Comparison of inflammatory markers in low-pressure pneumoperitoneum with deep neuromuscular block versus standard pressure pneumoperitoneum among patients undergoing laparoscopic cholecystectomy for gallstone disease: a randomized control trial.

BACKGROUND: Low-pressure pneumoperitoneum (LPP) is an attempt to improve laparoscopic surgery. Lower pressure causes lesser inflammation and better hemodynamics. There is a lack of literature comparing inflammatory markers in LPP with deep NMB to standard pressure pneumoperitoneum (SPP) with moderate NMB in laparoscopic cholecystectomy. METHODOLOGY: This was a single institutional prospective randomized control trial. Participants included all patients undergoing laparoscopic cholecystectomy for symptomatic gall stone disease. Participants were divided into 2 groups group A and B. Group A-Low-pressure group in which pneumoperitoneum pressure was kept low (8-10 mmHg) with deep Neuromuscular blockade (NMB) and Group B-Normal pressure group (12-14 mmHg) with moderate NMB. A convenience sample size of 80 with 40 in each group was selected. Lab investigations like CBC, LFT, RFT and serum IL-1, IL-6, IL-17, TNF alpha levels were measured at base line and 24 h after surgery and compared using appropriate statistical tests. Other parameters like length of hospital stay, post-operative pain score, conversion rate (low-pressure to standard pressure), and complications were also compared. RESULTS: Eighty participants were analysed with 40 in each group. Baseline characteristics and investigations were statistically similar. Difference (post-operative-pre-operative) of inflammatory markers were compared between both groups. Numerically there was a slightly higher rise in most of the inflammatory markers (TLC, ESR, CRP, IL-6, TNFα) in Group B compared to Group A but not statistically significant. Albumin showed significant fall (p < 0.001) in Group B compared to Group A. Post-operative pain was also significantly less (p < 0.001) in Group A compared to Group B at 6 h and 24 h. There were no differences in length of hospital stay and incidence of complications. There was no conversion from low-pressure to standard pressure. CONCLUSION: Laparoscopic cholecystectomy performed under low-pressure pneumoperitoneum with deep NMB may have lesser inflammation and lesser post-operative pain compared to standard pressure pneumoperitoneum with moderate NMB. Future studies with larger sample size need to be designed to support these findings.

Feasibility of the enhanced neuromuscular blockade recovery protocol with selective use of sugammadex in thyroid surgery with intraoperative neuromonitoring.

BACKGROUND: To investigate feasibility of utilizing enhanced neuromuscular blocking agents with selective recovery protocol during thyroid surgery with intraoperative neuromonitoring (IONM). METHODS: Two-hundred and ninety patients were randomized into two groups: group A 0.3 mg/kg rocuronium and group B 0.6 mg/kg. Sugammadex 2 mg/kg was injected if needed followed initial vagal stimulation (V0). Electromyography signals from vagus and recurrent laryngeal nerves before and after resection were recorded as V1, V2, R1, and R2. RESULTS: In group B, 30 patients (20.7%) had V0 signals <100 µV, compared to 9 (6.2%) in group A. After sugammadex administration, 144 patients (99.3%) in both groups achieved positive V1 signals. Group B demonstrated a shorter surgical time from rocuronium injection to V2 stimulation compared to group A, accompanied by a significantly lower incidence of intraoperative body movement (0 vs. 16 patients). CONCLUSIONS: 0.6 mg/kg rocuronium with selective use 2 mg/kg sugammadex for IONM in thyroid surgery can meet both anesthesia and surgery demands.

Sugammadex use in pediatric patients with stage IV-V chronic kidney disease in a quaternary referral hospital: a case series.

