The effect of glycopyrrolate vs. atropine in combination with neostigmine on cardiovascular system for reversal of residual neuromuscular blockade in the elderly: a randomized controlled trial.

BACKGROUND: Glycopyrrolate-neostigmine (G/N) for reversing neuromuscular blockade (NMB) causes fewer changes in heart rate (HR) than atropine-neostigmine (A/N). This advantage may be especially beneficial for elderly patients. Therefore, this study aimed to compare the cardiovascular effects of G/N and A/N for the reversal of NMB in elderly patients. METHODS: Elderly patients aged 65-80 years who were scheduled for elective non-cardiac surgery under general anesthesia were randomly assigned to the glycopyrrolate group (group G) or the atropine group (group A). Following the last administration of muscle relaxants for more than 30 min, group G received 4 ug/kg glycopyrrolate and 20 ug/kg neostigmine, while group A received 10 ug/kg atropine and 20 ug/kg neostigmine. HR, mean arterial pressure (MAP), and ST segment in lead II (ST-II) were measured 1 min before administration and 1-15 min after administration. RESULTS: HR was significantly lower in group G compared to group A at 2-8 min after administration (P < 0.05). MAP was significantly lower in group G compared to group A at 1-4 min after administration (P < 0.05). ST-II was significantly depressed in group A compared to group G at 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 14, and 15 min after administration (P < 0.05). CONCLUSIONS: In comparison to A/N, G/N for reversing residual NMB in the elderly has a more stable HR, MAP, and ST-II within 15 min after administration.

Central cholinergic transmission affects the compulsive-like behavior of mice in marble-burying test.

The presence of the cholinergic system in the brain areas implicated in the precipitation of obsessive-compulsive behavior (OCB) has been reported but the exact role of the central cholinergic system therein is still unexplored. Therefore, the current study assessed the effect of cholinergic analogs on central administration on the marble-burying behavior (MBB) of mice, a behavior correlated with OCB. The result reveals that the enhancement of central cholinergic transmission in mice achieved by intracerebroventricular (i.c.v.) injection of acetylcholine (0.01 µg) (Subeffective: 0.1 and 0.5 µg), cholinesterase inhibitor, neostigmine (0.1, 0.3, 0.5 µg/mouse) and neuronal nicotinic acetylcholine receptor agonist, nicotine (0.1, 2 µg/mouse) significantly attenuated the number of marbles buried by mice in MBB test without affecting basal locomotor activity. Similarly, central injection of mAChR antagonist, atropine (0.1, 0.5, 5 µg/mouse), nAChR antagonist, mecamylamine (0.1, 0.5, 3 µg/mouse) per se also reduced the MBB in mice, indicative of anti-OCB like effect of all the tested cholinergic mAChR or nAChR agonist and antagonist. Surprisingly, i.c.v. injection of acetylcholine (0.01 µg), and neostigmine (0.1 µg) failed to elicit an anti-OCB-like effect in mice pre-treated (i.c.v.) with atropine (0.1 µg), or mecamylamine (0.1 µg). Thus, the findings of the present investigationdelineate the role of central cholinergic transmission in the compulsive-like behavior of mice probably via mAChR or nAChR stimulation.

Effects of magnesium sulphate on neostigmine-induced recovery from moderate neuromuscular blockade with rocuronium: a randomized controlled trial.

Magnesium enhances the effects of neuromuscular blocking agents. However, there is a paucity of evidence demonstrating possible effects of magnesium on neostigmine-induced recovery from neuromuscular blockade with rocuronium. This study compared the profiles of recovery from neuromuscular blockade between groups treated with magnesium (Group M) and placebo controls (Group C). Sixty-four patients were randomly allocated to Group M or Group C. Patients in Group M received a loading dose of 50 mg/kg magnesium and continuous infusion of 15 mg/kg/hr. Patients in Group C received a comparable amount of saline. Rocuronium at 0.6 mg/kg was used for tracheal intubation and 0.1 mg/kg of rocuronium was additionally administered to maintain train-of-four (TOF) status of 2-3 during surgery. At the end of surgery, neostigmine (50 µg/kg) plus glycopyrrolate (10 µg/kg) were administered, and the recovery time for TOF ratios of 0.7, 0.8, and 0.9 was measured. The primary outcome was the time from neostigmine administration to recovery with a TOF ratio of 0.9. In addition, rocuronium onset time (time from administration of rocuronium to 95% suppression of the first TOF twitch response), additional requirements for rocuronium and spontaneous recovery period (the time from administration of rocuronium to reappearance of the first TOF twitch response) were also measured. Neostigmine-induced recovery time was comparable between Group M and Group C (10.6 ± 4.3 vs. 9.1 ± 5.0 min, respectively, p = 0.22). The rocuronium onset time was shorter in Group M, and the spontaneous recovery period was longer in Group M. The amount of additional rocuronium administered was 27% lower in Group M, but this difference was not significant. Magnesium was not shown to prolong neostigmine-induced recovery time from neuromuscular blockade with rocuronium, however, it enhanced the clinical effects of rocuronium.

