Plasma Concentrations Of Rocuronium Research Articles

Influence of the Pringle maneuver during partial hepatectomy on the neuromuscular block induced by intermittent and continuous dosing of rocuronium.

The Pringle maneuver (PM) is a common procedure in hepatectomy that is known to interrupt drug elimination. The purpose of this study was to examine the influence of PM on the duration of action of rocuronium administered by intermittent bolus dosing, the continuous rocuronium infusion dose required for maintenance of a moderate neuromuscular block, and changes in plasma concentrations of rocuronium. Twenty-seven adult patients undergoing partial hepatectomy with PM were enrolled in this study. The duration of action of 0.2mg/kg rocuronium boluses (DUR), and the continuous rocuronium infusion dose required for maintenance of the height of the first twitch of the train-of-four (T1) at 10-20% of the control value (%T1), respectively, were electromyographically monitored on the adductor digiti minimi muscle. The effects of PM on DUR, %T1, and the plasma concentration of rocuronium were measured. The DUR was significantly prolonged during PM [mean: 42.2 (SD: 8.0) min, P < 0.001] compared to baseline [29.7 (6.3) min]. It was prolonged even after completion of the PM [46.2 (10.5) min, P < 0.001]. The plasma concentration of rocuronium measured at every reappearance of T1 was comparable between before and during PM. %T1 [15.5 (5.6)%] was significantly depressed after the start of PM [6.5 (3.9)%, P < 0.001], with persistence of the depression even after completion of PM. However, there were no significant changes in the plasma concentration of rocuronium. Rocuronium-induced neuromuscular block is significantly augmented during PM. However, the augmentation is not associated with an increase in plasma rocuronium concentration.

Conventional reversal of rocuronium-induced neuromuscular blockade by sugammadex in Korean children: pharmacokinetics, efficacy, and safety analyses.

Background: Sugammadex is known to reverse neuromuscular blockade induced by non-depolarizing agents. In children, the recommended dose for reversal of moderate neuromuscular blockade is 2mg/kg. We investigated the pharmacokinetics and pharmacodynamics of sugammadex in Korean children. Methods: Children (2-17years of age) undergoing brain or spine surgery were enrolled and randomly assigned to control (neostigmine) and 2, 4, or 8mg/kg sugammadex groups. Following induction of anesthesia and monitoring of the response to train-of-four stimulation, 1mg/kg rocuronium was intravenously administered. Upon reappearance of the second twitch to train-of-four stimulation, the study drug was administered according to group allocation. The plasma concentrations of rocuronium and sugammadex were serially measured at nine predefined time points following study drug administration. To determine efficacy, we measured the time elapsed from drug administration to recovery of T4/T1 ≥ 0.9. For pharmacokinetics, non-compartmental analysis was performed and we monitored adverse event occurrence from the time of study drug administration until 24h post-surgery. Results: Among the 29 enrolled participants, the sugammadex (2mg/kg) and control groups showed recovery times [median (interquartile range)] of 1.3 (1.0-1.9) and 7.7 (5.3-21.0) min, respectively (p = 0.002). There were no significant differences in recovery time among the participants in sugammadex groups. The pharmacokinetics of sugammadex were comparable to those of literature findings. Although two hypotensive events related to sugammadex were observed, no intervention was necessary. Conclusion: The findings of this pharmacokinetic analysis and efficacy study of sugammadex in Korean children indicated that sugammadex (2mg/kg) may be safely administered for reversing moderate neuromuscular blockade. Some differences in pharmacokinetics of sugammadex were observed according to age. Clinical Trial Registration: http://clinicaltrials.gov (NCT04347486).

Reversal of rocuronium-induced intense neuromuscular blockade by sugammadex in Korean children: A pharmacokinetic and pharmacodynamic analysis.