BACKGROUND: Sugammadex is a pharmacologic agent that provides rapid reversal of neuromuscular blockade via encapsulation of the neuromuscular blocking agent (NMBA). The sugammadex-NMBA complex is primarily cleared through glomerular filtration from the kidney, raising the possibility that alterations in renal function could affect its elimination. In pediatric patients, the benefits of sugammadex have led to widespread utilization; however, there is limited information on its application in pediatric renal impairment. This study examined sugammadex use and postoperative outcomes in pediatric patients with severe chronic renal impairment at our quaternary pediatric referral hospital. METHODS: After IRB approval, we performed a retrospective analysis in pediatric patients with stage IV and V chronic kidney disease who received sugammadex from January 2017 to March 2022. Postoperative outcomes studied included new or increased respiratory requirement, unplanned intensive care unit (ICU) admission, postoperative pneumonia, anaphylaxis, and death within 48 h postoperatively, unplanned deferral of intraoperative extubation, and repeat administrations of NMBA reversal after leaving the operating room. RESULTS: The final cohort included 17 patients ranging from 8 months to 16 years old. One patient required new postoperative noninvasive ventilation on postoperative day 2, which was credited to hypervolemia. Another patient had bronchospasm intraoperatively resolving with medication, which could not definitively be associated sugammadex administration. There were no instances of deferred extubation, unplanned ICU or need for supplemental oxygen after tracheal extubation identified. CONCLUSION: No adverse effects directly attributable to sugammadex in pediatric patients with severe renal impairment were detected. There may be a role for utilization of sugammadex for neuromuscular reversal in this population.

The safety and efficacy of sugammadex for reversing neuromuscular blockade in younger children and infants.

INTRODUCTION: Sugammadex, a novel selective antagonist of non-depolarizing neuromuscular blocking agents, has been shown to rapidly and effectively reverse moderate and deep paralysis in adults and pediatric patients over age 2, improving patient recovery and reducing the risk of postoperative complications. AREAS COVERED: Since the use of sugammadex in patients under age 2 is not widely studied, we aim to provide an overview on the drug's application and potential use in infants and neonates. There is a limited but growing body of evidence for the safe, efficacious use of sugammadex in children under age 2. Relevant studies were identified from the most updated data including case reports, clinical trials, systematic reviews, and meta analyses. EXPERT OPINION: The results suggest that at a dose of 2 to 4 mg/kg of sugammadex can be safely used to rapidly and effectively reverse neuromuscular blockade in neonates and infants; it is non-inferior based on incidence of adverse events compared to neostigmine. Additionally, sugammadex doses between 8 and 16 mg/kg may be used as a rescue agent for infants during 'can't intubate, can't ventilate' crisis. Overall, sugammadex offers new value in the perioperative care of patients under age 2, with further studies warranted to better understand its application and full effect in the pediatric population.

Anesthetic Management of Patients With Morvan Syndrome: A Case Report and Literature Review.

Morvan syndrome is a rare condition distinguished by hyperactivity within the central, autonomic, and peripheral nervous systems. Due to the limited number of cases, this presents clinical challenges stemming from the scarcity of published literature. We present a successful anesthetic approach for a patient diagnosed with Morvan syndrome scheduled for elective major intra-thoracic surgery to remove metastases from a thymoma. The patient had previously undergone thymectomy, with the syndrome being diagnosed only one year after the surgery. Additionally, we conducted a literature review on the anesthetic management of this condition.

Evolution of a laboratory mechanomyograph.

Mechanomyography is currently the accepted laboratory reference standard for quantitative neuromuscular blockade monitoring. Mechanomyographs are not commercially available. Previously, a mechanomyograph was built by our laboratory and used in several clinical studies. It was subsequently redesigned to improve its usability and functionality and to accommodate a wider range of hand sizes and shapes using an iterative design process. Each version of the redesigned device was initially tested for usability and functionality in the lab with the investigators as subjects without electrical stimulation. The redesigned devices were then assessed on patients undergoing elective surgery under general anesthesia without neuromuscular blocking drugs. Since the patients were not paralyzed, the expected train-of-four ratio was 1.0. The device accuracy and precision were represented by the train-of-four ratio mean and standard deviation. If issues with the device's useability or functionality were discovered, changes were made, and the redesign processes repeated. The final mechanomyograph design was used to collect 2,362 train-of-four ratios from 21 patients. The mean and standard deviation of the train-of-four ratios were 0.99 ± 0.030. Additionally, the final mechanomyograph design was easier to use and adjust than the original design and fit a wider range of hand sizes. The final design also reduced the frequency of adjustments and the time needed for adjustments, facilitating data collection during a surgical procedure.

Association between reversal agents (sugammadex vs. neostigmine) for neuromuscular block and postoperative pulmonary complications: A retrospective analysis.