Optimal dose of neostigmine antagonizing cisatracurium-induced shallow neuromuscular block in elderly patients: a randomized control study.

BACKGROUND: Residual neuromuscular block after using neuromuscular blocking agents is a common and potentially harmful complication of general anesthesia. Neostigmine is a widely used antagonist, but its optimal dose for elderly patients is unclear. OBJECTIVES: To compare the optimal dosage and safety of neostigmine for reversing shallow residual block in elderly patients after cisatracurium-induced neuromuscular block. METHODS: A randomized controlled trial was conducted in 196 elderly patients undergoing non-cardiac surgery under general anesthesia with cisatracurium. Patients were assigned to receive either no neostigmine (control group) or neostigmine at 20 µg/kg, 40 µg/kg or 50 µg/kg when train-of-four (TOF) ratio reached 0.2 at the end of surgery. The primary outcome was the time to reach TOF ratio of 0.9 after administration. Secondary outcomes included TOF ratio at 10 min after administration, postoperative nausea and vomiting, postoperative cognitive impairment and post-anesthesia care unit (PACU) stay time. RESULTS: The time to reach TOF ratio of 0.9 in the 20 µg/kg, 40 µg/kg and 50 µg/kg groups was significantly shorter than the control group (H = 104.257, P < 0.01), and the time of 40 µg/kg group and 50 µg/kg group was significantly shorter than the 20 µg/kg group (P < 0.001). There was no significant difference between 40 µg/kg and 50 µg/kg groups (P = 0.249). The TOF ratio at 10 min after administration showed similar results. There were no significant differences among groups in postoperative nausea and vomiting, postoperative cognitive impairment or post-operation hospital stay. CONCLUSIONS: Timely use of neostigmine after general anesthesia in elderly patients can significantly shorten time of TOF value reaching 0.9, among which 40 µg/kg dosage may be a more optimized choice. TRIAL REGISTRATION: this study was registered on chictr.org.cn (ChiCTR2100054685, 24/12/2021).

Generalised neuromuscular blockade after intraurethral administration of atracurium besilate in a male cat with urethral obstruction.

A 4-year-old, entire, male, domestic long-haired cat was presented with an acute history of stranguria and dysuria and diagnosed with urolithiasis causing urethral obstruction. The patient was induced to general anaesthesia and several unsuccessful attempts to flush the uroliths retrogradely towards the bladder were made. An intraurethral administration of the neuromuscular blocking agent atracurium was performed as it has been reported to facilitate urethral catheterisation without any side effects. Respiratory arrest developed after 15 minutes from atracurium administration, which was promptly recognized and treated with mechanical ventilation. The absence of muscle contraction in response to a nerve stimulation confirmed a generalised muscle blockade. Approximately 35 minutes after, a muscle response to nerve stimulation appeared. Neostigmine combined with glycopyrrolate was administered resulting in complete recovery from neuromuscular blockade. In conclusion, the use of intraurethral atracurium can result in systemic absorption of the drug with subsequent generalised neuromuscular blockade.

