A randomized trial evaluating the safety profile of sugammadex in high surgical risk ASA physical class 3 or 4 participants.

BACKGROUND: The aim of this randomized, double-blind trial was to evaluate the safety and tolerability profile, including cardiac safety, of sugammadex-mediated recovery from neuromuscular block in participants undergoing surgery who met the American Society of Anesthesiologists (ASA) Physical Class 3 or 4 criteria. Specifically, this study assessed the impact of sugammadex on cardiac adverse events (AEs) and other prespecified AEs of clinical interest. METHODS: Participants meeting ASA Class 3 and 4 criteria were stratified by ASA Class and NMBA (rocuronium or vecuronium) then randomized to one of the following: 1) Moderate neuromuscular block, sugammadex 2 mg/kg; 2) Moderate neuromuscular block, neostigmine and glycopyrrolate (neostigmine/glycopyrrolate); 3) Deep neuromuscular block, sugammadex 4 mg/kg; 4) Deep neuromuscular block, sugammadex 16 mg/kg (rocuronium only). Primary endpoints included incidences of treatment-emergent (TE) sinus bradycardia, TE sinus tachycardia and other TE cardiac arrhythmias. RESULTS: Of 344 participants randomized, 331 received treatment (61% male, BMI 28.5 ± 5.3 kg/m2, age 69 ± 11 years). Incidence of TE sinus bradycardia was significantly lower in the sugammadex 2 mg/kg group vs neostigmine/glycopyrrolate. The incidence of TE sinus tachycardia was significantly lower in the sugammadex 2 and 4 mg/kg groups vs neostigmine/glycopyrrolate. No significant differences in other TE cardiac arrythmias were seen between sugammadex groups and neostigmine/glycopyrrolate. There were no cases of adjudicated anaphylaxis or hypersensitivity reactions in this study. CONCLUSIONS: Compared with neostigmine/glycopyrrolate, incidence of TE sinus bradycardia was significantly lower with sugammadex 2 mg/kg and incidence of TE sinus tachycardia was significantly lower with sugammadex 2 mg/kg and 4 mg/kg. These results support the safety of sugammadex for reversing rocuronium- or vecuronium-induced moderate and deep neuromuscular block in ASA Class 3 or 4 participants. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03346057 .

Pharmacokinetics of Sugammadex Dosed by Actual and Ideal Body Weight in Patients With Morbid Obesity Undergoing Surgery.

This analysis of a published study (NCT03346070) evaluated the pharmacokinetics (PKs) of sugammadex dosed by actual body weight (ABW) or ideal body weight (IBW) for reversal of moderate or deep neuromuscular block (M-NMB or D-NMB) in adults with morbid obesity. Adults with body mass index ≥ 40 kg/m2 , ABW ≥ 100 kg, and American Society of Anesthesiologists (ASA) Class 3 were stratified by NMB agent (rocuronium or vecuronium) and randomized 1:1:1:1:1 to (i) M-NMB, sugammadex 2 mg/kg ABW; (ii) M-NMB, sugammadex 2 mg/kg IBW; (iii) M-NMB, neostigmine 5 mg + glycopyrrolate 1 mg; (iv) D-NMB, sugammadex 4 mg/kg ABW; and (v) D-NMB, sugammadex 4 mg/kg IBW. Plasma samples for sugammadex quantification were collected predose, 2, 5, 15, 60, and 120 minutes, and 4, 6 hours postdose. Natural log PK parameters were analyzed using linear fixed effect model with treatment, mode (ABW and IBW), and mode by treatment interaction as fixed terms. The sugammadex PK profile showed rapid distribution followed by monophasic decline consistent with a two-compartment model examined by dose and mode. Absolute sugammadex exposures were ~ 50% higher in the ABW vs. IBW group; dose-independent parameters (clearance and volume of distribution) and terminal half-life remained constant. Sugammadex PK parameter values increased in dose-dependent, linear manner following dosing by ABW or IBW, such that PK continues to be predictive across the clinical dose range. In conjunction with previously published results showing faster recovery with ABW vs. IBW dosing across NMB agent and depth of NMB, these PK findings continue to support dosing by ABW in patients with morbid obesity irrespective of depth of NMB.

