- An Evaluation of Association Between Train-of-Four Values and Gas Exchange Indices in Moderate to Severe Acute Respiratory Distress Syndrome. [JOURNAL ARTICLE]
- Ann Pharmacother 2016 Aug 10.
Acute respiratory distress syndrome (ARDS) is associated with a mortality rate of approximately 40%. Neuromuscular blockade is associated with an improvement in oxygenation and a reduction in mortality in ARDS.The goal of this evaluation was to determine if the depth of paralysis, determined by train-of-four (TOF) monitoring, correlates with gas exchange in moderate to severe ARDS.This was a retrospective review of moderate to severe ARDS patients who were prescribed >12 hours of continuous infusion cisatracurium between January 1, 2013, and December 31, 2014, with a PaO2:FiO2 ratio <150 and documented TOF and arterial blood gases. Patients were evaluated for inclusion at 12, 24, and 48 hours after initiation of neuromuscular blockade.A total of 378 patients were screened for inclusion, with 107 evaluable patients meeting criteria at baseline. Poor correlation existed between TOF and oxygenation index (OI) at 12 (τ = 0.03), 24 (τ = 0.15) and 48 hours (τ = 0.08). When controlling for proning and baseline OI, the depth of paralysis did not have a significant effect on OI at 12, 24, or 48 hours.This evaluation demonstrates that the use of TOF monitoring for neuromuscular blockade does not correlate with gas exchange markers in moderate to severe ARDS.
- Synergism between rocuronium and cisatracurium: comparison of the Minto and Greco interaction models. [Journal Article]
- Korean J Anesthesiol 2016 Aug; 69(4):341-9.
This study was conducted to investigate the pharmacodynamic interaction between rocuronium and cisatracurium using the response surface model, which is not subject to the limitations of traditional isobolographic analysis.One hundred and twenty patients were randomly allocated to receive one of the fifteen predefined combinations of rocuronium and cisatracurium. To study single drugs, cisatracurium 0.2, 0.15, or 0.1 mg/kg or rocuronium 0.8, 0.6 or 0.4 mg/kg doses were administered alone. To study the pharmacodynamic interaction, drugs were applied in three types of combination ratio, i.e., half dose of each drug alone, 75% of each single dose of rocuronium and 25% of each single dose of cisatracurium, and vice versa. Train-of-four (TOF) ratio and T1% (first twitch of the TOF presented as percentage compared to the initial T1) were used as pharmacodynamic endpoints, and the Greco and Minto models were used as surface interaction models.The interaction term α of the Greco model for TOF ratio and T1% measurements showed synergism with values of 0.977 and 1.12, respectively. Application of the Minto model resulted in U50 (θ) values (normalized unit of concentration that produces 50% of the maximal effect in the 0 < θ < 1 region) less than 1 for both TOF ratio and T1% measurements, indicating that rocuronium and cisatracurium exhibit synergism.Response surface modeling of the interaction between rocuronium and cisatracurium, based on considerations of their effects on muscle relaxation as measured by TOF ratio and T1%, indicated that the two drugs show considerable synergism.
- The use of sugammadex for bariatric surgery: analysis of recovery time from neuromuscular blockade and possible economic impact. [Journal Article]
- Clinicoecon Outcomes Res 2016.:317-22.
Neuromuscular block (NMB) monitoring and use of reversal agents accelerate the recovery time and improve the workflow in the operating room. We aimed to compare recovery times after sugammadex or neostigmine administration, and estimate the time spent in operating theater and the possible economic impact of a faster recovery, in morbidly obese patients undergoing bariatric surgery.We conducted a retrospective study that analyzed data from records of morbidly obese patients (body mass index >40 kg/m(2)) undergoing elective laparoscopic bariatric surgery in which sugammadex or neostigmine were used to reverse NMB. Patients were divided in two groups: group 1 (sugammadex group [SUG]) received rocuronium and sugammadex for reversal and group 2 (neostigmine group [NEO]) received either rocuronium or cisatracurium and neostigmine. Data are presented as mean (standard deviation).Compared with NEO, SUG group showed shorter times to achieve train-of-four ratio of 0.9 (P<0.05) and an Aldrete score of 10 (P<0.05), a higher cost (€146.7 vs €3.6 [P<0.05]), plus a remarkable less duration of operating theater occupancy (P<0.05). Sugammadex cost accounted for 2.58% of the total cost per surgery, while neostigmine cost accounted for 0.06%. Total time saved in SUG group was 19.4 hours, which could be used to perform 12 extra laparoscopic sleeve gastrectomies.Reversal from NMB was significantly faster with sugammadex than with neostigmine. Although sugammadex was substantially more expensive, duration of operating theater occupancy was reduced with potentially workflow increase or personnel reduced cost.
- Stability of Drugs Used in Helicopter Air Medical Emergency Services: An Exploratory Study. [Journal Article]
- Air Med J 2016 Jul-Aug; 35(4):247-50.
