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Indian Journal of Anaesthesia Mar 2010This case report highlights the anaesthetic management of a patient who had residual muscle paralysis following neuromuscular blockade, which was attributed to...
This case report highlights the anaesthetic management of a patient who had residual muscle paralysis following neuromuscular blockade, which was attributed to hypothermia and corrected by administration of amino acid solution. The various causes of residual neuromuscular blockade should be considered when treating such a patient. Amino acid infusion has been found to hasten the recovery from neuromuscular block due to vecuronium bromide aggravated by hypothermia.
PubMed: 20661359
DOI: 10.4103/0019-5049.63649 -
Indian Journal of Anaesthesia Mar 2010This randomised, placebo-controlled, double-blind study was designed to assess the effect of intravenous clonidine and magnesium sulphate on intraoperative...
This randomised, placebo-controlled, double-blind study was designed to assess the effect of intravenous clonidine and magnesium sulphate on intraoperative haemodynamics, anaesthetic consumption and postoperative recovery. Seventy five patients undergoing elective upper limb orthopaedic surgery were randomised into three groups. Group C received clonidine 3 mug/kg as a bolus before induction and 1mug/kg/hour by infusion intraopertively. Group M received magnesium sulphate 30 mg/kg as a bolus before induction and 10 mg/kg/hour by infusion. Group P received same volume of isotonic saline. Anaesthesia was induced and maintained with fentanyl citrate and propofol. Muscular relaxation was achieved by vecuronium bromide. Induction time, recovery time and consumption of propofol as well as fentanyl citrate were recorded. Induction of anaesthesia was rapid with both clonidine and magnesium sulphate. Time of bispectral index (BIS) to reach 60 was significantly lower in Group C and Group M (P < 0.0001). Requirements of propofol and fentanyl were significantly less in Group C and Group M (P < 0.001). Postoperative recovery was slower in Group M compared with other two groups (P < 0.001). Perioperative use of both clonidine and magnesium sulphate significantly reduced the consumption of propofol and fentanyl citrate. Magnesium sulphate caused a delayed recovery.
PubMed: 20661352
DOI: 10.4103/0019-5049.63659 -
Indian Journal of Anaesthesia Jun 2009Hypothermia is a common occurrence under anaesthesia and may prolong the duration of action of neuromuscular blockade. By limiting fall in temperature, an infusion of...
Hypothermia is a common occurrence under anaesthesia and may prolong the duration of action of neuromuscular blockade. By limiting fall in temperature, an infusion of amino acid enriched solution may speed the recovery from neuromuscular blockade. We studied 60 ASA Grade - I/II patients of aged between 20 to 60 years scheduled for elective surgery under general anaesthesia. The patients were randomly divided into four groups to receive amino acid infusion with vecuronium bromide AV, normal saline with vecuronium bromide(CV), amino acid with atracurium besylate(A-At) and normal saline with atracurium besylate(C-At). Although there was a significantly lesser decrease in the core temperature from the baseline in all the patients receiving amino acid infusion (p<0.05), it significantly reduced the time to 25% recovery from the time of injection of vecuronium only. (60.59 +/- 11.39 in CV vs 51 +/- 14.72 min in AV) (P < 0.05), and not for atracurium.
PubMed: 20640140
DOI: No ID Found -
Fukushima Journal of Medical Science Dec 2009We investigated the differences between males and females in the reversal effect of neostigmine on neuromuscular blockade. Thirty male and 30 female patients undergoing... (Comparative Study)
Comparative Study
We investigated the differences between males and females in the reversal effect of neostigmine on neuromuscular blockade. Thirty male and 30 female patients undergoing elective general anesthesia were studied. Vecuronium was given in all patients anesthetized with nitrous oxide, oxygen, and sevoflurane. After the surgical procedure, when T1 (1st response in train-of-four (TOF))/control returned to 0.25, neostigmine 40 microg/kg in combination with atropine 20 microg/kg was given to antagonize residual neuromuscular blockade. Three, six, nine, 12, and 15 minutes after neostigmine reversal, T1/control or TOF ratio (T4/T1) did not significantly differ between the sexes. Also, 15 minutes after neostigmine administration, the number of patients in whom recovery from neuromuscular blockade was sufficient to guarantee good respiratory function, i.e., TOF ratio > 0.74, did not significantly differ between the sexes. In contrast, 15 minutes after neostigmine, the number of patients in whom recovery from neuromuscular blockade was adequate to ensure satisfactory recovery from neuromuscular blockade including the return of the faculty of sight, i.e., TOF ratio > 0.9, was significantly less in the males than in females (6 vs. 14, P = 0.028). In conclusion, 15 min after neostigmine, TOF ratio less often returns to a value of more than 0.9 in males than in females.
