Walter Buzello

Muskelrelaxanzien Neue Substanzen und neuromuskuläres Monitoring

ZusammenfassungEinführung: In einer Übersicht werden die aktuellen Entwicklungen in der Messung der neuromuskulären Blockade sowie die neuen Muskelrelaxanzien dargestellt.nn Muskelrelaxanzien: Von den seit 1995/96 in Deutschland neu zugelassenen Muskelrelaxanzien Rocuronium, Cisatracurium und Mivacurium, bietet Rocuronium die kürzeste Anschlagszeit bei ansonsten gleichem neuromuskulär blockierenden Wirkprofil wie Vecuronium. Die 2fache ED95 führt innerhalb von 60 bis 90u2005s zu guten bis sehr guten Intubationsbedingungen. Cisatracurium ist eines der zehn Isomere von Atracurium mit etwa der fünffachen neuromuskulär blockierenden Potenz. Unter Bewahrung der atracuriumtypischen mittellangen Wirkdauer und der Metabolisierung durch den Hofmann-Abbau, zeichnet sich Cisatracurium durch eine sehr viel geringere unspezifische Histaminfreisetzung aus. Mivacurium ist ein kurzwirkendes Benzylisochinolin-Muskelrelaxans, das einer raschen enzymatischen Inaktivierung durch die Plasmacholinesterase unterliegt. Es füllt die pharmakodynamische Lücke zwischen Succinylcholin und den mittellang wirkenden Muskelrelaxanzien, ohne jedoch den kurzen Wirkungseintritt von Rocuronium oder Succinylcholin zu erreichen. Nachteilig sind die mögliche Histaminfreisetzung und die Wirkungsverlängerung bei verminderter bzw. atypischer Plasmacholinesterase.AbstractIntroduction: Recent developments in both the quantitative evaluation of neuromuscular blockade and new muscle relaxants are reviewed. With respect to nerve stimulation, neuromuscular recording, and definition of parameters, the results of the 1994 Copenhagen International Consensus Conference are highlighted. Future clinical studies should adhere to these standards.nn Muscle relaxants: Rocuronium, cisatracurium, and mivacurium are new muscle relaxants that were released for clinical use in 1995/1996. Of these, rocuronium has the shortest time of onset, whereas its recovery characteristics closely resemble those of vecuronium. Rocuronium is five times less potent than vecuronium. Twice the ED95 of rocuronium provides good or excellent intubating conditions within 60 to 90u2005s. Slight vagolytic effects were reported following injection of 0.6u2005mg/kg rocuronium, while histamine release was not observed. Cisatracurium is one of the ten steroisomers of atracurium. It is five times as potent as the chiral mixture while having a similar pharmacodynamic and -kinetic profile. Up to eight times the ED95 did not cause significant histamine release or clinically relevant cardiovascular effects. Mivacurium is a short-acting nondepolarizing benzylisoquinoline muscle relaxant that undergoes rapid breakdown by plasma cholinesterase (PChE). Its duration of action is about one-half as long as that of equipotent doses of atracurium and vecuronium and three times as long as succinylcholine. Mivacurium has a moderate histamine-releasing potential. In patients with atypical or reduced PChE activity, the duration of action of mivacurium is prolonged.

