Comparison of the onset and offset times of two available formulations of rocuronium bromide in an animal model.

Rocuronium bromide is a neuromuscular blocker in widespread use in anaesthesia, emergency and intensive care. Reports of reduced efficacy of a new different formulation of rocuronium bromide were submitted to Medsafe, the New Zealand Medicines and Medical Devices Safety Authority, in 2020. Given the requirement for rapid and predictable paralysis for patient safety the efficacy of the two available formulations of rocuronium bromide was investigated in an animal model. After ethics committee approval, 19 rats were anaesthetised and paralysis, defined as loss of tibialis anterior flexion on direct electrical stimulation of the sciatic nerve, was assessed by mechanomyography in response to ED90 doses of rocuronium.Paralysis was observed at a median of 12 seconds for the new different formulation: A, Hameln Pharma (interquartile range (IQR) 6-106 seconds) and 28 seconds for formulation B: Pfizer (IQR 12-68 seconds) P = 0.48. Offset of paralysis was observed after 293 seconds for formulation A (IQR 250-372 seconds) and 241 seconds for formulation B (IQR 220-263 seconds). While the differences observed were substantial, they were not statistically significant. Moreover, the direction of observed difference was towards a shorter median onset and longer offset for the newer formulation, a finding in the opposite direction to the initial clinical concern.Relevance to the clinical situation is indeterminate given the study was stopped at low numbers for futility and limitations around the clinical applicability of animal pharmacokinetics and dynamics. Nevertheless our findings provide some reassurance that the newly available different formulation of this critical use medication does not exhibit a substantial increase in time to onset.

Antihypertensive treatment guided by genetics: PEARL-HT, the randomized proof-of-concept trial comparing rostafuroxin with losartan.

We compared a standard antihypertensive losartan treatment with a pharmacogenomics-guided rostafuroxin treatment in never-treated Caucasian and Chinese patients with primary hypertension. Rostafuroxin is a digitoxigenin derivative that selectively disrupts the binding to the cSrc-SH2 domain of mutant α-adducin and of the ouabain-activated Na-K pump at 10-11 M. Of 902 patients screened, 172 were enrolled in Italy and 107 in Taiwan. After stratification for country and genetic background, patients were randomized to rostafuroxin or losartan, being the difference in the fall in office systolic blood pressure (OSBP) after 2-month treatment the primary endpoint. Three pharmacogenomic profiles (P) were examined, considering: P1, adding to the gene variants included in the subsequent P2, the variants detected by post-hoc analysis of a previous trial; P2, variants of genes encoding enzymes for endogenous ouabain (EO) synthesis (LSS and HSD3B1), EO transport (MDR1/ABCB1), adducin (ADD1 and ADD3); P3, variants of the LSS gene only. In Caucasians, the group differences (rostafuroxin 50 µg minus losartan 50 mg in OSBP mmHg) were significant both in P2 adjusted for genetic heterogeneity (P2a) and P3 LSS rs2254524 AA [9.8 (0.6-19.0), P = 0.038 and 13.4 (25.4-2.5), P = 0.031, respectively]. In human H295R cells transfected with LSS A and LSS C variants, the EO production was greater in the former (P = 0.038); this difference was abolished by rostafuroxin at 10-11 M. Chinese patients had a similar drop in OSBP to Caucasians with losartan but no change in OSBP with rostafuroxin. These results show that genetics may guide drug treatment for primary hypertension in Caucasians.

What is the Role of Sugammadex in the Emergency Department?

