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).

Required dose of sugammadex or neostigmine for reversal of vecuronium-induced shallow residual neuromuscular block at a train-of-four ratio of 0.3.

Residual shallow neuromuscular block (NMB) is potentially harmful and contributes to critical respiratory events. Evidence for the optimal dose of sugammadex required to reverse vecuronium-induced shallow NMB is scarce. The aims of the present study were to find suitable doses of sugammadex and neostigmine to reverse a residual vecuronium-induced NMB from a time of flight (TOF) ratio of 0.3-0.9 and evaluate their safety and efficacy. In total, 121 patients aged 18-65 years were randomly assigned to 11 groups to receive placebo, sugammadex (doses of 0.125, 0.25, 0.5, 1.0, or 2.0 mg/kg), or neostigmine (doses of 10, 25, 40, 55, or 70 µg/kg). The reversal time of sugammadex and neostigmine to antagonize a vecuronium-induced shallow residual NMB (i.e., TOF ratio of 0.3) and related adverse reactions were recorded. Several statistical models were tested to find an appropriate statistical model to explore the suitable doses of sugammadex and neostigmine required to reverse a residual vecuronium-induced NMB. Based on a monoexponential model with the response variable on a logarithmic scale, sugammadex 0.56 mg/kg may be sufficient to reverse vecuronium-induced shallow residual NMB at a TOF ratio of 0.3 under anesthesia maintained with propofol. Neostigmine may not provide prompt and satisfactory antagonism as sugammadex, even in shallow NMB.

Sugammadex Reduces PACU Recovery Time after Abdominal Surgery Compared with Neostigmine.

OBJECTIVE: This study blindly evaluated sugammadex compared with neostigmine on length of stay in the postanesthesia care unit (PACU). METHODS: Fifty patients undergoing elective laparoscopic cholecystectomy or abdominal wall hernia repair consented to receive either sugammadex (2 mg/kg) or neostigmine (0.07 mg/kg) for the reversal of rocuronium neuromuscular blockade. Reversal agents were administered during surgical closing, and the train of four was measured until a twitch ratio of T4:T1 ≥ 0.9 was obtained to signify a robust reversal. Postreversal outcomes also were measured during PACU stay. Aldrete scores, pain visual analog scale score, and nausea were measured during the PACU stay. RESULTS: Patients receiving sugammadex experienced a shorter PACU stay at the time of discharge than patients receiving neostigmine, by an average of 12 minutes (P < 0.05). CONCLUSIONS: Sugammadex patients had a significantly shorter PACU stay.

A randomized trial evaluating the safety profile of sugammadex in high surgical risk ASA physical class 3 or 4 participants.

BACKGROUND: The aim of this randomized, double-blind trial was to evaluate the safety and tolerability profile, including cardiac safety, of sugammadex-mediated recovery from neuromuscular block in participants undergoing surgery who met the American Society of Anesthesiologists (ASA) Physical Class 3 or 4 criteria. Specifically, this study assessed the impact of sugammadex on cardiac adverse events (AEs) and other prespecified AEs of clinical interest. METHODS: Participants meeting ASA Class 3 and 4 criteria were stratified by ASA Class and NMBA (rocuronium or vecuronium) then randomized to one of the following: 1) Moderate neuromuscular block, sugammadex 2 mg/kg; 2) Moderate neuromuscular block, neostigmine and glycopyrrolate (neostigmine/glycopyrrolate); 3) Deep neuromuscular block, sugammadex 4 mg/kg; 4) Deep neuromuscular block, sugammadex 16 mg/kg (rocuronium only). Primary endpoints included incidences of treatment-emergent (TE) sinus bradycardia, TE sinus tachycardia and other TE cardiac arrhythmias. RESULTS: Of 344 participants randomized, 331 received treatment (61% male, BMI 28.5 ± 5.3 kg/m2, age 69 ± 11 years). Incidence of TE sinus bradycardia was significantly lower in the sugammadex 2 mg/kg group vs neostigmine/glycopyrrolate. The incidence of TE sinus tachycardia was significantly lower in the sugammadex 2 and 4 mg/kg groups vs neostigmine/glycopyrrolate. No significant differences in other TE cardiac arrythmias were seen between sugammadex groups and neostigmine/glycopyrrolate. There were no cases of adjudicated anaphylaxis or hypersensitivity reactions in this study. CONCLUSIONS: Compared with neostigmine/glycopyrrolate, incidence of TE sinus bradycardia was significantly lower with sugammadex 2 mg/kg and incidence of TE sinus tachycardia was significantly lower with sugammadex 2 mg/kg and 4 mg/kg. These results support the safety of sugammadex for reversing rocuronium- or vecuronium-induced moderate and deep neuromuscular block in ASA Class 3 or 4 participants. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03346057 .

