Reversal Of Neuromuscular Blockade Research Articles

785: EVALUATION OF SUGAMMADEX DOSING FOR DEEP NEUROMUSCULAR BLOCKADE REVERSAL IN THE EMERGENCY DEPARTMENT

Introduction: Neuromuscular blocking agents (NMBAs) are often administered to facilitate rapid sequence intubation (RSI). The effects of neuromuscular blockade may be prolonged in the setting of organ dysfunction or need for rapid attainment of a neurological examination may be necessary. The primary objective of this study is to evaluate low (2 mg/kg) versus standard dose (4 mg/kg) sugammadex for reversal of deep neuromuscular blockade in the emergency department (ED) to facilitate neurological examination. Methods: A single-center, retrospective cohort study was performed and approved by the local Institutional Review Board. Patients were identified using sugammadex charge codes between 01/01/2017 - 07/15/2022. Adult patients were included if they received sugammadex in the ED to facilitate neurological examination, were given rocuronium or vecuronium for RSI, and had a documented train-of-four (TOF) before and after sugammadex administration. Patients were excluded if records were incomplete, initial sugammadex dose other than 2 mg/kg or 4 mg/kg was used and if initial TOF was 1 – 4. The primary outcome of this study was successful deep neuromuscular blockade reversal defined by achieving a post-treatment TOF of 4. Results: Of 36 sugammadex doses administered in the ED, 26 patients were included in the final analysis, with 10 in the low-dose group and 16 patients in the standard-dose group. The median dose was 2.28 mg/kg and 4.09 mg/kg for low- and standard-dose, respectively. The overall cohort was predominantly male (65.4%) with a median age of 68.4 years (49.7-76.9). Most patients presented for intraparenchymal hemorrhage (53.8%), with 57.7% of bleeds being traumatic in origin. Median initial Glasgow Coma Score was 3, and all initial TOF were zero. Paralytics were administered in the pre-hospital setting in 85% of patients, with rocuronium use predominating (92.3%). No significant difference in success rate of NMBA reversal was found between low-dose versus standard-dose sugammadex (100.0% vs. 93.8%, P = 1.000). Conclusions: Low-dose sugammadex did not result in a significantly different success rate of NMBA reversal when compared to standard-dose. Low-dose sugammadex may be a viable option for deep NMBA reversal in the ED to facilitate neurological examinations.

812: PROLONGED NEUROMUSCULAR BLOCKADE IN THE ICU FROM INADVERTENT SUBCUTANEOUS ROCURONIUM DEPOT

Introduction: Neuromuscular blockade (NMB) is essential in endotracheal intubation. Peripheral IVs (PIV) commonly infiltrate causing prolonged medication effects. The pharmacokinetics of subcutaneous or depot NMB are poorly defined. We report a case of intubation complicated by PIV infiltration resulting in subcutaneous (SQ) depot of rocuronium with prolonged NMB. This case encourages the inclusion of residual NMB in the differential diagnosis for patients whose neurologic exam fails to recover. Description: A 68-year-old male with hypertension and cirrhosis was admitted with urosepsis, acute kidney injury (AKI), rhabdomyolysis, and was intubated for respiratory failure. During induction with rocuronium, ketamine, and midazolam, no drug effects were noted, due to PIV infiltration. Re-induction via a different PIV and intubation were performed, causing hypotension. Vasopressors administered via a second PIV had no effect and brief cardiac arrest occurred. Epinephrine administered via Interosseous access produced return of spontaneous circulation and resolution of hypotension. The next day, the patient remained a Glasgow Coma Scale (GCS) 3T without sedation or NMB. After exclusion of other causes, train of four (TOF) twitch and bispectral Index (BiS) monitors suggested residual NMB. An NMB reversal agent (sugammadex) was administered resulting in improvement of TOF, spontaneous movement, respiration, and GCS. Due to the unknown duration of depot rocuronium with renal and hepatic injury, he remained intubated for 72 hours, then successfully extubated. Discussion: The differential diagnosis in a comatose patient following intubation and cardiac arrest is broad. In this patient, most diagnoses were excluded prior to identifying prolonged NMB. Prolonged NMB should have been considered and investigated earlier. Neither BIS nor TOF are commonly used tools and earlier utilization may have led to prompter recognition of NMB as the etiology of his poor neurologic exam. There is a paucity of literature on the identification and management of depot NMB, limited to isolated case reports. The diagnosis of prolonged NMB should be considered in the differential of any post-procedure patient without improvement in GCS.

