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1.  Comparison of Intubating Conditions of Rocuronium Bromide and Vecuronium Bromide with Succinylcholine Using “Timing Principle” 
Rapid and safe endotracheal intubation is of paramount importance in general anaesthesia. The aim of this study was to compare the intubating conditions of succinylcholine with rocuronium bromide and vecuronium bromide using “Timing principle”. The timing principle entails administration of a single bolus dose of nondepolarizing muscle relaxant, followed by an induction drug at the onset of clinical weakness.
Patients & Methods:
75 patients were divided into three groups of 25 each. Patients allocated to Groups A and B received rocuronium 0.6 mg kg-1 and vecuronium 0.12 mg kg-1 respectively. At the onset of clinical weakness (ptosis), anesthesia was induced with propofol 2.5 mg kg-1; intubation was accomplished after 60 seconds of induction agent in both groups. Patients in Group C received propofol 2.5mg kg-1 followed by succinylcholine 2mg kg-1 and their tracheas were intubated at 60s.Train of four count was assessed at adductor pollicis muscle using nerve stimulator at intubation and time to loss of TOF was observed. in group A and B. Intubating conditions were assessed according to a grading scale and haemodynamic variables were compared at 1,3 and 5 minutes after intubation.
Intubating conditions were either excellent(84% in group A,48% in group B and 88% in group C) or good (16% in group A, 48% in group B and 12 %in group C)and only 4% pt had poor intubating conditions in group B. Patients were interviewed postoperatively, and all were satisfied with the technique of induction of anesthesia.Rocuronium and Vecuronium are haemodynamically stable drugs as compared to Succinylcholine.
Rocuronium 0.6 mg kg-1 provides good to excellent intubating conditions at 60 s comparable to succinylcholine after the induction of anesthesia using the timing principle.
PMCID: PMC3087261  PMID: 21547177
Rocuronium; Vecuronium; Timing Principle; Nerve stimulator
2.  Comparison of intubating conditions between rocuronium with priming and without priming: Randomized and double-blind study 
Indian Journal of Anaesthesia  2011;55(5):494-498.
Rocuronium produces faster neuromuscular blockade compared with other neuromuscular blocking drugs. It produces comparable intubating conditions to that of succinylcholine, but does not have the short intubation time of the latter. Hence, it may not be preferable for rapid sequence intubation, but rocuronium with priming may produce comparable intubating time and conditions to that of succinylcholine. Rocuronium with priming may be an alternative to succinylcholine in rapid sequence intubation in conditions where succinylcholine is contraindicated. The present study was conducted to compare the intubating conditions and intubation time of rocuronium with and without priming.
Sixty patients of ASA physical status I and II, aged between 18 and 60 years, of both sexes, were divided into priming and control groups of 30 each. Patients in the priming group received 0.06 mg/kg of rocuronium and those in the control group received normal saline. All patients received fentanyl 1 μg/kg, followed by thiopentone 5 mg/kg for induction. Intubating dose of rocuronium 0.54 mg/kg in the priming group and 0.6 mg/kg in the control group were administered 3 min after priming. Onset time of intubation was assessed using a Train of Four stimuli, and the intubating conditions were compared by the Cooper scoring system.
The onset time of intubation was 50.67±7.39 s in the priming group and 94.00±11.62 s in the control group, with excellent intubating conditions in both the groups and without any adverse effects.
Priming with rocuronium provides excellent intubating conditions in less than 60 s with no adverse effects.
PMCID: PMC3237150  PMID: 22174467
Endotracheal intubation; intubating conditions; priming; rocuronium
3.  A comparison of the clinical duration and recovery characteristics of cisatracurium after priming using rocuronium or cisatracurium: preliminary study 
The priming technique can speed up the onset of cisatracurium during intubation. However, there have been no reports on the effect of the priming technique on duration or recovery profile of cisatracurium. Therefore, we attempted to determine whether or not a priming technique with rocuronium or cisatracurium can affect clinical duration or recovery profiles of cisatracurium.