Sugammadex Versus Neostigmine for Reversal of Rocuronium Neuromuscular Block in Patients Having Catheter-Based Neurointerventional Procedures: A Randomized Trial.

BACKGROUND: Catheter-based endovascular neurointerventions require deep neuromuscular blocks during the procedure and rapid subsequent recovery of strength to facilitate neurological evaluation. We tested the primary hypothesis that sugammadex reverses deep neuromuscular blocks faster than neostigmine reverses moderate neuromuscular blocks. METHODS: Patients having catheter-based cerebral neurointerventional procedures were randomized to: (1) deep rocuronium neuromuscular block with posttetanic count 1 to 2 and 4-mg/kg sugammadex as the reversal agent or (2) moderate rocuronium neuromuscular block with train-of-four (TOF) count 1 during the procedure and neuromuscular reversal with 0.07-mg/kg neostigmine to a maximum of 5 mg. Recovery of diaphragmatic function was assessed by ultrasound at baseline before the procedure and 90 minutes thereafter. The primary outcome-time to reach a TOF ratio ≥0.9 after administration of the designated reversal agent-was analyzed with a log-rank test. Secondary outcomes included time to successful tracheal extubation and the difference between postoperative and preoperative diaphragmatic contraction speed and distance. RESULTS: Thirty-five patients were randomized to sugammadex and 33 to neostigmine. Baseline characteristics and surgical factors were well balanced. The median time to reach TOF ratio ≥0.9 was 3 minutes (95% confidence interval [CI], 2-3 minutes) in patients given sugammadex versus 8 minutes (95% CI, 6-10 minutes) in patients given neostigmine. Sugammadex was significantly faster by a median of 5 minutes (95% CI, 3-6 minutes; P < .001). However, times to tracheal extubation and diaphragmatic function at 90 minutes did not differ significantly. CONCLUSIONS: Sugammadex reversed deep rocuronium neuromuscular blocks considerably faster than neostigmine reversed moderate neuromuscular blocks. However, times to extubation did not differ significantly, apparently because extubation was largely determined by the time required for awaking from general anesthesia and because clinicians were willing to extubate before full neuromuscular recovery. Sugammadex may nonetheless be preferable to procedures that require a deep neuromuscular block and rapid recovery.

Effects of Sugammadex versus Neostigmine on Intraoperative Coagulation Profiles in Patients with Thyroidectomy.

BACKGROUND: Sugammadex has been a revolutionary reversal of neuromuscular blockade. It is known to be highly efficient. However, a change in the coagulation profile is one of the most dangerous potential complications which is a concern for both surgeon and anesthetist. Bleeding may cause hypovolemic shock, hematoma, and so on. To investigate the effects of sugammadex on coagulation profiles in patients with thyroidectomy, we compared patients that were treated with either sugammadex or neostigmine. PATIENTS AND METHODS: Eighty patients with thyroid neoplasms undergoing thyroidectomy were randomly allocated to sugammadex group (group S) or neostigmine group (group N). Induction of anesthesia was preformed using propofol, sufentanil, and rocuronium. Group S received sugammadex 2.0mg/kg after trachea intubation, similarly Group N received neostigmine 40 µg/kg, for reversal of rocuronium-induced neuromuscular blockade. The intraoperative coagulation profiles were monitored after the rocuronium injection (T0), 10 minutes after reversal (T1) and 30 minutes after reversal (T2) by testing activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), thrombin time (TT), and TEG-Haemonetics. Amount of bleeding was recorded during perioperative period. RESULTS: There was no significant difference in the thromboelastogram, APTT, PT, FIB, or TT measurements at each time point in Group N. The reaction time (R time) and kinetics time (K time) of Group S in T1 were significantly longer than the corresponding times at T0 and T2, and the R times were significantly longer than those in Group N at the same time points (P<0.05). Additionally, in Group S, the APTT was prolonged in T1 and returned to normal in T2. CONCLUSION: The result showed that sugammadex provided transient efficacy in prolonging the coagulation parameters, while neostigmine did not change the coagulation profile.