Sugammadex, a selective antagonist of steroidal non-depolarizing neuromuscular blocking agents, has been used in children in limited circumstances. However, neither pharmacokinetics (PKs) nor recovery profile of sugammadex for intense neuromuscular blockade reversal in children have been reported. This prospective study aimed to obtain a PK model of sugammadex and evaluate its efficacy and safety for intense neuromuscular blockade reversal in children. Forty children (age, 2-17 years) who underwent surgery that required early neuromuscular blockade reversal were enrolled. After neuromuscular blockade with 1mg∙kg-1 of rocuronium, sugammadex (2, 4, and 8mg∙kg-1 ) or a conventional dose of neostigmine (0.03 mg∙kg-1 ) was administered randomly after confirmation of zero post-tetanic count. The plasma concentrations of rocuronium and sugammadex were measured 2min after rocuronium injection; immediately before, 2, 5, 15, 60, 120, 240, and 480 min after the study drug injection. Response to train-of-four stimulation was continuously recorded. Noncompartmental analysis and population PK modeling were performed. For pharmacodynamics, the recovery profile was measured. Three-compartment PK model was established for sugammadex. The median (interquartile range [IQR]) time from injection of 8mg∙kg-1 of sugammadex to recovery of T4 /T1 greater than or equal to 0.9 at train-of-four stimulation was 1.1 (IQR: 0.88-1.8) min. No adverse events related to sugammadex were observed. We present a PK analysis of sugammadex for rocuronium-induced intense neuromuscular blockade reversal in children with its recovery profile. The time to recover T4 /T1 greater than or equal to 0.9 at train-of-four stimulation with 8mg∙kg-1 of sugammadex was less than 3min and comparable to that in adults.

Intravenous propofol, ketamine (ketofol) and rocuronium after sevoflurane induction provides long lasting anesthesia in ventilated rats.

Rats are commonly used animals for laboratory experiments and many experiments require general anesthesia. However, the lack of published and reproducible intravenous anesthesia protocols for rats results in unnecessary animal use to establish new anesthesia techniques across institutions. We therefore developed an anesthesia protocol with propofol, ketamine, and rocuronium for mechanically ventilated rats, and evaluated vital parameters and plasma concentrations. 15 male Sprague-Dawley rats underwent inhalation induction with sevoflurane and tracheal, venous and arterial cannulation. After established venous access, sevoflurane was substituted by propofol and ketamine (ketofol). Rocuronium was added under mechanical ventilation for 7 h. Drug dosages were stepwise reduced to prevent accumulation. All animals survived the observation period and showed adequate depth of anesthesia. Mean arterial pressure and heart rate remained within normal ranges. Median propofol plasma concentrations remained stable: 1, 4, 7 h: 2.0 (interquartile range (IQR): 1.8–2.2), 2.1 (1.8–2.2), 1.8 (1.6–2.1) µg/ml, whereas median ketamine concentrations slightly differed after 7 h compared to 1 h: 1, 4, 7 h: 3.7 (IQR: 3.5–4.5), 3.8 (3.3–4.1), 3.8 (3.0–4.1) µg/ml. Median rocuronium plasma concentrations were lower after 4 and 7 h compared to 1 h: 1, 4, 7 h: 3.9 (IQR: 3.5–4.9), 3.2 (2.7–3.3), 3.0 (2.4–3.4) µg/ml. Our anesthesia protocol provides stable and reliable anesthesia in mechanically ventilated rats for several hours.

Extravascular leakage of induction doses of rocuronium: four cases in which both depth of neuromuscular block and plasma concentration of rocuronium were assessed.

The duration of action of extravasated rocuronium varies depending on the patient's comorbidities. In patients who receive high doses of non-depolarizing neuromuscular blocking agents subcutaneously, anesthesiologists should be aware of unexpected prolongation of the progress and recovery of neuromuscular block. In such cases, the depth and recovery of neuromuscular block should be objectively monitored to avoid residual neuromuscular block and recurarization.

