthesia), we suggest that the potency of mivacurium did not differ from that observed after suxamethonium (17.4 (16.9-17.9) micrograms kg-1).

Interactions between mivacurium and atracurium.

We have studied the interaction between atracurium and mivacurium. The dose-response relationships of atracurium, mivacurium and their combination were studied in 96 ASA I or II patients during thiopentone-fentanyl-nitrous oxide-isoflurane (1.2% end-tidal) anaesthesia. Neuromuscular block was recorded as the evoked thenar mechanomyographic response to train-of-four stimulation of the ulnar nerve (2 Hz at 12-s intervals). The dose-response curves were determined by probit analysis. Isobolographic and algebraic (fractional) analyses were used to assess quantitatively the combined effect of equipotent doses of atracurium and mivacurium and to define the type of interaction between these drugs. Isobolograms were constructed by plotting single drug ED50 points on the dose co-ordinates and a combined ED50 point in the dose field. The calculated doses producing 50% depression (ED50) of the first twitch height were 50.5 (95% confidence intervals 48.9-52.1) and 20.8 (20.3-21.3) micrograms kg-1 for the atracurium and mivacurium groups, respectively. Isobolographic and fractional analyses of the atracurium-mivacurium combination demonstrated zero interaction (additivism). An additional 26 patients anaesthetized with thiopentone-fentanyl-nitrous oxide-isoflurane were allocated randomly to receive either atracurium 0.5 mg kg-1 (n = 13) or mivacurium 0.15 mg kg-1 (n = 13). Additional maintenance doses of mivacurium 0.1 mg kg-1 were administered to patients in both groups, whenever the first twitch recovered to 10% of control. The duration of the first maintenance dose of mivacurium to 10% recovery of the first twitch was greater (P < 0.0005) after atracurium (25 (21.8-28.5) min) than after mivacurium (14.2 (11.9-16.6) min).(ABSTRACT TRUNCATED AT 250 WORDS)

Thenar muscle blood flow and neuromuscular effects of vecuronium in patients receiving balanced or isoflurane anaesthesia.

We have tested the hypothesis that isoflurane potentiates non-depolarizing neuromuscular block via an increase in muscle blood flow. Anaesthesia was induced with thiopentone 4-5 mg kg-1 in 30 adult male patients of ASA physical status I or II and was maintained with 70% nitrous oxide in oxygen supplemented with either a bolus dose of fentanyl 4 micrograms kg-1 followed by an infusion of 1 microgram kg-1 h-1 (balanced anaesthesia group, n = 15) or 1.1% end-tidal isoflurane (isoflurane group, n = 15). Vecuronium 0.1 mg kg-1 was given for neuromuscular block. The force of contraction of the adductor pollicis of the thumb in response to ulnar nerve stimulation was recorded. Thenar muscle blood flow was measured continuously with a laser Doppler flowmeter. Times required for the first twitch in the train-of-four (T1) to recover to 25%, 75% and 90% of its control value were mean 26.3 (SD 5), 35.3 (10), 43.5 (7) min and 39.2 (15), 53 (12.5), 61.2 (10) min in the balanced anaesthesia and isoflurane groups, respectively (P < 0.01). Recovery index (time between T1 25% and 75%) was prolonged significantly in the isoflurane group. Administration of thiopentone significantly increased thenar muscle blood flow from 2.6 (1.9) and 2.2 (1.5) ml min-1/100 g to 19.2 (14) and 21.7 (16) ml min-1/100 g in the balanced anaesthesia and isoflurane groups, respectively (P < 0.001). The addition of fentanyl (balanced) or isoflurane to the anaesthetic mixture produced further increases in thenar muscle blood flow to reach, respectively, 26.2 (16) and 26.8 (13.6) ml min-1/100 g during steady state anaesthesia. Thenar muscle blood flow was comparable in the two groups throughout the study. We conclude that isoflurane prolonged vecuronium-induced neuromuscular block. This prolongation was not related primarily to increase in muscle blood flow.

Sodium nitroprusside induced hypotension: haemodynamic response and dose requirements during propofol or halothane anaesthesia.

This study was designed to investigate the influence of anaesthesia induced and maintained with propofol on the haemodynamic effects and the dose requirements of SNP during the course of induced hypotension. Twenty-four adult ASA physical status I patients undergoing middle ear surgery were randomly assigned to receive anaesthesia with either morphine, thiopentone, d-tubocurarine, halothane 0.6% end-tidal and N2O 70% in oxygen (group I n = 12), or morphine, propofol, d-tubocurarine, propofol infusion 108 micrograms.kg-1.min-1 and N2O in oxygen (group 2 n = 12). Mean arterial blood pressure (MAP) was reduced to 60-65 mmHg in all patients using a continuous infusion of sodium nitroprusside (SNP) 0.01%. Propofol produced a significant (17%) reduction in the MAP before institution of SNP infusion. This was related to a 24% reduction in the systemic vascular resistance index (SVRI). In the halothane group SVRI was significantly reduced during SNP infusion. Halothane anaesthesia was associated with significant reflex tachycardia in response to SNP induced hypotension. Eight patients in the halothane group (66%) required propranolol 0.5-3 mg to control tachycardia. Propofol anaesthesia attenuated significantly the reflex tachycardia in response to SNP induced hypotension. Two patients in the propofol group (16%) required 0.5 mg propranolol to control reflex tachycardia. The mean SNP dose requirements were 7.25 +/- 1.6 and 2.1 +/- 1.4 micrograms. kg-1.min-1 in the halothane and propofol groups, respectively (P < 0.0001). None of the patients in the two groups developed rebound hypertension following SNP withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-response relationships for edrophonium and neostigmine antagonism of pipecuronium-induced neuromuscular block.

We have studied the dose-response relationships for neostigmine and edrophonium during antagonism of neuromuscular block induced by pipecuronium bromide. Fifty-six ASA physical status I or II adults were given pipecuronium 70 micrograms/kg during fentanylthiopental-nitrous oxide-halothane anesthesia. Train-of-four (TOF) stimulation was applied to the ulnar nerve every 10 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height reached 20% of its initial control value, edrophonium (0.125, 0.25, 0.75, or 1 mg/kg) or neostigmine (0.015, 0.03, 0.045, or 0.06 mg/kg) was administered by random allocation. Neuromuscular function in another seven subjects was allowed to recover spontaneously. This study demonstrated that the dose-response curves for these two drugs for reversal of first twitch and TOF ratio were not parallel. The doses of neostigmine required to achieve 50% (ED50) and 80% (ED80) recovery of the first twitch after 10 min were 8.5 (7.3-9.7) and 17.4 (16.2-18.7) microgram/kg [mean (95% confidence intervals)], respectively. Corresponding ED50 and ED80 values for endrophonium were 84.1 (72.9-96.9) and 233 (215.7-253.3) microgram/kg, respectively. These values corresponded to neostigmine:edrophonium potency ratios of 9.89 (7.4-12.3) and 13.4 (11.8-14.9) for first twitch ED50 and ED80 height, respectively. The calculated doses producing 50% (ED50) recovery of the TOF ratio at 10 min were 18.8 (17.5-20.2) and 271.3 (246.5-298.6) microgram/kg for neostigmine and edrophonium, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)