Anti-D in a D-positive renal transplant patient

PURPOSE: We report a case of postoperative reparalysis in the recovery room, following nebulized epinephrine. The patient was pharmacologically reversed with edrophonium after paralysis with rocuronium. CLINICAL FINDINGS: A 12-yr-old girl developed postoperative reparalysis following the intraoperative administration of rocuronium. A total of 0.92 mg.kg-1 rocuronium was administered. After surgery, pharmacological reversal was achieved with 20 mg edrophonium with 0.15 mg atropine sulfate iv 35 min after the last administration of rocuronium. Muscular relaxation was monitored using an ulnar peripheral nerve stimulator (PNS). After reversal, a full train-of-four and sustained tetanus at 50 Hz were present. In the recovery room, following nebulized epinephrine, the patient became apneic. The patient was paralyzed and an ulnar PNS demonstrated only one faint twitch. The paralysis was reversed with 1.5 mg neostigmine with 0.3 mg glycopyrrolate. CONCLUSION: Postoperative reparalysis following rocuronium may be a cause of postoperative respiratory distress. The definitive diagnosis is made using PNS and observing the response to pharmacological reversal. Nebulized epinephrine may have a previously undescribed role in the development of postoperative reparalysis.     

An open-label study of the safety and tolerability of converting stable liver transplant recipients to neoral

STUDY OBJECTIVES: (1) To compare the dose-response relations of rocuronium and vecuronium in healthy adult patients anesthetized with nitrous oxide-oxygen-fentanyl-thiopental; and (2) to evaluate the time-course of action of two drugs following equipotent doses. DESIGN: Prospective, randomized, clinical comparison. SETTING: Operating room, Plastic Surgery Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College. PATIENTS: 60 ASA physical status I patients, aged 17-51 years, scheduled for elective plastic surgery. INTERVENTIONS: All patients were randomly assigned to either the rocuronium or vecuronium group. General anesthesia was induced with thiopental 4 to 6 mg/kg and fentanyl 2 to 4 micrograms/kg intravenously (i.v.), and maintained with 60% nitrous oxide (N2O) in oxygen. Further increments of thiopental or fentanyl were given as required. The dose-response relations of rocuronium and vecuronium were determined by the cumulative dose-response technique. MEASUREMENTS AND MAIN RESULTS: Neuromuscular function was assessed mechanomyographically with train-of-four (TOF) stimulation at the wrist every 12 seconds. The percentage depression of first twitch (T1) was used as the study parameter. The cumulative dose-response curve of vecuronium was shifted to the left in a parallel fashion compared with that of rocuronium. As assessed by linear regression, the potency ratio of vecuronium: rocuronium was 1:7.2. There were significant differences in the ED50, ED90, and ED95 between the two drugs. After i.v. administration of equipotent doses of both drugs (2 x ED90), the duration of peak effect, clinical duration, recovery index, and total duration were not significantly different between the two drugs. CONCLUSIONS: Compared with vecuronium, rocuronium is a low-potency, nondepolarizing relaxant, and its neuromuscular blocking potency is approximately 15% that of vecuronium in adult patients anesthetized with N2O and fentanyl. Following equipotent doses, the time-course of recovery for rocuronium is similar to that of vecuronium.     

Potency and time course of action of rocuronium during desflurane and isoflurane anaesthesia