Involvement of the basal nucleus of Meynert on regional cerebral cortical vasodilation associated with masticatory muscle activity in rats.

We examined the neural mechanisms for increases in regional cerebral blood flow (rCBF) in the neocortex associated with mastication, focusing on the cortical vasodilative system derived from the nucleus basalis of Meynert (NBM). In pentobarbital-anesthetized rats, parietal cortical rCBF was recorded simultaneously with electromyogram (EMG) of jaw muscles, local field potentials of frontal cortex, multi-unit activity of NBM neurons, and systemic mean arterial pressure (MAP). When spontaneous rhythmic EMG activity was observed with cortical desynchronization, an increase in NBM activity and a marked rCBF increase independent of MAP changes were observed. A similar rCBF increase was elicited by repetitive electrical stimulation of unilateral cortical masticatory areas. The magnitude of rCBF increase was partially attenuated by administration of the GABAergic agonist muscimol into the NBM. The rCBF increase persisted after immobilization with systemic muscle relaxant (vecuronium). rCBF did not change when jaw muscle activity was induced by electrical stimulation of the pyramidal tract. The results suggest that activation of NBM vasodilator neurons contributes at least in part to the rCBF increase associated with masticatory muscle activity, and that the NBM activation is induced by central commands from the motor cortex, independently of feedback from brainstem central pattern generator or contracting muscles.

Context-sensitive recovery of neuromuscular function from vecuronium in dogs: Effects of dose and dosing protocol.

Recovery of neuromuscular function is a gradual phenomenon whereby function progresses from absent to normal. The speed of spontaneous recovery can be used to predict the time when neuromuscular function is expected to be restored. However, the speed of recovery might be affected by the dose of the neuromuscular blocker administered, and by the dosing regimen of that dose. The effects of both factors on the speed of spontaneous recovery from vecuronium were evaluated. Seven dogs were anesthetized three times and the train-of-four (TOF) ratio was measured with acceleromyography. Vecuronium was administered at 0.1 mg/kg, 0.2 mg/kg, or 0.1 mg/kg followed by two doses of 0.05 mg/kg was administered each time. In the divided-dose treatment group, aliquots were administered on return of the first twitch (T1) of the TOF from the previous dose. The duration of surgical block, from injection to return of T1, was longest for the divided-dose protocol, intermediate for 0.2 mg/kg single bolus, and shortest for 0.1 mg/kg (P < 0.0001). The recovery period, from return of T1 to a TOF ratio ≥0.9, was longer for 0.2 mg/kg administered as a single bolus than for the other two groups (P = 0.007). Doubling the dose of a single bolus of vecuronium extended the time of surgical block and prolonged the duration of the recovery period. However, dividing that dose into smaller aliquots extended the period of surgical block while shortening the recovery period. Hence, the spontaneous reappearance of T1 should not be used in isolation to predict the time to complete recovery of neuromuscular function.

Investigation of intraoperative dosing patterns of neuromuscular blocking agents.

There is a growing body of literature documenting the use of deep neuromuscular block (NMB) during surgery. Traditional definitions of depth of NMB rely on train-of-four assessment, which can be less reliable in retrospective studies. The goal of our study was to investigate the real-world practice pattern of dosing of neuromuscular blocking agents (NMBA), utilizing the amount of NMBA used during the course of a case, adjusted for patient weight and case duration, as a surrogate measure of depth of NMB. We also aimed to identify case factors associated with larger NMBA doses. In this retrospective observational analysis of our anesthesia information management system, we analyzed all general endotracheal anesthesia cases from 2012 to 2015 in which an intermediate-acting NMBA was used. Cases using a long-acting NMBA or only succinylcholine were excluded. The expected duration of the case was calculated based on the cumulative dose of NMB used, normalized to the patient's ideal body weight and the ED95 of the drug. If the expected duration of the case was greater than the actual case duration documented in the case record, it was classified as higher dosing (HD). If the expected duration was equal to or less than the actual duration, it was considered predicted dosing (PD). Categorical comparisons between HD and PD groups were made for various patient, procedural, and provider factors. 72,684 cases were included in the final analysis, of which 46,358, or 64% of cases, used HD. Cases with patients who were morbidly obese, younger than 65 years, and who were lower ASA Physical Status classification (I or II) used more HD as opposed to PD. Cases that were non-open, used total intravenous anesthesia, emergent cases, or used non-rapid sequence anesthesia induction had higher rates of HD than their matched counterparts. All results were statistically significant. HD was more common in cases that documented train-of-four and used the reversal agent neostigmine. Approximately two-thirds of general endotracheal anesthesia cases using an intermediate-acting NMBA used HD. Cases with higher rates of HD may be those that are traditionally technically complex or emergent, would benefit from greater paralysis, or do not use adjunctive medications for muscle relaxation. Age greater than 65 years was shown to have lower rates of HD, likely due to provider awareness of age-related changes in pharmacokinetics and pharmacodynamics. Intraoperative monitoring and NMB antagonism with neostigmine were used more frequently with HD.

