Sugammadex For Reversal Research Articles

A retrospective study of sugammadex for reversal of neuromuscular blockade induced by rocuronium in critically ill patients in the ICU

Sugammadex has been approved for reversal of neuromuscular blockade by vecuronium and rocuronium in adults undergoing surgery. Although widely used in the operating room, sugammadex has not been investigated in the intensive care unit setting. This study aimed to evaluate the use of sugammadex in critically ill patients with a focus on known drug-related adverse reactions. In this single-center, retrospective, observational study, 91 critically ill patients who were administered sugammadex while in the ICU were evaluated. Electronic health records were reviewed, and baseline data, as well as indication and incidence of complications possibly related to sugammadex, were retrospectively collected. The most common procedures requiring neuromuscular blockade followed by reversal with sugammadex were bronchoscopy, percutaneous dilatative tracheostomy, and percutaneous endoscopic gastrostomy. Within 2 h following administration of sugammadex, skin rash and use of antihistamines were reported in 4 patients (4.4%) in total; bradycardia was observed in 9 patients (9.9%), and respiratory adverse events were described in 3 patients (3.3%). New-onset bleeding up to 24 h after sugammadex was reported in 7 patients (7.7%), 3of whom received transfusions of packed red blood cells. Sugammadex was well tolerated in critically ill patients and could be considered for reversal of neuromuscular blockade in this population. Larger prospective studies are required to determine the safety profile and evaluate the potential benefit and indications of sugammadex in the critical care setting.

Unanticipated Profound Paralysis and Sugammadex Dosing Implications After Videoscopic Thoracic Surgery.

A bedridden patient with empyema presented for thoracoscopic decortication. During the procedure, despite a post-tetanic count (PTC) of 0 via calibrated quantitative neuromuscular monitoring, persistent diaphragmatic movement impaired operating conditions, so rocuronium was re-dosed. After surgery, the patient had 0 PTC. Sugammadex was titrated to achieve baseline neuromuscular strength, monitoring the effect of each 200-mg dose. Ultimately, 1200 mg was required to achieve baseline strength. We describe monitor troubleshooting, considerations with unexpectedly deep neuromuscular blockade, the importance of routine quantitative neuromuscular monitoring, and one strategy for sugammadex reversal in patients with profound paralysis outside of the standard dosing guidelines.

Effects of age on sugammadex reversal of neuromuscular blockade induced by rocuronium in Chinese children: a prospective pilot trial

BackgroundSugammadex reverses neuromuscular blockade induced by steroidal relaxants. We compared the recovery for neuromuscular blockade reversal with sugammadex in children aged 1–12 years.MethodsFrom August 2019 to August 2020, patients who received 2.0 mg·kg− 1 sugammadex for neuromuscular blockade reversal after surgery were recruited. The primary outcome was the time for the train-of-four ratio (TOFR) to recover to 0.9; secondary outcomes included the incidence of the TOFR < 0.9, extubation time, length of stay at the post-anesthesia care unit, and adverse events. Hemodynamic parameters before and 5 min after sugammadex administration and vital signs in the recovery room were also recorded.ResultsEighty-six children were recruited (1 to < 3 years, n = 23; 3 to < 5 years, n = 33; 5 to ≤12 years, n = 30). Intergroup differences in the recovery of the TOFR to 0.9 were not statistically significant (F = 0.691, p = 0.504). Recurrence of the TOFR < 0.9 was not observed in any group. Five minutes after sugammadex administration, the heart rates of patients aged 3 to < 5 and 5 to ≤12 years were significantly lower than those at baseline (p < 0.05). Extubation time was similar in patients aged 1 to ≤12 years. Length of stay and end-tidal capnography at the post-anesthesia care unit as well as adverse events did not differ significantly.ConclusionA moderate (TOF count two) rocuronium-induced neuromuscular blockade can be effectively and similarly reversed with sugammadex 2 mg·kg− 1 in Chinese children aged 1–12 years.Trial registrationChinese Clinical Trial Registry: ChiCTR1900023715 (June 8, 2019).