We have studied the potency and onset and duration of action of rocuronium in patients anaesthetized with 1 MAC of desflurane or isoflurane (in 66% nitrous oxide). Potency was estimated using the single bolus dose technique. Neuromuscular block was measured by stimulation of the ulnar nerve and recording the force of contraction of the adductor pollicis muscle. The ED50 and ED95 of rocuronium were estimated as 138 (95% confidence limits 117-162) micrograms kg-1 and 281 (241-328) micrograms kg-1, and 126 (105-151) micrograms kg-1 and 283 (236-339) micrograms kg-1 during desflurane and isoflurane anaesthesia, respectively. The mean times to onset of maximum block after rocuronium 0.6 mg kg-1 were 1.0 (SD 0.10) min and 1.1 (0.15) min, respectively, during anaesthesia with desflurane and isoflurane. The respective times to recovery of T1 (the first response in the train-of-four (TOF) stimulation) to 25% and 90% were 36 (8.3) min and 54 (15.4) min during desflurane anaesthesia and 31 (8.2) min and 45 (12.7) min during isoflurane anaesthesia. The times to recovery of the TOF ratio to 0.7 were 66 (13.4) min and 52 (16.3) min and the 25-75% recovery indices 14 (5.3) min and 10 (3.2) min, respectively, in the desflurane and isoflurane groups. There were no differences in the estimated potency or onset of action of rocuronium during desflurane and isoflurane anaesthesia. However, duration of action tended to be longer curing desflurane anaesthesia although only the differences in times to TOF ratio of 0.7 and the recovery indices were close to being significantly different (P = 0.0503 and 0.0560).     

The use of demineralized laminar bone sheets in guided bone regeneration procedures: report of three cases

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.     

Fetal testing in twins

Mivacurium has a short duration of action because it is rapidly hydrolysed by plasma cholinesterase. There is ongoing controversy concerning the antagonism of mivacurium-induced neuromuscular block, firstly because of its short spontaneous recovery time, and secondly because the metabolism of mivacurium may be inhibited by anticholinesterases. We therefore compared neostigmine and edrophonium reversal of deep and moderate mivacurium-induced blocks. METHODS: After approval by the local ethics committee, 48 ASA class I and II adult patients were investigated during nitrous oxide-fentanyl-thiopental anaesthesia using train-of-four (TOF) stimulation and monitoring of the isometric force of adduction of a thumb. The patients received 0.2 mg/kg mivacurium i.v. Neuromuscular transmission was allowed to recover spontaneously in 10 patients (group SP). In 2 other groups the neuromuscular block was antagonised by administration of 0.04 mg/kg neostigmine (group N5; n = 9) or 1.0 mg/kg edrophonium (group E5; n = 10) when T1 had recovered spontaneously to 5% of control. In two other groups the neuromuscular block was antagonised with the same doses of neostigmine or edrophonium in 10 patients (group N25) and 9 patients (group E25), respectively, when T1 had recovered spontaneously to 25% of control. RESULTS: Neostigmine or edrophonium administered when T1 had recovered spontaneously to 25% of control shortened the recovery time (time from administration of ant-agonist to a T4/T1-ratio of 0.7) significantly from 10.7 +/- 2.2 min (mean +/- SD) in the SP group to 5.1 +/- 2.0 and 5.3 +/- 1.5 min in the N25 and E25 groups, respectively (P < 0.05). The corresponding recovery times in the SP, N5, and E5 groups were 15.9 +/- 2.9, 10.0 +/- 1.9, and 7.7 +/- 2.2 min, respectively. The difference between the SP and E5 groups was significant (P < 0.05). The recovery indices (time from 25% to 75% recovery of T1) of 3.0 +/- 1.3 and 1.7 +/- 0.9 min for the E5 and E25 groups, respectively, were shorter than those of the SP group at 6.1 +/- 2.0 min (P < 0.05). CONCLUSIONS: Two theoretical reasons, the very rapid onset time and the fact that it does not inhibit plasma cholinesterase, suggest edrophonium to be the preferred antagonist of a mivacurium-induced blockade. These two characteristics are reflected in our results: only edrophonium was able to shorten the recovery index significantly and, administered at a profound level of mivacurium-induced neuromuscular block, only edrophonium was successful in shortening recovery time significantly. Therefore, edrophonium should be the anticholinesterase of choice to antagonise a mivacurium-induced neuromuscular block.     