Transportation by air exposes drugs used in emergency medical services to vibrations. The aim of the study was to determine whether or not vibrations caused by a helicopter induce the degradation of 5 drugs used in this setting.A longitudinal study in an operating medical helicopter along with a worst case was conducted. The studied drugs were 3 drugs labeled for refrigeration (cisatracurium, lorazepam, and succinylcholine) and 2 albumin solutions (human albumin 4% and 20%). These drugs were stored for 4 months according to the following conditions: inside a helicopter, worst case with exposure to extreme vibrations, at room temperature, and according to manufacturers' recommendations. Samples were analyzed with validated high-performance liquid chromatography assay methods. A drug was considered stable if the remaining drug content was above 90% of the label claim. Except for the albumin solutions, visual inspection was used to determine instability by the formation of aggregates.Only the samples stored at room temperature became unstable after 4 months. No difference in extreme foaming was observed in the albumin solutions.These data suggest that the effect of degradation of drugs caused by vibrations is negligible. Temperature was observed as the main cause of drug degradation.
- Neuromuscular blockade in the elderly patient. [Journal Article, Review]
- J Pain Res 2016.:437-44.
Neuromuscular blockade is a desirable or even essential component of general anesthesia for major surgical operations. As the population continues to age, and more operations are conducted in the elderly, due consideration must be given to neuromuscular blockade in these patients to avoid possible complications. This review considers the pharmacokinetics and pharmacodynamics of neuromuscular blockade that may be altered in the elderly. Compartment distribution, metabolism, and excretion of drugs may vary due to age-related changes in physiology, altering the duration of action with a need for reduced dosage (eg, aminosteroids). Other drugs (atracurium, cisatracurium) have more reliable duration of action and should perhaps be considered for use in the elderly. The range of interpatient variability that neuromuscular blocking drugs may exhibit is then considered and drugs with a narrower range, such as cisatracurium, may produce more predictable, and inherently safer, outcomes. Ultimately, appropriate neuromuscular monitoring should be used to guide the administration of muscle relaxants so that the risk of residual neuromuscular blockade postoperatively can be minimized. The reliability of various monitoring is considered. This paper concludes with a review of the various reversal agents, namely, anticholinesterase drugs and sugammadex, and the alterations in dosing of these that should be considered for the elderly patient.
- Early skin and challenge testing after rocuronium anaphylaxis. [Case Reports, Journal Article]
- Anaesth Intensive Care 2016 May; 44(3):425-7.
We present a case of early skin and challenge testing in a patient following severe anaphylaxis to rocuronium. The patient presented for semi-elective laparoscopic cholecystectomy and developed anaphylaxis with severe cardiovascular collapse after induction of anaesthesia. Surgery was cancelled but was considered necessary before the recommended four to six weeks for formal allergy testing. Limited skin and challenge testing was performed to rocuronium and cisatracurium while the patient was in the intensive care unit to identify a safe neuromuscular blocking drug for subsequent early surgery. The subsequent surgery, 48 hours after the initial reaction, was uneventful. The case highlights the difficulties when anaesthetising patients with recent anaphylaxis who have not yet had formal allergy testing and presents a potential management strategy involving early skin testing.
- Do we really need sugammadex as an antagonist of muscle relaxants in anesthesia? [Journal Article]
- Curr Opin Anaesthesiol 2016 Aug; 29(4):462-7.
Sugammadex is a selective relaxant-binding agent that is designed to encapsulate rocuronium and chemically similar steroidal muscle relaxants such as vecuronium. This review summarizes recent information on the use of sugammadex in clinical practice.The main advantages of sugammadex when compared with conventional anticholinesterase agents are a much faster recovery time and its unique ability to reverse rapidly and efficiently, for the first time, deep levels of neuromuscular blockade. However, there is paucity of evidence-based studies on the benefit of deep neuromuscular block, and then routine administration of sugammadex to reverse any level of block, for example, during laparoscopic surgery. It appears that reduction of costs depends mainly on organizational factors. Finally it must be remembered that sugammadex only works with steroidal nondepolarizing muscle relaxants; therefore neostigmine should not be withdrawn because it is the only reversal agent effective against atracurium or cisatracurium.Sugammadex offers a significantly faster and more predictable recovery profile than neostigmine. It is now possible to reverse rapidly and efficiently any level of neuromuscular blockade and to avoid the risk of adverse events because of residual paralysis such as critical respiratory events during recovery from anesthesia.
- Under sevoflurane anaesthesia, a reduced dose of neostigmine can antagonize a shallow neuromuscular block: A double-blind, randomised study. [Journal Article]
- Anaesth Crit Care Pain Med 2016 Aug; 35(4):269-73.