BACKGROUND: Sugammadex is a medication newly available to many emergency physicians. It effectively, and within minutes, reverses neuromuscular blockade in patients who have received rocuronium or vecuronium. The role of sugammadex for the reversal of neuromuscular blockade after rapid sequence intubation in the emergency department (ED) is evolving, and limited emergency medicine-specific literature exists. OBJECTIVE: This narrative review evaluates the role of sugammadex for the reversal of neuromuscular blockade in the ED. DISCUSSION: The basic pharmacology, duration of action, adverse effects, and important medication and disease interactions specific to sugammadex are well described. Case reports suggest sugammadex can reverse neuromuscular blockade to facilitate an urgent, neurologic examination by an emergency physician or consultant. Multiple case reports of failure to improve airway patency with the use of sugammadex, even when neuromuscular blockade is completely reversed, and concern for added difficulty of definitive airway management in a patient with spontaneous movement suggest that sugammadex should largely be omitted from failed or difficult airway management strategies. Instead, it is important to focus on the ability to oxygenate and ventilate, including progression to surgical airway or jet ventilation if needed. CONCLUSION: Sugammadex is an effective, rapid reversal agent for rocuronium and has the potential use to facilitate an urgent neurologic examination shortly after administration of rocuronium. Its routine inclusion in a failed or difficult emergency airway is not supported by available literature.

Traumatic Tracheobronchial Laceration Causing Complete Tracheal Resection: Challenges of Anesthetic Management.

We report the case of a 9-year-old girl who sustained blunt trauma to the chest and presented for emergent repair of a complete tracheobronchial laceration. Tracheobronchial laceration is potentially life threatening. While conservative management has been described for simple tears, more complex injuries require surgical repair. We discuss the anesthetic challenges, airway management, and ventilation options for surgical repair in a child with a complex laceration involving the tracheobronchial tree.

A Randomized Trial of Respiratory Status during Airway Stenting under General Anesthesia Spontaneous Respiration vs. Controlled Ventilation with Muscle Relaxants.

Airway stenting is a procedure in which a stent is inserted into a stenotic site in the airway. However, the optimal ventilation for airway stenting remains controversial. We have planned a randomized, unblinded controlled study to compare intraoperative respiratory status by dividing patients, who underwent airway stenting, into spontaneous respiration (SP) and controlled ventilation with muscle relaxants (MR) groups. This study started in April 2016. The subjects, patients aged ≥20 years with airway stenosis caused by malignant neoplasms for which airway stenting was scheduled, are randomly allocated to SP and MR groups. Anesthesia management is performed in accordance with the anesthetic methods established in each group to compare parameters of the intraoperative respiratory status. The primary endpoint is the incidence of intraoperative oxygen desaturation events (SpO2 <95). Secondary endpoints are the mean intraoperative P/F ratio, pH, PaCO2, adverse events, and proportion of protocol treatment achievement. Currently, there is no evidence of anesthetic methods affecting airway stenting. Some studies have claimed that muscle relaxants worsen airway stenosis, while others have reported stable anesthetic management of controlled ventilation with muscle relaxants in airway stenting. This study may aid in clarifying anesthetic methods for airway stenting.

Perioperative Gabapentin Improves Patient-Centered Outcomes After Inguinal Hernia Repair.

INTRODUCTION: Over 5,300 inguinal hernia repairs (IHR) were performed in the Military Health System in 2015. Chronic pain can be a debilitating complication, occurring in up to 34% of patients after IHR and impacts mission readiness. Gabapentin has been shown to be effective for postoperative analgesia in a variety of operations. We evaluated the effect of a short course of perioperative gabapentin on chronic pain after IHR. METHODS: This was a double-blinded, randomized study involving male patients ≥18 years old with an initial inguinal hernia and no history of chronic pain or psychiatric disorder. Patients chose laparoscopic or open surgery and were then randomized to receive gabapentin 300 mg before surgery, then three times daily for 6 doses or placebo. There were 50 patients randomized to both the gabapentin and placebo groups for a total of 100 patients. Main outcomes were pain and health status, assessed with a visual analogue scale (VAS) and the Short Form-12v2 (SF-12v2). Assessments were performed preoperatively and 1, 6, 12, and 24 months postoperatively. Analysis of variance was used to compare groups. RESULTS: From the initial 100 patients, 19 withdrew or were excluded. Thus, 81 patients remained, 40 receiving gabapentin and 41 placebo. Throughout the 24-month follow-up, there was no difference in VAS pain scores between the gabapentin and placebo groups (p = 0.867). Beyond 1 month of follow-up, SF-12v2 physical component score (PCS) scores were improved in the gabapentin group (p = 0.039). When comparing open to laparoscopic groups, SF-12v2 PCS scores were improved in the laparoscopic group (p = 0.046) and SF-12v2 mental component summary scores were improved in the open group (p = 0.041). CONCLUSIONS: Perioperative gabapentin was not effective in decreasing chronic pain after IHR; however, patient perception of physical health, as measured by SF-12v2, did improve.