Comparison of assessment of vocal cord mobility following thyroid surgery using Macintosh Laryngoscope and Airtraq

Introduction: Vocal cord assessment after thyroidectomy, routinely performed by anaesthesiologist by direct laryngoscopy in the immediate postoperative period is associated with significant haemodynamic changes and patient discomfort. Aim: Comparison of patient comfort, haemodynamic response and accuracy of assessment of vocal cord mobility between Airtraq and Macintosh laryngoscope. Methodology: In a prospective, randomised controlled study, 82 euthyroid patients, ASA PS 1-2, aged 20-60 years, of either gender undergoing thyroidectomy under general anaesthesia were randomised to one of two groups, Group M and Group A. Anaesthesia was induced with propofol and fentanyl, maintained with morphine, vecuronium, nitrous oxide and isoflurane in oxygen to maintain a MAC of 1-1.3%. At the end of surgery, patients were extubated after complete reversal of neuromuscular blockade and when fully awake. Vocal cord movement and haemodynamic changes were assessed three minutes later using either Airtraq (Group A) or Macintosh laryngoscope (Group M). Patient reactivity score (Favourable - No grimace or facial grimace; Unfavourable – Any head, neck and limb movements or cough). Vocal cord movements were again assessed by an ENT surgeon 48 hours later. Results: Demographic data, type and duration of surgery were similar in both groups. 63.4% of patients in Group A had favourable scores compared to 29.3% in Group M even though duration of laryngoscopy was longer in Group A. There was no significant difference in haemodynamic changes between the groups. Conclusion: Patients are more comfortable during vocal cord assessment with Airtraq laryngoscopy even though duration of laryngoscopy is longer when compared to Macintosh laryngoscope.

Sugammadex versus neostigmine for neuromuscular blockade reversal in outpatient surgeries: A randomized controlled trial to evaluate efficacy and associated healthcare cost in an academic center.

Neuromuscular blockade is an essential component of the general anesthesia as it allows for a better airway management and optimal surgical conditions. Despite significant reductions in extubation and OR readiness-for-discharge times have been associated with the use of sugammadex, the cost-effectiveness of this drug remains controversial. We aimed to compare the time to reach a train-of-four (TOF) response of ≥0.9 and operating room readiness for discharge in patients who received sugammadex for moderate neuromuscular blockade reversal when compared to neostigmine during outpatient surgeries under general anesthesia. Potential reduction in time for OR discharge readiness as a result of sugammadex use may compensate for the existing cost-gap between sugammadex and neostigmine. We conducted a single-center, randomized, double arm, open-label, prospective clinical trial involving adult patients undergoing outpatient surgeries under general anesthesia. Eligible subjects were randomized (1:1 ratio) into two groups to receive either sugammadex (Groups S), or neostigmine/glycopyrrolate (Group N) at the time of neuromuscular blockade reversal. The primary outcome was the time to reverse moderate rocuronium-induced neuromuscular blockade (TOF ratio ≥0.9) in both groups. In addition, post-anesthesia care unit (PACU)/hospital length of stay (LOS) and perioperative costs were compared among groups as secondary outcomes. Thirty-seven subjects were included in our statistical analysis (Group S= 18 subjects and Group N= 19 subjects). The median time to reach a TOF ratio ≥0.9 was significantly reduced in Group S when compared to Group N (180 versus 540 seconds; p = 0.0052). PACU and hospital LOS were comparable among groups. Postoperative nausea and vomiting was the main adverse effect reported in Group S (22.2% versus 5.3% in Group N; p = 0.18), while urinary retention (10.5%) and shortness of breath (5.3%) were only experienced by some patients in Group N. Moreover, no statistical differences were found between groups regarding OR/anesthesia, PACU, and total admission costs. Sugammadex use was associated with a significantly faster moderate neuromuscular blockade reversal. We found no evidence of increased perioperative costs associated with the use of sugammadex in patients undergoing outpatient surgeries in our academic institution. [https://clinicaltrials.gov/] identifier number [NCT03579589].