Effect of hemorrhagic shock factor on pharmacokinetics of rocuronium in pigs

Objective To evaluate the effect of hemorrhagic shock factor on the pharmacokinetics of rocuronium in pigs. Methods Sixteen pathogen-free Bama miniature pigs of both sexes, aged 3-5 months, weighing 22-25 kg, were divided into 2 groups(n= 8 each)using a random number table: control group(group C)and hemorrhagic shock group(group HS). In group C, rocuronium 3.78 mg/kg was injected via the auricular vein.In group HS, the animals were subjected to volume-controlled hemorrhage, about 40% of blood volume was withdrawn from the left femoral artery over 15 min(30 ml/kg), and rocuronium 3.78 mg/kg was injected via the auricular vein after the model was successfully established.At 0, 2, 4, 7, 10, 15, 20, 30, 60, 120, 180, 240, 300, 360 and 420 min after rocuronium injection, blood samples were collected from the internal jugular vein for determination of the plasma concentration of rocuronium by high-performance liquid chromatography-tandem mass spectrometry.The pharmacokinetic parameters of rocuronium were calculated. Results Compared with group C, the plasma concentration of rocuronium was significantly increased at 20 and 60-420 min after rocuronium injection, the elimination half-life and mean residence time were prolonged, and the plasma effect-site equilibration rate constant was decreased in group HS(P 0.05). Conclusion The elimination of rocuronium is slower in a pig model of hemorrhagic shock. Key words: Shock, hemorrhagic; Androstanols; Pharmacokinetics

Influence of preoperative oral rehydration on arterial plasma rocuronium concentrations and neuromuscular blocking effects: A randomised controlled trial.

The influence of preoperative rehydration on the action of rocuronium has not yet been investigated. The objective is to evaluate the hypothesis that preoperative rehydration lowers arterial rocuronium plasma concentrations and changes its associated neuromuscular blocking effects during induction of anaesthesia. Randomised, single-blinded study. A secondary hospital from October 2013 to July 2014. In total, 46 men undergoing elective surgery were eligible to participate and were randomly allocated into two groups. Exclusion criteria were severe hepatic, renal or cardiovascular disorder; neuromuscular disease; history of allergy to rocuronium; BMI more than 30 kg m; receiving medication known to influence neuromuscular function. Participants received 1500 ml of oral rehydration solution (rehydration group) or none (control group) until 2 hours before anaesthesia. Arterial blood samples were obtained 60, 90 and 120 s and 30 min after rocuronium (0.6 mg kg) administration during total intravenous anaesthesia. Responses to 0.1-Hz twitch stimuli were measured at the adductor pollicis muscle using acceleromyography. Arterial plasma rocuronium concentrations. Arterial plasma rocuronium concentrations at 60, 90 and 120 s in the rehydration and control groups were 9.9 and 13.7, 6.8 and 9.5 and 6.2 and 8.1 μg ml, respectively (P = 0.02, 0.003 and 0.02, respectively); the onset times in the rehydration and control groups were 92.0 and 69.5 s (P = 0.01), and the times to twitch re-appearance were 25.3 and 30.4 min (P = 0.004), respectively. Preoperative rehydration significantly reduces arterial plasma rocuronium concentrations in the first 2 minutes after administration, prolonging the onset time and shortening the duration of effect. A higher dose or earlier administration should be considered for patients who receive preoperative rehydration. Umin identifier: UMIN000011981.

Effects of hypothermic cardiopulmonary bypass on rocuronium-induced neuromuscular blockade in patients undergoing open heart surgery

Objective To evaluate the effects of hypothermic cardiopulmonary bypass (CPB) on rocuronium-induced neuromuscular blockade in the patients undergoing open heart surgery.Methods Twenty ASA physical status Ⅰ or Ⅱ patients,scheduled for elective open heart surgery,aged 18-45 yr,with body mass index of 18-25 kg/m2,were randomly assigned into 2 groups (n =10 each) using a random number table:room temperature group (group R) and hypothermia group (group H).The nasopharyngeal temperature was maintained at 30-31 ℃ during CPB in group H or at 36-37 ℃ during CPB in group R,and it was maintained at 36-37 ℃ before and after CPB in both groups.Anesthesia was induced with iv etomidate 0.3 mg/kg,fentanyl 2-4 μg/kg and rocuronium 0.3 mg/kg.The patients were tracheally intubated and mechanically ventilated.Anesthesia was maintained with iv infusion of sufentanil and intermittent iv boluses of midazolam and fentanyl.BIS value was maintained at 40-60.Neuromuscular block was monitored using TOF-WATCH SX accelerometer.Train-of-four stimulation (intensity 40 mA,frequency 2 Hz,wave length 0.2 ms,interval 12 s) of ulnar nerve was used.Rocuronium was infused intravenously using an automatic feedback control system to maintain T1 at 8％-12％.At 10 min after start of operation (T0),10 min after onset of CPB (T1),and 10 min after termination of CPB,blood samples were collected for determination of the plasma concentration of rocuronium (by HPLC).The infusion rate and consumption of rocuronium were recorded before,during and after CPB.Results Compared with group R,the plasma concentration of rocuronium was significantly decreased at T1,2,and the infusion rate and consumption of rocuronium were decreased before and after CPB in group H.Conclusion Hypothermic CPB enhances rocuroniuminduced neuromuscular blockade in the patients undergoing open heart surgery. Key words: Hypothermia, induced; Cardiopulmonary bypass ; Androstanols ; Neuromuscular blockade