Comparative clinical pharmacology of rocuronium, cisatracurium, and their combination

BACKGROUND: The comparative clinical pharmacology of cisatracurium and rocuronium and their combinations has not been reported. In this study, the authors compared the relative potency and the clinical profile and characterized the interaction of both drugs. METHODS: Two hundred twenty adults classified as American Society of Anesthesiologists physical status I and anesthetized with propofol-fentanyl-nitrous oxide were studied. In part 1, the neuromuscular-blocking effects of cisatracurium and rocuronium were assessed after administration of bolus doses of 20-50 microg/kg and 100-300 microg/kg, respectively. In part 2, we compared the time course of 1xED50, 1, 1.5, and 2xED95 doses of both drugs (where ED50 and ED95 are, respectively, the doses producing 50% and 95% depression of the first twitch height [T1]). In part 3, equieffective combinations of both drugs were studied to characterize their interaction. RESULTS: The calculated ED50 values and their 95% confidence intervals were 111 (107-115) and 26.2 (25.8-26.5) microg/kg [corrected] for rocuronium and cisatracurium, respectively. Compared with equipotent doses of cisatracurium, rocuronium had a faster onset, and a faster spontaneous T1 and train-of-four recovery times that were significant except at maximum recovery with the 2xED95 dose. The interaction between rocuronium and cisatracurium was synergistic, and the time profile of the combination group was different from that of the single-dose groups. CONCLUSIONS: Cisatracurium is four to five times more potent than rocuronium. Rocuronium had a faster onset of action, a shorter clinical duration, and a faster spontaneous recovery rate compared with equipotent doses of cisatracurium.     

The comparative study of LUMIWARD immunoassay system and CAP RAST system for determination of specific IgE antibody against mite in infantile atopic dermatitis

The neuromuscular blocking effects and the reversibility of cisatracurium 0.1 or 0.15 mg.kg-1 were compared with those of atracurium 0.5 mg.kg-1 during anaesthesia with propofol, nitrous oxide and isoflurane. Neuromuscular block was monitored using train-of-four stimulation while recording the mechanomyographic response of the adductor pollicis muscle. The block was either allowed to recover spontaneously or was antagonised with neostigmine 50 micrograms.kg-1 at 10% or 25% recovery of the first twitch of the train-of-four. The median times to maximum block were 2.7, 2.2 and 1.5 min following cisatracurium 0.1 and 0.15 mg.kg-1 and atracurium 0.5 mg.kg-1, respectively. After cisatracurium 0.1 mg.kg-1 had been given, the median time to recovery of the train-of-four ratio to 0.8 ('adequate recovery') was 74 min during spontaneous recovery, 48 min after reversal with neostigmine when the first twitch of the train-of-four had returned to 10% of control and 50 min after reversal when the first twitch of the train-of-four had returned to 25% of control. These times for cisatracurium 0.15 mg.kg-1 and atracurium 0.5 mg.kg-1 were 90, 66 and 57 min and 75, 56 and 54 min, respectively. Administration of neostigmine significantly shortened the time to adequate recovery for both drugs but there were no significant differences in the case of either neuromuscular blocking drug between the groups of patients given neostigmine at 10 or 25% recovery of the first twitch of the train-of-four.     

Neuromuscular effects of rocuronium during sevoflurane, isoflurane, and intravenous anesthesia