Anaphylactic Bronchospasm during Induction of General Anaesthesia: A Case Report.

Bronchospasm represents the clinical manifestation of bronchial muscles contraction resulting in reduced alveolar air flow. Non-allergic mechanisms or anaphylaxis underlie the genesis of perioperative bronchospasm, a potential anaesthetic disaster. Early recognition and treatment are crucial. We report a rare incident of anaphylactic bronchospasm without hypotension during general anaesthesia. Urticaria appeared in chest and abdomen suggesting anaphylaxis. After the event resolved with bronchodilators, surgery continued uneventfully. Vecuronium was the most probable culprit but confirmation was not possible as the patient was lost to follow up. Rarely, perioperative anaphylaxis presents only with bronchospasm that requires prompt attention to avoid adverse outcome. Keywords: allergy; anaphylaxis; bronchial spasm; general anesthesia.

Is lower-dose sugammadex a cost-saving strategy for reversal of deep neuromuscular block? Facts and fiction.

BACKGROUND: Sugammadex, a γ-cyclodextrin derivative, belongs to a new class of selective relaxant binding agents. Sugammadex was approved 10-years ago by the European medicines agency and today is used in clinical anesthesia and emergency medicine globally. In this review, indications for neuromuscular block, the challenge of neuromuscular monitoring and the practice of under-dosing of sugammadex as a potential cost-saving strategy are discussed. MAIN BODY: Reversal of neuromuscular block is important to accelerate the spontaneous recovery of neuromuscular function. Sugammadex is able to reverse a rocuronium- or vecuronium-induced neuromuscular block rapidly and efficiently from every depth of neuromuscular block. However, since sugammadex was introduced in clinical anesthesia, several studies have reported administration of a lower-than-recommended dose of sugammadex. The decision to under-dose sugammadex is often motivated by cost reduction concerns, as the price of sugammadex is much higher than that of neostigmine outside the United States. However, under-dosing of sugammadex leads to an increased risk of recurrence of neuromuscular block after an initial successful (but transient) reversal. Similarly, when not using objective neuromuscular monitoring, under-dosing of sugammadex may result in residual neuromuscular block in the postoperative care unit, with its attendant negative pulmonary outcomes. Therefore, an appropriate dose of sugammadex, based on objective determination of the depth of neuromuscular block, should be administered to avoid residual or recurrent neuromuscular block and attendant postoperative complications. Whether the reduction in perioperative recovery time of the patient can be translated into additional procedural cases performed, faster operative turnover times, or improved organizational resource utilization, has yet to be determined in actual clinical practice that includes verification of neuromuscular recovery prior to tracheal extubation. CONCLUSIONS: The current review addresses the indications for neuromuscular block, the challenge of neuromuscular monitoring, the practice of under-dosing of sugammadex as a potential cost-saving strategy in reversal of deep neuromuscular block, the economics of sugammadex administration and the potential healthcare cost-saving strategies.

Practice Change From Intermittent Medication Boluses to Bolusing From a Continuous Infusion in Pediatric Critical Care: A Quality Improvement Project.