Muscle Relaxants as a Risk Factor for Vis-à-tergo During Penetrating Keratoplasty: A Prospective Interventional Study.

INTRODUCTION: This study aimed to investigate the influence of three muscle relaxants on intraocular pressure (IOP), ocular pulse amplitude (OPA), and vis-à-tergo (VAT) in patients undergoing penetrating keratoplasty (PKP) under general anesthesia. METHODS: Ninety-five patients undergoing PKP were included in this prospective single-center interventional study. IOP and OPA were measured with a dynamic contour tonometer before and 5 min after onset of general anesthesia. Mivacurium (n = 30), atracurium (n = 35), and rocuronium (n = 30) were administered as nondepolarizing muscle relaxants. VAT was assessed 15 min after surgery had begun. RESULTS: When mivacurium was used, IOP decreased by 2.2 mmHg [standard deviation (SD) ±2.2 mmHg; p < 0.001]. Atracurium decreased the IOP by an average of 5.8 mmHg (SD ±1.8 mmHg; p < 0.001) and rocuronium caused an IOP reduction of 7.2 mmHg (SD ±2 mmHg; p < 0.001). The relative IOP decrease was 12% with mivacurium, 29% with atracurium, and 37% with rocuronium (p < 0.001). OPA decreased by 0.6 mmHg with mivacurium (SD ±0.6 mmHg; 26%; p < 0.001), 1.3 mmHg with atracurium (SD ±1.3 mmHg; 40%; p < 0.001), and 1.2 mmHg with rocuronium (SD ±0.7 mmHg; 42%; p < 0.001). The relative OPA decrease was 26% with mivacurium, 40% with atracurium, and 42% with rocuronium (p < 0.001). VAT occurred in 36% of cases. Mivacurium was used in 77% of these cases, atracurium in 26%, and rocuronium in 6.6% (p < 0.001). CONCLUSIONS: Mivacurium is associated with a higher risk of VAT during PKP. Therefore, atracurium or rocuronium may minimize complications in ocular surgery with large incisions.

Sugammadex efficacy for reversal of rocuronium- and vecuronium-induced neuromuscular blockade: A pooled analysis of 26 studies.

STUDY OBJECTIVE: To summarize and compare efficacy of sugammadex with neostigmine or placebo for reversal of rocuronium- or vecuronium-induced neuromuscular blockade (NMB), and to demonstrate consistency of sugammadex results across various patient populations. DESIGN: Pooled analysis on data from 26 multicenter, randomized, Phase II and III studies. SETTING: Operating room. PATIENTS: 1855 adults undergoing surgery under general anesthesia and receiving rocuronium or vecuronium for NMB. INTERVENTIONS: Sugammadex (2.0mg/kg at second twitch reappearance [T2; moderate NMB], 4.0mg/kg at 1-2 post-tetanic counts [PTC; deep NMB] or 16.0mg/kg at 3min after rocuronium 1.2mg/kg), neostigmine or placebo. MEASUREMENTS: Time to recovery of the train-of-four (TOF) ratio to 0.9. MAIN RESULTS: Geometric mean (95% CI) times to recovery to TOF ratio of 0.9 were 1.9 (1.8-2.0) min following sugammadex 2.0mg/kg and 10.6 (9.8-11.6) min following neostigmine administration at T2 after rocuronium, and 2.9 (2.5-3.4) min and 17.4 (13.4-22.6) min, respectively, after vecuronium. Recovery times were 2.2 (2.1-2.3) min following sugammadex 4.0mg/kg and 19.0 (14.8-24.6) min following neostigmine administered at a target of 1-2 PTC after rocuronium, and 3.8 (3.0-5.0) min and 67.6 (56.3-81.2) min after vecuronium. Sugammadex administered 3min after rocuronium 1.2mg/kg resulted in rapid recovery (1.7 [1.5-2.0] min). Modest increases in mean recovery time were associated with vecuronium use (+1.6min [78%; (61%-98%)] versus rocuronium), mild-to-moderate renal impairment (+0.4min [20%; (9%-32%)] versus normal renal function) and geographic location (+1.0min [38%; (25%-52%)] in subjects in USA/Canada versus Europe/Japan). CONCLUSIONS: Sugammadex administered at recommended doses provides rapid and predictable reversal of rocuronium and vecuronium-induced moderate and deep NMB, and effective reversal 3min after rocuronium 1.2mg/kg. Robust recovery was seen across various patient factors, providing further confirmation of labeled dose recommendations.