USE OF VIDEO LARYNGOSCOPE FOR DIFFICULT AIRWAY MANAGEMENT IN THORACIC SURGERY: A CASE STUDY

We present the clinical case of a 76-year-old male with the following medical history: Active smoker (2 packs/day),moderate obesity, moderate COPD. arterial hypertension, mellitus diabetes 2, dyslipidemia. Lacunar stroke without neurological damage, infrarenal abdominal aortic aneurysm of 40 mm, under follow-up in policlinic of Vascular Surgery, 1st degree atrioventricular block, under follow-up by Cardiology. Normal Echocardiography. PET-CT: Hypermetabolic pulmonary nodule in RUL, suggestive of cancer. FUNCTIONAL TESTS: Moderate obstructive pattern. FEV1 2.20 (72%), FEV1/FVC 58. DLCO 5.80 (64%). AIRWAY EXPLORATION: Retrognatia, Mallampati III, significant cervical stiffness, thick neck and degree of movement of head and neck < 80°. Case Management: Placement of thoracic epidural catheter (T5-T6) prior to induction for analgesic control during intraoperative and postoperativeperiod. Non-invasive blood pressure monitoring, 5-lead ECG, temperature, peripheral oxygen saturation (SpO2), Bispectral Index (BIS) and Train-of-four (TOF). In the presence of predictors of possible difficult airway and ventilation, material is prepared for management of possible difficult airway Pre-oxygenation with face mask and FiO2 1 until EtO2 85 mmHg is reached. Rapid sequence induction was performed with intravenous midazolam, fentanyl, propofol and 1,2 mg/kg of rocuronium. After reaching TOF 0, direct laryngoscopy was initially performed but a Cormark-Lehane (CL) III was observed.Indirect laryngoscopy was then performed with a McGrath video laryngoscope with a n°4 disposable blade, showing a CL I. Subsequently, an 11 Fr airway exchange catheter was introduced through the vocal cords into the trachea; then, the proximal end of the airway exchange catheter was inserted into the endobronchial lumen of the 37Fr Vivasight DL, to permet its insertion into the trachea guided by this airway exchange catheter under the vision of the McGrath videolaryngoscope. Once the VivaSight DL was inserted into the trachea, the airway exchange catheter was removed and the VivaSight DL tube was turned left 90° and was inserted successful into the left main bronchus guided by embedded camera of this special type of DLT. Anesthesia maintenance was performed with inhalated sevoflurane and continuous intravenous infusion of remifentanil and rocuronium. Epidural elastomer of levobupivacaine 0.125% at 7 ml/h. Controlled ventilation is maintained in volume control mode, with Tidal Volume (TV) at 7 ml/kg ideal weight in two-lung ventilation and 5 ml/kg ideal weight in one-lung ventilation. Alveolar Recruitment Maneouvres (ARM) after intubation and at start of one-lung ventilation (OLV) were performed. Good mechanics and adequate gas exchange throughout the procedure, with no episodes of desaturation. After completion of surgery, reversal of neuromuscular blockade was achieved with sugammadex at 2 mg/kg. After checking TOF ratio> 90% and adequate level of consciousness, optimal respiratory mechanics and a 100% SpO2, extubation was performed without incident. He was transferred to the intensive care unit for post-surgical control during the first 24 hours.

Optimal anesthesia protocols for successful intraoperative neuromonitoring during thyroid surgery

There are several factors related to anesthesia that are required for successful intraoperative neuromonitoring (IONM) during thyroid and parathyroid surgery, including proper placement of endotracheal tube, adequate neuromuscular blockade, use of appropriate neuromuscular blockade reversal agent, and pain management. In this review, we summarize the anesthesia issues related to IONM during thyroid and parathyroid surgery.

Role of Cardiac Anesthesiologists in Intraoperative Enhanced Recovery After Cardiac Surgery (ERACS) Protocol: A Retrospective Single-Center Study Analyzing Preliminary Results of a Yearlong ERACS Protocol Implementation

Enhanced recovery after cardiac surgery (ERACS) has been gaining rapid acceptance after multiple studies have demonstrated promising results in improved outcomes of enhanced recovery after surgery in other surgical fields (eg, colorectal, orthopedic, thoracic, etc). Cardiac surgery has several unique challenges, including sternotomy, cardiopulmonary bypass and associated coagulopathy, blood transfusion, and postoperative intensive care requirement. Nonetheless, selective cardiac surgical patients can still benefit from ERACS. Guidelines for perioperative care in cardiac surgery, previously published by the ERACS Society, are weighted heavily in preoperative and postoperative management without much focus on intraoperative care provided by anesthesiologists. To address this gap and to explore anesthesiology's contribution in achieving ERACS, the study authors' cardiac anesthesiology division, in collaboration with cardiac surgery, introduced the ERACS protocol in their institution in February 2020. The cardiac anesthesiology division, in collaboration with cardiac surgery, introduced the ERACS protocol consisting of multimodal opioid-sparing analgesia, including the introduction of regional blocks, hemostasis management protocol, reversal of neuromuscular blockade, and administration of antiemetics in the authors' institution in February 2020. They have conducted a retrospective chart review study comparing patients who have received ERACS measures with a similar historic cohort who underwent cardiac surgery prior to initiation of an ERACS protocol. The primary outcomes of the study were to determine patients' time to extubation, postoperative opioid consumption, intensive care unit (ICU) length of stay (LOS), and incidence of postoperative complications (eg, postoperative nausea vomiting [PONV], bleeding, ICU readmission, delirium. The ERACS patients showed reduced opioid consumption (intraoperative fentanyl; postoperative fentanyl, as well as oxycodone, in the first 6 hours postoperatively), lesser mechanical ventilation (2.5 hours less), shorter ICU stays (5 hours less), shorter hospital LOS (1 day), and lesser incidence of PONV. None of the ERACS patients required blood transfusion. The study authors performed an anonymous survey among the anesthesiologists and ICU providers to assess providers' satisfaction, which showed 92% of survey takers agreed that the ERACS protocol should be continued for future cardiac patients, and 61% of survey takers reported superior pain control in ERACS group of patients while managing those patients. The ERACS is achievable after the careful implementation of a series of measures. It does not signify only fast-track extubation and opioid-sparing analgesia, and must be implemented in the entire perioperative period beginning from preoperative clinic to postoperative rehabilitation. Cardiac anesthesiologists play a vital role in execution of intraoperative ERACS measures. Both providers and patients themselves are key stakeholders. A larger randomized prospective trial is warranted to solidify the inference.