AIMS: Residual neuromuscular blockade has been linked to pulmonary complications in the postoperative period. This study aimed to determine whether sugammadex was associated with a lower risk of postoperative pulmonary complications (PPCs) compared with neostigmine. METHODS: This retrospective cohort study was conducted in a tertiary academic medical center. Patients ≥18 year of age undergoing noncardiac surgical procedures with general anesthesia and mechanical ventilation were enrolled between January 2019 and September 2021. We identified all patients receiving rocuronium and reversal with neostigmine or sugammadex via electronic medical record review. The primary endpoint was a composite of PPCs (including pneumonia, atelectasis, respiratory failure, pulmonary embolism, pleural effusion, or pneumothorax). The incidence of PPCs was compared using propensity score analysis. RESULTS: A total of 1786 patients were included in this study. Among these patients, 976 (54.6%) received neostigmine, and 810 (45.4%) received sugammadex. In the whole sample, PPCs occurred in 81 (4.54%) subjects (7.04% sugammadex vs. 2.46% neostigmine). Baseline covariates were well balanced between groups after overlap weighting. Patients in the sugammadex group had similar risk (overlap weighting OR: 0.75; 95% CI: 0.40 to 1.41) compared to neostigmine. The sensitivity analysis showed consistent results. In subgroup analysis, the interaction P-value for the reversal agents stratified by surgery duration was 0.011. CONCLUSION: There was no significant difference in the rate of PPCs when the neuromuscular blockade was reversed with sugammadex compared to neostigmine. Patients undergoing prolonged surgery may benefit from sugammadex, which needs to be further investigated.

Polymyxin-induced neuromuscular weakness: a case report.

Polymyxin-induced neuromuscular blockade is a rare but potentially fatal condition, with majority of cases that were reported between 1962 and 1973. We describe a patient who developed hypercapnic respiratory failure after initiation of polymyxin for multi-drug resistant Escherichia Coli bacteremia, due to polymyxin-induced neuromuscular dysfunction. After cessation of polymyxin, he regained full strength, had complete resolution of ptosis, and was successfully extubated. In light of the renewed use of polymyxin in this era of antimicrobial-resistance, this case aims to raise awareness about this rare but life-threatening condition, which is easily reversible with early recognition and prompt discontinuation of the drug.

Tolerance to preoperative placement of electrodes for neuromuscular monitoring using the Tetragraph™.

Background: Quantitative train-of-four (TOF) monitoring has recently been shown to be feasible in infants and children using a novel electromyography (EMG)-based monitor with a pediatric-sized self-adhesive sensor. However, placement of the sensor and initiation of TOF monitoring may require additional time in the operating room (OR), delaying workflow and the time to induction of anesthesia. The current study evaluates the feasibility of placing the self-adhesive sensor in the preoperative holding area in pediatric patients before arrival to the OR. Methods: Consented pediatric patients undergoing inpatient surgery requiring the administration of NMBAs were enrolled. The EMG electrode was placed along the ulnar nerve on the volar aspect of the distal forearm to provide neurostimulation. After the induction of anesthesia, monitoring was initiated and TOF recording started before the administration of the NMBA. A Likert score (0-10) was used to assess ease of placement, tolerability of the monitor during the preoperative period, and its ability to generate a recorded response in the OR. Results: The final study cohort included 40 patients with a median age of 3.7 years. Fourteen patients (35%) pulled off the sensor before arrival to the OR and 26 patients (65%) arrived at the OR with the sensor intact and functioning. Older children were more likely to maintain the sensor until arrival to the OR compared to younger patients (median age of 5.24 versus 1 year, P = 0.0521). A median age of 3.7 years correlated with an 80% chance of arriving in the OR with the sensor intact. Application ease and tolerance of the sensor were higher in the group that maintained the sensor until OR arrival. Conclusion: In patients more than 4 years of age, placement of the self-adhesive sensor for EMG-based TOF monitoring may be feasible. However, in younger patients, additional interventions may be required to achieve a similar success rate.

The feasibility of the posterior tibial nerve-flexor hallucis brevis pathway applied in neuromuscular monitoring: a multicentric, controlled, and prospective clinical trial.