Influence of obstructive jaundice on neuromuscular blocking effect and drug metabolism of rocuronium

Objective To observe the effect of obstructive jaundice on the neuromuscular blocking effect and drug metabolism of rocuronium,so as to guide proper use of rocuronium during anesthesia for patients undergoing hepatobiliary surgeries.Methods Thirty patients(with normal renal function and without muscle or nerves diseases,ASAⅠ-Ⅱ)receiving elective surgery were divided into 2groups:obstructive jaundice group(group Ⅰ,n=15)and control group(group Ⅱ,n=15).All patients received continuous peridural anesthesia and general anesthesia.Neuromuscular blockade was evaluated with train-of-four(TOF)stimuli of the ulnsar nerve using TOF Watch SX nerve stimulators.The onset time,clinical duration of rocuronium,the time of TOFR from 0 to 70% and recovery index(T1 from 25%-75%) were observed. Liquid chromatography-tandem mass spectrometry(LC/MS/MS)was used to determine the concentration of rocuronium in the plasma at 30,60,90,120,and 180 min after administration of 0.9 mg/kg rocuronium.Results The age,body mass index,and prothrombin time were matched between the two groups.The total bilirubin,direct bilirubin and indirect bilirubin in groupⅠ were significantly higher than that in group Ⅱ(P<0.01).The onset time was similar between the two groups;the clinical duration of rocuronium,the time of TOFR from 0to 70%,and the recovery index(to 10%,25%,50%,and 75% of T1)in groupⅠ were significantly longer than those in groupⅡ(P<0.01).The plasma concentrations of rocuronium in groupⅠ were significantly higher than those in group Ⅱat 60,90,120 min after administration of rocuronium(P<0.01 or P<0.05).Conclusion Obstructive jaundice may prolong the duration of rocuronium action and recovery time,and slows down themetabolism of rocuronium.So patients with obstructive jaundice should have a longer interval for drug addition.Peri-and postoperative monitoring of neuromuscular function is suggested for proper drug use and anesthesia extubation.

Comparison of actual and simulated plasma concentrations of rocuronium after continuous infusion under sevoflurane and propofol anaesthesia

Comparison of actual and simulated plasma concentrations of rocuronium after continuous infusion under sevoflurane and propofol anaesthesia

Rocuronium Profile During Orthotopic Liver Transplantation: Effect of Changing the Order of Vascular Clamp Release at Reperfusion of the Hepatic Graft

Background Clearance of rocuronium in the neohepatic period may be a criterion for graft function during orthotopic liver transplantation (OLT). Our goal was to demonstrate that changes in rocuronium elimination are caused mainly by variations in blood volume at reperfusion. We have explored the influence on rocuronium plasma concentrations of changing the order of vascular unclamping at graft reperfusion. Methods Thirty patients were randomized at graft reperfusion: initial arterial revascularization (IAR; n = 14) wherein the hepatic artery was released first, and initial portal revascularization (IPR; n = 16) wherein the portal vein was released first. Tracheal intubation was facilitated by rocuronium (1 mg/kg) with an infusion initiated at 0.25 mg kg −1 h −1 to maintain a response to the first stimulus of the train of four <25% of controls. Rocuronium plasma concentrations (RPC) were measured throughout the transplantation. Results No differences were observed in rocuronium consumption at different stages. RPCs decreased after reperfusion, with primarily portal unclamping responsible. In 6 patients of the IAR group and 5 patients of the IPR group, RPC at 60 minutes after reperfusion was higher than previous values. Indicators of graft dysfunction among those 11 did not differ from the other patients. Two patients in the IPR group required retransplantation without any relation to changes in RPCs. Conclusion The increase of blood flow produced by portal vein unclamping influenced RPCs; no relation was observed between RPCs and graft outcomes.