Reversal of rocuronium-induced intense neuromuscular blockade by sugammadex in Korean children: A pharmacokinetic and pharmacodynamic analysis.

Sugammadex, a selective antagonist of steroidal non-depolarizing neuromuscular blocking agents, has been used in children in limited circumstances. However, neither pharmacokinetics (PKs) nor recovery profile of sugammadex for intense neuromuscular blockade reversal in children have been reported. This prospective study aimed to obtain a PK model of sugammadex and evaluate its efficacy and safety for intense neuromuscular blockade reversal in children. Forty children (age, 2-17 years) who underwent surgery that required early neuromuscular blockade reversal were enrolled. After neuromuscular blockade with 1mg∙kg-1 of rocuronium, sugammadex (2, 4, and 8mg∙kg-1 ) or a conventional dose of neostigmine (0.03 mg∙kg-1 ) was administered randomly after confirmation of zero post-tetanic count. The plasma concentrations of rocuronium and sugammadex were measured 2min after rocuronium injection; immediately before, 2, 5, 15, 60, 120, 240, and 480 min after the study drug injection. Response to train-of-four stimulation was continuously recorded. Noncompartmental analysis and population PK modeling were performed. For pharmacodynamics, the recovery profile was measured. Three-compartment PK model was established for sugammadex. The median (interquartile range [IQR]) time from injection of 8mg∙kg-1 of sugammadex to recovery of T4 /T1 greater than or equal to 0.9 at train-of-four stimulation was 1.1 (IQR: 0.88-1.8) min. No adverse events related to sugammadex were observed. We present a PK analysis of sugammadex for rocuronium-induced intense neuromuscular blockade reversal in children with its recovery profile. The time to recover T4 /T1 greater than or equal to 0.9 at train-of-four stimulation with 8mg∙kg-1 of sugammadex was less than 3min and comparable to that in adults.

Reversal of Neuromuscular Blockade Based on Train of Four Response: a Prospective Randomized Controlled Trial

Background and aims: Use of neostigmine to reverse the non-depoloarizing neuromuscular block at the end of the surgery is a standard practice. Reversal with neostigmine based on body weight is still commonly followed. However, neostigmine may affect adversely if used empirically in the absence of residual blockade. This study compares the empirical technique of reversal based on body weight with reversal using neostigmine dose adjusted to train-of-four (TOF) response. Methods: This prospective, double-blinded, randomized controlled trial included 126 patients undergoing surgery under general anaesthesia, lasting for &gt;1 hour. They were randomized into group control receiving weight based reversal (0.05 mg/kg neostigmine) and group study receiving dose determined by TOF response. Signs of residual paralysis after extubation were observed. TOF ratios/count, reversal to extubation time, dose and side-effects of reversal agent were also noted. Results: Patient characteristics were comparable in both groups. Number of patients with signs of residual weakness was less in group study (26/63), but comparable to group control (40/63, p=0.094). Number of patients with TOF≥0.9 at reversal and extubation was significantly high in group study (40/63) than group control (22/63), and number of patients with TOF count &lt;4 were significantly high in group control than group study (17/63 vs 8/63). Overall TOF ratio at reversal and extubation, reversal-extubation time, time taken to reach TOF 0.9 and side-effects were comparable. Conclusion: Reversal of neuromuscular block with neostigmine dose based on TOF ratio is comparable to weight based reversal with respect to postoperative residual weakness, reversal-extubation time and side effects of reversal agent.

Sugammadex Efficacy and Dosing for Rocuronium Reversal Outside of Perioperative Settings.