This study aimed to investigate the clinical viability of utilizing the flexor hallucis brevis as an alternative site for neuromuscular monitoring compared to the conventional adductor pollicis. Patients were recruited from three medical centers. Cis-atracurium was administered, and two monitors were employed independently to assess neuromuscular blockade of the adductor pollicis and the ipsilateral flexor hallucis brevis, following a train of four (TOF) pattern until TOF ratios exceeded 0.9 or until the conclusion of surgery. Statistical analysis revealed significant differences in onset time, duration of no-twitch response, spontaneous recovery time, and total monitoring time between the two sites, with mean differences of -53.54 s, -2.49, 3.22, and 5.89 min, respectively (P < 0.001).The posterior tibial nerve-flexor hallucis brevis pathway presents a promising alternative for neuromuscular monitoring during anesthesia maintenance. Further investigation is warranted to explore its utility in anesthesia induction and recovery. Trial registration: The trial was registered at www.chictr.org.cn (20/11/2018, ChiCTR1800019651).

The Cloning and Characterization of a Three-Finger Toxin Homolog (NXH8) from the Coralsnake Micrurus corallinus That Interacts with Skeletal Muscle Nicotinic Acetylcholine Receptors.

Coralsnakes (Micrurus spp.) are the only elapids found throughout the Americas. They are recognized for their highly neurotoxic venom, which is comprised of a wide variety of toxins, including the stable, low-mass toxins known as three-finger toxins (3FTx). Due to difficulties in venom extraction and availability, research on coralsnake venoms is still very limited when compared to that of other Elapidae snakes like cobras, kraits, and mambas. In this study, two previously described 3FTx from the venom of M. corallinus, NXH1 (3SOC1_MICCO), and NXH8 (3NO48_MICCO) were characterized. Using in silico, in vitro, and ex vivo experiments, the biological activities of these toxins were predicted and evaluated. The results showed that only NXH8 was capable of binding to skeletal muscle cells and modulating the activity of nAChRs in nerve-diaphragm preparations. These effects were antagonized by anti-rNXH8 or antielapidic sera. Sequence analysis revealed that the NXH1 toxin possesses eight cysteine residues and four disulfide bonds, while the NXH8 toxin has a primary structure similar to that of non-conventional 3FTx, with an additional disulfide bond on the first loop. These findings add more information related to the structural diversity present within the 3FTx class, while expanding our understanding of the mechanisms of the toxicity of this coralsnake venom and opening new perspectives for developing more effective therapeutic interventions.

Comparison of Different Weight Scalars to Dose Sugammadex for the Reversal of Neuromuscular Blockade in Morbidly Obese Patients: A Systematic Review.

This systematic review was conducted to evaluate the optimal weight scalar to dose sugammadex in a morbidly obese (MO) patient population (BMI≥40 kg/m2). The primary outcome was recovery time from moderate neuromuscular blockade (NMB) or deep NMB. Secondary outcomes included time to extubation and incidence of postoperative residual curarization (PORC). Eight randomized controlled trials (RCTs) involving 645 participants were included. The different dose scalars included were total body weight (TBW), ideal body weight (IBW), 20% corrected body weight (CBW) and 40% CBW). A dose of 2 mg/kg of sugammadex based on 40% CBW and a 4 mg/kg dose of sugammadex based on 40% CBW provide a reliable and timely reversal of moderate and deep NMB respectively in the MO patients.

Relationship between muscle mass ratio and rocuronium dose required for maintaining deep neuromuscular blockade: A prospective observational study.

BACKGROUND: Deep neuromuscular blockade (NMB) has benefits in various surgical procedures, however, precise quantitative neuromuscular monitoring is crucial for its proper maintenance and recovery. Neuromuscular blocking agent dosage relies on actual body weight (ABW), but this varies among individuals. Therefore, this study hypothesizes that there is a correlation between the rocuronium requirement for deep NMB and muscle mass ratio measured by bioelectric impedance analysis. METHODS: Ninety adult female patients undergoing laparoscopic operation were enrolled in this study. Muscle and fat masses were assessed using a body composition analyser. Deep NMB, defined as a post-tetanic count of 1-2, was maintained through the continuous infusion of rocuronium. The primary outcome involves determining the correlation between the rocuronium dose required for deep NMB and the muscle mass ratio. Conversely, secondary outcomes included assessing the relationship between the rocuronium dose for deep NMB and fat mass ratio, and ABW. Additionally, we investigated their relationship with rocuronium onset time and profound blockade duration. RESULTS: No relationship was observed between the muscle mass ratio and rocuronium dose required for maintaining deep NMB (r = 0.059 [95% CI = 0.153-0.267], p = 0.586). Fat mass ratio and ABW showed no correlation with the rocuronium dose, whereas rocuronium onset time was positively correlated with muscle mass ratio (r = 0.327) and negatively correlated with fat mass ratio (r = -0.302), respectively. Profound blockade duration showed no correlation with any of the assessed variables. CONCLUSIONS: No correlation was detected between muscle mass ratio and the rocuronium dose required to achieve deep NMB.