Reduced clearance of rocuronium and sugammadex in patients with severe to end-stage renal failure: a pharmacokinetic study

Sugammadex is a selective relaxant binding agent designed to encapsulate the neuromuscular blocking agent, rocuronium. The sugammadex-rocuronium complex is eliminated by the kidneys. This trial investigated the pharmacokinetics (PKs) of sugammadex and rocuronium in patients with renal failure and healthy controls. Fifteen ASA class II-III renal patients [creatinine clearance (CL(CR)) <30 ml min(-1)] and 15 ASA I-II controls (CL(CR) > or =80 ml min(-1)) were included. After induction of anaesthesia, a single i.v. dose of rocuronium 0.6 mg kg(-1) was given, followed by a single i.v. dose of sugammadex 2.0 mg kg(-1) at reappearance of the second twitch of the train-of-four response. Plasma concentrations of rocuronium and sugammadex were estimated and PK variables determined using non-compartmental analyses. Percentages of sugammadex and rocuronium excreted in the urine were measured. PK data were obtained from 26 patients. Mean total plasma clearance (CL) of sugammadex was 5.5 ml min(-1) in renal patients and 95.2 ml min(-1) in controls (P<0.05). Rocuronium CL was 41.8 ml min(-1) in renal patients and 167 ml min(-1) in controls (P<0.05). The median amount of sugammadex and rocuronium excreted in the urine over 72 h in renal patients was 29% and 4%, respectively, and 73% and 42% over 24 h in controls. Large differences in the PKs of sugammadex and rocuronium between patients with renal failure and healthy controls were observed. The effect of renal impairment on the PK variables of rocuronium was less than with sugammadex. Urinary excretion of both drugs was reduced in renal patients.

Reversal of Rocuronium-induced Neuromuscular Blockade with Sugammadex in Pediatric and Adult Surgical Patients

Sugammadex reverses neuromuscular blockade by chemical encapsulation of rocuronium. This phase IIIA study explored efficacy and safety of sugammadex in infants (28 days to 23 months), children (2-11 yr), adolescents (12-17 yr), and adults (18-65 yr). Anesthetized patients (American Society of Anesthesiologists class 1-2) received 0.6 mg/kg rocuronium and were randomized to receive sugammadex (0.5, 1.0, 2.0, or 4.0 mg/kg) or placebo at reappearance of T2. Neuromuscular monitoring was performed using acceleromyography. Primary endpoint was time from sugammadex/placebo administration to recovery of the train-of-four ratio to 0.9. Adverse events and electrocardiograms were recorded, and blood samples were collected for safety and determination of sugammadex and rocuronium plasma concentrations. A dose-response relation was demonstrated in children (n = 22), adolescents (n = 28), and adults (n = 26), but not infants because of the small sample size (n = 8). After placebo, median recovery time of train-of-four to 0.9 was 21.0, 19.0, 23.4, and 28.5 min in infants, children, adolescents, and adults, respectively. After 2.0 mg/kg sugammadex train-of-four 0.9 was attained in 0.6, 1.2, 1.1, and 1.2 min, respectively. The sugammadex plasma concentrations were similar for the children, adolescent, and adult age groups across the dose range. Sugammadex was well tolerated: No reoccurrence of blockade, inadequate reversal, significant QT prolongation, or other abnormalities were observed. Sugammadex is a new reversal agent that rapidly, effectively, safely, and with similar recovery times reverses rocuronium-induced neuromuscular blockade in children, adolescents, adults, and the small number of infants studied.