Comparison of neuromuscular blockade recovery co-administered with neostigmine and different doses of calcium gluconate: a randomized control trial.

BACKGROUND: Calcium increases the probability of transmitter release at the neuromuscular junction. It is not known whether there is a dose-dependent relationship between the dosage of calcium gluconate and the probability of transmitter release for non-depolarizing neuromuscular blockade (NMB) recovery by acetylcholinesterase inhibitors (AchEIs). This study compared the neuromuscular recovery time and the incidence of postoperative residual curarization (PORC) according to the dosage of calcium gluconate co-administered with neostigmine in three patient groups. METHODS: Patients were randomly allocated to a control group, a 5 mg/kg calcium gluconate group (calcium 5 group), or a 10 mg/kg calcium gluconate group (calcium 10 group). In patients with a TOF ratio (TOFr) between 0.2-0.7, 0.04 mg/kg of neostigmine was administered and both 0.2 mg of glycopyrrolate and 0.4 mg of atropine per 1 mg of neostigmine were administered. And additional 5 or 10 mg/kg of calcium gluconate were administrated to the calcium 5 and 10 groups. The primary endpoint was neuromuscular recovery time (the time between reversal and TOFr≥0.9). The secondary endpoints were the incidence of PORC at 5, 10, and 20 min after reversal administration and the train-of-four ratio (TOFr) at each time point. RESULTS: The neuromuscular recovery time was 5.3 min in the control group, 3.9 min in the calcium 5 group, and 4.1 min in the calcium 10 group, respectively (P = 0.004). The incidence of PORC at 5 min after neostigmine administration was 12 in the control group, 4 in the calcium 5 group, and 4 in the calcium 10 group, respectively, with statistical significance (P = 0.014). CONCLUSIONS: The co-administration of calcium gluconate with neostigmine safely promoted early NMB recovery, and the neuromuscular recovery time of the calcium 10 group tended to be more evenly distributed than that of the calcium 5 group. TRIAL REGISTRATION: https://cris.nih.go.kr/cris/index.jsp(KCT0004182 ). Date of registration: August 122,019.

Effects of Sugammadex Plus Rocuronium vs Neostigmine Plus Cisatracurium During Renal Transplantation on Graft Function: A Retrospective, Case-Control Study.

BACKGROUND: Rocuronium can be used in patients with severe renal failure (creatinine clearance <30 mL/min), but the duration of muscle relaxation is longer and results in an increased risk of postoperative residual neuromuscular block. Rocuronium can be antagonized by sugammadex, but the elimination of the complex they make (rocuronium-sugammadex complex) varies according to the renal function. Two case reports/series have reported the use of rocuronium-sugammadex complex during renal transplantation. A recently published retrospective study showed no differences in postoperative creatinine levels in patients receiving kidney transplantation. This retrospective case-control study aims to investigate the effects of rocuronium-sugammadex, used during renal transplantation, on transplanted kidney function. METHODS: We analyzed 113 medical records of patients undergoing kidney transplantation from January 2015 to December 2018. Forty-seven medical records were excluded because they did not report the administration of one of the following drugs during the transplantation: rocuronium, sugammadex, cisatracurium, neostigmine. The demographics of patients and donors were collected along with the following data: blood urea and creatinine, serum and urinary electrolytes, and diuresis. Marginal, single, or double kidney transplantations; Karpinski scores; and histologic evaluations of transplanted kidney were collected. RESULTS: We included data from 66 medical reports from January 2015 to December 2018. Blood creatinine levels at 6, 12, and 24 hours were significantly lower in the rocuronium + sugammadex group than in the cisatracurium + neostigmine group (creatinine 6 hours P = .05, creatinine 12 hours P = .038, creatinine 24 hours P = .049). Blood urea levels for 24 hours after transplantation were significantly lower in the rocuronium + sugammadex group than in the cisatracurium + neostigmine group (urea 0 hours P = .025, urea 6 hours P = .011, urea 12 hours P = .03, urea 24 hours P = .011). We found no statistically significant differences in blood sodium, blood potassium, blood calcium, diuresis, urinary sodium, or urinary potassium levels before and after transplantation. CONCLUSIONS: In this retrospective case-control study, the use of rocuronium and sugammadex during renal transplant surgery did not affect relevant kidney recovery outcomes in the first week after transplantation.

