Lidocaine combined with magnesium sulfate preserved hemodynamic stability during general anesthesia without prolonging neuromuscular blockade: a randomized, double-blind, controlled trial.

BACKGROUND: Lidocaine and magnesium sulfate have become increasingly utilized in general anesthesia. The present study evaluated the effects of these drugs, isolated or combined, on hemodynamic parameters as well as on the cisatracurium-induced neuromuscular blockade (NMB). METHODS: At a university hospital, 64 patients, ASA physical status I and II, undergoing elective surgery with similar pain stimuli were randomly assigned to four groups. Patients received a bolus of lidocaine and magnesium sulfate before the tracheal intubation and a continuous infusion during the operation as follows: 3 mg.kg- 1 and 3 mg.kg- 1.h- 1 (lidocaine - L group), 40 mg.kg- 1 and 20 mg.kg- 1.h- 1 (magnesium - M group), equal doses of both drugs (magnesium plus lidocaine - ML group), and an equivalent volume of isotonic solution (control - C group). Hemodynamic parameters and neuromuscular blockade features were continuously monitored until spontaneous recovery of the train of four (TOF) ratio (TOFR > 0.9). RESULTS: The magnesium sulfate significantly prolonged all NMB recovery features, without changing the speed of onset of cisatracurium. The addition of lidocaine to Magnesium Sulfate did not influence the cisatracurium neuromuscular blockade. A similar finding was observed when this drug was used alone, with a significantly smaller fluctuation of mean arterial pressure (MAP) and heart rate (HR) measures during anesthesia induction and maintenance. Interestingly, the percentage of patients who achieved a TOFR of 90% without reaching T1-95% was higher in the M and ML groups. Than in the C and L groups. There were no adverse events reported in this study. CONCLUSION: Intravenous lidocaine plays a significant role in the hemodynamic stability of patients under general anesthesia without exerting any additional impact on the NMB, even combined with magnesium sulfate. Aside from prolonging all NMB recovery characteristics without altering the onset speed, magnesium sulfate enhances the TOF recovery rate without T1 recovery. Our findings may aid clinical decisions involving the use of these drugs by encouraging their association in multimodal anesthesia or other therapeutic purposes. TRIAL REGISTRATION: NCT02483611 (registration date: 06-29-2015).

New Drug Developments for Neuromuscular Blockade and Reversal: Gantacurium, CW002, CW011, and Calabadion.

PURPOSE OF REVIEW: The purpose of this chapter is to provide a brief review of the literature on the recent developments in neuromuscular blockade and reversal agents. RECENT FINDINGS: Novel drug development resulted in pharmacological advancements in neuromuscular management and led to a new series of compounds, chlorofumarates, such as gantacurium, CW002, and CW011. These drugs have a fast onset and rapid to intermediate duration of action and can be rapidly reversed by l-cysteine adduction without side effects that are commonly observed with anticholinesterase reversal drugs. Another new advancement is the development of a new class of reversal drugs, the calabadions. These drugs are able to reverse both steroidal and non-steroidal non-depolarizing neuromuscular blocking drugs rapidly. SUMMARY: Recent advancements in neuromuscular blocking agents and reversal drugs have shown promise in improving safety of management of neuromuscular blockade. Preclinical and clinical studies are discussed. However, to date these new drugs are not yet available for clinical use.

Train-of-four recovery precedes twitch recovery during reversal with sugammadex in pediatric patients: A retrospective analysis.

BACKGROUND: After reversal of a rocuronium-induced neuromuscular blockade with sugammadex, the recovery of train-of-four ratio to 0.9 is faster than recovery of first twitch of the train-of-four to 90% in adults. These findings after reversal of neuromuscular blockade with sugammadex have not yet been investigated in pediatric patients. AIMS: The aim of this retrospective analysis was to investigate the relationship of the recovery of first twitch of the train-of-four height and train-of-four ratio after reversal of rocuronium-induced neuromuscular blockade with sugammadex in pediatric patients. METHODS: Patients ASA I-III, aged 2-11 years, and who underwent abdominal and/or perineal surgery were included in the analysis. After extracting the necessary data from the hospital database, the patients were divided into 2 groups based on the dose of sugammadex received: group A: 2 mg.kg-1 for reversal of moderate neuromuscular blockade and group B: 4 mg.kg-1 for reversal of deep neuromuscular blockade. The relationship of the recovery of first twitch of the train-of-four height and train-of-four ratio in these 2 groups were analyzed. RESULTS: Data from 43 pediatric patients aged 2-11 years could be analyzed. The first twitch of the train-of-four height at the recovery of train-of-four ratio to 0.9 in group B was statistically significantly lower compared with group A. This height 3 and 5 minutes after the train-of-four ratio reached 0.9 showed no statistically significant differences between groups. CONCLUSION: The results were in line with the results found in adults and showed that the train-of-four ratio recovered to 0.9 was faster than first twitch of the train-of-four height recovered to the same level.