Estimation of the plasma–effect-site equilibration rate constant (ke0) of rocuronium by the time of maximum effect: a comparison with non-parametric and parametric approaches

The first order plasma-effect-site equilibration rate constant (k(e0)) links the pharmacokinetics (PK) and pharmacodynamics (PD) of a given drug. For the calculation of the k(e0), one method uses a single point of the response curve corresponding to the time to peak effect of a drug (t(peak)); however, it has not been validated. This study compares the k(e0) calculated with the method of t(peak) and the k(e0) calculated with traditional non-parametric and parametric methods. Fifteen adult patients receiving total intravenous anaesthesia (TIVA) were studied. All patients were monitored with an NMT Monitor 221 (GE Healthcare, Helsinki, Finland) to obtain the evoked compound EMG of the adductor pollicis to a train-of-four stimuli at 10 s intervals. During TIVA, rocuronium 0.15 mg kg(-1) was given i.v. as a bolus, and the neuromuscular response was recorded until recovery from block. Using the t(peak) and the complete response curve, k(e0) of rocuronium was calculated with the three methods using the predicted plasma concentrations of rocuronium from a PK model. Values of k(e0) are median (range). The k(e0)s obtained were 0.19 min(-1) (0.09-0.72) with the 't(peak)' method, 0.20 min(-1) (0.14-0.44) with the non-parametric method, and 0.19 min(-1) (0.11-0.38) [typical value (range)] with the parametric method (NS). If the t(peak) can be adequately estimated from the data, the 't(peak) method' is a valid alternative to traditional methods to calculate the k(e0).

Sevoflurane increases fade of neuromuscular response to TOF stimulation following rocuronium administration in children. A PK/PD analysis

Sevoflurane enhances neuromuscular block produced by rocuronium, affecting not only single twitch response but also the response to high-frequency stimulation, increasing tetanic [or train-of-four (TOF)] fade. We compared the degree of fade during spontaneous recovery from rocuronium-induced neuromuscular block in 24 children (3-11 years old, ASA groups I and II), anesthetized with nitrous oxide-sevoflurane (one MAC, endtidal concentration) or nitrous oxide-fentanyl. Neuromuscular transmission was monitored electromyographically (EMG), stimulating the ulnar nerve at the wrist with TOF, 2 Hz for 2 s, repeated at 20-s intervals and recording EMG potential from adductor pollicis brevis. Depression of the fourth twitch, T4, was used as a measure of fade. Following an intubating dose of rocuronium, 0.6 mgxkg(-1), continuous infusion of rocuronium was given to maintain stable 90-99% T1 depression. Plasma concentration of rocuronium was determined with high performance liquid chromatography with electrochemical detection (HPLC-EC) method at the moment of discontinuation of rocuronium infusion and 10, 20, 30, 40, 50, 60, and 75 min afterwards. A two compartment model was used for pharmacokinetic (PK) calculations. PK parameters were fixed and pharmacodynamic data were fitted to effect compartment model proposed by Sheiner. Sevoflurane reduced rocuronium concentration in effect compartment producing 50% inhibition of both T1 and T4 response and significantly delayed not only T1, but also T4 recovery. Potentiating effect of sevoflurane on rocuronium-induced neuromuscular block influences not only postsynaptic, but also the presynaptic part of the neuromuscular junction, enhancing fade of neuromuscular response to high-frequency stimulation. The intensity of this latter effect is clinically relevant.

The effect of bi-level positive airway pressure mechanical ventilation on gas exchange during general anaesthesia

Atelectasis may occur and ventilation-perfusion mismatch may increase during general anaesthesia with neuromuscular paralysis and mechanical ventilation, though preservation of some intermittent muscle contraction might mitigate this process. There is still no ideal manoeuvre to minimize such mismatch or atelectasis. Bi-level positive airway pressure (BiPAP) ventilation adjusts to extra breaths and improves gas exchange during recovery of diaphragm function after neuromuscular paralysis. We hypothesize that BiPAP ventilation may limit the development of pulmonary shunt and may improve ventilation-perfusion mismatch when compared with standard IPPV, with or without PEEP when neuromuscular paralysis has been used during surgery. Twenty ventilated patients either on BiPAP or IPPV with or without PEEP were studied randomly using the multiple inert gas elimination technique (MIGET) at 60 and 120 min after rocuronium at induction and after 60 min. Non-invasive cardiac output (NICO) monitoring and plasma concentrations of rocuronium were measured. We compared the data of MIGET, gas exchange, haemodynamic variables and pulmonary mechanics measurements between the different ventilatory modes. Intrapulmonary shunt (blood flow to V(A)/Q < 0.005) did not increase at 60 min of anaesthesia in any of the different ventilation modes compared with the shunt value before anaesthesia. Log standard deviation of perfusion increased in IPPV, with and without PEEP groups, compared with the baseline (P< 0.05) but did not increase in the BiPAP group. BiPAP ventilation generated a higher level of Pa(O2)than IPPV with or without PEEP (P<0.05). BiPAP ventilation was beneficial in decreasing ventilation-perfusion mismatch and improving oxygenation when compared with conventional IPPV (with or without PEEP).

