Interaction of magnesium sulphate with vecuronium-induced neuromuscular blockt

We have investigated the interaction between magnesium sulphate 40 mg kg−1 i.v. and vecuronium. First, we determined the effect of pretreatment with magnesium on the potency of vecuronium using a single bolus dose-response technique. In addition, we compared the time course of vecuronium-induced neuromuscular block (vecuronium 100 μg kg−1) with and without magnesium pretreatment. For both parts, neuromuscular block was assessed by electromyography. In addition, the effect of magnesium pretreatment on vecuronium-induced neuromuscular block was investigated in the context of rapid sequence induction of anaesthesia. We found that the neuromuscular potency of vecuronium was increased by pretreatment with magnesium sul phate. The ED50 and ED90 of vecuronium with MgSO4 were 25% lower than without MgSO4 (ED50 21.3 vs 26.9 μg kg−1 ED90 34.2 vs 45.7 μg kg−1 P < 0.05 for both). Mean onset time was 147.3 (SD 22.2) s in the MgSO4 group vs 297.3 (122) s for controls (P < 0.05). Clinical duration was prolonged (MgSO4-vecuronium 43.3 (9) min vs 25.2 (5.1) min for controls; P < 0.05). This was also true for the recovery index (20.1 (6.6) mm vs 10.6 (3.4) min; P < 0.05) and duration to 75% recovery (63.4 (9.9) min vs 35.8 (6.9) min; < 0.05). In the context of rapid sequence induction, pretreatment with MgSO4 improved the intubating score of vecuronium compared with vecuronium without MgSO4 reach ing the same quality as that with suxamethonium 1 mg kg−1. We conclude that magnesium pretreat ment increased the neuromuscular potency of vecuronium, in addition to modifying the time course of its neuromuscular bloc

Concentration of rocuronium in cerebrospinal fluid of patients undergoing cerebral aneurysm clipping†

Background. This study assessed the concentration of rocuronium in the cerebrospinal fluid (CSF) of patients undergoing cerebral aneurysm clipping, and investigated whether the mode of administration (single bolus vs continuous infusion) influenced the CSF concentration. Methods. Twenty patients with subarachnoid haemorrhage were randomly allocated to receive a bolus dose (bolus group), or a bolus followed by a continuous infusion of rocuronium (infusion group) (n=10 for each group). Arterial blood and ventricular CSF were sampled 2 h after the rocuronium bolus. Samples were analysed by liquid chromatography electrospray ionization‐tandem mass spectrometry. Results. Rocuronium could be detected in all the CSF samples. The mean (range) CSF concentration was 2.2 (0.9-4.6) ng ml-1 in the bolus group and 12.4 (2.4-34.6) ng ml-1 in the infusion group; P<0.01. Conclusions. This study demonstrated that rocuronium, normally not considered to cross the blood-brain barrier, is regularly found in the CSF of patients undergoing cerebral clipping; continuous infusion of the drug led to higher plasma and CSF concentrations than after a single bolus dose. Br J Anaesth 2004; 92: 419-2

Dermal reaction and bigeminal premature ventricular contractions due to neostigmine: a case report

<p>Abstract</p> <p>Introduction</p> <p>Neostigmine is a frequently used acetylcholinesterase inhibitor administered to reverse muscular relaxation caused by nondepolarizing neuromuscular relaxants in patients recovering from general anesthesia. Severe allergic reactions and urticaria are rarely reported following the use of neostigmine bromide, and never with methylsulfate-containing drugs. In this case, bigeminal premature ventricular contractions added to urticaria provides a warning about the possibility of a life-threatening situation.</p> <p>Case presentation</p> <p>We report the case of a 23-year-old Persian woman who presented with bigeminal premature ventricular contractions along with urticarial lesions on her arm and trunk as soon as she was administered neostigmine methylsulfate after undergoing a laparoscopy for ectopic pregnancy.</p> <p>Conclusion</p> <p>This case report could be of value not only for anesthesiologists who routinely use neostigmine but also for others who administer the pharmaceutical preparation in other situations. The report presents a rare case of drug reaction following neostigmine use. As a result, one should consider any drug a probable cause of drug reaction. The preparation of resuscitative facilities, therefore, is necessary prior to the prescription of the medication.</p

Effect of nitrous oxide on cisatracurium infusion demands: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Recent studies have questioned our previous understanding on the effect of nitrous oxide on muscle relaxants, since nitrous oxide has been shown to potentiate the action of bolus doses of mivacurium, rocuronium and vecuronium. This study was aimed to investigate the possible effect of nitrous oxide on the infusion requirements of cisatracurium.</p> <p>Methods</p> <p>70 ASA physical status I-III patients aged 18-75 years were enrolled in this randomized trial. The patients were undergoing elective surgery requiring general anesthesia with a duration of at least 90 minutes. Patients were randomized to receive propofol and remifentanil by target controlled infusion in combination with either a mixture of oxygen and nitrous oxide (Nitrous oxide/TIVA group) or oxygen in air (Air/TIVA group). A 0.1 mg/kg initial bolus of cisatracurium was administered before tracheal intubation, followed by a closed-loop computer controlled infusion of cisatracurium to produce and maintain a 90% neuromuscular block. Cumulative dose requirements of cisatracurium during the 90-min study period after bolus administration were measured and the asymptotic steady state rate of infusion to produce a constant 90% block was determined by applying nonlinear curve fitting to the data on the cumulative dose requirement during the study period.</p> <p>Results</p> <p>Controller performance, i.e. the ability of the controller to maintain neuromuscular block constant at the setpoint and patient characteristics were similar in both groups. The administration of nitrous oxide did not affect cisatracurium infusion requirements. The mean steady-state rates of infusion were 0.072 +/- 0.018 and 0.066 +/- 0.017 mg * kg-1 * h-1 in Air/TIVA and Nitrous oxide/TIVA groups, respectively.</p> <p>Conclusions</p> <p>Nitrous oxide does not affect the infusion requirements of cisatracurium.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT01152905; European Clinical Trials Database at <url>http://eudract.emea.eu.int/2006-006037-41</url>.</p

