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Frontiers in Physiology 2022A line of studies in the 1960s-1980s suggested that muscle relaxants do not work uniformly on all skeletal muscles, though its mechanism has not been clarified. We...
A line of studies in the 1960s-1980s suggested that muscle relaxants do not work uniformly on all skeletal muscles, though its mechanism has not been clarified. We showed here that a classical non-depolarizing muscle relaxant pancuronium inhibits fast muscle fibers at lower concentration compared to slow muscle fibers in zebrafish. The difference of effective concentration was observed in locomotion caused by tactile stimulation as well as in synaptic currents of the neuromuscular junction induced by motor neuron excitation. We further showed that this difference arises from the different composition of acetylcholine receptors between slow and fast muscle fibers in the neuromuscular junction of zebrafish. It will be interesting to examine the difference of subunit composition and sensitivity to muscle relaxants in other species.
PubMed: 36304584
DOI: 10.3389/fphys.2022.1026646 -
Nutrition in Clinical Practice :... Apr 2023The purpose of this study was to assess gastric feeding intolerance for critically ill patients who received sustained neuromuscular blocker (NMB) pharmacotherapy.
BACKGROUND
The purpose of this study was to assess gastric feeding intolerance for critically ill patients who received sustained neuromuscular blocker (NMB) pharmacotherapy.
METHODS
Adult patients (>17 years of age) admitted to the trauma intensive care unit who received continuous intravenous NMB pharmacotherapy (rocuronium, cisatracurium, vecuronium, or pancuronium) for ≥48 h during continuous intragastric enteral nutrition (EN) were retrospectively evaluated. Gastric feeding intolerance was defined by initiation of a prokinetic agent (metoclopramide, erythromycin, or both) for an elevated gastric residual volume (GRV) >300 ml and with distention of the abdomen by physical examination, observation of regurgitation or emesis, temporary discontinuation of EN with low intermittent gastric suctioning, or initiation of parenteral nutrition (PN). Patients were evaluated for gastric feeding intolerance for the first 3 days of combined EN and NMB pharmacotherapy. A P value < 0.05 was considered statistically significant.
RESULTS
Ten patients of the 47 patients (21%) were intolerant to EN during NMB pharmacotherapy. No statistically or clinically relevant differences in patient characteristics were found between patients who tolerated EN vs those who experienced gastric feeding intolerance, except for a higher median maximum GRV of 125 ml (28, 200) vs 300 (250, 400) ml, respectively (P < 0.001). Five patients responded to prokinetic therapy and five required PN.
CONCLUSION
Most patients tolerated intragastric EN during sustained NMB pharmacotherapy. Presence of NMB pharmacotherapy is not an absolute contraindication for EN.
Topics: Adult; Humans; Infant, Newborn; Enteral Nutrition; Neuromuscular Blockade; Critical Illness; Retrospective Studies; Gastric Emptying
PubMed: 36156827
DOI: 10.1002/ncp.10911 -
Frontiers in Cell and Developmental... 2021During embryonic development, tendons transform into a hypocellular tissue with robust tensile load-bearing capabilities. Previous work suggests that this mechanical...
During embryonic development, tendons transform into a hypocellular tissue with robust tensile load-bearing capabilities. Previous work suggests that this mechanical transformation is due to increases in collagen fibril length and is dependent on mechanical stimulation muscle activity. However, the relationship between changes in the microscale tissue structure and changes in macroscale tendon mechanics is still unclear. Additionally, the specific effect of mechanical stimulation on the multiscale structure-function relationships of developing tendons is also unknown. Therefore, the objective of this study was to measure the changes in tendon mechanics and structure at multiple length scales during embryonic development with and without skeletal muscle paralysis. Tensile testing of tendons from chick embryos was performed to determine the macroscale tensile modulus as well as the magnitude of the fibril strains and interfibrillar sliding with applied tissue strain. Embryos were also treated with either decamethonium bromide or pancuronium bromide to produce rigid or flaccid paralysis. Histology was performed to assess changes in tendon size, spacing between tendon subunits, and collagen fiber diameter. We found that the increase in the macroscale modulus observed with development is accompanied by an increase in the fibril:tissue strain ratio, which is consistent with an increase in collagen fibril length. Additionally, we found that flaccid paralysis reduced the macroscale tendon modulus and the fibril:tissue strain ratio, whereas less pronounced effects that were not statistically significant were observed with rigid paralysis. Finally, skeletal paralysis also reduced the size of collagen fibril bundles (i.e., fibers). Together, these data suggest that more of the applied tissue strain is transmitted to the collagen fibrils at later embryonic ages, which leads to an increase in the tendon macroscale tensile mechanics. Furthermore, our data suggest that mechanical stimulation during development is necessary to induce structural and mechanical changes at multiple physical length scales. This information provides valuable insight into the multiscale structure-function relationships of developing tendons and the importance of mechanical stimulation in producing a robust tensile load-bearing soft tissue.