Topics: Adult; Aged; Cholinesterase Inhibitors; Female; Humans; Male; Middle Aged; Neostigmine; Neuromuscular Blockade; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Sex Characteristics; Vecuronium Bromide
PubMed: 20608096
DOI: 10.5387/fms.55.61 -
British Journal of Anaesthesia Sep 2010Postoperative residual curarization (PORC) [train-of-four ratio (T4/T1) <0.9] is associated with increased morbidity and may delay postoperative recovery room (PACU)...
BACKGROUND
Postoperative residual curarization (PORC) [train-of-four ratio (T4/T1) <0.9] is associated with increased morbidity and may delay postoperative recovery room (PACU) discharge. We tested the hypothesis that postoperative T4/T1 <0.9 increases PACU length of stay.
METHODS
At admission to the PACU, neuromuscular transmission was assessed by acceleromyography (stimulation current: 30 mA) in 246 consecutive patients. The potential consequences of PORC-induced increases in PACU length of stay on PACU throughput were estimated by application of a validated queuing model taking into account the rate of PACU admissions and mean length of stay in the joint system of the PACU plus patients recovering in operation theatre waiting for PACU beds.
RESULTS
PACU length of stay was significantly longer in patients with T4/T1 <0.9 (323 min), compared with patients with adequate recovery of neuromuscular transmission (243 min). Age (P=0.021) and diagnosis of T4/T1 <0.9 (P=0.027), but not the type of neuromuscular blocking agent, were independently associated with PACU length of stay. The incidence of T4/T1 <0.9 was higher in patients receiving vecuronium. Delayed discharge significantly increases the chances of patients having to wait to enter the PACU. The presence of PORC is estimated to be associated with significant delays in recovery room admission.
CONCLUSIONS
PORC is associated with a delayed PACU discharge. The magnitude of the effect is clinically significant. In our system, PORC increases the chances of patients having to wait to enter the PACU.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anesthesia Recovery Period; Atracurium; Female; Humans; Length of Stay; Male; Middle Aged; Monitoring, Physiologic; Neuromuscular Blockade; Neuromuscular Blocking Agents; Neuromuscular Junction; Postoperative Period; Prospective Studies; Vecuronium Bromide; Young Adult
PubMed: 20576632
DOI: 10.1093/bja/aeq157 -
British Journal of Anaesthesia Jun 2010Traditionally, the clinical potency of neuromuscular blocking drugs has been measured using linear regression analysis (LRA) after log dose and probit or logit data...
BACKGROUND
Traditionally, the clinical potency of neuromuscular blocking drugs has been measured using linear regression analysis (LRA) after log dose and probit or logit data transformation. However, probit and logit analyses are meant to handle only quantal responses with binomial error distributions, not continuous data such as per cent of maximal response. Some statisticians now consider this approach outmoded and assert that non-linear regression (NLR) is the preferred way to analyse sigmoidal dose-response relationships. We were interested in the degree to which the method of regression analysis alters calculated ED(50) and ED(95) values.
METHODS
We analysed raw data for succinylcholine, rocuronium, rapacuronium, and cisatracurium from previously published studies using both LRA and NLR to determine the ED(50) and ED(95) values and the respective slopes of the dose-response relationships. We also estimated drug potency using the Hill equation (HE) using the slopes obtained from LRA and NLR.
RESULTS
ED(50) values calculated by NLR, LRA, or the HE were interchangeable. LRA resulted in ED(95) values that were 13-18% lower than those determined by NLR. The 95% confidence limits (CL) for the ED(50) did not exceed +/-8% of the estimated value no matter how it was calculated vs +/-20-30% for the ED(95).
