Rocuronium In Infants Research Articles

Clinical Pharmacology of Rocuronium in Infants and Children

The main clinical use of the neuromuscular blocking agents is an adjuvant in surgical anaesthesia to obtain relaxation of skeletal muscle, particularly of the abdominal wall, to facilitate surgical manipulations. Rocuronium can be used instead of suxamethonium to provide rapid muscle paralysis during tracheal intubation but the recovery is much slower. Rocuronium is administered intravenously to infants and children. In infants, rocuronium is administered at a dose of 450 µg/kg for providing muscle relaxation for laryngeal intubation. To provide sustained paralysis, rocuronium is given at a dose of 600 µg/kg. In children, the neuromuscular blockade is obtained with 600 µg/kg followed by an intravenous infusion of 150 µg/kg per hour. For assisted ventilation in intensive care, rocuronium is administered at a dose of 600 µg/kg followed by an intravenous infusion of 300 to 600 µg/kg per hour. The effects of rocuronium have been extensively studied in infants and children. Rocuronium is converted into 17-desacetyl rocuronium. The pharmacokinetics of rocuronium have been studied in infants and children and the mean residence time is 55.6 and 25.6 min (P-value < 0.01) in infant and children, respectively. Rocuronium interacts with drugs, the treatment of infants and children with rocuronium has been studied, and rocuronium poorly crosses the human placenta. The aim of this study is to review the published data on rocuronium dosing, pharmacokinetics, and treatment in infants and children, and rocuronium metabolism and transfer across the human placenta.

Appropriate sevoflurane concentration to stabilize autonomic activity during intubation with rocuronium in infants: a randomized controlled trial

BackgroundIn infants, sevoflurane is commonly used for induction of anesthesia, following which a muscle relaxant is administered to facilitate tracheal intubation. When rocuronium is used as the muscle relaxant, intubation may be performed before reaching an adequate depth of anesthesia because of its rapid onset. The purpose of this study was to investigate the optimal sevoflurane concentration that would minimize the impact of intubation on hemodynamics and autonomic nervous system (ANS) activity in infants.MethodsSixty-one infants aged 1–6 months, undergoing cleft lip repair, were enrolled. Patients were randomly assigned to three end-tidal sevoflurane concentration (E’Sevo) groups, 3%, 4% and 5%. Anesthesia was induced with 5% sevoflurane with 100% oxygen, and rocuronium (0.6 mg/kg) was administered. The concentration of sevoflurane was adjusted to the predetermined concentration in each group. Mechanical pressure control ventilation via a face mask was commenced. Five minutes after E’Sevo became stable at the predetermined concentration, tracheal intubation was performed. Immediately after tracheal intubation, ventilation was restarted at the same ventilator settings and continued for 150 seconds. Heart rate (HR) and mean arterial pressure (MAP) were measured 5 times in the 150 seconds after intubation. Normalized units (nu) of high frequency (HF: 0.04-0.15 Hz) and the ratio of low frequency (LF: 0.15-0.4 Hz) to HF components (LF/HF) of HR variability were calculated by MemCalc/Tonam2C™. Normalized units of HF (HFnu) and LF/HF reflect cardiac parasympathetic and sympathetic activity, respectively.ResultsAfter intubation, HR increased slightly in all groups and MAP increased by 9.2% in the E’Sevo-3% group. LF/HF increased (p < 0.01) and HFnu decreased (p < 0.01) in all groups 30 seconds after intubation. HFnu was lower (p < 0.001) and LF/HF was higher (p = 0.007) in the E’Sevo-3% group than in E’Sevo-5% group. ANS responses to intubation were reduced in a dose-dependent manner.ConclusionsSympathomimetic and parasympatholytic responses to intubation in the E’Sevo-3% group were much greater than those in the E’Sevo-5% group. During tracheal intubation in infants, 4% or 5% sevoflurane is appropriate for prevention of sympathetic hyperactivation and maintenance of ANS balance as compared to 3% sevoflurane, when a muscle relaxant is co-administered.Trial registrationThe study was registered at UMIN-CTR (UMIN000009933).