The rodent model of impaired gastric motility induced by allyl isothiocyanate, a pungent ingredient of wasabi, to evaluate therapeutic agents for functional dyspepsia.

Functional dyspepsia (FD) is thought to be mainly based on gastric motility dysfunction and chronic hypersensitivity, yet FD animal models has been reported a few. We studied to establish the mouse model of impaired gastric motility induced by a pungent ingredient of wasabi allyl isothiocyanate (AITC), which is reliable to evaluate prokinetic agents. Male ddY mice were used. Gastric motility was measured by 13C-acetic acid breath test in conscious mice. AITC (80 mM) was given 60 min before the measurement of motility. Prokinetic agents including itopride (30, 100 mg/kg), mosapride (0.1-1 mg/kg), neostigmine (30 µg/kg), acotiamide (10-100 mg/kg), and daikenchuto (100-1000 mg/kg) were given 40 min before the measurement. AITC impaired gastric motility without mucosal damages, which reverted 24 h after AITC treatment. The decreased motility induced by AITC was restored by prokinetic agents such as itopride, mosapride, neostigmine, and acotiamide. In separate experiment, daikenchuto recovered the decreased motility induced by AITC, although daikenchuto had no effect on motility in normal condition. In conclusion, it is considered that the AITC-induced impaired gastric motility mouse model is useful to develop new prokinetic agents for treatment of FD, and to re-evaluate traditional Japanese herbal medicines.

Comparison of the effects of sugammadex and neostigmine on hospital stay in robot-assisted laparoscopic prostatectomy: a retrospective study.

BACKGROUND: Sugammadex reduces postoperative complications. We sought to determine whether it could reduce the length of hospital stay, post-anesthetic recovery time, unplanned readmission, and charges for patients who underwent robot-assisted laparoscopic prostatectomy (RALP) when compared to neostigmine. METHODS: This was a retrospective observational study of patients who underwent RALP between July 2012 and July 2017, in whom rocuronium was used as a neuromuscular blocker. The primary outcome was the length of hospital stay after surgery in patients who underwent reversal with sugammadex when compared to those who underwent reversal with neostigmine. The secondary outcomes were post-anesthetic recovery time, hospital charges, and unplanned readmission within 30 days after RALP. RESULTS: In total, 1430 patients were enrolled. Using a generalized linear model in a propensity score-matched cohort, sugammadex use was associated with a 6% decrease in the length of hospital stay (mean: sugammadex 7.7 days vs. neostigmine 8.2 days; odds ratio [OR] 0.94, 95% confidence interval [CI] [0.89, 0.98], P = 0.008) and an 8% decrease in post-anesthetic recovery time (mean: sugammadex 36.7 min vs. neostigmine 40.2 min; OR 0.92, 95% CI [0.90, 0.94], P < 0.001) as compared to neostigmine use; however, it did not reduce the 30-day unplanned readmission rate (P = 0.288). The anesthesia charges were higher in the sugammadex group than in the neostigmine group (P < 0.001); however, there were no significant differences between the groups in terms of postoperative net charges (P = 0.061) and total charges (P = 0.100). CONCLUSIONS: Compared to the reversal of rocuronium effects with neostigmine, reversal with sugammadex after RALP was associated with a shorter hospital stay and post-anesthetic recovery time, and was not associated with 30-day unplanned readmission rates and net charges.

Strategies of analgesic treatment after cesarean delivery. Current state and new alternatives. / Estrategias de tratamiento analgésico tras cesárea. Estado actual y nuevas alternativas.

The number of caesarean sections performed worldwide is increasing, and with it, the need for the optimal analgesia strategies. Deficient postoperative analgesia increases the need for opioids, delays recovery, and is associated with chronic pain and postpartum depression. It is essential to find good postoperative pain control strategies that facilitate early mobility, early recovery, and early hospital discharge with minimal side effects on the mother and infant. Multimodal analgesia based on neuroaxial anaesthesia with morphine in combination with non-opioids such as non-steroidal anti-inflammatory drugs and paracetamol, gives the best post-caesarean analgesia outcome, and allows anaesthesiologists to reserve opioids, corticoids, gabapentin, magnesium or ketamine for situations where neuroaxial anaesthesia cannot be performed, for high-risk patients, or when pain is difficult to control. Peripheral nerve block techniques can also be added, such as transverse abdominis plane block, erector spinae block, or continuous wound infiltration.