OBJECTIVES: To determine whether implementing a guideline to bolus medications from continuous infusions in PICUs affects nursing satisfaction, patient safety, central line entries, medication utilization, or cost. DESIGN: This is a pre- and postimplementation quality improvement study. SETTING: An 11-bed ICU and 14-bed cardiac ICU in a university-affiliated children's hospital. PATIENTS: Patients less than 18 years old admitted to the PICU or pediatric cardiac ICU receiving a continuous infusion of dexmedetomidine, midazolam, fentanyl, morphine, vecuronium, or cisatracurium from May 2015 to May 2016, excluding November 2015 (washout period), were eligible for inclusion. INTERVENTIONS: Change in practice from administering bolus doses from an automated dispensing machine to administering bolus medications from continuous infusion in PICUs. MEASUREMENTS AND MAIN RESULTS: Timing studies were conducted pre- and post implementation in 29 and 26 occurrences, respectively. The median time from the decision to give a bolus until it began infusing decreased by 169 seconds (p < 0.01). Nursing satisfaction increased from 19.3% pre- to 100% post implementation. Safety was assessed via barcode scanning compliance, which decreased by 1.4% for patients and 1% for medications, and smart pump limit overrides. The percentage of infusion pump bolus overrides increased as expected, with the majority (99%) of these exceeding soft maximum limits by less than two-fold. Central line entries were unaffected post implementation. To assess medication utilization, a total of 50 patients in each intervention group were selected for retrospective chart review. Daily fentanyl boluses increased from one to three (p = 0.021). However, midazolam infusion dose and fentanyl infusion duration decreased (p = 0.026 and p = 0.005, respectively). Medication utilization was otherwise unchanged post implementation (p > 0.05). Annualized cost avoidance was $124,160. CONCLUSIONS: Implementation of bolus medications from continuous infusion in PICUs significantly decreased time to begin a bolus dose and increased nursing satisfaction. The practice change also improved medication utilization without negatively impacting patient safety.

Nitrous oxide added at the end of isoflurane anesthesia hastens early recovery without increasing the risk for postoperative nausea and vomiting: a randomized clinical trial.

BACKGROUND: Nitrous oxide (N2O) has been reported to increase the risk of postoperative nausea and vomiting (PONV) in a dose-dependent manner. We investigated the effect of adding N2O at the end of isoflurane inhalational anesthesia on the recovery and incidence of PONV. Our hypothesis was that N2O would reduce the time to early recovery without increasing the incidence of PONV. METHODS: After obtaining ethics committee approval and written informed consent, 100 women at American Society of Anesthesiologists physical status I-III and scheduled for laparoscopic-assisted vaginal hysterectomy were randomized into two groups (G) according to the carrier gas: GO2 (air in 30% oxygen) and GN2O (the same mixture until the last 30 min of surgery, when 70% N2O in 30% oxygen was used). No PONV prophylaxis was given. Anesthesia was induced with thiopental 5 mg·kg-1, vecuronium 0.1 mg·kg-1, and fentanyl 1-2 µg·kg-1 iv and maintained with isoflurane. Indicators of early recovery (time to extubation, eye opening, following commands, orientation) were assessed by an anesthesiologist unaware of the group assignment. The incidence and severity of PONV was measured at two and 24 hr postoperatively. RESULTS: Altogether, 82 participants completed the study (42 in GO2, 40 in GN2O) and were analyzed. The mean (SD) time of N2O administration in GN2O patients was 27.1 (10.1) min. The mean (SD) time to extubation was faster in GN2O patients [5.4 (2.9) min] than in GO2 patients [7.5 (3.7) min] (mean difference, 2.0 min; 95% confidence interval [CI], 0.6 to 3.4, P = 0.009). The ability to open eyes, follow commands, and being oriented were all faster in GN2O patients than in GO2 patients (differences of 3.9 min, 95% CI, 1.6 to 6.1, P = 0.001; 3.4 min, 95% CI, 1.0 to 5.7, P = 0.006; 3.8 min, 95% CI, 0.9 to 6.7, P = 0.010, respectively). The incidence of PONV was not different between the groups, but the rescue antiemetic was required less often in the GN2O patients (mean difference in metoclopramide dose between the GN2O and GO2 groups, 5.1 mg; 95% CI, 0.8 to 9.4, P = 0.019). CONCLUSIONS: Adding N2O during the last 30 min of an isoflurane-based inhalational anesthetic reduced the time to extubation, eye opening, and orientation.