Prolonged duration of action of suxamethonium in pregnant and postpartum patients: A registry study.

BACKGROUND: Suxamethonium is hydrolysed by butyrylcholinesterase (BChE) and a low BChE activity can result in a prolonged duration of action of suxamethonium. The BChE activity is reduced during pregnancy and postpartum period by up to 33%. However, it can also be reduced by mutations in the BChE gene. In this study, we assessed BChE activity and mutations in the BChE gene in pregnant and postpartum patients with prolonged duration of action of suxamethonium. It was hypothesised that at least 30% of patients with a low BChE activity did not have a mutation in the BChE gene. METHODS: In this registry study we focused on pregnant and postpartum patients with a history of prolonged duration of action of suxamethonium referred to the Danish Cholinesterase Research Unit (DCRU) between March 2007 and January 2023. Primary outcome was the proportion of patients without a mutation among patients with a low BChE activity. Secondary outcomes were the proportion of patients with a low BChE activity and the proportion of patients with a mutation out of the total number of patients. RESULTS: A total of 40 patients were included and among patients with a low BChE activity, 6% (95% CI: 1%-21%) did not have a mutation. Out of the total number of included patients referred to the DCRU, 90% (95% CI: 76%-97%) had a mutation and 94% (95% CI: 80%-99%) had a low BChE activity. CONCLUSION: Among pregnant and postpartum patients with a history of prolonged duration of action of suxamethonium and a low BChE activity, 6% did not have a mutation in the BChE gene. Our findings suggest that during pregnancy and postpartum clinically relevant prolonged duration of action of suxamethonium rarely occurs in genotypically normal patients.

Trapping and reversing neuromuscular blocking agent by anionic pillar[5]arenes: Understanding the structure-affinity-reversal effects.

Selective relaxant binding agents (SRBA) have great potential in clinical surgeries for the precise reversal of neuromuscular blockades. Understanding the relationship between the structure-affinity-reversal effects of SRBA and neuromuscular blockade is crucial for the design of new SRBAs, which has rarely been explored. Seven anionic pillar[5]arenes (AP5As) with different aliphatic chains and anionic groups at both edges were designed. Their binding affinities to the neuromuscular blocking agent decamonium bromide (DMBr) were investigated using 1H NMR, isothermal titration calorimetry (ITC), and theoretical calculations. The results indicate that the capture of DMBr by AP5As is primarily driven by electrostatic interactions, ion-dipole interactions and C-H‧‧‧π interactions. The optimal size matching between the carboxylate AP5As and DMBr was ∼0.80. The binding affinity increased with an increase in the charge quantity of AP5As. Further animal experiments indicated that the reversal efficiency increased with increasing binding affinity for carboxylate or phosphonate AP5As. However, phosphonate AP5As exhibited lower reversal efficiencies than carboxylate AP5As, despite having stronger affinities with DMBr. By understanding the structure-affinity-reversal relationships, this study provides valuable insights into the design of innovative SRBAs for reversing neuromuscular blockade.

Comparison of the effects of selected aminoglycoside antibiotics on motor behaviors in mice.