[Reversal of neuromuscular block with sugammadex in five heart transplant pediatric recipients]. / Reversão do bloqueio neuromuscular com sugamadex em cinco receptores pediátricos de transplante cardíaco.

Heart transplantation is a frequent procedure in the treatment of end-stage cardiac dysfunction. Therefore, these patient populations will also be more frequent exposed to other more common surgical procedures after their transplantation. Anesthesiologist should be aware in their assessment of these patients, especially regarding some specific issues related to patients with a history of heart transplantation, like reversal of neuromuscular block. Several reports described that cholinesterase inhibitors drugs, like neostigmine, may produce a dose-dependent life-threatening bradycardia in heart transplant recipients while other publication described the safe use of neostigmine. Reversal of neuromuscular block with sugammadex is another possibility, but limited data exists in literature. We describe five cases in which successful reversal of neuromuscular block was performed with sugammadex in heart transplant pediatric recipients without sequelae and discuss the reversal of neuromuscular block in this patient population.

The effect of prior tetanic stimulation on train-of-four monitoring in paediatric patients: A randomised open-label controlled trial.

BACKGROUND: In clinical research, neuromuscular monitoring must present a stable response for a period of 2 to 5 min before administration of a neuromuscular blocking agent. The time required to reach this stable response may be shortened by applying a 5-s tetanic stimulus. OBJECTIVES: The aim of this study was to test whether tetanic stimulation interferes with onset and recovery times after a single dose of rocuronium 0.6 mg kg followed by spontaneous recovery. DESIGN: A randomised, open-label, controlled trial. SETTING: A single-centre trial, study period from January 2014 to July 2015. PATIENTS: Fifty children aged 2 to 11 years scheduled for elective paediatric surgery. INTERVENTION: Patients were randomly allocated to receive either tetanic stimulation (group T) or not (group C) before calibration of the neuromuscular monitor. MAIN OUTCOME MEASURES: Onset and recovery times. Initial and final T1 height, time to obtain initial T1 height stability and monitor settings were also analysed. RESULTS: There was no significant difference in mean onset time [(C: 57.5 (± 16.9) vs. T: 58.3 (± 31.2) s; P = 0.917]. Mean times to normalised train-of-four (TOF) ratios of 0.7, 0.8 and 0.9 were significantly shorter in the tetanic stimulation group [C: 40.1 (±7.9) vs. T: 34.8 (±10) min; P = 0.047, C: 43.8 (±9.4) vs. T: 37.4 (±11) min; P = 0.045 and C: 49.9 (±12.2) vs. T: 41.7 (±13.1) min; P = 0.026, respectively]. The mean time required for T1 height stabilisation was similar in the two groups [C: 195.0 (± 203.0) vs. T: 116.0 (± 81.6) s; P = 0.093], but the initial and final T1 height values were significantly lower in the tetanic stimulation group (C: 98.0 vs. T: 82.7%; P < 0.001 and C: 95.3 vs. T: 69.3%; P < 0.001, respectively). CONCLUSION: Tetanic stimulation shortened the mean times to normalised TOF ratios of 0.7, 0.8 and 0.9, but there was no difference in the mean onset time or the mean time required for T1 height stabilisation after a single dose of rocuronium 0.6 mg kg followed by spontaneous recovery in children aged 2 to 11 years. TRIAL REGISTRATION: Clinicaltrials.gov. identifier: NCT02498678.

Opioid-related side effects: Postoperative ileus, urinary retention, nausea and vomiting, and shivering. A review of the literature.

Opioids are widely used in clinical anesthesia. However, side effects include postoperative nausea and vomiting, shivering, ileus, and urine retention and are specifically discussed here. From the available evidence, it appears that the use of opioids is strongly associated with impaired gastrointestinal motility. Therefore, to prevent postoperative ileus, the use of opioids should be minimized and opioids should be replaced by other drugs. With regard to the risk of postoperative urinary retention, one problem is the lack of standardized definition. Nevertheless, the use of opioids is clearly an important risk factor. Postoperative nausea and vomiting have high incidences. Even if the mechanisms are partially understood, opioid-sparing strategies have been shown to decrease its incidence. Finally, the problem of postoperative shivering has been, at least partially, solved by the avoidance of (high doses) remifentanil and the use of alpha-2 agonists. In conclusion, postoperative urinary retention, postoperative ileus, nausea and vomiting, and shivering are complex problems seen after surgery. Management is possible, but prevention is possible with the avoidance of high doses of intraoperative opioids, conjointly to opioid-sparing techniques.