Reversal of neuromuscular blockade and simultaneous increase in plasma rocuronium concentration after the intravenous infusion of the novel reversal agent Org 25969.

The purpose of this study was to determine the changes in the plasma concentration of rocuronium and the reversal of its neuromuscular blockade after the intravenous infusion of Org 25969, the novel neuromuscular block-reversal agent, in anesthetized guinea pigs. Rocuronium was infused for 1 h at a rate of 12-19 nmol.kg-1.min-1 to produce a steady-state 90% neuromuscular block. After 30 min, a concomitant infusion of either the reversal agent Org 25969 at a rate of 50 nmol.kg-1.min-1 or an infusion of an equivalent volume of saline was started. The time course of plasma concentrations of rocuronium was determined by use of liquid chromatography-mass spectrometry/mass spectrometry. In both treatment groups, a steady-state plasma concentration of rocuronium was obtained after 30 min. In the saline-treated group, the plasma concentration of rocuronium and depth of block remained constant. In the Org 25969 group, neuromuscular block was reversed while the rocuronium infusion was ongoing. Simultaneously, an increase in the total plasma concentration of rocuronium (free and complexed) was observed, even though the infusion rate of rocuronium was not changed. Compared with the saline-treated group, a small increase in the postmortem bladder concentration of rocuronium was detected. The authors propose that the capture of rocuronium by Org 25969 causes the rapid reversal of neuromuscular block. The reversal can be explained by the rapid transfer of free rocuronium from the effect compartment (neuromuscular junction) to the central compartment, in which it is bound to Org 25969. This explains the increase in total plasma concentration of rocuronium (free and bound to Org 25969).

THIS MONTH IN ANESTHESIOLOGY

THIS MONTH IN ANESTHESIOLOGY

Rocuronium infusion requirements and plasma concentrations at constant levels of neuromuscular paralysis during three phases of liver transplantation

Study objective To develop a rapid online test of graft liver function during liver transplantation. Design Prospective, observational study. Setting University hospital transplant unit. Patients 17 adult patients with end-stage liver disease who underwent liver transplantation surgery. Interventions Rocuronium infusion dose requirements and plasma concentrations to maintain constant levels of neuromuscular paralysis during three phases of liver transplantation and their relationship with early postoperative liver function tests were studied. Measurements Infusion dose requirements of rocuronium, assay of rocuronium plasma concentrations using gas chromatography-mass spectrometry, and intensity of neuromuscular blockade were measured. Main results A 24% decrease in rocuronium infusion requirements was observed during the an-hepatic phase. Rocuronium requirement during the neohepatic phase was increased only modestly or remained unchanged in 14 of the 16 patients who had normal graft function in the immediate postoperative period. Rocuronium plasma concentrations for maintaining constant levels of paralysis were significantly lower during the neohepatic phase than during the paleohepatic and anhepatic phases, indicating that there is likely to be a change in pharmacodynamics during this phase. Significant reduction in rocuronium infusion requirements during the neohepatic phase was observed in the only patient who had poor graft function in the early postoperative stage, suggesting that the reduced infusion requirement to maintain a constant neuromuscular paralysis may be related to the functional state of the graft liver after reperfusion. Conclusions A significant reduction in rocuronium infusion requirement during the neohepatic phase may be suggestive of impaired organ function after reperfusion of the graft liver. Rocuronium may serve as a potential online indicator of graft liver function during liver transplantation by measurement of its infusion requirements during transplantation.

Rocuronium Plasma Concentrations During Three Phases of Liver Transplantation: Relationship with Early Postoperative Graft Liver Function

Rocuronium Plasma Concentrations During Three Phases of Liver Transplantation: Relationship with Early Postoperative Graft Liver Function