CONCLUSIONS
The ED(50) is a very robust parameter. When comparing the potency of neuromuscular blockers, it is this value rather than the ED(95) that should be used. The CL for the ED(95), regardless of how it is calculated, are so wide that this parameter must be viewed, at best, as an approximation.
Topics: Adult; Androstanols; Atracurium; Dose-Response Relationship, Drug; Electric Stimulation; Humans; Nerve Block; Neuromuscular Blocking Agents; Neuromuscular Depolarizing Agents; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Regression Analysis; Rocuronium; Succinylcholine; Vecuronium Bromide
PubMed: 20430764
DOI: 10.1093/bja/aeq094 -
Zhongguo Dang Dai Er Ke Za Zhi =... Mar 2010
Topics: Humans; Infant, Newborn; Male; Neuromuscular Nondepolarizing Agents; Tetanus; Vecuronium Bromide
PubMed: 20350442
DOI: No ID Found -
Acta Pharmacologica Sinica Apr 2010To test the hypothesis that different magnitude of resistance of denervated skeletal muscle to nondepolarizing muscle relaxants (NDMRs) is related to their varying...
AIM
To test the hypothesis that different magnitude of resistance of denervated skeletal muscle to nondepolarizing muscle relaxants (NDMRs) is related to their varying potencies at epsilon-AChR and gamma-AChR.
METHODS
Both innervated and denervated mouse muscle cells, and human embryonic kidney 293 (HEK293) cells expressing epsilon-AChR or gamma-AChR were used. The effects of NDMRs on nAChR were explored using whole-cell patch clamp technique.
RESULTS
NDMRs vecuronium (VEC), atracurium (ATR) and rocuronium (ROC) produced reversible, dose-dependent inhibition on the currents induced by 30 micromol/L acetylcholine both in innervated and denervated skeletal muscle cells. Compared to those obtained in innervated skeletal muscle cells, denervation shifted the concentration-response curves rightward and significantly increased the 50% inhibitory concentration (IC(50)) values (VEC: from 11.2 to 39.2 nmol/L, P<0.01; ATR: from 24.4 to 129.0 nmol/L, P<0.01; ROC: from 37.9 to 101.4 nmol/L, P<0.01). In HEK293 cell expression system, ATR was less potent at gamma-AChR than epsilon-AChR (IC(50) values: 35.9 vs 22.3 nmol/L, P<0.01), VEC was equipotent at both receptor subtypes (IC(50) values: 9.9 vs 10.2 nmol/L, P>0.05), while ROC was more potent at gamma-AChR than epsilon-AChR (IC(50) values: 22.3 vs 33.5 nmol/L, P<0.05).
CONCLUSION
Magnitude differences of resistance to different NDMRs caused by denervation are associated with distinct potencies of NDMRs at nAChR subtypes.
Topics: Acetylcholine; Androstanols; Animals; Atracurium; Cells, Cultured; Humans; Mice; Mice, Inbred BALB C; Muscle Denervation; Muscle Fibers, Skeletal; Muscle, Skeletal; Neuromuscular Nondepolarizing Agents; Patch-Clamp Techniques; Receptors, Nicotinic; Rocuronium; Vecuronium Bromide
PubMed: 20305678
DOI: 10.1038/aps.2010.26 -
Anesthesiology Apr 2010Neuromuscular blocking agents are an integral component of general anesthesia. In addition to their intended pharmacologic target on skeletal muscle nicotinic receptors,...
BACKGROUND
Neuromuscular blocking agents are an integral component of general anesthesia. In addition to their intended pharmacologic target on skeletal muscle nicotinic receptors, undesirable airway effects (i.e., bronchoconstriction) can result from neuromuscular blocking agents' affinity for airway muscarinic receptors. We questioned whether two new members of a bisquaternary nondepolarizing muscle relaxant family, gantacurium and CW002, demonstrated detrimental effects of airway muscarinic receptors using an in vivo model in guinea pig airways.