[Analysis of sugammadex for antagonistic neuromuscular block in patients with radical resection of lung cancer under thoracoscope].

Objective: To investigate the efficacy and safety of sugammadex for antagonistic neuromuscular block in patients with radical resection of lung cancer under thoracoscope. Methods: One hundred patients undergoing radical resection of lung cancer under thoracoscope in Affiliated Cancer Hospital of Zhengzhou University from March to September in 2019, were randomly divided into control group (group C) and sugammadex group (group S). All patients were anaesthetized (induced and maintained) with intravenous target-controlled infusion of propofol and remifentanil, and intermittent intravenous injection of the neuromuscular block of rocuronium. During the operation, the bispectral index (BIS) was used to monitor the depth of anesthesia, and the neuromuscular block was assessed with TOF. Single-lung mechanical ventilation and double-lumen endotracheal intubation were carried out, and patient-controlled analgesia after operation were enforced. Patients in group C received neostigmine (2 mg) combined with atropine (0.5-1.0 mg) after thoracic closure, while patients in group S received sugammadex (2 mg/kg) at TOF count (≥2) after thoracic closure, and then double-lumen endotracheal tubes were extubated according to extubation indications. At these time points: T(0) (immediate before anesthesia induction), T(1) (immediate before tracheal intubation), T(2) (immediately after thoracic closure), T(3) (1 h after operation), T(4) (6 h after operation), T(5) (24 h after operation), T(6)(48 h after operation), the heart rate(HR) and mean arterial pressure (MAP) were recorded, QT interval (V3 ECG) were measured and calculated, indicators of liver function [alanine transaminase (ALT), aspartate transaminase(AST)], renal function [blood urea nitrogen (BUN), creatinine (Cre)] and clotting function [thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB)] were detected. The duration of operation, postoperative conditions within 48 hours after operation(the time of tracheal tube extubation, respiratory suppression/dysfunction, allergy, nausea and vomiting, itching of skin, abnormal sensation), pathological types and the postoperative hospital stay were recorded. Results: There were no significant differences of the age, sex ratio, body mass index (BMI), American Society of Anesthesiologists (ASA) grading ratio, duration of operation, pathological types and the postoperative hospital stay, HR, MAP and QT interval between two groups (all P>0.05). There were no remarkable differences of the levels of serum histamine, ALT, AST, BUN, Cre, TT, PT, APTT and FIB before and after administration of neuromuscular blockade antagonists (neostigmine or Sugammadex) in the same group patients (all P>0.05), also no significant differences between group C and group S at the same time points (all P>0.05). Average time of tracheal tube extubation in group S [(3.7±1.3) min] was sharply shorter than that in group C [(14.5±4.4) min, t=2.266, P<0.05)]. There were no patients with allergy, skin itching, sensory abnormality in these two groups. There were no significant difference of the incidence of postoperative nausea and vomiting between these two groups. There were 5 patients with respiratory depression in group C and no respiratory depression patient in group S, the difference was statistically significant between these two groups (χ(2)=5.263, P<0.05). Conclusion: Sugammadex is effective for antagonizing the neuromuscular blockade of rocuronium in patients with radical resection of lung cancer under thoracoscope, and can shorten the time of tracheal tube extubation after surgery.

Comparison of the Effects of Neostigmine and Sugammadex on Colonic Anastomotic Strength in Rats.