Muscle relaxants. New substances and neuromuscular monitoring

ZusammenfassungEinführung: In einer Übersicht werden die aktuellen Entwicklungen in der Messung der neuromuskulären Blockade sowie die neuen Muskelrelaxanzien dargestellt.nn Muskelrelaxanzien: Von den seit 1995/96 in Deutschland neu zugelassenen Muskelrelaxanzien Rocuronium, Cisatracurium und Mivacurium, bietet Rocuronium die kürzeste Anschlagszeit bei ansonsten gleichem neuromuskulär blockierenden Wirkprofil wie Vecuronium. Die 2fache ED95 führt innerhalb von 60 bis 90u2005s zu guten bis sehr guten Intubationsbedingungen. Cisatracurium ist eines der zehn Isomere von Atracurium mit etwa der fünffachen neuromuskulär blockierenden Potenz. Unter Bewahrung der atracuriumtypischen mittellangen Wirkdauer und der Metabolisierung durch den Hofmann-Abbau, zeichnet sich Cisatracurium durch eine sehr viel geringere unspezifische Histaminfreisetzung aus. Mivacurium ist ein kurzwirkendes Benzylisochinolin-Muskelrelaxans, das einer raschen enzymatischen Inaktivierung durch die Plasmacholinesterase unterliegt. Es füllt die pharmakodynamische Lücke zwischen Succinylcholin und den mittellang wirkenden Muskelrelaxanzien, ohne jedoch den kurzen Wirkungseintritt von Rocuronium oder Succinylcholin zu erreichen. Nachteilig sind die mögliche Histaminfreisetzung und die Wirkungsverlängerung bei verminderter bzw. atypischer Plasmacholinesterase.AbstractIntroduction: Recent developments in both the quantitative evaluation of neuromuscular blockade and new muscle relaxants are reviewed. With respect to nerve stimulation, neuromuscular recording, and definition of parameters, the results of the 1994 Copenhagen International Consensus Conference are highlighted. Future clinical studies should adhere to these standards.nn Muscle relaxants: Rocuronium, cisatracurium, and mivacurium are new muscle relaxants that were released for clinical use in 1995/1996. Of these, rocuronium has the shortest time of onset, whereas its recovery characteristics closely resemble those of vecuronium. Rocuronium is five times less potent than vecuronium. Twice the ED95 of rocuronium provides good or excellent intubating conditions within 60 to 90u2005s. Slight vagolytic effects were reported following injection of 0.6u2005mg/kg rocuronium, while histamine release was not observed. Cisatracurium is one of the ten steroisomers of atracurium. It is five times as potent as the chiral mixture while having a similar pharmacodynamic and -kinetic profile. Up to eight times the ED95 did not cause significant histamine release or clinically relevant cardiovascular effects. Mivacurium is a short-acting nondepolarizing benzylisoquinoline muscle relaxant that undergoes rapid breakdown by plasma cholinesterase (PChE). Its duration of action is about one-half as long as that of equipotent doses of atracurium and vecuronium and three times as long as succinylcholine. Mivacurium has a moderate histamine-releasing potential. In patients with atypical or reduced PChE activity, the duration of action of mivacurium is prolonged.

Variability of pipecuronium neuromuscular blockade

The dose‐response relationship and the variability of the time variables in pipecuronium neuromuscular blockade were studied in 29 patients (ASA physical status 3) during halothane anaesthesia. The ED95 (twitch tension) was determined in 9 patients using the cumulative dose response technique. Another 20 patients received the resulting ED95 as a single bolus. The mean ED95 was 35 μg‐kg‐1 (95% confidence interval: 29–41 μg.kg‐1). Following bolus injection of 1. ED95, an 80–100% twitch depression was achieved within 4.6±1.3 min (mean ± s.d.). The duration from end of injection of pipecuronium to 25% twitch recovery, the time from 25% to 75% twitch recovery, and the time from 25% twitch recovery to the train‐of‐four ratio (TOF) returning to 0.7 was 35 ± 14, 37 ± 26, and 63 ± 27 min, respectively. The time from end of injection to TOF = 0.7 varied within a 2‐h range (54–160 min). Thus, the time variables in pipecuronium neuromuscular blockade were as poorly predictable as those reported in the literature on pancuronium, alcuronium and doxacurium.

Lactated Ringer’s Solution versus Hydroxyethyl Starch for Volume Replacement in Autologous Blood Donors with Cardiovascular Disease: A Controlled, Randomized Trial

Background and Objectives: The study was designed to evaluate whether volume replacement following blood donation can prevent arterial hypotension in autologous blood donors with cardiovascular disease. Materials and Methods: One hundred nineteen autologous blood donors with known cardiovascular disease were randomly allocated to receive, following withdrawal of 500 ml of blood, either no infusion (control group) or a 25 ml/min intravenous infusion of either 1,500 ml of lactated Ringer’s solution (LRS) or 500 ml of 6% hydroxyethyl starch (HES). Starting before phlebotomy, arterial blood pressure was measured oscillometrically every 5 min until 90 min after donation. Results: Group means showed little difference between the groups in blood pressure throughout the monitoring period. The proportion of patients who at least once had a ≥ 20% decrease from baseline in systolic blood pressure was 3–5 times greater in the control group than in the LRS and the HES group (50 vs. 10 and 15%, respectively; p < 0.001 on χ2 analysis for a 2 × 3 table). Systolic hypertensive episodes (≥ 20% increase over baseline) were observed more frequently in the LRS group than in the control and the HES group (41 vs. 10 and 18%, respectively; p = 0.003). Conclusion: Both LRS and HES, administered at a volume ratio to blood loss of 3:1 and 1:1, respectively, significantly reduced the incidence of systolic hypotensive episodes in autologous blood donors with cardiovascular disease. LRS at a 3:1 volume ratio to blood loss was associated with a high rate of systolic hypertension.