Role of sugammadex in accelerating postoperative discharge: A meta-analysis.

STUDY OBJECTIVE: Sugammadex has been introduced for reversal of neuromuscular blockade (NMB) induced by rocuronium (or vecuronium). Although its efficacy and safety have been established, data are conflicting as to whether it accelerates discharge to the surgical ward compared with neostigmine, which is traditionally used for reversing NMB. The object of this systematic review and meta-analysis was to review the research comparing sugammadex and neostigmine in the context of patient discharge after general anesthesia. DESIGN: Systematic review and meta-analysis. SETTING: University medical hospital. PATIENTS: Five-hundred eighteen patients from six studies were included. METHODS: A comprehensive search was conducted using PubMed, Web of Science, Google Scholar, and Cochrane Library electronic databases to identify randomized controlled trials written in English. Two reviewers independently selected the studies, extracted data regarding postoperative discharge, and assessed the trials' methodological quality and evidence level. Postoperative discharge time was determined from the operating room (OR) to the postanesthesia care unit (PACU) and from the PACU to the surgical ward. This study was conducted using PRISMA methodology. MEASUREMENTS: Time to discharge after NMB reversal with sugammadex or neostigmine. MAIN RESULTS: Compared with neostigmine, sugammadex was associated with a significantly faster discharge from the OR to the PACU (mean difference [MD]=22.14min, 95% CI (14.62, 29.67), P<0.0001, I2=0%) and from the PACU to the surgical ward (MD=16.95min, 95% CI (0.23, 33.67), P=0.0469, I2=98.4%). Similarly, discharge-readiness was shorter for sugammadex than for neostigmine from the OR to the PACU (MD=5.58min, 95% CI (3.03, 8.14), P≤0.0001, I2=0%). However, discharge-readiness was similar in both groups for patients moving from the PACU to the surgical ward (MD=-1.10min, 95% CI (-5.69, 3.50), P=0.6394, I2=25.3%). CONCLUSIONS: Results from this meta-analysis suggest that sugammadex accelerates postoperative discharge of patients after general anesthesia compared with neostigmine.

Neuronal Effects of Sugammadex in combination with Rocuronium or Vecuronium.

Rocuronium (ROC) and Vecuronium (VEC) are the most currently used steroidal non-depolarizing neuromuscular blocking (MNB) agents. Sugammadex (SUG) rapidly reverses steroidal NMB agents after anaesthesia. The present study was conducted in order to evaluate neuronal effects of SUG alone and in combination with both ROC and VEC. Using MTT, CASP-3 activity and Western-blot we determined the toxicity of SUG, ROC or VEC in neurons in primary culture. SUG induces apoptosis/necrosis in neurons in primary culture and increases cytochrome C (CytC), apoptosis-inducing factor (AIF), Smac/Diablo and Caspase 3 (CASP-3) protein expression. Our results also demonstrated that both ROC and VEC prevent these SUG effects. The protective role of both ROC and VEC could be explained by the fact that SUG encapsulates NMB drugs. In BBB impaired conditions it would be desirable to control SUG doses to prevent the excess of free SUG in plasma that may induce neuronal damage. A balance between SUG, ROC or VEC would be necessary to prevent the risk of cell damage.

A Novel and Simple Method for Tracheal Intubation in a Swine Model: Preparing for the Era of Xenotransplantation.

