This may potentiate the neuromuscular blockade. ; The less highly substituted alkene is sometimes referred to as the Hofmann product. Patients with Renal Impairment: Results from a conventional PK study of Nimbex in 13 healthy adult patients and 15 patients with end-stage renal disease (ESRD) who had elective surgery are summarized in Table 9. Pharmacokinetic modeling suggests that 80% of the clearance is accounted for by Hofmann elimination and the remaining 20% by renal and hepatic elimination. 2017 Oct;70(5):500-510. doi: 10.4097/kjae.2017.70.5.500. The geriatric population included a subset of patients with significant cardiovascular disease [see Clinical Pharmacology (12.3)]. For the most updated list of ABA Keywords and definitions go to, OB Anesthesia Virtual Obstetric Grand Rounds, OA/SPA Pediatric Anesthesia Virtual Grand Rounds. In Study 6, a Nimbex dose of 0.1 mg/kg was evaluated in 16 pediatric patients (ages 2 years to 12 years) during opioid anesthesia. The CL was higher in healthy pediatric patients (5.89 mL/min/kg) than in healthy adult patients (4.57 mL/min/kg) during opioid anesthesia. Overdosage with neuromuscular blocking agents may result in neuromuscular blockade beyond the time needed for surgery and anesthesia. Confirm proper selection of intended product and avoid confusion with other injectable solutions that are present in critical care and other clinical settings. Nimbex has not been studied in MH-susceptible patients. The products of this reaction tertiary amines and alkenes are known as Hofmann products. Repeated administration of maintenance Nimbex doses or a continuous Nimbex infusion for up to 3 hours was not associated with development of tachyphylaxis or cumulative neuromuscular blocking effects. Reuse of OpenAnesthesia™ content for commercial purposes of any kind is prohibited. Maximum neuromuscular blockade generally occurred in within 4 minutes for this dose range. The use of rocuronium (ORG 9426) in patients with chronic renal failure. When prescribing the 10 mL multiple-dose Nimbex vials in infants consider the combined daily metabolic load of benzyl alcohol from all sources including Nimbex (multiple-dose vials contain 9 mg of benzyl alcohol per mL) and other drugs containing benzyl alcohol. Patients with hemiparesis or paraparesis may demonstrate resistance to nondepolarizing muscle relaxants in the affected limbs. Important administration instructions include: Accidental administration of neuromuscular blocking agents may be fatal. There was no clinically significant alteration in the recovery profile of Nimbex in patients with end-stage renal disease following a 0.1 mg/kg dose of Nimbex. Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Hofmann elimination: Hofmann elimination, also known a s exhaustive methylation, is a process wh ere an amine is reacted to create a tertiary amine and The three open-label studies are summarized below. Jonker G, Hoogenboom LJ, van Ramshorst B, Bruins P. J Anesth. Protect from light. Metabolism and kinetics of atracurium: an overview. There were no differences in the durations or rates of recovery of Nimbex between ESRD and healthy adult patients. Precautions should also be taken in those patients who have had previous anaphylactic reactions to other neuromuscular blocking agents since cross-reactivity between neuromuscular blocking agents, both depolarizing and non-depolarizing, has been reported. HHS The minor differences in the PK/PD parameters of cisatracurium were associated with a faster time to onset and a shorter duration of cisatracurium-induced neuromuscular blockade in pediatric patients. Upon removal from refrigeration to room temperature storage conditions (25°C/77°F), use Nimbex within 21 days, even if re-refrigerated. The authors conclude that more than one-half of the clearance of atracurium occurs via pathways other than Hofmann elimination and ester hydrolysis. The 20 mL single-dose vials contain 10 mg/mL cisatracurium, equivalent to 13.38 mg/mL cisatracurium besylate. In Studies 2 and 3, Nimbex doses of 0.25 and 0.4 mg/kg were evaluated in 30 patients under opioid/nitrous oxide/oxygen anesthesia and provided 78 (66-86) and 91 (59-107) minutes of clinical relaxation, respectively. That said,according to Miller, “the duration of action of single and repeated doses, though, is not significantly affected. Plasma clearances of cisatracurium were not affected by age; however, the volumes of distribution were slightly larger in elderly patients than in young patients resulting in slightly longer t½β values for cisatracurium. 1995;106:13-7. doi: 10.1111/j.1399-6576.1995.tb04302.x. Select one or more newsletters to continue. When administered during induction using thiopental or propofol and co-induction agents (i.e., fentanyl and midazolam), excellent to good intubating conditions were generally achieved within 2 minutes (excellent intubation conditions most frequently achieved with the 0.2 mg/kg dose of Nimbex). Nimbex had no dose-related effects on mean arterial blood pressure (MAP) or heart rate (HR) following doses ranging from 0.1 mg/kg to 0.4 mg/kg, administered over 5 to 10 seconds, in healthy adult patients (see Figure 1) or in patients with serious cardiovascular disease (see Figure 2). Table 4 displays clinically significant drug interactions with Nimbex. 2009;23(3):442-4. doi: 10.1007/s00540-009-0773-0. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to Nimbex: anaphylaxis, histamine release, prolonged neuromuscular block, muscle weakness, myopathy. Minor differences in the pharmacokinetics of cisatracurium between elderly and young adult patients were not associated with clinically significant differences in the recovery profile of Nimbex following a single 0.1 mg/kg dose. Following recovery from neuromuscular blockade, it may be necessary to re-administer a bolus dose to quickly re-establish neuromuscular blockade prior to starting the continuous infusion. In Study 4, two minutes after fentanyl and midazolam were administered, patients received thiopental anesthesia. Nimbex-treated patients with renal or hepatic impairment may have higher metabolite concentrations (including laudanosine) than patients with normal renal and hepatic function [see Clinical Pharmacology (12.3)]. Doses up to 0.4 mg/kg have been safely administered by bolus intravenous injection to healthy patients and patients with serious cardiovascular disease [see Clinical Pharmacology (12.2)]. Use peripheral nerve stimulation to assess the level of neuromuscular blockade and to appropriately titrate the Nimbex infusion rate. Severe hypersensitivity reactions, including fatal and life-threatening anaphylactic reactions, have been reported [see Contraindications (4)]. Nimbex is not compatible with propofol injection or ketorolac injection for Y-site administration. Burn patients have been shown to develop resistance to nondepolarizing neuromuscular blocking agents; therefore, consider increasing the Nimbex dosages for intubation and maintenance [see Use in Specific Populations (8.8)]. Excellent or good intubating conditions were produced 120 seconds following 0.15 mg/kg of Nimbex in 88 of 90 of patients induced with halothane and in 85 of 90 of patients induced with thiopentone and fentanyl. 2005 Sep;6(9):869-72. doi: 10.1631/jzus.2005.B0869. The average infusion rate requirement was decreased by as much as 30% to 40%. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Study 5 evaluated intubating conditions after 3 and 4 × ED95 (0.15 mg/kg and 0.20 mg/kg) following induction with fentanyl and midazolam and either thiopental or propofol anesthesia.