Effect of patient weight on first pass success and neuromuscular blocking agent dosing for rapid sequence intubation in the emergency department.

OBJECTIVES: The primary objective of this study was to determine the association between patient weight and first pass success (FPS) during rapid sequence intubation (RSI) in the ED. The secondary objective was to evaluate the association between patient weight and neuromuscular blocking agent (NMBA) dosing. METHODS: This was a retrospective cohort study conducted in a tertiary care academic ED. Consecutive adult patients who underwent RSI in the ED between January 2014 and June 2016 were included. Data were collected on patient, operator and procedural characteristics. The cohort was categorised into the following weight strata: <80 kg, 80 to <100 kg, 100 to <120 kg and ≥120 kg. The primary outcome of interest was FPS. A multivariable logistic regression analysis was conducted to evaluate the relationship between patient weight category and FPS. NMBA dosing was reported descriptively. RESULTS: The sample included 891 patients. FPS for each weight category was as follows: <80 kg (91%), 80 to <100 kg (90%), 100 to <120 kg (91%) and ≥120 kg (76%). After adjusting for potential confounders, the heaviest weight category was associated with decreased odds of FPS (OR 0.2, 95% CI 0.1 to 0.5, p<0.001). Median doses for succinylcholine (based on total body weight) decreased as weight increased: <80 kg (1.5 mg/kg), 80 to <100 kg (1.3 mg/kg), 100 to <120 kg (1.2 mg/kg) and ≥120 kg (1.0 mg/kg). Median doses for rocuronium (based on ideal body weight) were similar across weight categories: <80 kg (1.3 mg/kg), 80 to <100 kg (1.4 mg/kg), 100 to <120 kg (1.3 mg/kg) and ≥120 kg (1.4 mg/kg). CONCLUSIONS: Very heavy patients (>120 kg) undergoing RSI in the ED had a reduced FPS, and succinylcholine was more commonly underdosed than rocuronium in the heavier weight group.

The feasibility of sugammadex for general anesthesia and facial nerve monitoring in patients undergoing parotid surgery.

The use of neuromuscular blocking agent (NMBA) during anesthesia may interfere with facial nerve monitoring (FNM) during parotid surgery. Sugammadex has been reported to be an effective and safe reversal of rocuronium-induced neuromuscular block (NMB) during surgery. This study investigated the feasibility and clinical effectiveness of sugammadex for NMB reversal during FNM in Parotid surgery. Fifty patients undergoing parotid surgery were randomized allocated into conventional anesthesia group (Group C, n = 25) and sugammadex group (Group S, n = 25). Group C did not receive any NMBA. Group S received rocuronium 0.6 mg/kg at anesthesia induction and sugammadex 2 mg/kg at skin incision. The intubating condition and influence on FNM evoked EMG results were compared between groups. The intubation condition showed significantly better in group S patients than C group patients (excellent in 96% v.s. 24%). In group S, rapid reverse of NMB was found and the twitch (%) recovered from 0 to >90% within 10 min. Positive and high EMG signals were obtained in all patients at the time point of initial facial nerve stimulation in both groups. There was no significant difference as comparing the EMG amplitudes detected at the time point of initial and final facial nerve stimulation in both groups. Implementation of sugammadex in anesthesia protocol is feasible and reliable for successful FNM during parotid surgery.