The potency and time course of action of rocuronium were studied in patients anesthetized with 66% nitrous oxide in oxygen and 1.5 minimum alveolar anesthetic concentration of sevoflurane or isoflurane, or a propofol infusion. Potency was estimated by using the single-bolus technique. Neuromuscular block was measured by stimulation of the ulnar nerve and by recording the force of contraction of the adductor pollicis muscle. The mean (95% confidence limits) of the 50% and 95% effective doses were estimated tobe 142 (129-157) and 265 (233-301) microg/ kg, 165 (146-187) and 324 (265-396) microg/kg, and 183 (163-207) and 398 (316-502) microg/kg during sevoflurane, isoflurane, and propofol anesthesia, respectively (P < 0.05 for sevoflurane versus propofol). The mean +/- SD times to onset of maximal block after rocuronium 0.6 mg/kg were 0.96 +/- 0.16, 0.90 +/- 0.16, and 1.02 +/- 0.15 min during sevoflurane, isoflurane, and propofol anesthesia, respectively. The respective times to recovery of the first response in the train-of-four (TOF) stimulation (T1) to 25% and 90% were 45 +/- 13.1 and 83 +/- 29.3 min, 35 +/- 6.1 and 56 +/- 15.9 min, and 35 +/- 9.2 and 55 +/- 19.4 min. The times to recovery of the TOF ratio to 0.8 were 103 +/- 30.7, 69 +/- 20.4, and 62 +/- 21.1 min, and the 25%-75% recovery indices were 26 +/- 11.7, 12 +/- 5.0, and 14 +/- 6.9 min, respectively. There were no differences among groups in the times for onset of action or to recovery of T1 to 25%. However, the times for recovery of T1 to 90%, TOF ratio to 0.8, and recovery index in the sevoflurane group were all significantly longer compared with the other two groups (P < 0.05, < 0.01, and < 0.01, respectively). We conclude that the effects of rocuronium, especially duration of action, are significantly enhanced during sevoflurane compared with isoflurane and propofol anesthesia. IMPLICATIONS: In routine clinical use, the effects of rocuronium are enhanced by sevoflurane, in comparison with isoflurane and propofol anesthesia, and the recovery is slower. Particular attention should be paid to monitoring of neuromuscular block during sevoflurane anesthesia.     

Pharmacodynamic dose-response and safety study of cisatracurium (51W89) in adult surgical patients during N2O-O2-opioid anesthesia

After administration of doses ranging from 0.025 to 0.25 mg/kg, the neuromuscular blocking effect of cisatracurium was assessed in 119 adult surgical patients receiving N2O-opioid-midazolam-thiopental anesthesia. The calculated 95% effective dose (ED95) for inhibition of adductor pollicis twitch evoked at 0.1 Hz was 0.053 mg/kg. With 0.10 mg/kg injected over 5-10 and 20-30 s, median onset times (range) were 5.8 (3.0-7.7) and 4.8 (1.2-10.2) min, respectively, and median times to 5% and 95% recovery (range) were 27 (19-46) and 48 (25-68) min, respectively. For doses of 0.10, 0.20, and 0.25 mg/kg, median 5%-95% and 25%-75% recovery indexes ranged from 48 to 90 min and 8 to 9 min, respectively. After administration of neostigmine (0.06 mg/kg) at 10%-15% or 16%-30% recovery, the median times to 95% recovery (range) were 6 (2-22) and 4 (2-5) min, respectively. There were no changes in heart rate, blood pressure, or plasma histamine concentrations during the first 5 min after administration of cisatracurium at doses up to 5 x ED95 injected over 5-10 s. No cutaneous flushing or bronchospasm was noted. In summary, cisatracurium is a potent neuromuscular blocking drug with an intermediate duration of action, characterized by excellent cardiovascular stability, with no apparent histamine release.     

The onset of rocuronium, but not of vecuronium or mivacurium, is modified by tourniquet inflation

A previous investigation showed that inflation of a tourniquet did not interrupt onset of vecuronium neuromuscular block. To test the hypothesis that this effect depended on potency, twitch tension was measured in an arm with a tourniquet inflated during onset and compared with a control arm in 30 patients under fentanyl-thiopental-nitrous oxide-isoflurane anesthesia. Patients were randomly allocated to receive either vecuronium 0.1 mg/kg (n = 10), rocuronium 0.6 mg/kg (n = 10), or mivacurium 0.2 mg/kg (n = 10). The electromyographic response of the first dorsal interosseus to single twitch stimulation of the ulnar nerve every 10 s was recorded in both arms. When neuromuscular block was 20% (i.e., twitch tension was 80% of control), the tourniquet was inflated to a pressure of 300 mm Hg. It was deflated 5 min later. In the vecuronium and mivacurium groups, the tourniquet did not influence onset of block. In the rocuronium group, maximum neuromuscular block was (mean +/- SD) 79% +/- 10% in the tourniquet arm, compared with 96% +/- 4% in the perfused arm (P < 0.05). The maximum rate of onset was half that of the perfused arm. The difference in maximum neuromuscular block between arms was 17% +/- 7%, 5% +/- 5%, and 0% +/- 2% in the rocuronium, vecuronium, and mivacurium groups (P < 0.05). To explain that onset of block continues in spite of interruption of blood flow, drug molecules must gain access to the neuromuscular junction via routes other than the circulation. The results of this investigation are consistent with the hypothesis that there is redistribution of drug from extrajunctional to junctional areas during onset of action of muscle relaxants and this process is more important for the more potent drugs (vecuronium and mivacurium) than for rocuronium.     