Postoperative pulmonary complications after sugammadex reversal of neuromuscular blockade: a systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Sugammadex has been reported to lower the incidence of postoperative residual neuromuscular blockade. Despite the advantages, until recently the effects of sugammadex on postoperative pulmonary complications (PPCs) were controversial. We conducted a systematic review and meta-analysis to determine whether reversal with sugammadex was associated with a lower risk of PPCs compared with neostigmine. METHODS: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from inception to May 2022. Randomized controlled trials (RCTs) and observational studies comparing PPCs in patients receiving sugammadex or neostigmine as reversal agent at the end of surgery were included. The primary outcomes focused on PPCs including desaturation, pneumonia, atelectasis, noninvasive ventilation (NIV) and reintubation. Trial sequential analysis was performed on the primary outcomes to confirm whether firm evidence was reached. RESULTS: Meta-analysis of included studies showed that the rate of desaturation (43.2% vs 45.0%, RR = 0.82; 95% CI 0.63 to 1.05; p = 0.11) were comparable between the two groups. When looking at other primary outcomes, significantly lower risk of pneumonia (1.37% vs 2.45%, RR = 0.65; 95% CI 0.49 to 0.85; p = 0.002), atelectasis (24.6% vs 30.4%, RR = 0.64; 95% CI 0.42 to 0.98; p = 0.04), NIV (1.37% vs 2.33%, RR = 0.65; 95% CI 0.43 to 0.98; p = 0.04) and reintubation (0.99% vs 1.65%, RR = 0.62; 95% CI 0.43 to 0.91; p = 0.01) in the sugammadex group were detected compared with the neostigmine group. CONCLUSIONS: We concluded that sugammadex is more effective at reducing the incidence of PPCs including pneumonia, atelectasis, NIV and reintubation compared with neostigmine. Further evidence, preferably from RCTs, is required to confirm these findings.

Subclinical involvement of eye movements detected by video-based eye tracking in myasthenia gravis.

BACKGRO UND: Ocular abnormalities in myasthenia gravis (MG) are characterized by severely limited movements and rapid saccades. Data about eye motility of MG patients whose ocular movements are apparently normal are lacking. Our study assessed the eye movement parameters in MG patients without clinical eye motility dysfunctions and investigated the effects of neostigmine administration on the eye motility in these patients. MATERIALS: In this longitudinal study, we screened all patients diagnosed with MG referring to the Neurologic Clinic of the University of Catania between October 1, 2019, and June 30, 2021. Ten age- and sex-matched healthy controls were enrolled. Patients underwent eye movement recording using the EyeLink1000 Plus® eye tracker at baseline and after 90 min from the intramuscular administration of neostigmine (0.5 mg). RESULTS: A total of 14 MG patients with no clinical signs of ocular motor dysfunction (64.3% men, with a mean age of 50.4 ± 14.4 years) were enrolled. At baseline, saccades in MG patients showed slower velocities and longer latencies compared to controls. Moreover, the fatigue test induced a reduction in saccadic velocity and an increase in latencies. After neostigmine administration, the ocular motility analysis showed shorter saccadic latencies and a significant improvement of velocities. CONCLUSIONS: Eye motility is impaired even in MG patients with no clinical evidence of ocular movement disturbance. Video-based eye tracking may detect subclinical involvement of eye movements in patients with MG.

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.

Case Report: Successful Reversal of Residual Block with Sugammadex in a Patient Not Known to Have Myasthenia Gravis.

BACKGROUND Incomplete recovery from residual neuromuscular block agent (NMBA) after anesthesia is a serious adverse event in the post-anesthesia care unit. Acetylcholinesterase neostigmine is usually used to reverse residual neuromuscular blockade and facilitate spontaneous breathing and endotracheal extubation. CASE REPORT A 40-year-old woman received general anesthesia for strabismus correction surgery. At the end of surgery, repeated doses of neostigmine up to 85 µg/kg failed to reverse the residual neuromuscular blockade (train-of-four [TOF] ratio below 21%). Sugammadex (200 mg) provided immediate reversal, with the TOF ratio up to 100%. The patient regained spontaneous breathing, and the endotracheal tube was removed. After surgery, myasthenia gravis was diagnosed. CONCLUSIONS When unexpected prolonged neuromuscular blockade presents, the TOF ratio should be used to detect its depth and guide a reasonable dose of reversal agents. Anticholinesterase has a ceiling effect; once acetylcholinesterase activity is fully inhibited, administration of additional anticholinesterase can result in no further recovery. Furthermore, excessive acetylcholine can cause muscle weakness. In contrast, sugammadex is a selective reversal agent for steroidal NMBA, which works by encapsulation via tight water-soluble complexes with amino steroids (eg, rocuronium) rather than increasing acetylcholine at the neuromuscular junction. In this case, the recovery from moderate neuromuscular blockade by sugammadex was more effective and rapid than that by neostigmine. When refractory and prolonged residual neuromuscular blockade presents after repeated doses of anticholinesterase, sugammadex should be considered as an effective reversal agent. Particularly in cases of myasthenia gravis, sugammadex is superior to neostigmine for reversing rocuronium-induced NMBA in patients undergoing surgery.