The Role of Sugammadex in Symptomatic Transient Neonatal Myasthenia Gravis: A Case Report.

We describe the case of a 3-week-old boy with pyloric stenosis who presented for laparoscopic pyloromyotomy in the setting of symptomatic transient neonatal myasthenia gravis. The patient received muscle relaxation with rocuronium, and neuromuscular blockade was successfully reversed with sugammadex with recovery guided by train-of-four monitoring. He was extubated uneventfully without complications. Because sugammadex binds directly to rocuronium rather than interfering with acetylcholine metabolism, it might provide a good option for reversal of neuromuscular blockade in transient neonatal myasthenia gravis.

Use of sugammadex in a patient with progressive muscular atrophy and in a patient with amyotrophic lateral sclerosis: Case report.

INTRODUCTION: We herein present 2 cases involving the combination of rocuronium and sugammadex in patients with motor neuron disease. The patients were a 54-year-old man with progressive muscular atrophy who underwent removal of internal fixators in the arm and leg, and a 66-year-old woman with amyotrophic lateral sclerosis who underwent skin grafting in the left lower leg. General anesthesia was induced with propofol, rocuronium, and remifentanil and maintained with desflurane and remifentanil. At the end of the surgical procedure, we administered sugammadex. Three or 4 minutes after administration of sugammadex, the patients began to breathe spontaneously and were extubated without complications. CONCLUSION: Sugammadex can be used successfully to reverse neuromuscular blockade in patients with motor neuron disease.

Is neuromuscular blocker needed in children undergoing inguinal herniorrhaphy?: A prospective, randomized, and controlled trial.

BACKGROUND: Intraoperative neuromuscular blocker is widely used, but is known to be associated with postoperative residual paralysis, which is known to be associated with increased risk of pulmonary complications. Hence, its use should be individualized and restricted to procedures where it is mandatory. We examined whether not using a neuromuscular blocker affects the surgical conditions in children undergoing inguinal herniorrhaphy. METHODS: Anesthesia was induced and maintained with sevoflurane in 60% nitrous oxide, and the airway was maintained using an I-gel. In total, 66 children aged 1 to 6 years were randomized to receive rocuronium (rocuronium group, n = 33) or saline (control group, n = 33); 61 children of them finished the study. A single surgeon who performed the operation rated the surgical condition of each patient on a 4-point scale (1 = poor, 2 = acceptable, 3 = good, and 4 = excellent). Intraoperative patient movement, recovery time, emergence agitation, and postoperative pain scores were evaluated. RESULTS: One patient in control group and no patient in rocuronium group showed intraoperative movement. When noninferiority test was done for intraoperative patient movement, with the noninferiority margin of 20%, the difference of absolute risk was 3.3% (95% confidence interval -8.0% to 16.7%) and saline group was noninferior to rocuronium group. All of the patients showed good to excellent surgical conditions, and no difference was found between the 2 groups. The recovery time was shorter in the control group than in the rocuronium group (4.5 ±â€Š1.8 vs 5.6 ±â€Š2.2 minutes, respectively; P = .028). CONCLUSION: In children aged 1 to 6 years undergoing inguinal herniorhaphy under sevoflurane anesthesia using an I-gel, not using neuromuscular blocker showed similar intraoperative condition and shortened recovery time compared with using neuromouscular blocker.

Use of neuromuscular blockers and neostigmine for general anesthesia and its association with neuraxial blockade: A retrospective study.

