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Therapeutic Advances in Drug Safety 2019Sugammadex is used for the reversal of neuromuscular blockade caused by rocuronium bromide and vecuronium bromide. As part of the post licensing phase of drug...
INTRODUCTION
Sugammadex is used for the reversal of neuromuscular blockade caused by rocuronium bromide and vecuronium bromide. As part of the post licensing phase of drug development, adverse events related to the use of sugammadex are still being uncovered and being reported. The potential association between sugammadex and adverse events bronchospasm and coronary arteriospasm using a retrospective pharmacovigilance signal analysis was carried out.
METHODS
Food and Drug Administration's Adverse Event Reporting System database was used to run disproportionality analyses to investigate the potential association of sugammadex with bronchospasm or coronary arteriospasm. In this analysis we report the adverse event signal using frequentist methods of Relative reporting ratio (RRR), proportional reporting ratio (PRR), reporting odds ratio (ROR) and the Bayesian based Information Component metric.
RESULTS
A statistically significant disproportionality signal is found between sugammadex and bronchospasm ( = 44; chi-squared = 2993.87; PRR = 71.95 [95% CI: 54.00-95.85]) and sugammadex and coronary arteriospasm ( = 6; chi-squared = 209.39; PRR = 43.82 [95% CI: 19.73-97.33]) as per Evans criteria. Both statistically significant disproportionality signals persisted when stratified by gender. Based upon dynamic cumulative PRR graph, the PRR value has steadily increased and the 95% CI narrowed since December 2012.
CONCLUSION
The results of the pharmacovigilance analysis highlight a statistically significant disproportionality signal between sugammadex usage and bronchospasm and coronary arteriospasm adverse events. Physicians need to be aware of these adverse events when using sugammadex. The results of the pharmacovigilance signal analysis highlight a statistically significant disproportionality signal between sugammadex usage and bronchospasm and coronary arteriospasm adverse events. Physicians need to be aware of these adverse events when using sugammadex.
PubMed: 31452867
DOI: 10.1177/2042098619869077 -
Medicinski Glasnik : Official... Feb 2020Aim To compare the quality of the conditions for endotracheal intubation and muscle relaxation between rocuronium bromide and vecuronium bromide using the ''timing... (Randomized Controlled Trial)
Randomized Controlled Trial
Aim To compare the quality of the conditions for endotracheal intubation and muscle relaxation between rocuronium bromide and vecuronium bromide using the ''timing principle'' method for induction in anaesthesia. The "timing principle" includes the administration of muscle relaxants before the hypnotic agent during induction in anaesthesia. Method Sixty patients who had undergone elective surgery were randomly allocated into two equal groups using muscle relaxants: rocuronium (group R) and vecuronium (group V). The intubation conditions were assessed using Cooper's scoring system, based on jaw relaxation, vocal cords position and response to intubation. The quality of muscle relaxation was evaluated by recording the time of clinical weakness, a count of ''train of four'' (TOF) twitches at intubation, the time of loss TOF response and duration of direct laryngoscopy. Results The intubation conditions were excellent in 100% of patients in the group R versus excellent in 80% and good in 20% of patients in the group V (p<0.05). The time of clinical weakness was statistically significantly shorter in the group R than in the group V (p<0.000). The time of loss of TOF response was statistically significantly shorter in the group R (p<0.000). The absence of TOF twitches (the level of muscle relaxation of 100%) at intubation recorded in 25 (83.3%) patients in the group R versus five (16.7%) patients in the group V (p<0.000). Duration of direct laryngoscopy did not significantly differ between the groups. Conclusion Rocuronium bromide provides better intubation conditions and greater quality of muscle relaxation than vecuronium bromide using ''timing principle'' technique.
Topics: Androstanols; Humans; Intubation, Intratracheal; Muscle Relaxation; Neuromuscular Nondepolarizing Agents; Rocuronium; Time Factors; Vecuronium Bromide
PubMed: 31402637
DOI: 10.17392/1045-20 -
Anesthesia and Analgesia Jun 2020Since its clinical introduction in 2008, sugammadex has demonstrated a high degree of safety and superior effectiveness compared to neostigmine when used to antagonize... (Review)
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.
Topics: Adult; Anesthesia Recovery Period; Anesthesia, General; Anesthesia, Obstetrical; Cesarean Section; Cholinesterase Inhibitors; Female; Humans; Intubation; Lactation; Neostigmine; Neuromuscular Blockade; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Placenta; Postpartum Period; Pregnancy; Pregnancy Complications; Rocuronium; Sugammadex; Vecuronium Bromide
PubMed: 31283616
DOI: 10.1213/ANE.0000000000004305 -
A&A Practice Oct 2019A variety of factors are known to prolong neuromuscular blockade, including several medications commonly used in anesthetic practice. We present a patient who underwent...
A variety of factors are known to prolong neuromuscular blockade, including several medications commonly used in anesthetic practice. We present a patient who underwent general anesthesia using desflurane, vecuronium, and magnesium infusion with delayed neuromuscular blockade reversal after sugammadex administration. A higher than anticipated total dose of sugammadex was required for adequate reversal, and quantitative neuromuscular monitoring was essential to ensuring complete neuromuscular recovery before extubation in this case.