ABSTRACT 331

Background and aims: Sugammadex was synthesized as a selective reversal agent for the neuromuscular blocking agent, rocuronium. Several authors have reported the use of sugammadex and rocuronium in infants, but there have been few reports of its use for laparoscopic pyloromyotomy. Aims: The aim of this study was to investigate the relationship between the dose of sugammadex and rocuronium, time to extubation both after the end of surgery and after administration of sugammadex for laparoscopic pyloromyotomy in infants with hypertrophic pyloric stenosis. Methods: This study was approved by the institutional review board. The data was collected retrospectively from 8 consecutive laparoscopic pyloromyotomy procedures in infants with hypertrophic pyloric stenosis between May 2012 and April 2013. Results: At the time of surgery, the median age was 33 days (range 15–84) and the weight was 3.7 kg (2.9–5.1). The median duration of surgery was 29.5 minutes (23–46). The median doses of sugammadex and rocuronium were 2.2 (1.7–11.3) and 0.83 mg/kg (0.48–2.12), respectively. The time to extubation after surgery was 16 minutes (6–62), and the time to extubation after administration of sugammadex was 10 minutes (5–60). Greater doses of sugammadex were directly associated with greater doses of rocuronium (p=0.013, r2=0.67). Greater doses of sugammadex and rocuronium were associated with longer times to extubation after surgery (p=0.0016, r2=0.83; p=0.0019, r2=0.82) and longer times to extubation after administration of sugammadex (p=0.0037, r2=0.78; p=0.0014, r2=0.84), respectively. Conclusions: Greater doses of sugammadex and rocuronium were related to a longer time to extubation after the end of surgery.

Target-Controlled Infusion of Rocuronium in Infants, Children, and Adults

Survey of Anesthesiology: August 2004 - Volume 48 - Issue 4 - p 192-193 doi: 10.1097/01.sa.0000132015.49890.7b

Target-Controlled Infusion of Rocuronium in Infants, Children, and Adults: A Comparison of the Pharmacokinetic and Pharmacodynamic Relationship

Target-controlled infusion (TCI) of rocuronium can be used to maintain a stable blood concentration (Cp). At steady-state, the pharmacokinetics (PK) are compensated for by TCI, and a stable effect can be observed. The theoretical Cp may represent effect-site concentration (EC). We used the EC-effect relationship to study pharmacodynamics (PD) in infants, children, and adults. After giving their written, informed consent, 14 infants, 23 children, and 21 adults scheduled for elective surgical procedures received 3 to 6 ascending Cp targets of TCI rocuronium according to PD data. Just before each increase of TCI, venous blood samples were taken to measure Cp. Neuromuscular block was evaluated acceleromyographically. Individual effect data and measured Cp were fitted to the Hill equation. Maximum block during TCI targets-1000, 1300, and 1600 ng/mL-was smaller in children in comparison with infants and adults. The concentration in the effect compartment associated with a 50% drug effect (EC(50)) was significantly smaller in infants (mean [SD]) (652 [215] ng/mL) than in adults (954 [276] ng/mL) and was the largest in children (1200 [295] ng/mL). Calculated mean EC(90) values were 1705, 2230, and 2035 ng/mL, respectively, in infants, children, and adults. TCI rocuronium established steady-state PK/PD at different TCI targets and allowed us to define PK/PD relationships in a standardized way. Steady-state TCI rocuronium revealed the most potency of rocuronium in infants and the least in children. Target-controlled infusion (TCI) of rocuronium in infants, children, and adults was used to analyze the pharmacokinetic/pharmacodynamic relationship. Steady-state TCI rocuronium revealed the most potency of rocuronium in infants and the least in children.