This research aimed to assess the use of neuromuscular blockers (NMB) and its reversal, associated or not with neuraxial blockade, after general anesthesia.This retrospective study analyzed 1295 patients that underwent surgery with general anesthesia at Prof. Dr. José Aristodemo Pinotti Hospital in 2013. The study included patients aged >1 year, with complete, readable medical charts and anesthetic records.Rocuronium (ROC) was the most used NMB (96.7%), with an initial dose of 0.60 (0.52-0.74) mg/kg and total dose of 0.38 (0.27-0.53) mg/kg/h. In 24.3% of the cases, neuraxial blockade was associated with a significantly longer anesthesia (P < .001) than in cases without neuraxial block, regardless of technique (total intravenous (TIV) vs intravenous and inhalational (IV+IN)). In 71.9% of the cases, a single dose of NMB was used. Patients under TIV general anesthesia associated with neuraxial blockade had a lower total dose of ROC (mg/kg/h) in comparison with TIV GA alone (0.30 (0.23-0.39) and 0.42 (0.30-0.56) mg/kg/h, respectively, P < .001). The same was observed for patients under IV+IN GA (0.32 (0.23-0.41) and 0.43 (0.31-0.56) mg/kg/h, respectively, P < .001). The duration of anesthesia was longer according to increasing number of additional NMB doses (P < .001). Dose of neostigmine was 2.00 (2.00-2.00) mg or 29.41 (25.31-33.89) µg/kg. The interval between neostigmine and extubation was >30 minutes in 10.9% of cases.The most widely used NMB was ROC. Neuroaxial blockade (spinal or epidural) was significantly associated with reduced total dose of ROC (mg/kg/h) during general anesthesia, even in the absence of neuromuscular monitoring and regardless of general anesthetic technique chosen. In most cases, neostigmine was used to reverse neuromuscular block. The prolonged interval between neostigmine and extubation (>30 minutes) was neither associated with total doses of ROC or neostigmine, nor with the time of NMB administration. This study corroborates the important role of quantitative neuromuscular monitors and demonstrates that neuraxial blockade is associated with reduced total ROC dose. Further studies are needed to evaluate the possible role of neuraxial blockade in reducing the incidence of postoperative residual curarization.

Administration of rocuronium based on real body weight versus fat-free mass in patients with lymphedema.

Objective To compare the clinical pharmacokinetics of rocuronium when applied according to fat-free mass versus real body weight during anesthetic induction of patients with lymphedema. Methods Sixty patients with lymphedema (age, 18-60 years; American Society of Anesthesiologists physical status, I-II) undergoing elective surgery with general anesthesia were randomly divided into two groups. Rocuronium was administered based on the fat-free mass in 30 patients and real body weight in 30 patients. General anesthesia was induced with propofol and remifentanil by target-controlled infusion. Intubation was attempted when the onset time (T1) (time from end of bolus injection to 100% twitch depression) reached maximal inhibition, and respiratory support with mechanical ventilation was then applied. The T1, clinical duration (time from end of bolus injection to recovery of twitch tension to 25% of control), recovery index (time from 25% to 75% of recovery of T1), and dosage were recorded. Results Complete data were recorded for 59 patients, and there were no significant differences in the general condition, intubation condition, or median duration of action of rocuronium between the two groups. However, the median T1, recovery index, and dosage of rocuronium were significantly different. Conclusion Good intubation conditions and a shortened clinical duration can be obtained for patients with lymphedema when induction with rocuronium is based on the fat-free mass.

Sugammadex ED90 dose to reverse the rocuronium neuromuscular blockade in obese patients.

Objective: to determine the ED90 (minimum effective dose in 90% of patients) of sugammadex for the reversal of rocuronium-induced moderate neuromuscular blockade (NMB) in patients with grade III obesity undergoing bariatric surgery. Methods: we conducted a prospective study with the biased coin up-and-down sequential design. We chosen the following doses: 2.0mg/Kg, 2.2mg/Kg, 2.4mg/Kg, 2.6mg/Kg, 2.8mg/Kg. The complete reversal of rocuronium-induced NMB considered a T4/T1 ratio ≥0.9 as measured by TOF. After induction of general anesthesia and calibration of the peripheral nerve stimulator and accelerometer, we injected rocuronium 0.6mg/kg. We administered propofol and remifentanil by continuous infusion, and intermittent boluses of rocuronium throughout the procedure. Results: we evaluated 31 patients, of whom 26 had displayed successful reversal of the NMB with sugammadex, and failure in five. The mean time to complete moderate NMB reversal was 213 seconds (172-300, median 25-75%). The ED90 of sugammadex calculated by regression was 2.39mg/kg, with a 95% confidence interval of 2.27-2.46 mg/kg. Conclusion: the ED90 of sugammadex in patients with grade III obesity or higher was 2.39mg/kg.