BACKGROUND: After colorectal surgery, anastomotic leakage is a major cause of mortality and morbidity. There are many factors affecting anastomotic leakage. It is known that agents such as neostigmine that is used to reverse neuromuscular blockade have certain effects on anastomosis. In our study, in which we planned to test this hypothesis, we aimed to compare the possible effects of different doses of sugammadex and neostigmine on colon anastomosis strength in a colonic resection anastomosis model in rats. MATERIALS AND METHODS: Forty adult Wistar albino male rats were divided into five groups as control (group C), Sugammadex 16 mg/kg (group SL), sugammadex 96 mg/kg (group SH), neostigmine 0.3 µmol/kg (group NL), and neostigmine 1.5 µmol/kg (group NH). The transverse colons of all rats were resected, and colonic anastomosis was performed. Appropriate drug doses according to the groups were given on the postoperative seventh day, and tissue hydroxyproline (TH) level and anastomotic bursting pressure were measured. RESULTS: Anastomotic bursting pressure values were statistically significantly different between the groups (P = 0.001). The bursting pressure in group SH was significantly higher compared with group C, group NL, and group NH. The hydroxyproline values were statistically significantly different between the groups (P = 0.015). According to the post hoc test results, the difference was between group SH and group C (P = 0.007). There were no significant differences between the other groups (P > 0.05). There was no significant difference in terms of intra-abdominal adhesion rates between the groups. CONCLUSIONS: In our study, we found that low and high doses of neostigmine had no variable effect on anastomosis, but high dose of sugammadex (96 mg/kg) had an increasing effect on intestinal anastomosis strength.

Myasthenia gravis masquerading as acute stroke: a case report.

Among non-iatrogenic neuromuscular disorders, myasthenia gravis remains the most prevalent. Diagnosing this disorder may become challenging in certain cases such as in patients with coexisting comorbid illnesses and non-specific clinical symptoms. This is a case of atypical myasthenia gravis in a middle-aged hypertensive male, who initially presented symptoms suggestive of an acute ischemic stroke. Upon later investigation, prompted by persistent symptoms, the patient was found to have AchR antibodies and had the rare finding of a fissured and atrophied tongue (reversible on treatment). It is a well-known fact that brainstem strokes can present with bulbar weakness resulting in aspiration pneumonitis, as was with the clinical presentation in the below mentioned report. Due to the initial misdiagnosis, he had received medical therapy aimed towards stroke management and prevention. Further investigation leading to a definitive diagnosis, was followed by medical therapy with neostigmine, pyridostigmine and oral prednisolone, leading to significant improvement in symptoms. Hence as a mandatory measure, while dealing with a case of a new onset of weakness, especially in cranial musculature, myasthenia gravis must not be excluded from the list of differential diagnosis. Myasthenia gravis (MG) is a potential "stroke mimic" especially in the elderly. However, due to recent change in trends of stroke statistics, this disease should be considered a possibility even in younger patients.

Administering Neostigmine as a Subcutaneous Infusion: A Case Report of a Patient Dying With Myasthenia Gravis.

BACKGROUND: Abrupt withdrawal of pharmacological therapies for myasthenia gravis can exacerbate muscle weakness and even trigger myasthenic crisis. Such medications should ideally be continued, but how this can be achieved in patients approaching the end of life, particularly when enteral administration is compromised, has not been defined. CASE HISTORY: An 83-year-old man with a history of generalized myasthenia gravis and palliative metastatic anal adenocarcinoma was admitted to his local hospital with general decline, where he was considered by more than one physician to be actively dying from his cancer. In the days preceding admission, the patient had not taken his medications consistently, including the acetylcholinesterase inhibitor, pyridostigmine, for the management of his myasthenia gravis. CASE MANAGEMENT AND OUTCOME: Reintroduction of the patient's usual myasthenia therapy improved his clinical condition to the point where he was no longer thought to be dying. When enteral administration of pyridostigmine was no longer possible, the patient was successfully converted to neostigmine, which was administered as a continuous subcutaneous infusion. CONCLUSION: Undertreated myasthenia gravis can lead to a rapid deterioration in a patient's clinical condition, and such patients may be mistakenly diagnosed as dying. Undertreated myasthenia gravis should therefore be considered as a potentially reversible cause of acute deterioration, especially in patients with complex comorbidities. The use of neostigmine as a continuous subcutaneous infusion may have a role in the management of such patients, particularly when enteral administration of acetylcholinesterase inhibitors is no longer possible.

Sugammadex Administration in Pregnant Women and in Women of Reproductive Potential: A Narrative Review.