Topics: Anesthesia Recovery Period; Anesthesia, General; Anesthetics; Desflurane; Dose-Response Relationship, Drug; Humans; Magnesium Sulfate; Male; Middle Aged; Neuromuscular Blockade; Neuromuscular Monitoring; Neuromuscular Nondepolarizing Agents; Sugammadex; Vecuronium Bromide
PubMed: 31283534
DOI: 10.1213/XAA.0000000000001058 -
Veterinary Journal (London, England :... Jun 2019Recovery of neuromuscular function is a gradual phenomenon whereby function progresses from absent to normal. The speed of spontaneous recovery can be used to predict...
Recovery of neuromuscular function is a gradual phenomenon whereby function progresses from absent to normal. The speed of spontaneous recovery can be used to predict the time when neuromuscular function is expected to be restored. However, the speed of recovery might be affected by the dose of the neuromuscular blocker administered, and by the dosing regimen of that dose. The effects of both factors on the speed of spontaneous recovery from vecuronium were evaluated. Seven dogs were anesthetized three times and the train-of-four (TOF) ratio was measured with acceleromyography. Vecuronium was administered at 0.1 mg/kg, 0.2 mg/kg, or 0.1 mg/kg followed by two doses of 0.05 mg/kg was administered each time. In the divided-dose treatment group, aliquots were administered on return of the first twitch (T1) of the TOF from the previous dose. The duration of surgical block, from injection to return of T1, was longest for the divided-dose protocol, intermediate for 0.2 mg/kg single bolus, and shortest for 0.1 mg/kg (P < 0.0001). The recovery period, from return of T1 to a TOF ratio ≥0.9, was longer for 0.2 mg/kg administered as a single bolus than for the other two groups (P = 0.007). Doubling the dose of a single bolus of vecuronium extended the time of surgical block and prolonged the duration of the recovery period. However, dividing that dose into smaller aliquots extended the period of surgical block while shortening the recovery period. Hence, the spontaneous reappearance of T1 should not be used in isolation to predict the time to complete recovery of neuromuscular function.
Topics: Anesthesia Recovery Period; Anesthesia, General; Animals; Dogs; Dose-Response Relationship, Drug; Electric Stimulation; Female; Injections, Epidural; Male; Muscle, Skeletal; Neuromuscular Blocking Agents; Neuromuscular Junction; Random Allocation; Thoracic Vertebrae; Vecuronium Bromide
PubMed: 31113556
DOI: 10.1016/j.tvjl.2019.04.004 -
Anesthesia and Analgesia Jun 2019Postoperative residual neuromuscular blockade continues to be a frequent occurrence with a reported incidence rate of up to 64%. However, the effect of postoperative... (Observational Study)
Observational Study
BACKGROUND
Postoperative residual neuromuscular blockade continues to be a frequent occurrence with a reported incidence rate of up to 64%. However, the effect of postoperative residual neuromuscular blockade on health care utilization remains unclear. We conducted a retrospective cohort study to investigate the effects of postoperative residual neuromuscular blockade on hospital costs (primary outcome), intensive care unit admission rate, and hospital length of stay (secondary outcomes).
METHODS
We performed a prespecified secondary analysis of data obtained in 2233 adult patients undergoing surgery under general anesthesia. Postoperative residual neuromuscular blockade was defined as a train-of-four ratio <0.9 in the postanesthesia care unit (PACU). Our confounder model adjusted for a variety of patient, surgical, and anesthesia-related factors. We fitted truncated negative binomial regression models for hospital cost and hospital length of stay analyses and a logistic regression model for our intensive care unit admission analysis.
RESULTS
Overall, 457 (20.5%) patients in our cohort had residual neuromuscular blockade on admission to the PACU. Postoperative residual neuromuscular blockade was not independently associated with increased hospital costs (adjusted incidence rate ratio, 1.04, CI, 0.98-1.11; P = .22). There were significantly higher odds of intensive care unit admission in those with postoperative residual neuromuscular blockade compared to those without (adjusted odds ratio, 3.03, CI, 1.33-6.87; P < .01). Further, we found a trend toward increased hospital length of stay in patients with postoperative residual neuromuscular blockade (adjusted incidence rate ratio, 1.09; P = .06). Sensitivity analysis using the same model in the day of surgery admissions and ambulatory surgery confirmed our findings.
CONCLUSIONS
Postoperative residual neuromuscular blockade at PACU admission was not significantly associated with increased hospital costs, but was associated with higher rates of intensive care unit admission. These findings support the view that clinicians should continue to work to reduce the rate of postoperative residual neuromuscular blockade.
Topics: Adult; Aged; Atracurium; Critical Care; Data Interpretation, Statistical; Delayed Emergence from Anesthesia; Female; Humans; Incidence; Intensive Care Units; Length of Stay; Male; Middle Aged; Neuromuscular Blockade; Patient Admission; Postoperative Period; Prospective Studies; Retrospective Studies; Rocuronium; Treatment Outcome; Vecuronium Bromide
PubMed: 31094777
DOI: 10.1213/ANE.0000000000004028 -
Food and Chemical Toxicology : An... Jun 2019Prenatal nicotine exposure (PNE) could induce ovarian dysplasia in offspring. This study aimed to confirm its intrauterine origin and explore a programming mechanism of...