A total of 36 patients, ASA I and II, who were scheduled to undergo elective surgery, were enrolled. The patients were randomized into three groups and administered different drugs for the priming technique. Patients in group 1 received normal saline (control group). Patients in group 2 received rocuronium (0.06 mg/kg), and those in group 3 received cisatracurium (0.01 mg/kg) as a priming agent. Three minutes after injection of drugs, intubation doses of cisatracurium were administered (Group 1, 0.15 mg/kg; Groups 2 and 3, 0.14 mg/kg). Anesthesia was induced and maintained with propofol and remifentanil. Onset time, clinical duration, recovery index, recovery time, and total recovery time were measured by train of four monitoring.
Onset time in the group 2 was significantly shorter than that of group 1 or 3 (P < 0.05). However, no significant differences in clinical duration, recovery index, recovery time, and total recovery time were observed among the three groups.
Priming with rocuronium for 3 minutes resulted in significantly accelerated onset of cisatracurium. However, it did not affect the clinical duration and recovery profiles of cisatracurium.
PMCID: PMC3926995  PMID: 24567808
Cisatracurium; Neuromuscular monitoring; Recovery of function; Rocuronium
4.  Tracheal intubation with rocuronium using a "modified timing principle" 
Korean Journal of Anesthesiology  2013;64(3):218-222.
Rapid sequence induction (RSI) is indicated in various situations. Succinylcholine has been the muscle relaxant of choice for RSI, and rocuronium has become an alternative medicine for patients who cannot be administered succinylcholine for various reasons. Although rocuronium has the most rapid onset time among non-depolarizing muscle relaxants, the standard dose of rocuronium (0.6 mg/kg) takes 60 seconds to achieve appropriate muscle relaxation. We evaluated intubating conditions using the "modified timing principle" with rocuronium and succinylcholine.
In this prospective controlled blinded study, all patients received 1.5 µg/kg fentanyl intravenously with preoxygenation for 2 minutes and were randomized to receive 0.6 mg/kg rocuronium followed by 1.5 mg/kg propofol or 1.5 mg/kg propofol and 1.5 mg/kg succinylcholine. The rocuronium group was intubated just after confirming loss of consciousness, and the succinylcholine group was intubated 1 minute after injecting succinylcholine. Intubation condition, timing of events, and complications were recorded.
All patients were successfully intubated in both groups. Apnea time of the rocuronium group (38.5 seconds) was significantly shorter than that in the succinylcholine group (100.7 seconds). No significant differences were observed in loss of consciousness time or intubation time. The succinylcholine group tended to show better intubation conditions, but no significant difference was observed. None of the patients complained awareness of the intubation procedure or had respiratory difficulty during a postoperative interview.
The modified RSI with rocuronium showed shorter intubation sequence, acceptable intubation conditions, and a similar level of complications compared to those of conventional RSI with succinylcholine.
PMCID: PMC3611070  PMID: 23560186
Intratracheal; Intubation; Rocuronium; Succinylcholine
5.  Neuromuscular pharmacodynamics of mivacurium in adults with major burns 
BJA: British Journal of Anaesthesia  2011;106(5):675-679.
Mivacurium is metabolized by plasma pseudocholinesterase (PChE) enzyme, which is decreased in burns. We tested whether the decreased metabolism of mivacurium due to decreased PChE activity can overcome the pharmacodynamic resistance to non-depolarizing relaxants previously seen in major burns.
Thirty adults with 35 (13)% [mean (sd)] burn were studied at 5–91 post-burn days and 31 non-burns matched controls. Mivacurium 0.2 mg kg−1 was administered as a single bolus. Neuromuscular block was monitored with single-twitch response using TOF-Watch™. Onset time (drug administration to maximal twitch suppression) and spontaneous recovery were measured.
Onset time was significantly prolonged in burns when compared with non-burns (115 vs 90 s; P<0.001). The PChE levels were lower in burns [1432 (916) vs 2866 (731) IU litre−1; P<0.001] and the neuromuscular recovery to 50% of baseline twitch height was prolonged in burns (41 vs 26 min; P<0.001). There was a significant correlation between PChE and time to 50% recovery for the whole group together (r=−0.6; P<0.001). The dibucaine numbers were not different.
The prolonged onset time suggests resistance to neuromuscular effects, whereas the prolonged recovery suggests increased sensitivity. This divergent response can be explained by qualitative and quantitative changes in acetylcholine receptor expression causing resistance and decreased PChE activity causing sensitivity. Despite using a relatively large dose of mivacurium (0.2 mg kg−1) in the presence of decreased PChE levels, this did not overcome the resistance resulting from up-regulated receptors.