OBJECTIVES: Organ transplant in humans is an established therapy for a variety of end-stage organ diseases. However, due to organ shortages and lack of donors, the need for xenotransplant has gradually increased. Xenotransplantation has great potential to solve many of the problems facing organ transplantation. Pigs are being developed as xenogeneic organ donors for use in humans. In this study, we propose a novel and simple method for tracheal intubation in a swine model using neuromuscular blocking agents and laryngeal mask airway. MATERIALS AND METHODS: Eight Yorkshire pigs were used for the 2 separate experiments, which were conducted 1 week apart. In the first experiment, an anesthesiologist with no previous comparable experience performed endotracheal intubation of pigs. One week later, using the same pig, a second experiment was performed by an experienced anesthesiologist. Anesthesia was induced with intramuscular injection of a mixture of 1 mg/kg xylazine (Rompun, Bayer Korea Ltd., Seoul, Korea) and 7 mg/kg Zoletil (a mixture of tiletamine hydrochloride and zolazepam hydro-chloride, Virbac Laboratory, Carros, France). The laryngeal mask was then placed, and 0.15 mg/kg vecuronium bromide was injected intravenously. Tracheal intubation was attempted after mask removal. The duration and number of intubation attempts were recorded, and the degree of intubation difficulty was scored. RESULTS: In all cases, the laryngeal mask was easily inserted, and endotracheal intubation was successfully completed. Oxygen saturation did not fall below 95%, and there were no hypoxemia episodes. Degree of intubation difficulty and duration were not significantly different between the 2 anesthesiologists. CONCLUSIONS: Tracheal intubation in our swine model was successfully performed using neuromuscular blocking agents and laryngeal masks without resulting in hypoxemia, with even anesthesiologists who are unfamiliar with endotracheal intubation of pigs easily able to do so using our protocol. Therefore, our protocol will enable all investigators to perform successful tracheal intubation in swine models.

Intraoperative aberrant bispectral index values due to facial nerve monitoring.

Bispectral index is an accepted depth of anaesthesia monitor for guiding intraoperative hypnotic agent administration. Frontalis EMG displayed on BIS monitor may increase due to twitching of frontalis muscle. EMG increases are also known to cause artefactual increases in BIS values. We report a case of artefactual increase of EMG and subsequently BIS values, due to electrical artefact from cranial nerve stimulator being used to identify the facial nerve. An explanation of the effect of stimulator signal on BIS EMG and BIS values has been provided.

Neuromuscular blockade and inspiratory breath hold during stereotactic body radiation therapy for treatment of heart base tumors in four dogs.

CASE DESCRIPTION 4 dogs were examined because of pleural effusion and ventricular tachycardia, coughing and supraventricular tachycardia, appendicular osteosarcoma, and syncopal episodes. CLINICAL FINDINGS In all 4 dogs, a heart base tumor was identified by means of thoracic CT. TREATMENT AND OUTCOME In all 4 dogs, the heart base tumors were treated by means of stereotactic body radiation therapy. Dogs were anesthetized, and neuromuscular blockade was achieved with atracurium or vecuronium. A circle rebreathing system with 15 m (50 feet) of anesthetic tubing coursing through the vault wall was used to connect the patient to the anesthesia machine, which was located in the control room. After a brief period of hyperventilation, an inspiratory breath was held at 20 cm H2O for the duration of beam delivery. Each beam delivery lasted between 30 and 100 seconds. Immediately following the breath hold, assisted ventilation was resumed. Mean treatment delivery time for each patient was 26 minutes; mean total anesthesia time was 89 minutes. All patients recovered without complications. There was no evidence of hemoglobin desaturation or hypercapnia during the anesthetic procedure. CLINICAL RELEVANCE The technique allowed for control of the respiration cycle from outside the radiation vault and a short overall treatment time. No adverse effects were encountered. This procedure should be considered when delivering radiation to structures within the thoracic cavity.

Use of Sugammadex in Patients With Obesity: A Pooled Analysis.