Since its clinical introduction in 2008, sugammadex has demonstrated a high degree of safety and superior effectiveness compared to neostigmine when used to antagonize muscle relaxation produced by steroid nondepolarizing neuromuscular blockers. This includes its use in special populations, such as the elderly, children over 2 years old, and patients with renal, hepatic, or lung disease. In contrast, clinical evidence guiding its use during pregnancy, in women of childbearing potential, and in lactating women, is sparse. An exception is administration at the end of surgery in parturients undergoing cesarean delivery (CD) with general anesthesia (GA), for whom effectiveness and safety evidence is rapidly accumulating. We review evidence regarding sugammadex rescue reversal shortly after high-dose rocuronium in cases of cannot intubate/cannot ventilate (CICV), the extent of placental transfer of maternally administered sugammadex, adverse fetal effects of sugammadex exposure, potential effects on maintenance of early pregnancy, and the extent of transfer to breast milk. Finally, many anesthesiologists appear to heed the manufacturer's warning regarding informing women of childbearing potential regarding the risk of hormone contraceptive failure after sugammadex exposure. We provide a medical ethics analysis of the ex post facto counseling commonly reported after sugammadex administration, which favors either preoperative discussion and shared decision making, or the decision by the physician to use neostigmine. This review highlights the disparity in evidence regarding sugammadex use in various contexts of female reproductive health, including current research gaps that prevent this population from sharing in the benefits of sugammadex enjoyed by most perioperative patients.

Comparison of neostigmine vs. sugammadex for recovery of muscle function after neuromuscular block by means of diaphragm ultrasonography in microlaryngeal surgery: A randomised controlled trial.

BACKGROUND: Postoperative residual curarisation (PORC) is a risk directly related to the use of neuromuscular blocking agents during surgical procedures. Acceleromyography is distressing for conscious patients when assessing PORC. Diaphragm ultrasonography could be a valid alternative. OBJECTIVES: The primary objective was to achieve a 28% lower incidence of PORC in patients who, after rocuronium administration, received neostigmine or sugammadex at 30 min after surgery. To assess PORC, diaphragm ultrasonography was used, and thickening fractioning [the difference of thickness at the end of inspiration (TEI) and at the end of expiration (TEE), normalised for TEE (TEI - TEE/TEE)] was measured. PORC was defined as thickening fractioning of 0.36 or less. The secondary object was the comparison, in the two treatment groups, of the return to baseline thickening fractioning at 30 min after surgery (ΔTF30). DESIGN: Randomised, double-blind, single-centre study. SETTING: University Hospital Careggi, Florence, Italy. PATIENTS: Patients of American Society Anesthesiologists' physical status 1 or 2, 18 to 80 years, receiving rocuronium during microlaryngeal surgery. INTERVENTIONS: At the end of surgery participants were randomised to receive neostigmine (NEO group) or sugammadex (SUG group) as the reversal drug. Thickening fractioning and ΔTF30 were evaluated at baseline and at 0, 10 and 30 min after surgery. MAIN OUTCOME MEASURES: TEE and TEI at each time point. RESULTS: A total of 59 patients with similar demographic characteristics were enrolled. An association between lack of recovery (thickening fractioning ≤0.36) and drug treatment was only observed at 0 min (SUG vs. NEO, P < 0.05). Concerning ΔTF, at 30 min more patients in the SUG group returned to baseline than those in the NEO group (P < 0.001), after adjusting for side (P = 0.52), baseline thickening fractioning (P < 0.0001) and time of measurement (P < 0.01). CONCLUSION: We found an early (0 min) but not long-lasting (30 min) association between diaphragm failure and treatment allocation; a full recovery in baseline diaphragm function was observed only in patients receiving sugammadex. We cannot exclude that further differences have not been found due to interpatients variability in assessing diaphragm contractility by ultrasonography. TRIAL REGISTRATION: EudraCT Identifier: 2013-004787-62, Clinicaltrials.gov Identifier: NCT02698969.

Safety and Efficacy of Intermittent Bolus and Continuous Infusion Neostigmine for Acute Colonic Pseudo-Obstruction.