It has been demonstrated that small doses of neostigmine (10-30μg.kg(-1)) effectively antagonize atracurium blocks at a train-of-four (TOF) ratio of 0.4 under propofol anaesthesia. The results might not be valid with halogenated agents, which potentiate neuromuscular blockades. The goal of this study was to determine the dose of neostigmine required to antagonize a block corresponding to a TOF ratio of 0.4, a level at which fade is not visually detected.Sixty patients were included and anaesthesia was induced with propofol, remifentanil and cisatracurium, and maintained with sevoflurane and remifentanil. Patients were randomized to receive neostigmine at 40, 20, 10μg.kg(-1) or placebo with atropine (20, 10, 5 or 0μg.kg(-1), respectively) as soon as the TOF ratio reached 0.4. Elapsed times to 0.9 and 1.0 TOF ratios were measured.The median times elapsed from 0.4 to 0.9 and 1.0 TOF ratios in the placebo group were 19 (10.5-36) min and 26 (20-50) min, respectively, and significantly shorter (I=0.002) with any dose of neostigmine than without. Times for complete recovery after 40 and 20μg.kg(-1) neostigmine were similar [5.5 (4-11) min and 7.8 (3.5-11) min, respectively] but significantly shorter than after 10μg.kg(-1) neostigmine [17min (7-55); I=0.001].Under sevoflurane anaesthesia, in absence of tactile or visual TOF fade, which corresponds to a TOF ratio≥0.4, 20μg.kg(-1) neostigmine is as effective as 40μg.kg(-1) in antagonizing shallow cisatracurium block.
- Effects of pretreatment with different doses of cisatracurium on succinylcholine-induced fasciculations. [Journal Article, Randomized Controlled Trial]
- Int J Clin Pharmacol Ther 2016 Jun; 54(6):426-32.
To compare the effects of different doses of cisatracurium pretreatment on succinylcholine-induced fasciculations.90 patients scheduled for laparoscopic cholecystectomies were equally randomized into three groups to receive pretreatment of 0.005, 0.01, and 0.02 mg/kg cisatracurium, respectively. After the pretreatments, general anesthesia was induced 3.5 minutes later, train-of-four stimulation was monitored 4.5 minutes later, succinylcholine 1.5 mg/kg was injected 5 minutes later, and endotracheal intubation was implemented 6.5 minutes later. Side effects of cisatracurium, intensity of fasciculations, intubating conditions, time and extent to maximal depression of twitch and time for its recovery to 20% of control value, and severity of myalgia at 24 hours postoperatively were recorded.Fasciculations were alleviated significantly after the cisatracurium pretreatment of 0.02 mg/kg, more than with the other two doses (p < 0.01). Intubating conditions, time and extent to maximal depression of twitch, time for its recovery to 20% of the controls, and incidence of myalgia had no significant changes among the three groups (p > 0.05). Transient and tolerable diplopia and difficulty opening eyes emerged after pretreatment of 0.02 mg/kg cisatracurium.The pretreatment of 0.02 mg/kg cisatracurium given 5 minutes before succinylcholine injection could alleviate succinylcholine-induced fasciculations without influence on muscle relaxation effects or endotracheal intubating conditions, but did not affect the occurrence of myalgia, and might produce transient diplopia and difficulty opening eyes.
- Autophagic Cell Death and Apoptosis Jointly Mediate Cisatracurium Besylate-Induced Cell Injury. [Journal Article, Research Support, Non-U.S. Gov't]
- Int J Mol Sci 2016; 17(4):515.
Cisatracurium besylate is an ideal non-depolarizing muscle relaxant which is widely used in clinical application. However, some studies have suggested that cisatracurium besylate can affect cell proliferation. Moreover, its specific mechanism of action remains unclear. Here, we found that the number of GFP-LC3 (green fluoresent protein-light chain 3) positive autophagosomes and the rate of mitochondria fracture both increased significantly in drug-treated GFP-LC3 and MitoDsRed stable HeLa cells. Moreover, cisatracurium promoted the co-localization of LC3 and mitochondria and induced formation of autolysosomes. Levels of mitochondrial proteins decreased, which were reversed by the lysosome inhibitor Bafinomycin A1. Similar results with evidence of dose-dependent effects were found in both HeLa and Human Umbilical Vein Endothelial Cells (HUVECs). Cisatracurium lowered HUVEC viability to 0.16 (OD490) at 100 µM and to 0.05 (OD490) after 48 h in vitro; it increased the cell death rate to 56% at 100 µM and to 60% after 24 h in a concentration- and time-dependent manner (p < 0.01). Cell proliferation decreased significantly by four fold in Atg5 WT (wildtype) MEF (mouse embryonic fibroblast) (p < 0.01) but was unaffected in Atg5 KO (Knockout) MEF, even upon treatment with a high dose of cisatracurium. Cisatracurium induced significant increase in cell death of wild-type MEFs even in the presence of the apoptosis inhibitor zVAD. Thus, we conclude that activation of both the autophagic cell death and cell apoptosis pathways contributes to cisatracurium-mediated cell injury.