A growing proportion of patients undergoing surgical procedures are obese, providing anesthesiologists with numerous challenges for patient management. The current pooled analysis evaluated recovery times following sugammadex reversal of neuromuscular blockade by body mass index (BMI) in general, and in particular, in patients with BMIs ≥30 kg/m (defined as obese) and <30 kg/m (defined as non-obese). Data were pooled from 27 trials evaluating recommended sugammadex doses for reversal of moderate [reappearance of the second twitch of the train-of-four (TOF); sugammadex 2 mg/kg] or deep (1-2 post-tetanic counts or 15 minutes after rocuronium; sugammadex 4 mg/kg) rocuronium- or vecuronium-induced neuromuscular blockade. All doses of sugammadex were administered based on actual body weight. The recovery time from sugammadex administration to a TOF ratio ≥0.9 was the primary efficacy variable in all individual studies and in the pooled analysis. This analysis comprised a total of 1418 adult patients treated with sugammadex; 267 (18.8%) of these patients had a BMI ≥30 kg/m. The average time to recovery of the TOF ratio to 0.9 was 1.9 minutes for rocuronium-induced blockade and 3.0 minutes for vecuronium-induced blockade. No clinically relevant correlation was observed between BMI and recovery time. The recommended sugammadex doses based on actual body weight provide rapid recovery from neuromuscular blockade in both obese and non-obese patients; no dose adjustments are required in the obese patient.

Sugammadex at both high and low doses does not affect the depth of anesthesia or hemodynamics: a randomized double blind trial.

Previous studies have shown that sugammadex decreases the anesthetic depth when administered to reverse the neuromuscular blockade produced by rocuronium/vecuronium. The aim of the present study was to investigate the effect of sugammadex alone on anesthetic depth and hemodynamics. Sixty patients scheduled for abdominal surgery participated in the study. Anesthesia was induced with thiopental/fentanyl and maintained with N2O/oxygen and sevoflurane concentrations adjusted to maintain Entropy and Bispectral Index (BIS) values between 40 and 50. Cis-atracurium 0.2 mg/kg was administered for neuromuscular blockade which was monitored with a TOF-Watch® SX acceleromyograph. State entropy (SE), response entropy (RE), Bispectral Index (BIS), systolic (SAP) and diastolic blood pressure (DAP), heart rate (HR), SpO2, end-tidal CO2 and sevoflurane concentrations were recorded every 3 min intraoperatively. Sugammadex 2 mg/kg (Group-2), 4 mg/kg (Group-4) or 16 mg/kg (Group-16) was given intravenously when a count of two responses of the train-of-four (TOF) or a post-tetanic count (PTC) 1-3 appeared or when no response at all (PTC = 0) was observed, respectively. The overall SE values, thus the primary outcome of the study, were 44 ± 11, 43 ± 10 and 43 ± 11 for Group-2, Group-4 and Group-16, respectively (p = 0.812). Also, the secondary endpoints, namely RE, BIS, SAP and DAP, HR and SpO2 did not differ between the three groups. Comparisons between Group-2 versus Group-4, Group-2 versus Group-16 and Group-4 versus Group-16 showed no differences (p > 0.05) for all the studied variables. Sugammadex alone at low, medium or high clinical doses has no effect on anesthetic depth as assessed by Entropy and BIS or on hemodynamics.

Efficacy and safety of sugammadex compared to neostigmine for reversal of neuromuscular blockade: a meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Sugammadex has been introduced for reversal of rocuronium (or vecuronium)-induced neuromuscular blockade (NMB). Although its efficacy has been established, data are conflicting whether it is safer than neostigmine traditionally used for reversing NMB. DESIGN: Meta-analysis of data about effectiveness and safety of sugammadex compared to neostigmine for reversing NMB in adults was performed using the PRISMA methodology. SETTING: University medical hospital. METHODS: A comprehensive search was conducted using PubMed, Web of Science, and Cochrane Library electronic databases to identify English-language randomized controlled trials. Two reviewers independently selected the trials; extracted data on reversal times, incomplete reversals of NMB, and adverse events (AEs); and assessed the trials' methodological quality and evidence level. Only AEs that were related to study drug by a blinded safety assessor were considered for meta-analysis. PATIENTS: A total of 1384 patients from 13 articles were included in this meta-analysis. MAIN RESULTS: Compared to neostigmine, sugammadex was faster in reversing NMB (P<.0001) and more likely to be associated with higher train-of-four ratio values at extubation (mean difference, 0.18; 95% confidence interval [CI], 0.14-0.22; P<.0001) and lower risk of postoperative residual curarization after extubation (odds ratio [OR], 0.05; 95% CI, 0.01-0.43; P=.0068). Compared to neostigmine, sugammadex was associated with a significantly lower likelihood of global AEs (OR, 0.47; 95% CI, 0.34-0.66; P<.0001), respiratory AEs (OR, 0.36; 95% CI, 0.14-0.95; P=.0386), cardiovascular AEs (OR, 0.23; 95% CI, 0.08-0.61; P=.0036), and postoperative weakness (OR, 0.45; 95% CI, 0.21-0.97; P=.0409). Sugammadex and neostigmine were associated with a similar likelihood of postoperative nausea and vomiting (OR, 1.23; 95% CI, 0.70-2.15; P=.4719), pain (OR, 1.06; 95% CI, 0.15-7.36; P=.9559), neurologic AEs (OR, 1.47; 95% CI, 0.52-4.17; P=.4699), general AEs (OR, 0.75; 95% CI, 0.47-1.21; P=.2448), and changes in laboratory tests' values (OR, 0.57; 95% CI, 0.18-1.78; P=.3368). CONCLUSIONS: Results from this meta-analysis suggest that sugammadex is superior to neostigmine, as it reverses NMB faster and more reliably, with a lower risk of AEs.