Rocuronium vs Succinylcholine: Emergency Airway Management of the COVID-19 Patient

Tracheal Intubation is routinely performed in many settings. Anesthesia providers are experts in this procedure. Determination for the best possible approach for tracheal intubation include patient and provider specific considerations. Severe acute respiratory syndrome-coronavirus-2 (SARS CoV-2) infection has led to the COVID-19 pandemic. SARS CoV-2 is a highly contagious RNA virus that has caused widespread infections, severe respiratory disease, and deaths. The purpose of this article is to describe the airway management currently recommended in Germany as well as the United States, the multi-systems pathophysiologic complications of these patients, and review the need for minimum airway manipulation prior to intubation of the trachea. Further, this article discusses the pharmacologic options that are available for muscle relaxation during rapid sequence induction. A review of the literature was performed. Further, some authors of this article have actively participated in airway management of COVID-19 patients. Available literature and guidelines suggest that rapid sequence induction with minimal airway manipulation is superior to standard induction. The article suggests that appropriate doses of rocuronium with an option of sugammadex reversal is a safer and superior choice to succinylcholine.

The effect of dexamethasone on sugammadex reversal of rocuronium-induced neuromuscular blockade in surgical patients undergoing general anesthesia: A systematic review and meta-analysis.

Background:There have been conflicting results regarding clinical dexamethasone-sugammadex interactions in adults and pediatric patients under general anesthesia.Methods:This study used a systematic review with meta-analysis of randomized controlled trials and non-randomized studies based on the Cochrane Review Methods. A comprehensive literature search was conducted to identify clinical trials that investigated the effect of dexamethasone on sugammadex reversal of rocuronium-induced neuromuscular blockade in surgical patients undergoing general anesthesia.Results:Among the 314 patients in the 6 studies, 147 received intravenous dexamethasone (dexamethasone group), and 167 received intravenous saline or other antiemetics (control group). The primary outcome, the time to recovery after sugammadex administration (the time to recovery of the train-of-four ratio to 0.9 after sugammadex administration; s) was comparable between the 2 groups, the weighted mean difference (95% confidence interval [CI]) being –2.93 (–36.19, 30.33) (I2 = 94%). The time to extubation after sugammadex administration (s) and incidence of postoperative nausea and vomiting was not different between the 2 groups, the weighted mean difference (95% CI) being 23.31 (−2.26, 48.88) (I2 = 86%) and the pooled risk ratio (95% CI) being 0.25 (0.03, 2.11), respectively. The time to recovery after sugammadex administration might be different according to the study design or study region.Conclusion:This meta-analysis showed that use of dexamethasone in the perioperative period neither delayed nor facilitated the reversal of rocuronium-induced neuromuscular blockade with sugammadex in patients undergoing elective surgery with general anesthesia. However, given that the results showed high heterogeneity, further randomized controlled trials are needed to confirm these findings.

Sugammadex Neuromuscular Blockade Reversal Associated With Lower Postoperative Arterial Carbon Dioxide Levels After Congenital Cardiac Surgery

To compare postoperative arterial blood gas samples and requirement for respiratory support between patients who received sugammadex versus neostigmine reversal before extubation after congenital cardiac surgery. Retrospective, cross-sectional study. Single-center, university-based, tertiary care hospital. Patients with congenital heart disease undergoing surgery with cardiopulmonary bypass. Chart review. The first postoperative arterial blood gas measurements were abstracted from electronic medical records, and reintubation or use of positive- pressure respiratory support within the first 24 postoperative hours was documented. Of the 237 charts reviewed, 111 (47%) patients received sugammadex reversal and 126 (53%) received neostigmine. Multivariate models showed that patients with 2-ventricle congenital heart disease who received sugammadex had lower postoperative arterial carbon dioxide partial pressure (PaCO2) values (coefficient -3.1, 95% confidence interval [CI] -5.9 to -0.4; p = 0.026) and required less- noninvasive positive- pressure ventilation (odds ratio 0.3, 95% CI 0.1-0.8; p = 0.021). Single-ventricle congenital heart disease patients who received sugammadex had higher postoperative pH values (coefficient 0.04, 95% CI 0.01-0.06; p = 0.01) and lower PaCO2 values (coefficient -5.2, 95% CI -9.6 to -0.8; p = 0.021). Sugammadex reversal was associated with lower postoperative PaCO2 values. In addition, sugammadex reversal was associated with less need for noninvasive positive- pressure ventilation in 2-ventricle patients. The magnitude of the effect appears modest, therefore the clinical significance remains unclear. Additional studies focused on investigating particular patient populations, such as infants, single-ventricle congenital heart disease, or patients with pulmonary hypertension, are needed to identify whether these patients appreciate a greater benefit from sugammadex reversal.