PMCID: PMC3077750  PMID: 21354998
neuromuscular relaxants, mivacurium; pharmacodynamics; trauma, burns
6.  The effect of long-term oral dantrolene on the neuromuscular action of rocuronium: a case report 
Korean Journal of Anesthesiology  2014;66(2):153-156.
Oral dantrolene causes a dose-dependent depression of skeletal muscle contractility. A 52-year-old man treated with oral dantrolene for spasticity after spinal cord injury was scheduled to undergo irrigation and drainage of a thigh abscess under general anesthesia. He had taken 50 mg oral dantrolene per day for 3 years. Under standard neuromuscular monitoring, anesthesia was performed with propofol, rocuronium, and sevoflurane. A bolus dose of ED95 (0.3 mg/kg) of rocuronium could not depress T1 up to 95%. An additional dose of rocuronium depressed T1 completely and decreased the train-of-four (TOF) count to zero. There was no apparent prolongation of the neuromuscular blocking action of rocuronium. The TOF ratio was recovered to more than 0.9 within 40 minutes after the last dose of rocuronium. A small dose of oral dantrolene does not prolong the duration of action and recovery of rocuronium.
PMCID: PMC3948443  PMID: 24624274
Dantrolene; Relaxant; Rocuronium
7.  Sugammadex: clinical development and practical use 
Korean Journal of Anesthesiology  2013;65(6):495-500.
Sugammadex is belonging to a new class of drugs: the selective relaxant binding agents. Sugammadex can reverse residual paralysis by encapsulating free circulating non depolarizing muscle relaxants. The mains advantages of sugammadex when compared with conventional anticholinesterase agents are a much faster recovery time and the unique ability, for the first time, to reverse rapidly and efficiently deep levels of neuromuscular blockade. However it only works for reversal of rocuronium or vecuronium-induced neuromuscular blockade. When administered 3 min after rocuronium the use of a large dose (16 mg/kg) can even reverse rocuronium significantly faster than the spontaneous recovery after succinylcholine.
PMCID: PMC3888841  PMID: 24427454
Cyclodextrins; Neostigmine; Neuromuscular block; Residual neuromuscular blockade; Rocuronium; Sugammadex
8.  Comparison of the variability of the onset and recovery from neuromuscular blockade with cisatracurium versus rocuronium in elderly patients under total intravenous anesthesia 
This study was designed to compare the variability of the onset and offset of the effect of two neuromuscular blocking drugs with different elimination pathways in adult and elderly patients during total intravenous anesthesia (TIVA). After Ethics Committee approval and patients' informed consent, the drugs were compared in 40 adult and 40 elderly patients scheduled for elective surgery under TIVA with tracheal intubation who were randomized to receive a single bolus dose of 0.15 mg/kg cisatracurium or 0.9 mg/kg rocuronium. The time of onset of maximum depression, duration of action, and recovery index time were measured and recorded for each patient and variability is reported as means ± standard deviation. Time of onset was significantly shorter for rocuronium than cisatracurium for the adult and elderly groups (P = 0.000), but the variability of cisatracurium was significantly greater compared with rocuronium for the same age groups (93.25 vs 37.01 s in the adult group and 64.56 vs 33.75 s in the elderly group; P = 0.000). The duration of the effect in the elderly group receiving rocuronium was significantly longer than in the elderly group receiving cisatracurium, and the variability of the duration was significantly greater in the rocuronium group than in the cisatracurium group. Mean time of recovery was significantly longer for the elderly group receiving rocuronium than for the elderly group receiving cisatracurium (P = 0.022), and variability was also greater (P = 0.002). Both drugs favored good intubating conditions. In conclusion, cisatracurium showed less variability in these parameters than rocuronium, especially in the elderly, a fact that may be of particular clinical interest.
PMCID: PMC3854273  PMID: 22584638
Neuromuscular relaxant; Rocuronium; Cisatracurium; Variability; Elderly
9.  Effect of nitrous oxide on cisatracurium infusion demands: a randomized controlled trial 
BMC Anesthesiology  2010;10:14.
