Effects of Reversal Technique for Neuromuscular Paralysis on Time to Recovery of Bowel Function after Craniotomy

Background Non-depolarizing neuromuscular blockade can be reversed with neostigmine/glycopyrrolate or sugammadex. We test the hypothesis that sugammadex is associated with earlier postoperative recovery of bowel function (first bowel movement, BM). Methods In adult patients undergoing craniotomy from 2016 to 2019, we identified time of first postoperative BM after receiving neostigmine/glycopyrrolate or sugammadex to reverse neuromuscular blockade. Logistic and proportional hazard regression, with and without inverse probability of treatment weighting (IPTW), were used to assess whether sugammadex is associated with earlier recovery of bowel function. Results Seven hundred and thirty-one patients underwent craniotomy, 323 (44.2%) received neostigmine/glycopyrrolate, and 408 (55.8%) sugammadex. From logistic regression analysis, the proportion of patients having a BM within the first 24 and 48 hours was higher in sugammadex group (unadjusted OR [95% CI]) 1.79 [1.16 to 2.77] P = .009; and 1.45 [1.08 to 1.94] P = .014; IPTW adjusted OR [95% CI]) 1.58 [.95, 2.61] P = .078; and 1.38 [.95 to 2.02] P = .095 for 24 and 48 h, respectively). From proportional hazards regression, sugammadex was associated with improved bowel function recovery (unadjusted hazard ratio (HR) [95% CI] 1.35 [1.08, 1.68], P = .008; IPTW adjusted HR 1.29 [.97 to 1.71], P = .076). Conclusion Patients undergoing craniotomy who had neuromuscular blockade reversed with sugammadex may have earlier recovered bowel function compared to patients reversed with neostigmine/glycopyrrolate.

Residual paralysis caused by 50 mg rocuronium after reversal with 4 mg/kg sugammadex: a case report

Background Rocuronium-induced neuromuscular blockade can be quickly and completely reversed by administration of an optimal dose of sugammadex. Sugammadex antagonizes rocuronium-induced neuromuscular blockade by encapsulating rocuronium. Herein, we report a case of residual neuromuscular paralysis in which the recommended dose of sugammadex (4 mg·kg− 1) failed to antagonize a rocuronium-induced blockade. Case presentation A 71-year-old man (body mass index: 26.7 kg·m− 2) underwent endoscopic submucosal dissection of early-stage gastric cancer. He had no known factors that may have affected the effects of rocuronium and sugammadex. He received rocuronium (50 mg; 0.7 mg·kg− 1) for anesthesia induction. No additional rocuronium was administered during the 71-min procedure. Ninety-four minutes after rocuronium administration, neuromuscular monitoring showed 20 twitches in response to post-tetanic count stimulation. The train-of-four (TOF) ratio was not measurable despite sugammadex (280 mg; 4 mg/kg) administration, although four weak twitches in response to TOF stimulation appeared in 3 min. The TOF ratio became detectable following administration of an additional dose of sugammadex (120 mg; 1.7 mg·kg− 1), and it recovered to 107% 8 min after the second dose. The patient opened his eyes; moved his neck, arms, and limbs; and regained consciousness. The trachea was extubated and the patient was transferred to the ward. Conclusions Neuromuscular monitoring should be used if a neuromuscular blockage agent is administered, even if the recommended dose of sugammadex is administered.

Deep neuromuscular paralysis during hip arthroscopic surgery: influence on perineal tissue pressures and hip joint width

Pudendal nerve injuries are not an uncommon side effect of patient positioning on a traction table, and muscle relaxation has been suggested to mitigate this risk by reducing pressure on the perineum. A total of 40 patients scheduled for hip arthroscopic surgery under general anaesthesia were recruited. After induction of anaesthesia, pressures on the perineum were measured in 20 subjects by means of an ultra-thin pressure sensor mat wrapped around the perineal post. Perineal pressures were assessed after the induction of anaesthesia, after leg traction and after deep muscle relaxation. In 22 subjects, the hip joint width was measured radiographically at the same time points. Pressures on the perineum were high after traction (median maximum pressure 2540 g cm−2). Neuromuscular paralysis reduced perineal pressures only minimally, but significantly (−5 g cm−2; P = 0.007). Traction increased hip joint width significantly [mean 66 (12)%; P = 0.001) and muscle relaxation further increased joint width by a mean of 3.2 (0–20)% (P = 0.001). Muscle relaxation was more beneficial for male patients (joint width increase 6.8% versus 2.8%; P = 0.04), as well as patients in whom traction alone did not achieve sufficient joint width. Muscle relaxation reduced the perineal pressure during hip arthroscopic surgery by only a negligible amount. With regard to joint space, relaxation may be of highest benefit in male patients and/or patients in whom traction alone produces only a relatively small increase in joint width (trial registration: ANZCTR 12617000191392).