Individual pharmacometric analysis for sugammadex reversal and re-administration of neuromuscular blockade.

Sugammadex is an innovative reversal agent for neuromuscular blockade (NMB) induced by rocuronium. Although there is a case that re-paralysis is necessary after sugammadex administration, limited reports can be found on the sugammadex dosage for reversal from profound paralysis after induction and immediate re-paralysis following such reversal in detail. We experienced a case in which NMB reversal was required in a short period after paralysis for induction due to the discovery of anisocoria. We successfully re-induced general anesthesia with tracheal intubation soon after. To examine the validity of the dosing, we performed a pharmacometric analysis. A pharmacokinetic-pharmacodynamic model was developed for the patient based on a published pharmacokinetic-pharmacodynamic model for rocuronium and sugammadex. The developed model appropriately describes the train of four ratio observed. In this case, the dose of approximately 8mg/kg sugammadex but not the conventional dose of 16mg/kg would be enough for immediate reversal after induction. For the re-paralysis 30min after NMB reversal, not 1.4mg/kg but 2.2mg/kg rocuronium was an adequate dose. Taking individual differences including given dose and time intervals in consideration, NMB monitoring should be used to determine the necessary dose of rocuronium and sugammadex in such situations.

A Meta-Analysis on the Effect of Dexamethasone on the Sugammadex Reversal of Rocuronium-Induced Neuromuscular Block.

Sugammadex reverses the rocuronium-induced neuromuscular block by trapping the cyclopentanoperhydrophenanthrene ring of rocuronium. Dexamethasone shares the same steroidal structure with rocuronium. The purpose of this study was to evaluate the influence of dexamethasone on neuromuscular reversal of sugammadex after general anesthesia. Electronic databases were searched to identify all trials investigating the effect of dexamethasone on neuromuscular reversal of sugammadex after general anesthesia. The primary outcome was time for neuromuscular reversal, defined as the time to reach a Train-of-Four (TOF) ratio of 0.9 after sugammadex administration. The secondary outcome was the time to extubation after sugammadex administration. The mean difference (MD) and 95% CI were used for these continuous variables. Six trials were identified; a total of 329 patients were included. The analyses indicated that dexamethasone did not influence the time for neuromuscular reversal of sugammadex (MD −3.28, 95% CI −36.56 to 29.99, p = 0.847) and time to extubation (MD 25.99, 95% CI −4.32 to 56.31, p = 0.093) after general anesthesia. The results indicate that dexamethasone did not influence the neuromuscular reversal of sugammadex in patients after general anesthesia. Therefore, the dexamethasone does not appear to interfere with reversal of neuromuscular blockade with sugammadex in patients undergoing general anesthesia for elective surgery.

Potency estimation of sugammadex for the reversal of moderate rocuronium-induced neuromuscular block: a non-randomized dose-response study.

There is no report investigating the precise potency of sugammadex for antagonizing various intensities of rocuronium-induced neuromuscular block. The aim of this study was to evaluate the ED95 of reversibility of sugammadex and reveal the safety factor of 2mg/kg of sugammadex for moderate rocuronium-induced neuromuscular block. Fifteen patients were enrolled in this study. After induction of anesthesia, we recorded the adductor pollicis muscle response to ulnar nerve stimulation using acceleromyography. All patients received 0.6mg/kg rocuronium. When the first twitch (T1) of the train-of-four (TOF) response reappeared, rocuronium infusion was commenced to maintain T1 at 10% of the control. After the surgery was completed and infusion of rocuronium was stopped, patients were given sugammadex by a cumulative dose technique. The effective doses of sugammadex that led to recovery of the amplitude of T1 and the TOF ratio by 95% (ED95) were calculated from the regression lines of least-squares regression analysis. The mean ED95 of sugammadex for recovery of T1 and the TOF ratio from rocuronium-induced moderate neuromuscular block was 1.34 (0.24) and 1.14 (0.24) mg/kg, respectively. The ED95 of sugammadex for the recovery of T1 was significantly greater than that for the TOF ratio. However, a sugammadex dose of 2mg/kg is equivalent to about 1.5 times the ED95 of sugammadex for reversal of moderate rocuronium-induced block, indicating its safety margin.