Comparative pharmacokinetics of four cholinesterase inhibitors in rats

Pharmacokinetics of a very short-acting, a short-acting and two long-acting cholinesterase (ChE) inhibitors, edrophonium, neostigmine, pyridostigmine and ambenonium, respectively, were compared to elucidate the major determinant of their pharmacokinetics. No dose-dependency in pharmacokinetic behavior was observed within the range of 2-10 mumol/kg for edrophonium, 0.5-2 mumol/kg for pyridostigmine, 0.1-0.5 mumol/kg for neostigmine and 0.3-3 mumol/kg for ambenonium, respectively. Neostigmine has the shortest elimination half-life, and edrophonium, pyridostigmine and ambenonium follow in that. Four ChE inhibitors have similar Vdss values within the range of 0.3-0.7 l/kg, which is similar to the muscle/plasma concentration ratio of these drugs. The liver or kidney to plasma concentration ratio of all ChE inhibitors at 20min after i.v. administration ranged from 5 to 15. Small distribution volumes estimated from the plasma concentration profiles may reflect the distribution to muscle and to the extracellular space of other organs/tissues, while the rapid disappearance of ChE inhibitors from plasma may reflect the concentrative uptake to the liver and kidney.     

Comparison of neuromuscular effects, efficacy and safety of rocuronium and atracurium in ambulatory anaesthesia

PURPOSE: To compare the neuromuscular effects, efficacy, and safety of equi-effective doses of rocuronium and atracurium in ambulatory female patients undergoing surgery. METHODS: Forty-one patients undergoing laparoscopic gynaecological surgery were randomized to receive 2 X ED90 rocuronium (0.6 mg.kg-1; n = 20) or atracurium (0.5 mg.kg-1; n = 21) during intravenous propofol/alfentanil anaesthesia with N2O/O2 ventilation. Neuromuscular block was measured with a mechanomyogram eliciting a train-of-four (TOF) response at the wrist. Intubation conditions 60 sec after administration of muscle relaxant and immediate cardiovascular disturbances or adverse events during the hospital stay were noted by blinded observers. RESULTS: Compared with atracurium, rocuronium was associated with a shorter onset time (59.0 +/- 22.2 vs 98.6 +/- 41.4 sec; P < 0.001) and clinical duration of action (33.3 +/- 7.1 vs 44.7 +/- 7.2 min; P < 0.001), but longer spontaneous recovery index (9.6 +/- 2.41 vs 6.9 +/- 1.89 min; P = 0.023) and a similar time to spontaneous recovery to TOF 70%; 53 +/- 6.31 vs 59.2 +/- 7.59 min; P = 0.139). Tracheal intubation was accomplished in < 90 sec in all patients receiving rocuronium but in only 14 of 21 patients receiving atracurium. The incidence of adverse events and the cardiovascular profiles for the two drugs were similar, although one patient receiving atracurium experienced transient flushing of the head and neck. CONCLUSION: Rocuronium has minimal side effects, provides conditions more suitable for rapid tracheal intubation, and is associated with a shorter clinical duration than atracurium. Once begun, the spontaneous recovery profile of rocuronium is slightly slower than that of atracurium.     