Recent studies have questioned our previous understanding on the effect of nitrous oxide on muscle relaxants, since nitrous oxide has been shown to potentiate the action of bolus doses of mivacurium, rocuronium and vecuronium. This study was aimed to investigate the possible effect of nitrous oxide on the infusion requirements of cisatracurium.
70 ASA physical status I-III patients aged 18-75 years were enrolled in this randomized trial. The patients were undergoing elective surgery requiring general anesthesia with a duration of at least 90 minutes. Patients were randomized to receive propofol and remifentanil by target controlled infusion in combination with either a mixture of oxygen and nitrous oxide (Nitrous oxide/TIVA group) or oxygen in air (Air/TIVA group). A 0.1 mg/kg initial bolus of cisatracurium was administered before tracheal intubation, followed by a closed-loop computer controlled infusion of cisatracurium to produce and maintain a 90% neuromuscular block. Cumulative dose requirements of cisatracurium during the 90-min study period after bolus administration were measured and the asymptotic steady state rate of infusion to produce a constant 90% block was determined by applying nonlinear curve fitting to the data on the cumulative dose requirement during the study period.
Controller performance, i.e. the ability of the controller to maintain neuromuscular block constant at the setpoint and patient characteristics were similar in both groups. The administration of nitrous oxide did not affect cisatracurium infusion requirements. The mean steady-state rates of infusion were 0.072 +/- 0.018 and 0.066 +/- 0.017 mg * kg-1 * h-1 in Air/TIVA and Nitrous oxide/TIVA groups, respectively.
Nitrous oxide does not affect the infusion requirements of cisatracurium.
Trial registration NCT01152905; European Clinical Trials Database at
PMCID: PMC2931508  PMID: 20718983
10.  Rocuronium bromide induced anaphylaxis in a child -A case report- 
Korean Journal of Anesthesiology  2010;59(6):411-415.
Anaphylaxis or anaphylactoid reaction in pediatric patient during anesthesia is rare. We report a rocuronium induced anaphylactic reaction in a 33-month-old female. The patient was scheduled to undergo escharectomy due to injuries suffered from a major burn. Shortly after administration of rocuronium, the patient developed severe hypotension, tachycardia, and hypoxia. A similar reaction occurred after administration of rocuronium on subsequent anesthesia. She underwent uneventful anesthesia with volatile induction and maintenance of anesthesia with sevoflurane on her next 7 operations without using of muscle relaxant.
PMCID: PMC3022135  PMID: 21253379
Anaphylactoid reaction; Anaphylaxis; Muscle relaxant; Pediatrics; Rocuronium
11.  A Computer Program to Evaluate Experimental Therapies for Treating Burned Patients 
Determining the worth of new therapies for burn patients has been difficult because of the rarity of the burn injury and the disparate survival chances associated with different sizes of burns. Recently a burn survival model has been developed that estimates the risk of death from a burn as a function of the patient's age, sex, area of full thickness (third degree) burn, area of partial thickness burn, involvement of the perineum, and time from burn to admission. An alternative risk model uses the total area burned in place of the areas of partial thickness burn and full thickness burn, and is appropriate if the amount of full thickness burn is not determined accurately. This paper describes a program that uses these risk models to correct or standardize for demographic and severity factors, then, after that adjustment, tests whether a group of burn patients who received a new or experimental therapy shows a significantly better survival rate than that predicted by a baseline model. The program is a simple one written in Fortran for easy adaptation to other computer systems.
PMCID: PMC2203672
12.  Effect of nitrous oxide on pain due to rocuronium injection: A randomised, double-blind, controlled clinical trial 
Indian Journal of Anaesthesia  2010;54(2):142-146.