Sugammadex reversal of large subcutaneous injection of rocuronium in an obese patient

Sugammadex reversal of large subcutaneous injection of rocuronium in an obese patient

Effect of reversal of deep neuromuscular block with sugammadex or moderate block by neostigmine on shoulder pain in elderly patients undergoing robotic prostatectomy

BackgroundFor some laparoscopic procedures, deep neuromuscular block has been shown to facilitate lower insufflation pressures and lower patient pain scores, and enhance postoperative recovery. We investigated the impact of deep neuromuscular block and its reversal on postoperative shoulder pain and outcomes after robotic prostate surgery. MethodsElderly men undergoing robotic prostatectomy were randomised to deep neuromuscular block (target post-tetanic twitch of 1–2 at the facial nerve) with sugammadex reversal or moderate neuromuscular block (target 1–2 train-of-four ratio) with neostigmine reversal. The primary endpoint was postoperative shoulder pain. The secondary endpoints included intraoperative insufflation pressure, surgical rating score, incidence of residual neuromuscular block, and postoperative recovery. ResultsA total of 50 subjects for each treatment arm were included in the analysis. The degree of neuromuscular block had no effect on the incidence of shoulder pain (deep block group 12% vs moderate block group 10%; P=1.0) or average insufflation pressure (median [inter-quartile range]) (13.3 [12.5–13.6] mm Hg vs 13.3 [11.7–14] mm Hg, P=0.86). After surgery, the deep block group had a higher normalised train-of-four ratio (0.98 [0.79–1.11] vs 0.85 [0.74–1.00]; P=0.008). The presence of postoperative shoulder pain was associated with higher BMI (31.8 [28–33.9] kg m−2vs 28 [24.8–31.1] kg m−2; P=0.036) and longer insufflation time (186 [156–257] min vs 154 [126–198] min; P=0.028). ConclusionsThe use of deep neuromuscular block during surgery does not decrease postoperative shoulder pain or enhance recovery after robotic prostatectomy. Clinical trial registrationNCT03210376.

Respiratory muscle activity after spontaneous, neostigmine- or sugammadex-enhanced recovery of neuromuscular blockade: a double blind prospective randomized controlled trial

BackgroundThe use of neostigmine after neuromuscular blockade (NMB) has been associated with postoperative respiratory complications. In previous studies, we found lower diaphragmatic activity after neostigmine reversal of NMB, compared to sugammadex. It is still unclear whether the adequate use of neostigmine guarantees normal respiratory muscle function after NMB. In this study, we wanted to assess the effect of commonly used degrees of NMB and their possible reversal strategies on respiratory muscle activity after the return of normal neuromuscular transmission.MethodsThis is a randomized, controlled, parallel-group, single-centre, double-blind study in patients scheduled for intracranial surgery at a tertiary academic hospital in Belgium. All participants received target controlled propofol/remifentanil anesthesia and were randomized into one of five groups, receiving either a shallow NMB with no reversal (shallow/saline), a shallow NMB with sugammadex reversal (shallow/sugammadex), a moderate NMB with neostigmine reversal (moderate/neostigmine), a moderate NMB with sugammadex reversal (moderate/sugammadex), or a deep NMB with sugammadex reversal (deep/sugammadex). Primary and secondary outcome parameters were diaphragm and intercostal electromyographic (EMG) activity at the moment of resumed spontaneous breathing activity, defined as a maximal interval of 10 min after the first spontaneous breath.ResultsFor the five groups, a total of 55 patients could be included in the final analysis. Median time of spontaneous breathing analyzed was 5 min (IQR 3–9.5 min). Both the moderate/sugammadex and the moderate/neostigmine groups had lower levels of diaphragm EMG compared to the shallow/sugammadex group. The moderate/neostigmine group had lower levels of intercostal EMG activity compared to the shallow/saline group.ConclusionsIn this study, the depth of neuromuscular blockade and type of reversal strategy impacts respiratory muscle activity at the moment of resumed spontaneous breathing and recovery of neuromuscular blockade. Both groups that received moderate NMB had lower levels of diaphragm EMG, compared to the shallow NMB group with sugammadex reversal. Compared to the shallow NMB group with no reversal, the moderate NMB with neostigmine reversal group had lower intercostal EMG activity.Trial registrationClinicaltrials.gov NCT01962298 on October 9, 2013 and EudraCT 2013–001926-25 on October 10, 2013.