The impact of deep versus standard neuromuscular block on intraoperative safety during laparoscopic surgery: an international multicenter randomized controlled double-blind strategy trial - EURO-RELAX TRIAL

Background: Muscle relaxants are routinely used during anesthesia to facilitate endotracheal intubation and to optimize surgical conditions. However, controversy remains about the required depth of neuromuscular block (NMB) needed for optimal surgical working conditions and how this relates to other outcomes. For instance, a deep neuromuscular block yields superior surgical working conditions compared to a standard NMB in laparoscopic surgery, however, a robust association to other (safety) outcomes has not yet been established.Methods: Trial design: an international multicenter randomized controlled double-blind strategy trial. Trial population: 922 patients planned for elective, laparoscopic or robotic, abdominal surgery. Intervention: Patients will be randomized to a deep NMB (post-tetanic count 1-2 twitches) or standard care (single-dose muscle relaxant administration at induction and repeated only if warranted by surgical team). Main trial endpoints: Primary endpoint is the difference in incidence of intraoperative adverse events during laparoscopic surgery graded according to ClassIntra (R) classification (i.e., ClassIntra (R) grade >= 2) between both groups. Secondary endpoints include the surgical working conditions, 30-day postoperative complications, and patients' quality of recovery.Discussion: This trial was designed to analyze the effect of deep neuromuscular block compared to standard neuromuscular block on intra- and postoperative adverse events in patients undergoing laparoscopic surgery.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

Systemic versus localized coagulation activation contributing to organ failure in critically ill patients

In the pathogenesis of sepsis, inflammation and coagulation play a pivotal role. Increasing evidence points to an extensive cross-talk between these two systems, whereby inflammation not only leads to activation of coagulation but coagulation also considerably affects inflammatory activity. The intricate relationship between inflammation and coagulation may not only be relevant for vascular atherothrombotic disease in general but has in certain clinical settings considerable consequences, for example in the pathogenesis of microvascular failure and subsequent multiple organ failure, as a result of severe infection and the associated systemic inflammatory response. Molecular pathways that contribute to inflammation-induced activation of coagulation have been precisely identified. Pro-inflammatory cytokines and other mediators are capable of activating the coagulation system and downregulating important physiological anticoagulant pathways. Activation of the coagulation system and ensuing thrombin generation is dependent on an interleukin-6-induced expression of tissue factor on activated mononuclear cells and endothelial cells and is insufficiently counteracted by physiological anticoagulant mechanisms and endogenous fibrinolysis. Interestingly, apart from the overall systemic responses, a differential local response in various vascular beds related to specific organs may occur

Magnesium sulphate enhances residual neuromuscular block induced by vecuronium

Magnesium sulphate (MgSO4) is currently used for haemodynamic control during anaesthesia and the early postoperative period. We have investigated the effect of this treatment on residual neuromuscular block after administration of vecuronium. Twenty adult patients were allocated randomly to one of two groups to receive MgSO4 60 mg kg-1 either at recovery from vecuronium block to a train-of-four (TOF) ratio of 0.7, or 1 h after recovery to a TOF ratio of 0.7. Neuromuscular transmission was monitored using electromyography and TOF stimulation. MgSO4 caused rapid and profound recurarization in all 20 patients. MgSO4 decreased the amount of acetylcholine released at the motor nerve terminal and thus may lead to recurarization in patients previously exposed to neuromuscular blocking agent

Omitting antagonism of neuromuscular block: effect on postoperative nausea and vomiting and risk of residual paralysis. A systematic review

We have estimated the effect of omitting antagonism of neuromuscular block on postoperative nausea and vomiting. A systematic search (MEDLINE, EMBASE, Biological Abstracts, Cochrane library, reference lists and hand searching; no language restriction, up to March 1998) was performed for relevant randomized controlled trials. In eight studies (1134 patients), antagonism with neostigmine or edrophonium was compared with spontaneous recovery after general anesthesia with pancuronium, vecuronium, mivacurium or tubocurarine. On combining neostigmine data, there was no evidence of an antiemetic effect when it was omitted. However, the highest incidence of emesis with neostigmine 1.5 mg was lower than the lowest incidence of emesis with 2.5 mg. Numbers-needed-to-treat to prevent emesis by omitting neostigmine compared with using it were consistently negative with 1.5 mg, and consistently positive (3-6) with 2.5 mg. There was a lack of evidence for edrophonium. In two studies, three patients with spontaneous recovery after mivacurium or vecuronium needed rescue anticholinesterase drugs because of clinically relevant muscle weakness (number-needed-to-harm, 30). Omitting neostigmine may have a clinically relevant antiemetic effect when high doses are used. Omitting antagonism, however, introduces a non-negligent risk of residual paralysis even with short-acting neuromuscular blocking agent