Intramuscular Rocuronium in Infants and Children: A Multicenter Study to Evaluate Tracheal Intubating Conditions, Onset, and Duration of Action

Background This multicenter, assessor-blinded, randomized study was done to confirm and extend a pilot study showing that intramuscular rocuronium can provide adequate tracheal intubating conditions in infants (2.5 min) and children (3 min) during halothane anesthesia. Methods Thirty-eight infants (age range, 3-12 months) and 38 children (age range, 1 to 5 yr) classified as American Society of Anesthesiologists physical status 1 and 2 were evaluated at four investigational sites. Anesthesia was maintained with halothane and oxygen (1% end-tidal concentration if 2.5 yr) for 5 min. One half of the patients received 0.45 mg/kg intravenous rocuronium. The others received 1 mg/kg (infants) or 1.8 mg/kg (children) of intramuscular rocuronium into the deltoid muscle. Intubating conditions and mechanomyographic responses to ulnar nerve stimulation were assessed. Results The conditions for tracheal intubation at 2.5 and 3 min in infants and children, respectively, were inadequate in a high percentage of patients in the intramuscular group. Nine of 16 infants and 10 of 17 children had adequate or better intubating conditions at 3.5 and 4 min, respectively, after intramuscular rocuronium. Better-than-adequate intubating conditions were achieved in 14 of 15 infants and 16 of 17 children given intravenous rocuronium. Intramuscular rocuronium provided > or =98% blockade in 7.4+/-3.4 min (in infants) and 8+/-6.3 min (in children). Twenty-five percent recovery occurred in 79+/-26 min (in infants) and in 86+/-22 min (in children). Conclusions Intramuscular rocuronium, in the doses and conditions tested, does not consistently provide satisfactory tracheal intubating conditions in infants and children and is not an adequate alternative to intramuscular succinylcholine when rapid intubation is necessary.

Intramuscular Rocuronium in Infants and Children

Intramuscular Rocuronium in Infants and Children

Bioavailability of intramuscular rocuronium in infants and children.

Intramuscular rocuronium, in doses of 1,000 microg/kg in infants and 1,800 microg/kg in children, produces complete twitch depression in 5-6 min. To determine the rate and extent of absorption of rocuronium after intramuscular administration, blood was sampled at various intervals after rocuronium administration by both intramuscular and intravenous routes to determine plasma concentrations (Cp) of rocuronium. Twenty-nine pediatric patients ages 3 months to 5 yr were anesthetized with N2O and halothane. The trachea was intubated, ventilation was controlled, and adductor pollicis twitch tension was measured. When anesthetic conditions were stable, rocuronium (1,000 microg/kg for infants and 1,800 microg/kg for children) was injected either intramuscularly (in the deltoid muscle) or intravenously. Four venous plasma samples were obtained from each child 2-240 min after rocuronium administration. A mixed-effects population pharmacokinetic analysis was applied to these values to determine bioavailability, absorption rate constant, and time to peak Cp with intramuscular administration. With intramuscular administration, rocuronium's bioavailability averaged 82.6% and its absorption rate constant was 0.105 min(-1). Simulation indicated that Cp peaked 13 min after rocuronium was given intramuscularly, and that 30 min after intramuscular administration, less than 4% of the administered dose remained to be absorbed from the intramuscular depot. After rocuronium is administered into the deltoid muscle, plasma concentrations peak at 13 min, and approximately 80% of the administered drug is absorbed systemically.

Pharmacokinetics and pharmacokinetic-dynamic modelling of rocuronium in infants and children