Objetivos: determinar a ED90 (dose mínima eficaz em 90% dos pacientes) de sugamadex para a reversão de bloqueio neuromuscular (BNM) moderado induzido pelo rocurônio em pacientes com obesidade grau III submetidos à cirurgia bariátrica. Métodos: estudo prospectivo com o método de projeção sequencial para cima e para baixo da moeda enviesada. As seguintes doses foram escolhidas: 2,0mg/kg-1, 2,2mg/kg-1, 2,4mg/kg-1, 2,6mg/kg-1, 2,8mg/kg-1. A reversão completa de BNM induzido por rocurônio considerou uma relação T4/T1 ≥0,9 na medida do TOF. Após a indução da anestesia geral e calibração do estimulador de nervo periférico e acelerômetro, rocurônio 0,6mg/kg-1 foi injetado. Infusão contínua de propofol e remifentanil, e bolus intermitente de rocurônio foram injetados durante todo o procedimento. Resultados: trinta e um pacientes foram avaliados, 26 dos quais bem-sucedidos e cinco sem reversão completa do BNM moderado promovido pelo sugamadex. O tempo médio para completar reversão de BNM foi 213 segundos (172 a 300 segundos; mediana, 25-75%). O ED90 de sugamadex calculado pela regressão foi de 2,39mg/kg-1 com um intervalo de confiança de 95% (2,27 a 2,46mg/kg-1). Conclusão: o ED90 de sugamadex em pacientes com obesidade grau III ou superior foi 2,39mg/kg-1.

Sugammadex ED90 dose to reverse the rocuronium neuromuscular blockade in obese patients / Dose ED90 de Sugamadex para reverter o bloqueio neuromuscular com rocurônio em pacientes obesos

ABSTRACT Objective: to determine the ED90 (minimum effective dose in 90% of patients) of sugammadex for the reversal of rocuronium-induced moderate neuromuscular blockade (NMB) in patients with grade III obesity undergoing bariatric surgery. Methods: we conducted a prospective study with the biased coin up-and-down sequential design. We chosen the following doses: 2.0mg/Kg, 2.2mg/Kg, 2.4mg/Kg, 2.6mg/Kg, 2.8mg/Kg. The complete reversal of rocuronium-induced NMB considered a T4/T1 ratio ≥0.9 as measured by TOF. After induction of general anesthesia and calibration of the peripheral nerve stimulator and accelerometer, we injected rocuronium 0.6mg/kg. We administered propofol and remifentanil by continuous infusion, and intermittent boluses of rocuronium throughout the procedure. Results: we evaluated 31 patients, of whom 26 had displayed successful reversal of the NMB with sugammadex, and failure in five. The mean time to complete moderate NMB reversal was 213 seconds (172-300, median 25-75%). The ED90 of sugammadex calculated by regression was 2.39mg/kg, with a 95% confidence interval of 2.27-2.46 mg/kg. Conclusion: the ED90 of sugammadex in patients with grade III obesity or higher was 2.39mg/kg.

RESUMO Objetivos: determinar a ED90 (dose mínima eficaz em 90% dos pacientes) de sugamadex para a reversão de bloqueio neuromuscular (BNM) moderado induzido pelo rocurônio em pacientes com obesidade grau III submetidos à cirurgia bariátrica. Métodos: estudo prospectivo com o método de projeção sequencial para cima e para baixo da moeda enviesada. As seguintes doses foram escolhidas: 2,0mg/kg-1, 2,2mg/kg-1, 2,4mg/kg-1, 2,6mg/kg-1, 2,8mg/kg-1. A reversão completa de BNM induzido por rocurônio considerou uma relação T4/T1 ≥0,9 na medida do TOF. Após a indução da anestesia geral e calibração do estimulador de nervo periférico e acelerômetro, rocurônio 0,6mg/kg-1 foi injetado. Infusão contínua de propofol e remifentanil, e bolus intermitente de rocurônio foram injetados durante todo o procedimento. Resultados: trinta e um pacientes foram avaliados, 26 dos quais bem-sucedidos e cinco sem reversão completa do BNM moderado promovido pelo sugamadex. O tempo médio para completar reversão de BNM foi 213 segundos (172 a 300 segundos; mediana, 25-75%). O ED90 de sugamadex calculado pela regressão foi de 2,39mg/kg-1 com um intervalo de confiança de 95% (2,27 a 2,46mg/kg-1). Conclusão: o ED90 de sugamadex em pacientes com obesidade grau III ou superior foi 2,39mg/kg-1.