PURPOSE: To compare clinical response of intermittent bolus versus continuous infusion neostigmine for acute colonic pseudo-obstruction (ACPO). Acute colonic pseudo-obstruction occurs due to reduced colonic parasympathetic activity. Neostigmine is an acetylcholinesterase inhibitor that increases frequency of smooth muscle contraction by increasing acetylcholine at autonomic nervous system synapses. Although these administration modalities have been studied separately, they have never been compared. METHODS: This retrospective study compared bolus versus continuous infusion neostigmine for ACPO. The primary outcome was initial clinical response, defined as bowel movement (BM) within 4 hours of bolus dose or 24 hours of initiation of continuous infusion. Secondary outcomes included time to BM, bowel diameter reduction at 24 hours, incidence of bradycardia, additional neostigmine requirements, and need for colonic decompression or surgical intervention. RESULTS: Seventy-five patients were included (bolus n = 37; infusion n = 38). Median total 24-hour neostigmine dose was 2.0 mg (interquartile range [IQR]: 2.0-2.6) with bolus and 9.6 mg (IQR: 6.3-9.6) with continuous infusion. Initial clinical response was similar (infusion 81.6% vs bolus 62.2%, P = .06), but continuous infusion was associated with greater bowel diameter reduction (73.7% vs 40.5%, P = .004). Bolus administration had shorter time to BM (1.4 vs 3.5 hours, P = .0478) and increased need for colonic decompression (67.6% vs 39.5%, P = .0148). Bolus dosing was associated with less bradycardia (13.5% vs 39.5%, P = 0.011), with no difference in atropine usage (10.8% vs 5.3%, P = .43). CONCLUSION: Initial clinical response was similar between groups; however, continuous infusion neostigmine was associated with greater bowel diameter reduction at 24 hours. Bolus administration resulted in less bradycardia; however, given the lack of difference in atropine use, clinical significance is unknown. This study is the first to compare bolus versus continuous infusion neostigmine for ACPO. Further studies are needed to confirm findings.

Neostigmine Versus Sugammadex for Reversal of Neuromuscular Blockade and Effects on Reintubation for Respiratory Failure or Newly Initiated Noninvasive Ventilation: An Interrupted Time Series Design.

BACKGROUND: Pulmonary complications related to residual neuromuscular blockade lead to morbidity and mortality. Using an interrupted time series design, we tested whether proportions of reintubation for respiratory failure or new noninvasive ventilation were changed after a system-wide transition of the standard reversal agent from neostigmine to sugammadex. METHODS: Adult patients undergoing a procedure with general anesthesia that included pharmacologic reversal of neuromuscular blockade and admission ≥1 night were eligible. Groups were determined by date of surgery: August 15, 2015 to May 10, 2016 (presugammadex), and August 15, 2016 to May 11, 2017 (postsugammadex). The period from May 11, 2016 to August 14, 2016 marked the institutional transition (washout/wash-in) from neostigmine to sugammadex. The primary outcome was defined as a composite of reintubation for respiratory failure or new noninvasive ventilation. Event proportions were parsed into 10-day intervals in each cohort, and trend lines were fitted. Segmented logistic regression models appropriate for an interrupted time series design and adjusting for potential confounders were utilized to evaluate the immediate effect of the implementation of sugammadex and on the difference between preintervention and postintervention slopes of the outcomes. Models containing all parameters (full) and only significant parameters (parsimonious) were fitted and are reported. RESULTS: Of 13,031 screened patients, 7316 patients were included. The composite respiratory outcome occurred in 6.1% of the presugammadex group and 4.2% of the postsugammadex group. Adjusted odds ratio (OR) and 95% confidence intervals (CIs) for the composite respiratory outcome were 0.795 (95% CI, 0.523-1.208) for the immediate effect of intervention, 0.986 (95% CI, 0.959-1.013) for the difference between preintervention and postintervention slopes in the full model, and 0.667 (95% CI, 0.536-0.830) for the immediate effect of the intervention in the parsimonious model. CONCLUSIONS: The system-wide transition of the standard pharmacologic reversal agent from neostigmine to sugammadex was associated with a reduction in the odds of the composite respiratory outcome. This observation is supported by nonsignificant within-group time trends and a significant reduction in intercept/level from presugammadex to postsugammadex in a parsimonious logistic regression model adjusting for covariates.

[Hypothyroidism and myasthenia: a case study]. / Hypothyroïdie et myasthénie: à propos d'un cas.

Several disorders of immunological origin, in particular thyroid disorders have been reported in patients with myasthenia. This relationship has been little elucidated but in patients with myasthenia and Graves' disease was found an immunological cross-reaction between the neuromuscular junction and thyroid components. It is generally accepted that the association between hyperthyroidism and myasthenia is much more common than between myasthenia and hypothyroidism. However, there has been no clear explanation for this difference. We here report the case of a 53-year old patient treated for hypothyroidism due to suspected Hashimoto's disease well balanced under replacement therapy and whose evolution was marked by the detection of myasthenia during the follow up period. Myasthenia responded well to treatment based on neostigmine.