Aminoglycoside antibiotics (AGs) can cause neuromuscular blockade and paralysis of skeletal muscles. To compare the paralytic effects of selected AGs on some motor behaviors in mice, 24 male mice were divided into four groups. Each group was given one of AGs (gentamicin, dihydro-streptomycin, apramycin and amikacin) at incremental doses that increased half-logarithmically compared to the therapeutic dose (16.00 mg kg-1). Motor behavioral tests included open field test, inclined plane, horizontal bars, static rods, parallel bars and rotarod. Finally, the data were analyzed using descriptive and analytical statistics. Gentamicin and dihydrostreptomycin at 32.00 times of the therapeutic dose produced complete paralysis of the limbs, respiratory arrest, and even death in some animals. However, apramycin and amikacin did not show significant effects on skeletal muscle and motor behaviors at 32.00 times of the therapeutic dose. After administration of apramycin at 100 times of the therapeutic dose, four out of six mice (66.67%) died from respiratory depression. Amikacin at this dose did not cause animal death, although it caused some changes in motor behaviors with a significant difference in comparison with control values. Gentamicin demonstrated significantly more potent effects on motor behaviors compared to the other AGs. Overall, the order of potency was gentamicin > dihydrostreptomycin > apramycin > amikacin. High doses of AGs could impair the skeletal muscle function and disrupt motor behaviors in mice. Furthermore, the paralytic potency of selected AGs on skeletal muscle was significantly different.

Pharmacologic Treatments in Acute Respiratory Failure.

Acute respiratory failure relies on supportive care using non-invasive and invasive oxygen and ventilatory support. Pharmacologic therapies for the most severe form of respiratory failure, acute respiratory distress syndrome (ARDS), are limited. This review focuses on the most promising therapies for ARDS, targeting different mechanisms that contribute to dysregulated inflammation and resultant hypoxemia. Significant heterogeneity exists within the ARDS population. Treatment requires prompt recognition of ARDS and an understanding of which patients may benefit most from specific pharmacologic interventions. The key to finding effective pharmacotherapies for ARDS may rely on deeper understanding of pathophysiology and bedside identification of ARDS subphenotypes.

Adjunctive Therapies in Acute Respiratory Distress Syndrome.

Despite significant advances in understanding acute respiratory distress syndrome (ARDS), mortality rates remain high. The appropriate use of adjunctive therapies can improve outcomes, particularly for patients with moderate to severe hypoxia. In this review, the authors discuss the evidence basis behind prone positioning, recruitment maneuvers, neuromuscular blocking agents, corticosteroids, pulmonary vasodilators, and extracorporeal membrane oxygenation and considerations for their use in individual patients and specific clinical scenarios. Because the heterogeneity of ARDS poses challenges in finding universally effective treatments, an individualized approach and continued research efforts are crucial for optimizing the utilization of adjunctive therapies and improving patient outcomes.

Managing a difficult airway due to supraglottic masses: successful videolaryngoscopic intubation after induction of general anesthesia.

BACKGROUND: While awake, flexible bronchoscopic intubation has long been considered the gold standard for managing anticipated difficult airways, the videolaryngoscope has emerged as a viable alternative. In addition, the decision to perform awake intubation or to proceed with airway management after induction of general anesthesia should be grounded in a comprehensive assessment of risks and benefits. CASE PRESENTATION: A 41-year old female patient was scheduled for excision of bilateral, mobile, and pedunculated masses on both aryepiglottic folds, which covered almost the entire upper part of the glottis. We conducted a comprehensive evaluation of the patient's signs and symptoms, which included neither stridor nor dyspnea in any position, along with the otolaryngologist's opinion and the findings from the laryngeal fiberscopic examination. Given the potential challenges and risks associated with awake flexible bronchoscopic intubation for this patient, we decided to proceed with gentle tracheal intubation using a videolaryngoscope under general anesthesia. In case of failed mask ventilation and tracheal intubation, we had preplanned strategies, including awakening the patient or performing an emergent tracheostomy, along with preparations to support these strategies. Ensuring that mask ventilation was maintained with ease, the patient was sequentially administered intravenous propofol, remifentanil, and rocuronium. Under sufficient depth of anesthesia, intubation using a videolaryngoscope was successfully performed without any complications. CONCLUSIONS: Videolaryngoscopic intubation after induction of general anesthesia can be a feasible alternative for managing difficult airways in patients with supraglottic masses. This approachshould be based on a comprehensive preoperative evaluation, adequate preparation, and preplanned strategies to address potential challenges, such as inadequate oxygenation and unsuccessful tracheal intubation.