Background: Sugammadex is approved for postoperative recovery from rocuronium neuromuscular blockade with train-of-four (TOF) guided dosing. Data for non-perioperative sugammadex efficacy and dosing are limited when TOF is not available and reversal is not immediate. Objective: This study evaluated the efficacy, safety, and dose of sugammadex when administered in the emergency department (ED) or intensive care unit (ICU) for delayed rocuronium reversal when TOF guidance was not consistently available. Methods: This single-center, retrospective cohort study included patients over a 6-year period who received sugammadex in the ED or ICU at least 30 minutes after rocuronium administration for rapid sequence intubation (RSI). Patients who received sugammadex for intra-operative neuromuscular blockade reversal were excluded. Efficacy was defined as successful reversal documented in progress notes, TOF assessment, or improvement in Glasgow Coma Scale (GCS). Dose was evaluated in patients with successful reversal by correlating sugammadex and rocuronium dose with reversal time after paralysis. Results: Thirty-four patients were included with 19 (55.9%) patients receiving sugammadex in the ED. Sugammadex indication was acute neurologic assessment in 31 (91.1%) patients. Twenty-nine patients (85.2%) had successful reversal documented. The remaining 5 patients had fatal neurologic injuries with GCS 3 limiting non-TOF efficacy assessment. The median (IQR) sugammadex dose was 3.4 (2.5-4.1) mg/kg administered 89 (56.3-158) minutes after rocuronium. No correlation was identified between sugammadex dose, rocuronium dose, and administration time. No adverse events were noted. Conclusion: This pilot investigation demonstrated safe and effective rocuronium reversal with sugammadex 3 to 4 mg/kg administered in the non-operative setting 1 to 2 hours after RSI. Larger, prospective studies are necessary to determine the safety in patients outside of the operating room when TOF is not available.

Characterizing the Heart Rate Effects From Administration of Sugammadex to Reverse Neuromuscular Blockade: An Observational Study in Patients.

Reversal of neuromuscular blockade (NMB) with sugammadex can cause marked bradycardia and asystole. Administration of sugammadex typically occurs in a dynamic period when anesthetic adjuvants and gas concentrations are being titrated to achieve emergence. This evaluation examined the heart rate (HR) responses to sugammadex to reverse moderate to deep NMB during a steady-state period and sought mechanisms for HR changes. Patients with normal sinus rhythm, who were undergoing elective surgery that included rocuronium for NMB, were evaluated. After surgery, while at steady-state surgical depth anesthesia with sevoflurane and mechanical ventilation, patients received either placebo or 2 or 4 mg/kg of sugammadex to reverse moderate to deep NMB. Study personnel involved in data analysis were blinded to treatment. Continuous electrocardiogram (ECG) was recorded from the 5 minutes before and 5 minutes after sugammadex/placebo administration. R-R intervals were converted to HR and averaged in 1-minute increments. The maximum prolongation of an R-R interval after sugammadex was converted to an instantaneous HR. A total of 63 patients were evaluated: 8 received placebo, and 38 and 17 received 2 and 4 mg/kg sugammadex. Age, body mass index, and patient factors were similar in groups. Placebo did not elicit HR changes, whereas sugammadex caused maximum instantaneous HR slowing (calculated from the longest R-R interval), ranging from 2 to 19 beats/min. There were 7 patients with maximum HR slowing >10 beats/min. The average HR change and 95% confidence interval (CI) during the 5 minutes after 2 mg/kg sugammadex were 3.1 (CI, 2.3-4.1) beats/min, and this was not different from the 4 mg/kg sugammadex group (4.1 beats/min [CI, 2.5-5.6]). HR variability derived from the standard deviation of consecutive R-R intervals increased after sugammadex. Sugammadex to reverse moderate and deep NMB resulted in a fast onset and variable magnitude of HR slowing in patients. A difference in HR slowing as a function of dose did not achieve statistical significance. The observational nature of the investigation prevented a full understanding of the mechanism(s) of the HR slowing.

Predictive study of pharmacological reversal for residual neuromuscular blockade and postoperative pulmonary complications: a prospective, observational, cohort study

In recent years, some studies have generated controversy since they conclude that intraoperatively pharmacological reversal of neuromuscular blockade does not contribute to the reduction of postoperative residual neuromuscular blockade or pulmonary complications. Therefore, the main objective of this study was to assess the incidence of residual neuromuscular blockade and postoperative pulmonary complications according to spontaneous or pharmacological neuromuscular reversal. The secondary aim was to present a prognostic model to predict the probability of having postoperative residual neuromuscular blockade depending on a patient's comorbidities and intraoperative neuromuscular blocking agents management. A single-center, prospective, observational cohort study including patients undergoing surgical procedures with general anesthesia was designed. A total of 714 patients were analyzed. Patients were divided into four groups: cisatracurium with spontaneous reversal, cisatracurium with neostigmine antagonism, rocuronium with spontaneous reversal, and rocuronium with sugammadex antagonism. According to our binomial generalized linear model, none of the studied comorbidities was a predisposing factor for an increase in the residual neuromuscular blockade. However, in our study, pharmacological reversal of rocuronium with sugammadex and, particularly, neuromuscular monitoring during surgery were the factors that most effectively reduced the risk of residual neuromuscular blockade as well as early and late postoperative pulmonary complications.