Targeted temperature management after cardiac arrest with anaphylaxis.

Fatal anaphylaxis is uncommon but not rare. Extrapolated mortality rates are 0.52% of total anaphylaxis patients Bock et al. (Jan. 2001) [1]. Nevertheless, compared with the incidence of the other cardiac arrest events, the incidence of cardiac arrest due to anaphylaxis is relatively small. As a result, the effect using targeted temperature management after anaphylaxis is not clearly understood. We report the case of a 63-year-old man who developed cardiac arrest after ingestion of two pieces of peach. He was resuscitated and his circulation returned spontaneously after approximately 11min of cardiopulmonary resuscitation, but he was unresponsive and had fixed dilated pupils. We initiated therapeutic hypothermia on the basis of protocol for 24h. The patient was gradually and successfully cooled and rewarmed. The patient opened his eyes spontaneously on day 5, obeyed commands on day 6, and was discharged on day 18. At the time of discharge, he had no neurologic deficiencies or other complications.

Difficulty Inserting Cuffed Endotracheal Tubes in a Child: A Case Report.

We experienced difficulty inserting cuffed inner diameter (ID) 4.5- and 5.0-mm endotracheal tubes (ETTs) in a 5-year-old boy. Postoperative ultrasound investigations showed that the internal transverse width of the cricoid cartilage was 8.0 mm. The maximum outer diameter (OD) of the deflated cuff portion of the cuffed ID 4.5- and 5.0-mm ETTs was 8.5 and 9.6 mm, respectively. The OD of an uncuffed ID 5.5-mm ETT was 7.6 mm; this tube passed the cricoid cartilage. Hence, the transverse width of the cricoid cartilage and ETT diameter including cuff folds should be considered when selecting cuffed ETTs.

Ouabain Contributes to Kidney Damage in a Rat Model of Renal Ischemia-Reperfusion Injury.

Warm renal ischemia performed during partial nephrectomy has been found to be associated with kidney disease. Since endogenous ouabain (EO) is a neuro-endocrine hormone involved in renal damage, we evaluated the role of EO in renal ischemia-reperfusion injury (IRI). We measured plasma and renal EO variations and markers of glomerular and tubular damage (nephrin, KIM-1, Kidney-Injury-Molecule-1, α1 Na-K ATPase) and the protective effect of the ouabain inhibitor, rostafuroxin. We studied five groups of rats: (1) normal; (2) infused for eight weeks with ouabain (30 µg/kg/day, OHR) or (3) saline; (4) ouabain; or (5) saline-infused rats orally treated with 100 µg/kg/day rostafuroxin for four weeks. In group 1, 2-3 h after IRI, EO increased in ischemic kidneys while decreased in plasma. Nephrin progressively decreased and KIM-1 mRNA increased starting from 24 h. Ouabain infusion (group 2) increased blood pressure (from 111.7 to 153.4 mmHg) and ouabain levels in plasma and kidneys. In OHR ischemic kidneys at 120 h from IRI, nephrin, and KIM-1 changes were greater than those detected in the controls infused with saline (group 3). All these changes were blunted by rostafuroxin treatment (groups 4 and 5). These findings support the role of EO in IRI and suggest that rostafuroxin pre-treatment of patients before partial nephrectomy with warm ischemia may reduce IRI, particularly in those with high EO.