Decreased levels of H3K9ac and H3K27ac in the promotor region of ovarian P450 aromatase mediated low estradiol synthesis in female offspring rats induced by prenatal nicotine exposure as well as in human granulosa cells after nicotine treatment.
Prenatal nicotine exposure (PNE) could induce ovarian dysplasia in offspring. This study aimed to confirm its intrauterine origin and explore a programming mechanism of ovarian dysplasia caused by PNE. Pregnant Wistar rats were injected subcutaneously with nicotine (2 mg/kg.d) from gestation day (GD) 9 to GD20. Serum of female offspring was obtained for hormone assays and ovarian tissues were collected. The results showed that PNE impaired ovarian development, and inhibited estradiol production and cytochrome P450 aromatase (P450arom) expression before and after birth. Moreover, the nicotinic acetylcholine receptors (nAChRs) expression was increased in utero, while histone 3 lysine 9 acetylation (H3K9ac) and H3K27ac levels in the P450arom promoter region were decreased persistently in PNE group before and after birth. In vitro, nicotine decreased P450arom expression and estradiol production in human granulosa cell line KGN. Furthermore, nicotine treatment up-regulated nAChRα6 and α9 expression and down-regulated the H3K9ac and H3K27ac levels of the P450arom promoter region. Non-specific nAChRs inhibitor vecuronium bromide reversed these effects. These results suggest that PNE could induce ovarian dysplasia and inhibit estradiol synthesis in the female offspring rats, which was related to the decreased H3K9ac and H3K27ac levels in the promotor region of the P450arom via the nAChRs.
Topics: Acetylation; Animals; Aromatase; Estradiol; Female; Granulosa Cells; Histones; Humans; Maternal Exposure; Nicotine; Ovary; Pregnancy; Promoter Regions, Genetic; Rats; Rats, Wistar; Receptors, Nicotinic
PubMed: 30959089
DOI: 10.1016/j.fct.2019.03.055 -
Der Anaesthesist Jan 2019
Topics: Anesthesia, General; Humans; Intubation, Intratracheal; Vecuronium Bromide
PubMed: 30645693
DOI: 10.1007/s00101-018-0530-6 -
Der Anaesthesist Jan 2019
Topics: Anesthesia; Anesthesiology; Humans; Intubation, Intratracheal; Vecuronium Bromide
PubMed: 30627736
DOI: 10.1007/s00101-018-0531-5 -
BMC Anesthesiology Nov 2018Sugammadex, a γ-cyclodextrin derivative, belongs to a new class of selective relaxant binding agents. Sugammadex was approved 10-years ago by the European medicines... (Review)
Review
BACKGROUND
Sugammadex, a γ-cyclodextrin derivative, belongs to a new class of selective relaxant binding agents. Sugammadex was approved 10-years ago by the European medicines agency and today is used in clinical anesthesia and emergency medicine globally. In this review, indications for neuromuscular block, the challenge of neuromuscular monitoring and the practice of under-dosing of sugammadex as a potential cost-saving strategy are discussed.
MAIN BODY
Reversal of neuromuscular block is important to accelerate the spontaneous recovery of neuromuscular function. Sugammadex is able to reverse a rocuronium- or vecuronium-induced neuromuscular block rapidly and efficiently from every depth of neuromuscular block. However, since sugammadex was introduced in clinical anesthesia, several studies have reported administration of a lower-than-recommended dose of sugammadex. The decision to under-dose sugammadex is often motivated by cost reduction concerns, as the price of sugammadex is much higher than that of neostigmine outside the United States. However, under-dosing of sugammadex leads to an increased risk of recurrence of neuromuscular block after an initial successful (but transient) reversal. Similarly, when not using objective neuromuscular monitoring, under-dosing of sugammadex may result in residual neuromuscular block in the postoperative care unit, with its attendant negative pulmonary outcomes. Therefore, an appropriate dose of sugammadex, based on objective determination of the depth of neuromuscular block, should be administered to avoid residual or recurrent neuromuscular block and attendant postoperative complications. Whether the reduction in perioperative recovery time of the patient can be translated into additional procedural cases performed, faster operative turnover times, or improved organizational resource utilization, has yet to be determined in actual clinical practice that includes verification of neuromuscular recovery prior to tracheal extubation.
CONCLUSIONS
The current review addresses the indications for neuromuscular block, the challenge of neuromuscular monitoring, the practice of under-dosing of sugammadex as a potential cost-saving strategy in reversal of deep neuromuscular block, the economics of sugammadex administration and the potential healthcare cost-saving strategies.
Topics: Cost Savings; Dose-Response Relationship, Drug; Humans; Neostigmine; Neuromuscular Blockade; Neuromuscular Monitoring; Neuromuscular Nondepolarizing Agents; Rocuronium; Sugammadex; Vecuronium Bromide
PubMed: 30400850
DOI: 10.1186/s12871-018-0605-6