Utility of neuromuscular blockade reversal in the evaluation of acute neurosurgical patients: A retrospective case-series

ObjectiveSugammadex reversal of neuromuscular blocking agents (NMBAs) is usually performed postoperatively. A scarcity of literature exists exploring sugammadex use for timely neurological examination of neurosurgical patients. NMBAs, like rocuronium, are used in the Emergency Department during intubation and their unpredictable duration of action often impedes timely and accurate assessment of patient neurological status. We aim to explore the role of sugammadex in evaluating patients in need of acute neurosurgical care. MethodsRetrospective assessment of patients presenting with traumatic brain injury or intracranial hemorrhage was conducted at our level 1 trauma center. Patients of interest were those for whom sugammadex reversal of rocuronium neuromuscular blockade, from intubating doses, was pursued to ensure timely neurologic assessment. Nine patients were identified for whom GCS pre-/post-sugammadex, rocuronium dosing, elapsed time between rocuronium administration and reversal, and clinical course data were retrieved. ResultsArrival GCS was 5.2 ± 3.2, with intubation accomplished within 10 ± 2.5 min of presentation. Rocuronium dosing was consistent between patients, average single dose of 1.2 ± 0.3 mg/kg. Lingering neuromuscular blockade ranged from 28 to 132 min (87.3 ± 34.3 min). All patients exhibited a GCS of 3 T upon initial neurosurgical evaluation, prior to reversal. Post-reversal GCS rose to 6.0 T ± 2.2. Sugammadex facilitated more accurate clinical decision making in 8 of 9 patients, including prevention of unnecessary invasive procedures. Two of 9 patients were eventually discharged home or to a rehabilitation facility. ConclusionsRocuronium neuromuscular blockade can linger beyond pharmacokinetic predictions, thus delaying timely and precise neurologic assessment. Our data suggests sugammadex may be a useful addition to the clinician’s armamentarium for acute neurologic assessment in the neurosurgical population. Sugammadex may impact clinical decision-making in certain patients and allow for more informed decision-making by families and physicians alike. Prospective studies are needed to definitively assess the impact of sugammadex on outcomes in acute neurosurgical settings.

Optimizing Reversal of Neuromuscular Block in Older Adults: Sugammadex or Neostigmine.

Residual neuromuscular paralysis, the presence of clinically significant weakness after administration of pharmacologic neuromuscular blockade reversal, is associated with postoperative pulmonary complications and is more common in older patients. In contemporary anesthesia practice, reversal of neuromuscular blockade is accomplished with neostigmine or sugammadex. Neostigmine, an acetylcholinesterase inhibitor, increases the concentration of acetylcholine at the neuromuscular junction, providing competitive antagonism of neuromuscular blocking drug and facilitating muscle contraction. Sugammadex, a modified gamma-cyclodextrin, antagonizes neuromuscular blockade by encapsulating rocuronium and vecuronium in a one-to-one ratio for renal clearance, a pharmacokinetic property that led to the recommendation that sugammadex not be administered to those with end-stage renal disease. While data are limited, reports suggest sugammadex is efficacious and well tolerated in individuals with reduced renal function. Sugammadex provides a more rapid and complete reversal of neuromuscular blockade than neostigmine. There is also accumulating evidence that sugammadex may provide a protective effect against the development of postoperative pulmonary complications, nausea, and vomiting, and that it may have beneficial effects on the rate of bowel and bladder recovery after surgery. Accordingly, sugammadex administration is beneficial for most older patients undergoing surgery.

Appropriate dosing of sugammadex for reversal of rocuronium-/vecuronium-induced muscle relaxation in morbidly obese patients: a meta-analysis of randomized controlled trials.

ObjectiveTo conduct a meta-analysis to compare different dosing scalars of sugammadex in a morbidly obese population for reversal of neuromuscular blockade (NMB).MethodsPubMed®, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar were searched for relevant randomized controlled trials (RCTs) comparing lower-dose sugammadex using ideal body weight (IBW) or corrected body weight (CBW) as dosing scalars with standard-dose sugammadex based on total body weight (TBW) among morbidly obese people after NMB. Mean difference with SD was used to estimate the results.ResultsThe analysis included five RCT with a total of 444 morbidly obese patients. The reversal time was significantly longer in patients receiving sugammadex with dosing scalar based on IBW than in patients receiving sugammadex with dosing scalar based on TBW (mean difference 55.77 s, 95% confidence interval [CI] 32.01, 79.53 s), but it was not significantly different between patients receiving sugammadex with dosing scalars based on CBW versus TBW (mean difference 2.28 s, 95% CI –10.34, 14.89 s).ConclusionCompared with standard-dose sugammadex based on TBW, lower-dose sugammadex based on IBW had 56 s longer reversal time whereas lower-dose sugammadex based on CBW had a comparable reversal time.