Pharmacokinetic and Pharmacodynamics of Sugammadex in Reversal of Vecuronium-induced Neuromuscular Blockade

Pharmacokinetic and Pharmacodynamics of Sugammadex in Reversal of Vecuronium-induced Neuromuscular Blockade

Effect of Concurrent Lidocaine, Remifentanil and Methylprednisolone Use on the Clinical Effect of Sugammadex under General Anaesthesia in Rats.

In an in vitro study, lidocaine, remifentanil and methylprednisolone produced inclusion complexes with sugammadex, which lead to a decrease in free and active concentrations of sugammadex. When used concurrently with these drugs, it is likely that the time for sugammadex to reverse a neuromuscular blockade is going to be prolonged due to a synergistic pharmacokinetic or pharmacodynamic interaction. The aim of the present study was to investigate whether concurrent use of sugammadex with remifentanil, lidocaine and methylprednisolone led to a decrease in the neuromuscular blockade reversal effect of sugammadex produced with neuromuscular blockade agent (NMBA) rocuronium. The present study included 42 male Wistar rats. They were randomised into 7 groups, with 6 rats per group. The first group was the control group, the second group received remifentanil and methylprednisolone, the third lidocaine and methylprednisolone, the fourth remifentanil, the fifth lidocaine, the sixth methylprednisolone and the seventh lidocaine and remifentanil. All groups were administered 3.2 mg kg-1 rocuronium for neuromuscular blockade after the administration of study drugs. When the train of four (TOF) value was 0, all groups were administered 16 mg kg-1 sugammadex for the reversal of neuromuscular blockade. With a TOF Watch SX device, the time to TOF ≥0.9 was recorded. When the control group was compared with Groups 3, 4, 5, 6 and 7, no statistically significant difference was found. However, in Group 2, time to TOF ≥0.9 was prolonged significantly when compared with the control group. We suggest that remifentanil and methylprednisolone used concurrently with sugammadex lead to a decrease in sugammadex reversal effect by giving rise to decrease in its free and active concentrations probably via displacement in rats.

Remifentanil does not inhibit sugammadex reversal after rocuronium-induced neuromuscular block in the isolated hemidiaphragm of the rat: an ex vivo study

Sugammadex is used to reverse neuromuscular block induced by rocuronium or vecuronium by forming a stable complex. If the binding capacity of any substance to sugammadex is large enough, this molecule will displace rocuronium or vecuronium from the complex. For drugs used in anesthesia, the binding affinity of remifentanil for sugammadex was highest. The aim of the current study was to investigate the decrease in the reversal of neuromuscular blockade with sugammadex by complex formation between remifentanil and sugammadex in the model using isolated hemidiaphragm of the rat. Phrenic nerve-hemidiaphragms from 34 male Sprague-Dawley rats were allocated randomly to four groups: 0 or 100ng/ml remifentanil with equimolar amounts of sugammadex and 0 or 100ng/ml remifentanil with three-quarter dose of sugammadex. Muscle contraction responses were recorded during the stimulation of the phrenic nerve by train-of-four (TOF) stimulation. Rocuronium was added to the organ bath with or without 100ng/ml remifentanil until the first height response (T1) of TOF disappeared completely. Then, equimolar amounts or three-quarter dose of sugammadex was added. Remifentanil has no significant effects on the concentration-response curves of rocuronium. No significant differences were observed in the recoveries of T1 and TOF ratio with time after administration of equimolar amounts or three-quarter dose of sugammadex regardless of the presence of 100ng/ml remifentanil. Clinical concentration of remifentanil does not inhibit sugammadex reversal after rocuronium-induced neuromuscular block. Sugammadex can be used safely without worrying about the interaction with remifentanil.

Reversal of Partial Neuromuscular Block and the Ventilatory Response to Hypoxia: A Randomized Controlled Trial in Healthy Volunteers.