We have determined the pharmacokinetics and pharmacokinetic-pharmacodynamic relationship of rocuronium in infants and children. We studied infants (n = 5, 0.1-0.8 yr) and children (n = 5, 2.3-8 yr), ASA II, in the ICU while undergoing artificial ventilation under i.v. anaesthesia with an arterial cannula in situ and the EMG of the adductor pollicis muscle was monitored. Rocuronium 0.06 (infants) and 0.09 (children) mg kg-1 min-1 was given i.v. over +/- 5 min until 85% neuromuscular block was obtained. Arterial blood samples were obtained over 240 min. Plasma concentrations were measured by HPLC. Pharmacokinetic-dynamic variables were calculated using the Sheiner model and the Hill equation. Statistical analysis was performed using the Mann-Whitney U test (P < 0.05). The mean administered dose was 0.32 (SD 0.08) mg kg-1 and 0.4 (0.1) mg kg-1 for infants and children, respectively. Infants differed from children in plasma clearance (4.2 (0.4) vs 6.7 (1.1) ml min-1 kg-1), distribution volume at steady state (231 (32) vs 165 (44) ml kg-1), mean residence time (56 (10) vs 26 (9) min), concentration in the effect compartment at 50% block (1.2 (0.4) vs 1.7 (0.4) mg litre-1) and the slope of the concentration-effect relationship (5.7 (1.3) vs 3.9 (0.5)). Calculated mean ED90 values were 0.26 and 0.34 mg kg-1 for infants and children, respectively. The time course of neuromuscular block after equipotent doses did not differ.

Rocuronium in infants, children and adults during balanced anaesthesia.

We studied 20 infants, 20 children and 20 adults during balanced anaesthesia to compare the neuromuscular blocking effects of rocuronium in these age groups. Neuromuscular function was recorded by adductor pollicis emg and a cumulative log-probit dose-response curve of rocuronium was established. Thereafter, full spontaneous recovery of the neuromuscular function was recorded. Onset time of the first dose of rocuronium was shorter in children than in infants or adults. The potency of rocuronium was greatest in infants and least in children; the ED50 doses (mean +/- SD) being 149 +/- 36 micrograms.kg-1 in infants, 205 +/- 52 micrograms.kg-1 in children and 169 +/- 47 micrograms.kg-1 in adults (P < 0.05 between infants and children) and the ED95 doses being 251 +/- 73 micrograms.kg-1, 409 +/- 71 micrograms.kg-1 and 350 +/- 77 micrograms.kg-1, respectively (P < 0.05 between all groups). The emg recovery following an average 94.5 +/- 4.8% neuromuscular blockade established by rocuronium was roughly similar in all study groups. Thus, one ED95 dose of rocuronium, unlike vecuronium, acts as an intermediate-acting agent in all age groups.

Rocuronium in Infants, Children, and Adults

Rocuronium in Infants, Children, and Adults

Neuromuscular effects of 600 μg·kg−1 of rocuronium in infants during nitrous oxide‐halothane anaesthesia

SummaryRocuronium bromide (Zemuron) is a new steroidal nondepolarizing neuromuscular blocking drug. We were interested in determining the effect of a bolus of rocuronium in infants during halothane anaesthesia as we did previously in older children. Eighteen infants (2‐11 months) received a bolus of 600 μg·kg−1, which is equal to twice the dose of rocuronium estimated to produce 95% depression of neuromuscular function (ED95) in children (2‐12 yr). Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10‐s intervals. Time (mean ± SEM, range) from administration of 600 μg·kg−1 rocuronium to 90% (B90) and 100% (B100) neuromuscular block was 37 ± 2 (20‐60) s and 64 ± 10 (20‐180) s, respectively. The time to recovery of neuromuscular transmission to 10% (T10) was 35.3 ± 3.0 (20.7‐57.8) min and to 25% of baseline (T25) was 41.9 ± 3.2 (24.3‐67.7) min. The recovery index (T25‐T75) was 26.6 ± 2.7 (11.7‐44.5) min, and the time to recovery of the train‐of‐four ratio (T4/T1) ± 0.75 was 82.1 ± 6.9 (53.2‐138.3) min. The plasma concentration of rocuronium when T1 had recovered to about 30% was 654 ± 34 (417‐852) ng·ml−1 which is similar to that observed in children. Six‐hundred μg·kg−1 of rocuronium has a rapid onset of effect in infants and prolonged duration of action in infants compared to children.