A single center analysis of sugammadex and neostigmine/glycopyrrolate utilization for post-operative neuromuscular blockade reversal

BackgroundPrevious cost-effective analyses and studies analyzing post-anesthesia care unit length of stay between sugammadex and neostigmine/glycopyrrolate for neuromuscular blockade reversal revealed mixed results. Baseline characteristics between adult surgical patients receiving these agents were controlled and matched in this study to describe these differences in cost and first neuromuscular blocking agent (NMBA) reversal dose to recovery room time. AimTo evaluate the differences in the time from the first NMBA reversal dose to recovery room arrival between sugammadex and neostigmine/glycopyrrolate. MethodsIn this retrospective matched cohort study, 142 adult surgical patients who received sugammadex were matched to 142 neostigmine/glycopyrrolate adult surgical patients that received at least one dose of rocuronium or vecuronium. The primary outcome was the time from the first NMBA reversal dose to recovery room arrival. Secondary outcomes included: differences in the time from the recovery room to the floor, evaluation of the total cost, and total drug cost. ResultsThe time from first NMBA reversal dose to recovery room arrival was similar between groups (neostigmine/glycopyrrolate 19.5 min (14–31 min) versus sugammadex 19.0 min (13.8–24.3 min); p = 0.165). The medium time from the recovery room to the floor is 91.0 and 94.5 min in the sugammadex and neostigmine/glycopyrrolate groups, respectively (p = 0.302). The incidence of reintubation was not statistically different (p = 1.00). The total drug cost was higher in the sugammadex group versus the neostigmine/glycopyrrolate group, $97.00 USD (97–114.48) versus $8.99 USD (6.23–11.52), respectively (p < 0.05). However, the medium total cost was $985.32 USD for neostigmine/glycopyrrolate whereas it was $1047.00 USD for sugammadex. ConclusionThe time from the first NMBA reversal dose to recovery room and time from recovery room to the floor were comparable between sugammadex and neostigmine/glycopyrrolate. There were no differences in reintubation rates. While the difference in total drug cost was statistically significant between the two groups, the total cost was not. Further analysis is needed to assess these safety and economic implications of these findings.

Prevention of Postoperative Events following Reversal with Sugammadex or Neostigmine (the P-PERSoN Trial): Pilot Data Following Early Termination of a Prospective, Blinded, Randomised Trial.

Background Residual paralysis following anaesthesia is common and can lead to postoperative morbidity. While sugammadex has been shown to be effective in minimising residual paralysis, uncertainty exists as to whether its use reduces any associated morbidity. We designed this trial to determine if the use of sugammadex for the reversal of intraoperative aminosteroid neuromuscular blockade results in improvements in postoperative pulmonary complications, complications in the recovery unit, postoperative nausea and vomiting, and patient satisfaction, when compared to reversal with neostigmine. Methods A prospective, double-blind, randomised controlled trial in adult patients admitted for surgical operations at two Australian hospitals between December 2018 and March 2019 was performed comparing the reversal of neuromuscular paralysis using sugammadex 2 mg/kg versus neostigmine 50mcg/kg. Statistical analysis of continuous data was performed using two tailed t-tests, with categorical and ordinal data being assessed by chi-squared analysis. Results The trial was terminated due to a combination of resource constraints and the 2019 novel coronavirus disease (COVID-19) pandemic. Of 51 patients screened, 33 were eligible for participation and 30 subsequently recruited and randomised. All patients received the intended treatment allocated. Data for the primary outcome was obtained in all patients. There was no difference in the rates of postoperative pulmonary complications between the sugammadex and neostigmine groups (0% (0/19) vs 9% (1/11) RR 5.0 (95% CI 0.22–113) p=0.37. There was no difference in any of the secondary outcomes between the groups. Conclusions The P-PERSoN trial showed no difference in postoperative pulmonary complications between sugammadex and neostigmine based reversal of aminosteroid neuromuscular block, but was underpowered to show any difference due to early trial termination. The randomisation and data collection was feasible. We support the need for an adequately resourced and funded randomised controlled trial to address this important clinical question.

Reversal of Neuromuscular Blockade by Sugammadex for Stimulator-Guided Nerve Blocks After Tracheal Intubation: Is It Necessary?