Mivacurium chloride--a comparative profile.

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

Muskelrelaxanzien Neue Substanzen und neuromuskuläres Monitoring (Muscle relaxants)

ZusammenfassungEinführung: In einer Übersicht werden die aktuellen Entwicklungen in der Messung der neuromuskulären Blockade sowie die neuen Muskelrelaxanzien dargestellt.nn Muskelrelaxanzien: Von den seit 1995/96 in Deutschland neu zugelassenen Muskelrelaxanzien Rocuronium, Cisatracurium und Mivacurium, bietet Rocuronium die kürzeste Anschlagszeit bei ansonsten gleichem neuromuskulär blockierenden Wirkprofil wie Vecuronium. Die 2fache ED95 führt innerhalb von 60 bis 90u2005s zu guten bis sehr guten Intubationsbedingungen. Cisatracurium ist eines der zehn Isomere von Atracurium mit etwa der fünffachen neuromuskulär blockierenden Potenz. Unter Bewahrung der atracuriumtypischen mittellangen Wirkdauer und der Metabolisierung durch den Hofmann-Abbau, zeichnet sich Cisatracurium durch eine sehr viel geringere unspezifische Histaminfreisetzung aus. Mivacurium ist ein kurzwirkendes Benzylisochinolin-Muskelrelaxans, das einer raschen enzymatischen Inaktivierung durch die Plasmacholinesterase unterliegt. Es füllt die pharmakodynamische Lücke zwischen Succinylcholin und den mittellang wirkenden Muskelrelaxanzien, ohne jedoch den kurzen Wirkungseintritt von Rocuronium oder Succinylcholin zu erreichen. Nachteilig sind die mögliche Histaminfreisetzung und die Wirkungsverlängerung bei verminderter bzw. atypischer Plasmacholinesterase.AbstractIntroduction: Recent developments in both the quantitative evaluation of neuromuscular blockade and new muscle relaxants are reviewed. With respect to nerve stimulation, neuromuscular recording, and definition of parameters, the results of the 1994 Copenhagen International Consensus Conference are highlighted. Future clinical studies should adhere to these standards.nn Muscle relaxants: Rocuronium, cisatracurium, and mivacurium are new muscle relaxants that were released for clinical use in 1995/1996. Of these, rocuronium has the shortest time of onset, whereas its recovery characteristics closely resemble those of vecuronium. Rocuronium is five times less potent than vecuronium. Twice the ED95 of rocuronium provides good or excellent intubating conditions within 60 to 90u2005s. Slight vagolytic effects were reported following injection of 0.6u2005mg/kg rocuronium, while histamine release was not observed. Cisatracurium is one of the ten steroisomers of atracurium. It is five times as potent as the chiral mixture while having a similar pharmacodynamic and -kinetic profile. Up to eight times the ED95 did not cause significant histamine release or clinically relevant cardiovascular effects. Mivacurium is a short-acting nondepolarizing benzylisoquinoline muscle relaxant that undergoes rapid breakdown by plasma cholinesterase (PChE). Its duration of action is about one-half as long as that of equipotent doses of atracurium and vecuronium and three times as long as succinylcholine. Mivacurium has a moderate histamine-releasing potential. In patients with atypical or reduced PChE activity, the duration of action of mivacurium is prolonged.

Disposition of Mivacurium Isomers in Patients Undergoing Hypothermic Cardiopulmonary Bypass

The muscle relaxant mivacurium (MIV), is made up of 3 isomers: trans-trans (tt; 55%), cis-trans (ct; 36%), and cis-cis (cc; 6%). Plasma cholinesterase (ChE) converts these compounds into 2 alcohol and 2 acid isomers. Hypothermic cardiopulmonary bypass (CPB) may be expected to impair these metabolic pathways by both reducing ChE activity and a direct effect of hypothermia. The present study was designed to analyse the disposition of the MIV isomers before, during and after CPB in the clinical setting.