The interaction between hippocampal cholinergic and nitrergic neurotransmission coordinates NMDA-dependent behavior and autonomic changes induced by contextual fear retrieval.

RATIONALE: Re-exposing an animal to an environment previously paired with an aversive stimulus evokes large alterations in behavioral and cardiovascular parameters. Dorsal hippocampus (dHC) receives important cholinergic inputs from the basal forebrain, and respective acetylcholine (ACh) levels are described to influence defensive behavior. Activation of muscarinic M1 and M3 receptors facilitates autonomic and behavioral responses along threats. Evidence show activation of cholinergic receptors promoting formation of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) in dHC. Altogether, the action of ACh and NO on conditioned responses appears to converge within dHC. OBJECTIVES: As answer about how ACh and NO interact to modulate defensive responses has so far been barely addressed, we aimed to shed additional light on this topic. METHODS: Male Wistar rats had guide cannula implanted into the dHC before being submitted to the contextual fear conditioning (3footshocks/085 mA/2 s). A catheter was implanted in the femoral artery the next day for cardiovascular recordings. Drugs were delivered into dHC 10 min before contextual re-exposure, which occurred 48 h after the conditioning procedure. RESULTS: Neostigmine (Neo) amplified the retrieval of conditioned responses. Neo effects (1 nmol) were prevented by the prior infusion of a M1-M3 antagonist (fumarate), a neuronal nitric oxide synthase inhibitor (NPLA), a NO scavenger (cPTIO), a guanylyl cyclase inhibitor (ODQ), and a NMDA antagonist (AP-7). Pretreatment with a selective M1 antagonist (pirenzepine) only prevented the increase in autonomic responses induced by Neo. CONCLUSION: The results show that modulation in the retrieval of contextual fear responses involves coordination of the dHC M1-M3/NO/cGMP/NMDA pathway.

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.

A comparison between cisatracurium and rocuronium-induced neuromuscular block on laryngeal electromyography recovery after neostigmine reversal in a porcine model.

Background: Inducing and reversing neuromuscular block is essential to a positive outcome of thyroid surgery, with intraoperative neuromonitoring (IONM) being used to decrease recurrent and superior laryngeal nerve injuries and improve vocal outcome. Neostigmine is a non-specific broad-spectrum and inexpensive reversal agent for neuromuscular blocking agents (NMBAs). The aim of this porcine study was to explore the effect of neostigmine on electromyography (EMG) signal recovery profile following the commonly used NMBAs, cisatracurium and rocuronium. Methods: Twelve piglets were allocated into two groups with six piglets in each group. When stable baseline EMG signals were obtained, a neuromuscular block was induced by intravenous cisatracurium 0.2 mg/kg (group C) or rocuronium 0.6 mg/kg (group R) for each piglet. We compared laryngeal EMG tracing with spontaneous recovery (control) and neostigmine (0.04 mg/kg) reversal for each group. The time course of real-time laryngeal EMG signals was observed for 30 min from NMBA injection. Effects of neostigmine on EMG signal were assessed at 50% EMG recovery and by the maximum neuromuscular block recovery degree from the baseline value. Results: Neostigmine shortened the recovery time to 50% EMG amplitude in both group C (16.5 [2.5] vs. 29.0 [2.0] min, P<0.01) and group R (16.5[2.5] vs. 26.5 [1.5] min, P<0.05) compared to spontaneous recovery, respectively. Neostigmine reversal also enhanced the maximum degree of EMG amplitude recovery in both group C (83.6 [5.1] vs. 47.2 [6.1] %, P<0.01) and group R (85.6 [18.2]vs. 57.1 [6.3] %, P<0.05) compared to spontaneous recovery, respectively. The reversal effect of neostigmine did not differ significantly between cisatracurium and rocuronium. Conclusions: This porcine model demonstrated that neostigmine provides an adequate and timely IONM signal suppressed by both cisatracurium and rocuronium. These results can potentially expand the options for precision neuromuscular block management during IONM to improve vocal outcomes in thyroid surgery patients.