Reversal of Neuromuscular Blockade by Sugammadex for Stimulator-Guided Nerve Blocks After Tracheal Intubation: Is It Necessary?

Pro-Con Debate: Do We Need Quantitative Neuromuscular Monitoring in the Era of Sugammadex?

In this Pro-Con article, we debate the merits of using quantitative neuromuscular blockade monitoring. Consensus guidelines recommend their use to guide the administration of nondepolarizing neuromuscular blockade and reversal agents. A major impediment to this guideline is that until recently, reliable quantitative neuromuscular blockade monitors have not been widely available. Without them, anesthesia providers have been trained with and are adept at using a variety of qualitative neuromuscular blockade monitors otherwise known as peripheral nerve stimulators. Although perhaps less accurate, anesthesia providers find them reliable and easy to use. They have a long track record of using them with the perception that their use leads to effective neuromuscular blockade reversal and minimizes clinically significant adverse events from residual neuromuscular blockade. In the recent past, 2 disruptive developments have called upon anesthesia care providers to reconsider their practice in neuromuscular blockade administration, reversal, and monitoring. These include: (1) commercialization of more reliable quantitative neuromuscular monitors and (2) widespread use of sugammadex, a versatile reversal agent of neuromuscular blockade. Sugammadex appears to be so effective at rapidly and effectively reversing even the deepest of neuromuscular blockades, and it has left anesthesia providers wondering whether quantitative monitoring is indeed necessary or whether conventional, familiar, and less expensive qualitative monitoring will suffice? This Pro-Con debate will contrast anesthesia provider perceptions with evidence surrounding the use of quantitative neuromuscular blockade monitors to explore whether quantitative neuromuscular monitoring (NMM) is just another technology solution looking for a problem or a significant advance in NMM that will improve patient safety and outcomes.

Self-double Emulsified Drug Delivery System of Pyridostigmine Bromide Augmented Permeation Across Caco-2 Cells

Aim: The study aims to enhance the permeability of pyridostigmine bromide by developing a self-double emulsifying drug delivery system (SDEDDS) and enteric-coated spheroids. Background: Pyridostigmine bromide is a reversible anticholinesterase used to treat Myasthenia Gravis, reverse neuromuscular blockade, and prevent nerve gas (i.e., soman) poisoning. It is readily soluble in water, but its poor and irregular intestinal absorption is responsible for its poor oral bioavailability (7.6±2.4%). Many approaches have been made to increase the bioavailability of this drug, but no significant improvement has been achieved to date. Presently pyridostigmine tablets are given orally, and a treatment schedule of multiple doses every day (3–6 times per day) is recommended for adult patients, while sustained-release pyridostigmine (Timespan®) tablets can be taken once or twice daily. An increase in permeability of pyridostigmine bromide may also result in reduced dosage frequency. Objective: In the present work, it is proposed to develop a self-double emulsifying drug delivery system (SDEDDS) of pyridostigmine bromide which will increase its intestinal permeability and hence its oral bioavailability. Methods: For the preparation of PB-SDEDDS, the primary water in oil emulsion was mixed with the optimized concentration of Tween 80 using a magnetic stirrer. PB-SDEDDS were converted into spheroids and were then characterized. Results: The pseudo ternary phase diagram was constructed, showing a double emulsion region. The viscosity of PB-SDEDDS at the different shear rates was found to be 125 mPas. The optimized PBSDEDDS formulation formed a bright white emulsion within 2 minutes, having droplet size around 20-25 μm. In vitro uptake studies of PB-SDEDDS on Caco2 cells demonstrated the increase in Papp value from (4.38±0.27) ×10-4 cm/s to (9.488±0.182) ×10-4 cm/s (2.166 folds) that was attributed to the PB-SDEDDS formulation. In vitro cytotoxicity studies on Caco2 cells revealed that the blank SDEDDS showed almost no toxicity after incubation for 2 hours at various dilutions tested. Among all formulations, F3 was optimized for the concentration of adsorbent and binder at a concentration of 10% each. SEM showed that the spheroids were spherical, and 73.92% of spheroids were in between 0.595-0.841 mm of size. The optimized formulation had 70.29% spheroids retained on sieve no. 30. The angle of repose showed good flow properties with 25.20 and stability with friability of 0.52 %. The disintegration time of the developed formulation was 3.30 minutes, and drug content was found to be 97.83%. The release studies showed that PB-SDEDDS improved the release significantly compared to the market formulation. Conclusion: The solid PB-SDEDDS resulted in favorable physical properties and did not affect its drug content and in vitro drug release profile. The self-double emulsifying drug delivery system of pyridostigmine bromide can be explored as a suitable alternative to its solid oral dosage form.