Resistance to decamethonium neuromuscular block after prior administration of vecuronium

Prior administration of nondepolarizing neuromuscular blocking drugs reduces the potency of subsequently administered succinylcholine. To assess whether this interaction is also observed with the depolarizing drug, decamethonium, the potency of decamethonium alone and decamethonium after vecuronium (10 micrograms/kg) were assessed using a cumulative dose-response technique in two groups of six healthy patients each. Patients were premedicated with meperidine and promethazine and anesthetized with thiopental, isoflurane, and nitrous oxide in oxygen. Twitch tension was monitored using adductor pollicis mechanomyography in response to ulnar nerve stimulation at 0.1 Hz. The mean (SEM) dose of decamethonium producing 80% twitch tension depression (ED80) when administered alone was 37 (4.0) micrograms/kg. After recovery of twitch tension (but persistence of train-of-four fade) from vecuronium, the mean (SEM) ED80 for decamethonium was increased to 89 (4.4) micrograms/kg (P < 0.01). The shift to the right of the dose-response curve for decamethonium was nonparallel. Antagonism is observed when decamethonium is administered after a small dose of vercuronium; this interaction, which is also seen with succinylcholine, is likely to be a feature of depolarizing block. Nonparallel shift of the dose-response curve to decamethonium indicates that this is not likely to be a simple agonist-antagonist effect at a single site.     

Acute cytotoxicity testing with cultured human lung and dermal cells

STUDY OBJECTIVE: To determine if 450 micrograms/kg (1.5 times the ED95) of rocuronium would result in a comparable onset with a shorter duration of action when compared with 600 micrograms/kg (2 times the ED95). DESIGN: Randomized, single-blind study. SETTING: Teaching hospital. PATIENTS: 85 ASA physical status I and II children ages 2 through 12, undergoing elective surgery with an inhalation induction using halothane. INTERVENTIONS: Group 1 received 600 micrograms/kg rocuronium, and Group 2 received 450 micrograms/kg rocuronium. MEASUREMENTS AND MAIN RESULTS: The two groups were compared using a Student's t-test, with p < 0.05 significant. The time of onset, or time to 95% suppression of neuromuscular twitch with standard errors, was 140 +/- 13 seconds (range 46 to 365 sec) in Group 1 and 148 +/- 13 seconds (range 82 to 345 sec) in Group 2 (NS = not significant). The times to 25% return of twitch from baseline (T25) in Groups 1 and 2 were 28 +/- 1.5 minutes (range 14 to 45 min) and 26 +/- 1.6 minutes (range 10 to 55 min), respectively (NS). The differences between these two doses in onset of, and recovery from, block were not found to be statistically significant. The results, however, excluded 5% of the higher dose group and 31% of the lower dose group who did not achieve 95% suppression of twitch. Time to maximal suppression of neuromuscular blockade, however, was not statistically significant for the 85 patients with a time of 270 +/- 28 seconds (range 91 to 605 sec) with a mean maximal suppression of 98.7% in Group 1 and 313 +/- 25 seconds (range 91 to 899 sec) with a mean maximal suppression of 93.1% in Group 2. CONCLUSION: The two doses of rocuronium did not differ statistically in onset or duration. Rocuronium at 600 micrograms/kg offers more reliability than 450 micrograms/kg in achieving adequate muscle relaxation, and the lower dose may result in a significantly large number of patients who may have inadequate intubating conditions.     

Clindamycin enhances a nondepolarizing neuromuscular blockade

Neuromuscular blockades induced by clindamycin alone and with d-tubocurarine or pancuronium were examined in the in-vitro guinea pig lumbrical muscle-nerve preparation. Clindamycin, 80-240 mug/ml, initially increased twitch tension. With higher concentrations (180-240 mug/ml) twitch tension subsequently decreased. With 15 to 20 per cent depression of twitch tension by clindamycin, neostigmine (5-20 ng/ml) or calcium (81 mug/ml) slightly but not completely antagonized the blockade. Clindamycin, 40 mug/ml, a dose that did not depress twitch tension, potentiated d-tubocurarine- or pancuronium-induced neuromuscular bloackade. Plasma concentrations of clindamycin of 10-40 mug/ml were recommended for treating serious infections. The authors conclude that the administration of clindamycin may augment nondepolarizing blockade in man, and antagonism by neostigmine and calcium may be incomplete.     