Effects of sugammadex and neostigmine on mucociliary clearance in general anesthesia.

OBJECTIVE: The aim of this study was to evaluate the effects of sugammadex and neostigmine used in general anesthesia on postoperative mucociliary clearance. PATIENTS AND METHODS: This prospective, randomized and double-blind study was performed on 60 non-smokers with ASA I-III underwent inguinal hernia repair under general anesthesia. Mucociliary clearance was assessed by nasal saccharine transit time (STT). After the preoperative STT measurement, the patients were taken to the operating room, and divided into two equal groups as group 1 and 2 (n= 30 for each group). Midazolam, propofol, and rocuronium were used in all patients. Anesthesia was maintained by sevoflurane at a flow rate of 6 lt/min (50% O2 - 50% N2O) with a minimum alveolar concentration of 1.3-1.5. After the surgical procedure, atropine-neostigmine (20 mcg/kg - 50 mcg/kg) and sugammadex (2 mg/kg) were administered to group 1 and group 2, respectively, and then the patients were extubated. The postoperative STT was measured in postoperative period. RESULTS: The mean age of the patients was 53 (±16) years, and 56 (93%) of them were male. There were no differences between the groups in terms of age, gender, height, weight, ASA score, and duration of anesthesia, duration of surgery, postoperative period, preoperative STT, and postoperative STT. However, when each group was evaluated separately, there was a statistically significant increase in the postoperative STT compared to the preoperative STT in both groups (p=0.005 for group 1, p<0.001 for group 2). CONCLUSIONS: The effects of sugammadex and neostigmine used in general anesthesia on postoperative mucociliary clearance are similar, and postoperative mucociliary clearance is delayed.

Fentanyl and neostigmine delivered to mouse prefrontal cortex differentially alter breathing.

Opioids impair many functions modulated by the prefrontal cortex (PFC), including wakefulness, cognition, and breathing. In contrast, cholinergic activity in the PFC increases wakefulness. This study tested the hypothesis that microinjecting the opioid fentanyl and the acetylcholinesterase inhibitor neostigmine into the PFC of awake C57BL/6J male mice (n = 27) alters breathing. The lateral and medial PFC were unilaterally microinjected with saline (control) and fentanyl. The medial PFC received additional microinjections of neostigmine. The results show that fentanyl caused site-specific changes in breathing. Fentanyl delivered to the lateral PFC significantly decreased minute ventilation variability, whereas fentanyl delivered to the medial PFC significantly increased tidal volume and duty cycle. Neostigmine microinjected into the medial PFC significantly increased respiratory rate, tidal volume, and minute ventilation. A final series of experiments revealed that decreased minute ventilation caused by systemic fentanyl administration was mitigated by PFC microinjection of neostigmine.

Antinociceptive Effects and Interaction Mechanisms of Intrathecal Pentazocine and Neostigmine in Two Different Pain Models in Rats.