PubMed: 34540841
DOI: 10.3389/fcell.2021.725563 -
Journal of Cardiothoracic and Vascular... Aug 2021Minimum alveolar concentration (MAC) of volatile anesthetic agents to maintain bispectral index (BIS) below 50 in 50% of patients was defined as MACBIS50. The primary... (Observational Study)
Observational Study
OBJECTIVES
Minimum alveolar concentration (MAC) of volatile anesthetic agents to maintain bispectral index (BIS) below 50 in 50% of patients was defined as MACBIS50. The primary objective of this study was to determine the minimum alveolar concentration of sevoflurane as a single hypnotic agent to maintain BIS below 50 in patients during normothermic cardiopulmonary bypass.
DESIGN
Prospective and observational study.
SETTING
Dante Pazzanese Institute of Cardiology, Brazil.
PARTICIPANTS
Eighteen consecutive patients scheduled for elective coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) under general anesthesia, American Society of Anesthesiologists physical status classes III and IV, between the ages of 40 and 70, were included in the study.
METHODS
All patients underwent inhalation induction with facial mask using sevoflurane (Cristália) in 100% oxygen, pancuronium (Cristália) 0.1 mg/kg, and sufentanil (Cristália) 0.5 µg/kg intravenously (IV) administered. A single bolus dose of sufentanil, 1.0 µg/kg IV, was administered before surgical incision. MACBIS50 was calculated using the midpoint concentration of patients involving a crossover (BIS < or ≥50) according to Dixon's Up-and-Down method. The Up-and-Down sequence also was analyzed by probit test that enabled the authors to obtain the effective dose 50 (ED50) and effective dose 95 (ED95) of sevoflurane to maintain a BIS value <50, with a 95% confidence interval (95% CI) of the mean.
RESULTS
A total of 15 patients were analyzed in this study. MACBIS50 of sevoflurane as a single hypnotic agent was 0.82% (95% CI 0.47-1.16) in patients aged 40 to 70 undergoing CABG during normothermic CPB. The ED50 and ED95 of sevoflurane to maintain a BIS value <50 for the same context were 0.73% (95% CI 0.45-1.00) and 1.39 (95% CI 0.42-2.37) by means of probit analysis, respectively.
CONCLUSION
MACBIS50 of sevoflurane as a single hypnotic agent was 0.82% in patients undergoing CABG during normothermic CPB.
Topics: Adult; Aged; Anesthetics, Inhalation; Brazil; Cardiopulmonary Bypass; Humans; Hypnotics and Sedatives; Methyl Ethers; Middle Aged; Prospective Studies; Sevoflurane
PubMed: 33483271
DOI: 10.1053/j.jvca.2020.12.032 -
British Journal of Anaesthesia Jul 2019Following diagnosis of neuromuscular blocking agent (NMBA) anaphylaxis, identifying safe alternatives for subsequent anaesthesia is critical. A patient with anaphylaxis...
BACKGROUND
Following diagnosis of neuromuscular blocking agent (NMBA) anaphylaxis, identifying safe alternatives for subsequent anaesthesia is critical. A patient with anaphylaxis to one NMBA can also have an allergic reaction to other NMBAs (cross-reactivity). Whilst drug provocation testing is standard for identifying or excluding allergy, there is significant risk. In vitro, after an allergen activates basophils, basophils express surface activation markers that can be measured by basophil activation testing (BAT). We compared cross-reactivity between NMBAs assessed by BAT against that by skin testing.
METHODS
All patients attending an anaesthetic allergy clinic in Sydney, Australia between May 2017 and July 2018 diagnosed with NMBA anaphylaxis qualified for this study comparing intradermal skin tests and BAT with a panel of NMBAs (rocuronium, vecuronium, pancuronium, suxamethonium, cisatracurium).
RESULTS
Of the 61 patients participating, sensitisation on skin testing and on BAT completely matched in only nine patients (15%). Sensitisation was not in agreement for pancuronium, cisatracurium and rocuronium, but was in agreement for vecuronium and suxamethonium. Nine patients with negative skin tests subsequently tolerated cisatracurium, and one false positive on BAT to cisatracurium was detected.
CONCLUSIONS
The utility of BAT in identifying safe NMBAs for subsequent anaesthesia needs further evaluation. BAT detects a different cross-reactivity profile to skin tests. Negative skin testing and BAT might increase confidence in performing drug provocation testing, but this and follow-up of subsequent anaesthesia in our cohort is necessary to determine the clinical significance of BAT sensitisation.
Topics: Adolescent; Adult; Aged; Anaphylaxis; Australia; Basophils; Cross Reactions; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; Neuromuscular Blocking Agents; Skin Tests; Young Adult
PubMed: 30961915
DOI: 10.1016/j.bja.2019.03.001 -
Journal of Clinical Anesthesia Apr 2020Neuromuscular blocking agents (NMBAs) have revolutionized the field of anesthesiology as they facilitate airway management and ensure optimal surgical conditions....
Incidence of residual neuromuscular blockade and use of neuromuscular blocking agents with or without antagonists: A systematic review and meta-analysis of randomized controlled trials.