Evidence for regulation of the NADH peroxidase gene (npr) from Enterococcus faecalis by OxyR

To evaluate residual effects of inhalational anesthetics after reversal of neuromuscular blocking agent, neuromuscular function was monitored after halothane or sevoflurane anesthesia in thirty-seven patients (ASA physical status I or II) for elective surgery after obtaining informed consent. Electromyograph of the adductor pollicis muscle in response to train of four (TOF) stimulation was monitored throughout the study. The first twitch of TOF (T1; % of its control) and the ratio of the fourth twitch to the first twitch of TOF (T4/T1; TR) were recorded at 0, 2, 5, 10, and 15 min after reversal. The patients were divided into five groups; 1) the fentanyl group (n = 7) received fentanyl/N2O; 2) in the halothane stop group (n = 6), halothane was discontinued at least fifteen minutes before neostigmine administration; 3) in the halothane stable group (n = 7), 0.7% halothane was maintained until fifteen minutes after neostigmine; 4) in the sevoflurane stop group (n = 12), sevoflurane was discontinued fifteen minutes before the reversal; 5) in the sevoflurane stable group (n = 5), 3% sevoflurane was maintained until fifteen minutes after the reversal. Anesthesia was induced by thiopental 4 mg.kg-1 and suxamethonium 1 mg.kg-1 and the patients were intubated. After initial dose of vecuronium 0.1 mg.kg-1, the additional dose of 0.02 mg.kg-1 was administered to maintain T1 under 10% of the control value. At the end of the surgery atropine 0.015 mg.kg-1 and neostigmine 0.04 mg.kg-1 were administered to reverse vecuronium when T1 had recovered to 25% of its control. Halothane groups did not differ from fentanyl group. Recovery of T1 at 15 min was suppressed after discontinuation of sevoflurane (86.0 +/- 8.2%) in comparison with fentanyl (97.0 +/- 8.3%). Both T1 (75.4 +/- 12.2%) and TR (68.0 +/- 12.6%) at 15 min after the reversal during 3% sevoflurane inhalation were below those of the stable group. We conclude that the residual sevofulrane after discontinuation of inhalation may impair the neuromuscular transmission after the reversal of neuromuscular blockade. Neuromuscular function should be monitored after the end of anesthesia even though the patient is fully awake.     

Neuromuscular blockade with vecuronium and its reversal with edrophonium during total intravenous anesthesia, neuroleptanalgesia and sevoflurane anesthesia

The neuromuscular blocking effect of vecuronium and its reversibility ith edrophonium were studied under total intravenous anesthesia (TIVA) and compared with those under NLA or sevoflurane anesthesia (SA) in 30 surgical patients. The degree of neuromuscular blockade was evaluated by acceleration of thumb adduction in response to supramaximal stimulation of the ulnar nerve using Accelograph (Biometer). TIVA was induced with droperidol 0.25 mg.kg-1, fentanyl 2-4 micrograms.kg-1 and ketamine 2 mg.kg-1, and maintained with continuous infusion of ketamine 2 mg.kg-1.h-1 with 30-35% O2 in air. NLA was induced with droperidol 0.25 mg.kg-1 and fentanyl 5-10 micrograms.kg-1 and maintained with 66% nitrous oxide in oxygen. SA was induced with thiamylal 5 mg.kg-1 i.v. and maintained with 66% nitrous oxide in oxygen supplemented with sevoflurane (1 MAC). A single bolus intravenous injection of vecuronium 0.1 mg.kg-1 was used for paralysis and reversed with edrophonium 0.75 mg.kg-1 followed by atropine 0.015 mg.kg-1 when the TOF ratio returned to 25%. The times required from administration of vecuronium to completion of maximal block with TIVA, NLA and SA were 196.5 +/- 52.2 sec, 182.5 +/- 47.6 sec and 166.0 +/- 69.0 sec, respectively. There was no significant difference among them. The times from completion of maximal block to 25% recovery of the twitch height in TIVA and NLA were 39.5 +/- 11.0 min and 37.4 +/- 5.8 min without significant difference. Those values, however, were significantly shorter than 64.5 +/- 35.2 min of SA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Toxicodynamic analysis of cardiac effects induced by four cholinesterase inhibitors in rats