Background: Pentazocine produces a wide variety of actions in the treatment of perioperative analgesia. Neostigmine is a cholinesterase inhibitor used to antagonize the residual effects of muscle relaxants and also produces an analgesic effect. Objectives: To investigate the analgesic effects of intrathecally injected pentazocine and neostigmine and their interaction. Methods: Sprague-Dawley rats were used to test the analgesic effect of pentazocine and neostigmine using the paw formalin pain model and the incision mechanical allodynia model. Pentazocine (3, 10, 30, and 100 µg), neostigmine (0.3, 1, 3, and 10 µg) or a pentazocine-neostigmine mixture were separately injected to evaluate their antinociceptive effects alone on the treatment groups. The corresponding control group received an intrathecal injection containing the same volume of saline. The formalin pain test, or the plantar incision pain behavior test were performed 30 minutes later. Isobolographic analysis was used to evaluate the interaction between pentazocine and neostigmine. Intrathecally administered selective mu-opioid receptor antagonist CTAP, selective kappa-opioid receptor antagonist nor-Binaltorphimine (nor-BNI), nonselective opioid receptor antagonist naloxone, and muscarinic acetylcholine receptor antagonist atropine were also used to test the possible interaction mechanism. These antagonists were used 30 minutes before the pentazocine and neostigmine mixtures which were intrathecally injected. Results: Intrathecally administered pentazocine (3, 10, 30, and 100 µg) and neostigmine (0.3, 1, 3, and 10 µg) alone had a marked dose-related impact on suppressing the biphasic responses in the formalin test. Pentazocine (3, 10, 30, and 100 µg) and neostigmine (0.3, 1, 3, and 10 µg) alone attenuated the mechanical allodynia in a plantar incision model in a dose-dependent manner. Isobolographic analysis revealed that the mixture of intrathecal pentazocine and neostigmine synergistically decreased both phase I and II activity in the formalin test and mechanical allodynia in the plantar incision model. Pretreatment of intrathecally administered nor-BNI, naloxone, atropine, but not CTAP, antagonized the analgesic effect of the pentazocine-neostigmine mixture. Conclusions: All of these results suggest that the combined application of pentazocine and neostigmine is an effective way to relieve pain from formalin and acute incision mechanical allodynia. The synergistic effect between pentazocine and neostigmine is mostly attributed to the kappa-opioid receptor and the cholinergic receptor in the spinal cord.

Risk factors for administration of additional reversal following neuromuscular blockade with rocuronium in children: A retrospective case-control study.

BACKGROUND: The prevalence and risk factors for residual neuromuscular blockade in children remain poorly characterized. We hypothesize that specific patient and anesthetic risk factors may be associated with the administration of additional reversal in children following initial reversal of rocuronium with neostigmine. METHODS: Our electronic health record was queried for patients <18 years of age who received rocuronium and reversal with neostigmine from 2017 through 2020. Patients receiving other nondepolarizing neuromuscular blocking drugs were excluded. The outcome of interest was defined as the administration of additional neostigmine or sugammadex following primary reversal with neostigmine. Time between the last dose of rocuronium and initial dose of neostigmine, and the cumulative dose of rocuronium were dichotomized. These were combined with other covariates including age, weight, sex, racial group, procedure type, ASA physical status, >1 rocuronium dose administered during the procedure, initial neostigmine dose <0.05 mg kg-1 , use of train-of-four monitoring, duration of anesthesia, inpatient or outpatient, emergency case, neuromuscular disease, and extremes of weight, to assess possible associations with the primary outcome. RESULTS: During the study period, 101/6373 (1.58%) patients received rocuronium and additional reversal. Dichotomization of time between last dose of rocuronium and neostigmine yielded <28 min since the last dose of rocuronium and cumulative dose of rocuronium >0.45 mg kg-1 hr-1 . These were associated with the administration of additional reversal with an OR 1.52 (95% CI, 1.08-2.35) and OR 1.71 (95% CI, 1.10-2.67), respectively. Other risk factors included an initial neostigmine dose <0.05 mg kg-1 , OR 4.98 (95% CI, 2.84-6.49), and African American race, OR 1.78 (95% CI, 1.07-2.87). CONCLUSION: Risk factors associated with the administration of additional reversal included time <28 min from the last dose of rocuronium to initial dose of neostigmine, cumulative dose of rocuronium >0.45 mg kg-1 hr-1 , initial neostigmine dose <0.05 mg kg-1 , and African American race.

Early-Onset Myasthenia Gravis Following COVID-19 Vaccination.

As coronavirus disease 2019 (COVID-19) has spread worldwide, the rate of COVID-19 vaccination uptake is encouraging. Neurological complications associated with COVID-19 vaccines such as stroke, Guillain-Barré syndrome, and Bell's palsy have been reported. Recently, late-onset myasthenia gravis (MG) following COVID-19 vaccination has been reported. To date, however, there has been no evidence of increased risk of early-onset MG following COVID-19. Here, we report a case of a patient with new-onset MG that arose after receiving a COVID-19 vaccine. A 33-year-old woman suddenly experienced generalized weakness and diplopia on the evening she had received the second dose of the Pfizer-BioNTech COVID-19 vaccine. The temporal relationship suggests that this new-onset MG is related to the vaccination. It also implies that COVID-19 vaccination could trigger early-onset MG symptoms in patients at risk of MG.