The ventilatory response to hypoxia is a critical reflex that is impaired by neuromuscular blocking drugs. However, the degree to which this reflex is restored after reversal of blockade is unknown. Despite full reversal of neuromuscular blockade at the thumb using different drug classes, this hypoxic chemoreflex is not fully restored. The ventilatory response to hypoxia is a life-saving chemoreflex originating at the carotid bodies that is impaired by nondepolarizing neuromuscular blocking agents. This study evaluated the effect of three strategies for reversal of a partial neuromuscular block on ventilatory control in 34 healthy male volunteers on the chemoreflex. The hypothesis was that the hypoxic ventilatory response is fully restored following the return to a train-of-four ratio of 1. In this single-center, experimental, randomized, controlled trial, ventilatory responses to 5-min hypoxia (oxygen saturation, 80 ± 2%) and ventilation at hyperoxic isohypercapnia (end-tidal carbon dioxide concentration, 55 mmHg) were obtained at baseline, during rocuronium-induced partial neuromuscular block (train-of-four ratio of 0.7 measured at the adductor pollicis muscle by electromyography), and following reversal until the train-of-four ratio reached unity with placebo (n = 12), 1 mg neostigmine/0.5 mg atropine (n = 11), or 2 mg/kg sugammadex (n = 11). This study confirmed that low-dose rocuronium reduced the ventilatory response to hypoxia from 0.55 ± 0.22 (baseline) to 0.31 ± 0.21 l · min · % (train-of-four ratio, 0.7; P < 0.001). Following full reversal as measured at the thumb, there was persistent residual blunting of the hypoxic ventilatory response (0.45 ± 0.16 l · min · %; train-of-four ratio, 1.0; P < 0.001). Treatment effect was not significant (analysis of covariance, P = 0.299) with chemoreflex impairment in 5 (45%) subjects following sugammadex reversal, in 7 subjects (64%) following neostigmine reversal, and in 10 subjects (83%) after spontaneous reversal to a train-of-four ratio of 1. Despite full reversal of partial neuromuscular block at the thumb, impairment of the peripheral chemoreflex may persist at train-of-four ratios greater than 0.9 following reversal with neostigmine and sugammadex or spontaneous recovery of the neuromuscular block.

Effects of Sugammadex on Time of First Postoperative Bowel Movement: A Retrospective Analysis.

ObjectiveTo determine whether time to first postoperative bowel movement after intraperitoneal surgery differs among neuromuscular blockade reversal with either anticholinesterase/anticholinergic combination vs sugammadex.Patients and MethodsSugammadex was introduced to our practice in October 2016. Patients were identified who underwent intraperitoneal surgery between January 1, through June 30, 2016, and January 1 through June 30, 2017, and received aminosteroid neuromuscular blockade for paralysis. Reversal was initiated with neostigmine, coadministered with glycopyrrolate (neostigmine/glycopyrrolate) for control participants and sugammadex for patients. Time to first bowel movement was determined from nursing documentation for study cohorts (2016 and 2017). We compared times to first bowel movement between cases and controls using raw and inverse probability of treatment weighting (IPTW) analyses.ResultsIn the 2016 cohort, 2583 received neostigmine/glycopyrrolate. Of 2750 patients in 2017, sugammadex reversal technique was administered to 1500 patients and neostigmine/glycopyrrolate to 1250 participants. Without weighting, the groups were relatively balanced for most baseline characteristics, and after IPTW, all standardized differences were <0.035. In comparison with the 2016 and 2017 controls, sugammadex treatment was associated with faster occurrence of first bowel movement. For 2016, unweighted hazard ratio (HR) (95% confidence interval [CI]) was 1.35 (1.21-1.51) (P<.001). After IPTW, HR (95% CI) was 1.27 (1.12-1.43) (P<.001). For 2017, unweighted HR (95% CI) was 1.51 (1.31-1.72) (P<.001); after IPTW, it was 1.25 (1.08-1.45) (P =.003).ConclusionPatients undergoing intraperitoneal surgery who had aminosteroid neuromuscular blockade reversal with sugammadex had earlier first postoperative bowel movement than patients with reversal through neostigmine/glycopyrrolate.

Effect of protracted dexamethasone exposure and its withdrawal on rocuronium-induced neuromuscular blockade and sugammadex reversal: an ex vivo rat study

Studies have reported that protracted dexamethasone treatment induces resistance to nondepolarizing neuromuscular blocking agents (NMBAs) and the association with nicotinic acetylcholine receptors in the diaphragm of rats. Here, we investigated the effect of protracted dexamethasone administration on the sensitivity to rocuronium and the recovery profile when reversed by sugammadex; additionally, we observed the recovery period of pharmacodynamic change after withdrawal. Sprague-Dawley rats received daily intraperitoneal injections of dexamethasone or saline for 14 days. On days 1, 3, and 7 after the last dexamethasone treatment (Dexa1, Dexa3, and Dexa7, respectively) or 1 day after saline (control group), the phrenic nerve-hemidiaphragm preparation was dissected for assay. The dose-response curve of rocuronium in Dexa1 was shifted to the right compared to controls, but curves in Dexa3 and Dexa7 were not significantly different. Groups were not significantly different in attaining the train-of-four ratio ≥ 0.9, but the recovery index in Dexa7 was shorter than that in control and Dexa1. Recovery profiles (period of sugammadex reversal) were not correlated with resistance properties but rather with total administered drugs (binding capacity of NMBAs and sugammadex). Protracted dexamethasone exposure induced resistance to rocuronium but seemed to have no effect on sugammadex reversal in the rat diaphragm.