The cardiac effect of edrophonium (2-20 mumol kg-1), pyridostigmine (0.5-5 mumol kg-1), neostigmine (0.05-0.5 mumol kg-1) and ambenonium (0.02-0.3 mumol kg-1) was investigated after intravenous administration to rats. For pyridostigmine and neostigmine, the heart rate decreased in a dose-dependent manner, and then gradually recovered to the basal level at about 10 min. Rapid decrease of heart rate was observed after edrophonium and ambenonium administration, and rapid recovery to the basal level within 1 min. For ambenonium, a dose-dependent tachycardiac response was observed. The time-course of heart rate change was analysed by the effect-compartment model. Significant correlation was observed between bradycardiac EC50 values obtained by effect-compartment model analysis and inhibitory constant (Ki) to acetylcholinesterase in-vitro, suggesting that the bradycardiac response was induced by inhibition of this enzyme and following elevation of acetylcholine concentration in the synaptic elect. On the other hand, the tachycardiac EC50 values of edrophonium and ambenonium based on the effect-compartment model analysis were similar to dissociation constants (Kd) of these drugs to muscarinic receptors in-vitro, suggesting that the tachycardiac activity of these drugs may be associated with antagonistic activity to postsynaptic muscarinic receptors. We conclude that, clinically, edrophonium and ambenonium are safer drugs than pyridostigmine and neostigmine, at least as regards muscarinic side-effects, including bradycardia.     

Survey on the pharmacodynamics of the new antipsychotic risperidone

This review reports on the pharmacodynamics of the new antipsychotic risperidone. The primary action of risperidone is serotonin 5-HT2 receptor blockade as shown by displacement of radioligand binding (Ki: 0.16 nM), activity on isolated tissues (EC50: 0.5 nM), and antagonism of peripherally (ED50: 0.0011 mg/kg) and centrally (ED50: 0.014 mg/kg) acting 5-HT2 receptor agonists in rats. Risperidone is at least as potent as the specific 5-HT2 receptor antagonist ritanserin in these tests. Risperidone is also a potent dopamine D2 receptor antagonist as indicated by displacement of radioligand binding (Ki: 1.4 nM), activity in isolated striatal slices (IC50: 0.89 nM), and antagonism of peripherally (ED50: 0.0057 mg/kg in dogs) and centrally acting D2 receptor agonists (ED50: 0.056-0.15 mg/kg in rats). Risperidone shows all effects common to D2 antagonists, including enhancement of prolactin release. However, some central effects such as catalepsy and blockade of motor activity occur at high doses only. Risperidone is 4-10 times less potent than haloperidol as a central D2 antagonist in rats and it differs from haloperidol by the following characteristics: predominant 5-HT2 antagonism; LSD antagonism; effects on sleep; smooth dose-response curves for D2 antagonism; synergism of combined 5-HT2/D2 antagonism; pronounced effects on amphetamine-induced oxygen consumption; increased social interaction; and pronounced effects on dopamine (DA) turnover. Risperidone displays similar activity at pre- and postsynaptic D2 receptors and at D2 receptors from various rat brain regions. The binding affinity for D4 and D3 receptors is 5 and 9 times weaker, respectively, than for D2 receptors; interaction with D1 receptors occurs only at very high concentrations. The pharmacological profile of risperidone includes interaction with histamine H1 and alpha-adrenergic receptors but the compound is devoid of significant interaction with cholinergic and a variety of other types of receptors. Risperidone has excellent oral activity, a rapid onset, and a 24-h duration of action. Its major metabolite, 9-hydroxyrisperidone, closely mimics risperidone in pharmacodynamics. Risperidone can be characterized as a potent D2 antagonist with predominant 5HT2 antagonistic activity and optimal pharmacokinetic properties.     

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) micrograms.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) micrograms.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.