In-Vitro Neutralization of the Neurotoxicity of Coastal Taipan Venom by Australian Polyvalent Antivenom: The Window of Opportunity

Coastal taipan (Oxyuranus scutellatus) envenoming causes life-threatening neuromuscular paralysis in humans. We studied the time period during which antivenom remains effective in preventing and arresting in vitro neuromuscular block caused by taipan venom and taipoxin. Venom showed predominant pre-synaptic neurotoxicity at 3 µg/mL and post-synaptic neurotoxicity at 10 µg/mL. Pre-synaptic neurotoxicity was prevented by addition of Australian polyvalent antivenom before the venom and taipoxin and, reversed when antivenom was added 5 min after venom and taipoxin. Antivenom only partially reversed the neurotoxicity when added 15 min after venom and had no significant effect when added 30 min after venom. In contrast, post-synaptic activity was fully reversed when antivenom was added 30 min after venom. The effect of antivenom on pre-synaptic neuromuscular block was reproduced by washing the bath at similar time intervals for 3 µg/mL, but not for 10 µg/mL. We found an approximate 10–15 min time window in which antivenom can prevent pre-synaptic neuromuscular block. This time window is likely to be longer in envenomed patients due to the delay in venom absorption. Similar effectiveness of antivenom and washing with 3 µg/mL venom suggests that antivenom most likely acts by neutralizing pre-synaptic toxins before they interfere with neurotransmission inside the motor nerve terminals.

Break the Spasm with Succinylcholine, but Risk Intraoperative Awareness with Undiagnosed Pseudocholinesterase Deficiency

Succinylcholine is a commonly used medication in all aspects of anesthetic care, and there are a number of known side effects and complications associated with its use. However, when succinylcholine is used emergently, anesthesia providers must remain vigilant to undiagnosed conditions that pose additional risks to patients. We report the use of succinylcholine to treat acute, refractory laryngospasm after extubation leading to prolonged neuromuscular paralysis. There are unique challenges presented by this case including the risk of anesthesia awareness with recall due to the cognitive biases that prevent the clinical diagnosis of pseudocholinesterase deficiency.

Venomics Approach Reveals a High Proportion of Lactrodectus-Like Toxins in the Venom of the Noble False Widow Spider Steatoda nobilis

The noble false widow spider Steatoda nobilis originates from the Macaronesian archipelago and has expanded its range globally. Outside of its natural range, it may have a negative impact on native wildlife, and in temperate regions it lives in synanthropic environments where it frequently encounters humans, subsequently leading to envenomations. S. nobilis is the only medically significant spider in Ireland and the UK, and envenomations have resulted in local and systemic neurotoxic symptoms similar to true black widows (genus Latrodectus). S. nobilis is a sister group to Latrodectus which possesses the highly potent neurotoxins called α-latrotoxins that can induce neuromuscular paralysis and is responsible for human fatalities. However, and despite this close relationship, the venom composition of S. nobilis has never been investigated. In this context, a combination of transcriptomic and proteomic cutting-edge approaches has been used to deeply characterise S. nobilis venom. Mining of transcriptome data for the peptides identified by proteomics revealed 240 annotated sequences, of which 118 are related to toxins, 37 as enzymes, 43 as proteins involved in various biological functions, and 42 proteins without any identified function to date. Among the toxins, the most represented in numbers are α-latrotoxins (61), δ-latroinsectotoxins (44) and latrodectins (6), all of which were first characterised from black widow venoms. Transcriptomics alone provided a similar representation to proteomics, thus demonstrating that our approach is highly sensitive and accurate. More precisely, a relative quantification approach revealed that latrodectins are the most concentrated toxin (28%), followed by α-latrotoxins (11%), δ-latroinsectotoxins (11%) and α-latrocrustotoxins (11%). Approximately two-thirds of the venom is composed of Latrodectus-like toxins. Such toxins are highly potent towards the nervous system of vertebrates and likely responsible for the array of symptoms occurring after envenomation by black widows and false widows. Thus, caution should be taken in dismissing S. nobilis as harmless. This work paves the way towards a better understanding of the competitiveness of S. nobilis and its potential medical importance.

Kinetic modelling of processes in the cholinergic synapse. Mechanisms of functioning and control methods

The kinetic model describing the dynamics of synaptic “discharge” taking into account the kinetics of the injection of the neurotransmitter into the synaptic cleft, the pH-dependence of catalytic activity of the enzyme and diffusion withdrawal of protons is proposed and studied. In the framework of the kinetic model, the functioning of the cholinergic synapse is considered. The results of mathematical modeling of changes in the level of acetylcholine, induced pH impulse, the influence of the frequency of impulse transfer and inhibition of acetylcholinesterase are presented. Physico-chemical explanation for a number of important physiological phenomena, such as neuromuscular paralysis, the molecular mechanism of neurological memory, actions of nerve poisons and toxins and Alzheimer’s disease is given.

Kinetic modelling of processes in the cholinergic synapse. Mechanisms of functioning and control methods

The kinetic model describing the dynamics of synaptic “discharge” taking into account the kinetics of the injection of the neurotransmitter into the synaptic cleft, the pH-dependence of catalytic activity of the enzyme and diffusion withdrawal of protons is proposed and studied. In the framework of the kinetic model, the functioning of the cholinergic synapse is considered. The results of mathematical modeling of changes in the level of acetylcholine, induced pH impulse, the influence of the frequency of impulse transfer and inhibition of acetylcholinesterase are presented. Physico-chemical explanation for a number of important physiological phenomena, such as neuromuscular paralysis, the molecular mechanism of neurological memory, actions of nerve poisons and toxins and Alzheimer’s disease is given.