OBJECTIVES
Neuromuscular blocking agents (NMBAs) have revolutionized the field of anesthesiology as they facilitate airway management and ensure optimal surgical conditions. Despite their beneficial and ubiquitous use during surgery, delayed or partial recovery from NMBAs, referred to as residual neuromuscular block (rNMB), is a common clinical problem. While it is well accepted that the antagonist sugammadex, compared to neostigmine, can more rapidly reverse rocuronium-induced NMB regardless of depth of block, the occurrence of rNMB for routinely used combinations of NMBAs with sugammadex or neostigmine has not yet been quantified or evaluated systematically.
REVIEW METHODS
We conducted a systematic literature review and meta-analysis of randomized controlled trials (RCTs) to quantify and compare the incidence of rNMB [defined as train-of-four ratio (TOFR) <0.9] in patients with moderate and deep neuromuscular block. Methods recommended by Cochrane Collaboration and PRISMA group were followed.
RESULTS
A total of 35 RCTs were identified, of which 20 contributed to the meta-analysis. For moderate block, rNMB incidence at 2 min after sugammadex administration was 19.2% (95% CI 0.0-57.8; 122 patients) and declined to 2.8% (95% CI 0.0-16.7; 93 patients) at 6 min post administration. For timepoints 10 to 60 min after administration, rNMB incidence ranged between 0.05% to 2.8%. In contrast, rNMB incidence at 2 min after neostigmine administration was 100% (95% CI 89.9-100; 182 patients) and was 82% (95% CI 71.4-91.2; 93 patients) at 6 min post administration. For timepoints 10 to 60 min after administration, rNMB incidence ranged between 14 and 32%. For deep block, rNMB incidence following sugammadex was essentially reduced to 1% at 15 min after administration. Residual NMB incidence following neostigmine remained at or above 95% for the first 60 min after administration.
CONCLUSIONS
Overall, based on evidence from 20 RCTs, our results suggest that the combination of rocuronium or vecuronium plus sugammadex is more effective and more rapid in reversing NMB compared with combinations of rocuronium, vecuronium, cisatracurium, or pancuronium plus neostigmine.
PubMed: 32304958
DOI: 10.1016/j.jclinane.2020.109818 -
European Journal of Anaesthesiology May 2024Extravascular injection of neuromuscular blocking drugs (NMBDs) can cause a neuromuscular block because of systemic absorption. Currently, there are no guidelines...
Extravascular injection of neuromuscular blocking drugs (NMBDs) can cause a neuromuscular block because of systemic absorption. Currently, there are no guidelines available on managing extravasation of NMBDs. This article reviews the available literature on extravasation of NMBDs. Medline and Embase databases were searched for studies concerning the paravenous or subcutaneous injection of NMBDs. Nine articles were included consisting of seven case reports, one case series and one clinical trial. Rocuronium was used as primary NMBD in nine cases, vecuronium in two cases and pancuronium in one case. Although there exists significant heterogeneity between the reported information in the included studies, the majority of the case reports describe a slower onset, with a median delay of 20 min and prolonged duration of the neuromuscular block. Nine patients had a residual neuromuscular block at the end of the surgery. Postoperative monitoring in the recovery room was prolonged (median time 4 h). Most studies suggest that the delay in NMBD onset and recovery is caused by the formation of a subcutaneous depot, from which the NMBD is slowly absorbed into the systemic circulation. According to the current literature, extravasation of NMBDs results in an unpredictable neuromuscular block. Strategies to prevent potentially harmful side effects, such as frequent train-of-four (TOF) monitoring, the use of NMBD reversal agents and prolonged length of stay in the postanaesthesia care unit (PACU), should be considered. This article suggests a clinical pathway that can be used after extravascular injection of NMBDs.
Topics: Humans; Neuromuscular Blockade; Rocuronium; Vecuronium Bromide; Delayed Emergence from Anesthesia; Monitoring, Intraoperative
PubMed: 38410855
DOI: 10.1097/EJA.0000000000001967 -
Indian Journal of Anaesthesia Nov 2019We report a case of an 8-year-old girl who presented with syncopal attacks and a history of viral illness a month ago. On examination, she was conscious, oriented but...
We report a case of an 8-year-old girl who presented with syncopal attacks and a history of viral illness a month ago. On examination, she was conscious, oriented but had a heart rate of 42/min which was unresponsive to atropine. She was started on dobutamine and isoproterenol. Electrocardiography and echocardiography revealed complete heart block with moderate tricuspid regurgitation, dilated cardiomyopathy and low ejection fraction. Patient was planned for urgent permanent pacemaker insertion. General anaesthesia was administered with endotracheal tube and controlled ventilation using fentanyl, ketamine and pancuronium. For patient safety, invasive arterial monitoring was instituted and external pacing was kept standby. Transvenous pacemaker leads were implanted onto the right ventricular wall through the left subclavian vein.
PubMed: 31772403
DOI: 10.4103/ija.IJA_411_19