Effects of dexamethasone and hydrocortisone on rocuroniuminduced neuromuscular blockade and reversal by sugammadex in phrenic nerve-hemidiaphragm rat model.

BackgroundThe facilitator effects of steroids on neuromuscular transmission may cause resistance to neuromuscular blocking agents. Additionally, steroids may hinder sugammadex reversal of neuromuscular blockade, but these findings remain controversial. Therefore, we explored the effect of dexamethasone and hydrocortisone on rocuronium-induced neuromuscular blockade and their inhibitory effect on sugammadex.MethodsWe explored the effects of steroids, dexamethasone and hydrocortisone, in vitro using a phrenic nerve-hemidiaphragm rat model. In the first phase, an effective dose of rocuronium was calculated, and in the second phase, following sugammadex administration, the recovery of the train-of-four (TOF) ratio and T1 was evaluated for 30 minutes, and the recovery index was calculated in dexamethasone 0, 0.5, 5, and 50 μg/ml, or hydrocortisone 0, 1, 10, or 100 μg/ml.ResultsNo significant effect of steroids on the effective dose of rocuronium was observed. The TOF ratios at 30 minutes after sugammadex administration were decreased significantly only at high experimental concentrations of steroids: dexamethasone 50 μg/ml and hydrocortisone 100 μg/ml (P < 0.001 and P = 0.042, respectively). There were no statistical significances in other concentrations. No differences were observed in T1. Recovery index was significantly different only in 100 μg/ml of hydrocortisone (P = 0.03).ConclusionsAcute exposure to steroids did not resist the neuromuscular blockade caused by rocuronium. And inhibition of sugammadex reversal on rocuronium-induced neuromuscular blockade is unlikely at typical clinical doses of dexamethasone and also hydrocortisone. Conclusively, we can expect proper effects of rocuronium and sugammadex when dexamethasone or hydrocortisone is used during general anesthesia.

Dexamethasone concentration affecting rocuronium-induced neuromuscular blockade and sugammadex reversal in a rat phrenic nerve-hemidiaphragm model: An ex vivo study.

The concentration range of dexamethasone that inhibits neuromuscular blockade (NMB) and sugammadex reversal remains unclear. To evaluate the effects of dexamethasone on rocuronium-induced NMB and sugammadex reversal. Ex vivo study. Asan Institute for Life Sciences, Asan Medical Center, Korea, from July 2015 to November 2015. One hundred sixty male Sprague-Dawley rats. We assessed the effect of four concentrations of dexamethasone [0, 0.5, 5 (clinical concentrations) and 50 μg ml (experimental concentration)] on partial NMB on 40 phrenic nerve-hemidiaphragm preparations (n=10 per concentration). Once the first twitch of train-of-four (TOF) had been depressed by 50% with rocuronium, dexamethasone was administered. To assess the effect of dexamethasone on sugammadex reversal, 120 phrenic nerve-hemidiaphragm preparations were used in three subexperiments (n=40 per experiment), using three administration regimens of rocuronium-equimolar sugammadex: a single dose, a split-dose (split and ) and a reduced split-dose (split and ). After complete NMB was achieved, dexamethasone and sugammadex were administered. The change in the first twitch height, the recovery time to a TOF ratio at least 0.9, and the TOF ratio at 30 min were evaluated. There were no significant differences in the first twitch height among groups (P = 0.532). With a single dose of sugammadex, dexamethasone did not affect the recovery time to a TOF ratio at least 0.9 (P = 0.070). After using a split-dose of sugammadex, the recovery time to a TOF ratio at least 0.9 was delayed only at a concentration of 50 μg ml of dexamethasone. With a reduced split-dose of sugammadex, the TOF ratio at 30 min was lowered only by a concentration of 50 μg ml of dexamethasone (P < 0.010). Acute bolus administration of dexamethasone at clinical concentrations had no effect on NMB or on sugammadex reversal.