METHODS
Urethane-anesthetized male guinea pigs were ventilated through a tracheostomy with continuous digital recordings of pulmonary inflation pressure and heart rate. The dose for 95% twitch suppression for gantacurium, CW002, cisatracurium, and rapacuronium was defined in the guinea pig. Transient and reproducible changes in pulmonary inflation pressure and heart rate were recorded after vagal nerve stimulation or intravenous injection of acetylcholine before and after pretreatment with cumulatively increasing concentrations of gantacurium, CW002, cisatracurium or a single concentration of rapacuronium.
RESULTS
The doses for 95% twitch suppression for gantacurium, CW002, cisatracurium, and rapacuronium were 0.064 +/- 0.006, 0.012 +/- 0.0006, 0.10 +/- 0.003, and 0.31 +/- 0.05 mg/kg, respectively. Gantacurium, CW002, and cisatracurium were without effects on baseline pulmonary inflation pressures and were devoid of significant interactions with M2 and M3 muscarinic receptors in vivo.
CONCLUSION
These findings suggest that gantacurium and CW002 are devoid of significant effects at airway muscarinic receptors particularly M3 receptors on bronchial smooth musculature at doses several fold higher than those required for functional muscle paralysis.
Topics: Acetylcholine; Anesthesia; Animals; Atracurium; Dose-Response Relationship, Drug; Drug Interactions; Guinea Pigs; Heart Rate; Isoquinolines; Lung; Male; Muscle Contraction; Muscle, Smooth; Neuromuscular Depolarizing Agents; Receptor, Muscarinic M2; Receptor, Muscarinic M3; Receptors, Muscarinic; Respiratory System; Vagus Nerve; Vecuronium Bromide
PubMed: 20216393
DOI: 10.1097/ALN.0b013e3181d32016 -
BMC Pharmacology Dec 2009Many neuromuscular blockers act as negative allosteric modulators of muscarinic acetylcholine receptors by decreasing affinity and potency of acetylcholine. The...
BACKGROUND
Many neuromuscular blockers act as negative allosteric modulators of muscarinic acetylcholine receptors by decreasing affinity and potency of acetylcholine. The neuromuscular blocker rapacuronium has been shown to have facilitatory effects at muscarinic receptors leading to bronchospasm. We examined the influence of rapacuronium on acetylcholine (ACh) binding to and activation of individual subtypes of muscarinic receptors expressed in Chinese hamster ovary cells to determine its receptor selectivity.
RESULTS
At equilibrium rapacuronium bound to all subtypes of muscarinic receptors with micromolar affinity (2.7-17 microM) and displayed negative cooperativity with both high- and low-affinity ACh binding states. Rapacuronium accelerated [3H]ACh association with and dissociation from odd-numbered receptor subtypes. With respect to [35S]GTPgammaS binding rapacuronium alone behaved as an inverse agonist at all subtypes. Rapacuronium concentration-dependently decreased the potency of ACh-induced [35S]GTPgammaS binding at M2 and M4 receptors. In contrast, 0.1 microM rapacuronium significantly increased ACh potency at M1, M3, and M5 receptors. Kinetic measurements at M3 receptors showed acceleration of the rate of ACh-induced [35S]GTPgammaS binding by rapacuronium.
CONCLUSIONS
Our data demonstrate a novel dichotomy in rapacuronium effects at odd-numbered muscarinic receptors. Rapacuronium accelerates the rate of ACh binding but decreases its affinity under equilibrium conditions. This results in potentiation of receptor activation at low concentrations of rapacuronium (1 microM) but not at high concentrations (10 microM). These observations highlight the relevance and necessity of performing physiological tests under non-equilibrium conditions in evaluating the functional effects of allosteric modulators at muscarinic receptors. They also provide molecular basis for potentiating M3 receptor-mediated bronchoconstriction.
Topics: Acetylcholine; Allosteric Regulation; Allosteric Site; Animals; Binding, Competitive; CHO Cells; Cricetinae; Cricetulus; Female; Guanosine 5'-O-(3-Thiotriphosphate); Muscarinic Agonists; N-Methylscopolamine; Neuromuscular Nondepolarizing Agents; Radioligand Assay; Receptors, Muscarinic; Vecuronium Bromide
PubMed: 20038295
DOI: 10.1186/1471-2210-9-15