The effects of intravenous anesthetics on QT interval during anesthetic induction with sevoflurane.

PURPOSE: Sevoflurane is known to prolong the QT interval. This study aimed to determine the effect of the interaction between intravenous anesthetics and sevoflurane on the QT interval. METHODS: The study included 48 patients who underwent lumbar spine surgery. Patients received 3 µg/kg fentanyl and were then randomly allocated to either Group T, in which they received 5 mg/kg thiamylal, or Group P, in which they received 1.5 mg/kg propofol, at 2 min after administration of fentanyl injection for anesthetic induction. Vecuronium (1.5 mg/kg) and sevoflurane (3 % inhaled concentration) were administered immediately after loss of consciousness and tracheal intubation was performed 3 min after vecuronium injection. Heart rate (HR), mean arterial pressure (MAP), bispectral index score (BIS), and the heart rate-corrected QT (QTc) interval on a 12-lead electrocardiogram were recorded immediately before fentanyl administration (T1), 2 min after fentanyl injection (T2), immediately before intubation (T3), and 2 min after intubation (T4). RESULTS: There were no significant differences between the two groups in baseline patient characteristics. BIS and MAP significantly decreased after anesthesia induction in both groups. At T3, MAP in Group T was higher than in Group P, while HR had reduced in both groups. The QTc interval was prolonged after anesthesia induction in Group T, but did not change at any time point in Group P. The QTc interval after anesthesia induction in Group T was longer than in Group P. CONCLUSION: We concluded that an injection of propofol could counteract QTc interval prolongation associated with sevoflurane anesthesia induction.

Feasibility of monitoring stress using skin conduction measurements during intubation of newborns.

The objective of this study was to assess the feasibility of monitoring stress responses in newborns during naso-tracheal intubation after two different premedication regimens, using skin conductance measurements (SCM). Twenty-two newborns were randomised and premedicated with morphine + vecuronium or propofol. SCM (peaks/s) were collected prior to, during and after the procedure. Threshold for interpreting responses as stressful was 0.21 peaks/s. Intubation conditions and physiological parameters were registered. Intubation conditions were good in all newborns. Administration of morphine (range 1.4-10.3 min) before administration of vecuronium did not affect SCM when a stressful stimulus was applied. Within 1.6 min (range 0.8-3 min) after administration of vecuronium, SCM disappeared in 10 of 11 newborns. Propofol reduced SCM in 10 of 11 newborns at the first attempt. Further attempts were associated with increasing SCM, mostly above a threshold of 0.21 peaks/s. There were no significant changes in physiological parameters during the procedure for either premedication regimen. CONCLUSION: The variation in SCM between individual newborns limits the usefulness of SCM as stress monitor during intubation. The use of neuromuscular blockers for premedication precludes monitoring of SCM completely in newborns. WHAT IS KNOWN: Skin conductance measurements have been used successfully to monitor pain in awake newborn infants. WHAT IS NEW: Premedicated newborns display significant interindividual variation in skin conductance measurements during an intubation procedure. Neuromuscular blockade causes skin conductance measurements to disappear completely.