A prospective, randomised, double-blind, placebo-controlled study was carried out to determine the effect of nitrous oxide (N2O) on the frequency and severity of pain and withdrawal reactions after injection of rocuronium. Eighty ASA physical status I and II patients undergoing general anaesthesia for elective surgery were enrolled. The patients were randomised to receive 100% oxygen (O2), or 50% N2O in O2 for 3 minutes followed by a subparalysing dose of rocuronium 0.06 mg/kg. After induction of anaesthesia with thiopentone 5 mg/kg, an intubating dose of rocuronium 0.6 mg/kg was given. The patients were observed after injection of rocuronium 0.06 mg/kg, and asked to rate pain in the arm on a 4-point (0–3) verbal rating scale (none, mild, moderate or severe). After the intubating dose of rocuronium, withdrawal reactions were recorded. Thirty-six patients (90%) in the group N2O and 15 patients (37.5%) in the group O2 reported no pain (P < 0.001). The pain was mild in 1 (2.5%) and 9 (22.5%) patients in N2O and O2 groups, respectively (P = 0.006). Moderate pain occurred in 2 (5%) patients in group N2O and 15 (37.5%) patients in group O2 (P = 0.001). Severe pain was reported by one patient in each group (P = 0.47). Withdrawal response after an intubating dose of rocuronium was observed in 6 (15%) and 18 (45%) patients in the N2O and O2 groups, respectively (P < 0.05). Inhalation of 50% N2O in O2 reduces the incidence and severity of pain and the withdrawal reactions associated with rocuronium injection.
PMCID: PMC2900738  PMID: 20661353
Nitrous oxide; pain; rocuronium
13.  Effect of ulinastatin on the rocuronium-induced neuromuscular blockade 
Korean Journal of Anesthesiology  2012;62(3):240-244.
Ulinastatin is a glycoprotein derived from human urine and a serine protease inhibitor found in human urine and blood. Ulinastatin increases both liver blood flow and urine output. Rocuronium is eliminated mainly through the liver and partly through the kidney, hepatic elimination of rocuronium might be enhanced by ulinastatin. We examined the effect of ulinastatin on the neuromuscular block caused by rocuronium.
Forty four adult patients were randomly divided into two groups of 22 patients each, i.e. the study group and the control group. In the study group, a bolus dose of ulinastatin 5,000 U/kg was administered 2 min before the injection of rocuronium 0.6 mg/kg. In the control group, normal saline was administered instead of ulinastatin. For the monitoring of both onset and recovery from neuromuscular blockade, train-of-four (TOF) and post-tetanic count were used with TOF-Watch Sx. All patients underwent general anesthesia with total intravenous anesthesia (TIVA) of remifentanil and propofol, using the effect site target infusion system.
In the study group, the onset of neuromuscular block was significantly slower than in the control group (P < 0.05). The recovery time from the rocuronium injection to the return of PTC was also significantly shorter in the study group than in the control group (P < 0.05). Similarly, times to the return of T1, T2, T3, and T4 (i.e. the first, second, third, and fourth response of TOF) were significantly shorter in the study group than in the control group (P < 0.05).
Ulinastatin significantly delays the onset of neuromuscular block and accelerates the recovery from the block caused by rocuronium.
PMCID: PMC3315653  PMID: 22474550
Neuromuscular junction; Rocuronium; Ulinastatin
14.  Does a single dose of intravenous nicardipine or nimodipine affect the bispectral index following rapid sequence intubation? 
Korean Journal of Anesthesiology  2010;59(4):256-259.
Theoretically, L-type calcium channel blockers could modulate anesthetic effects. Nicardipine does not affect the bispectral index (BIS), but nimodipine, which can penetrate the blood-brain barrier, has not been studied. The aim of this study was to evaluate whether a single dose of intravenous nicardipine or nimodipine could affect BIS following rapid sequence intubation.
This study was done in a double-blind, randomized fashion. Anesthesia was induced with fentanyl 2 µg/kg, thiopental sodium 5 mg/kg, and 100% oxygen. After loss of consciousness, patients received rocuronium 1.0 mg/kg and either a bolus of 20 µg/kg nicardipine, nimodipine, or a comparable volume of normal saline (n = 20). Intubation was performed 1 min after study drug administration. BIS, mean blood pressure (MBP), and heart rate (HR) were measured before anesthetic induction, after loss of consciousness, before intubation, during intubation, and 1, 2 and 5 min after intubation.
BIS dropped rapidly after induction but increased to 60 before intubation in all groups irrespective of study drug. In nimodipine, the increase in BIS during intubation was not significant compared to pre-intubation, in contrast to the other two groups, but there was no difference in BIS during intubation. HR significantly increased, but MBP just rose to pre-induction values after intubation in nicardipine and nimodipine groups. BIS, MBP, and HR following intubation increased in control group.
A single dose of intravenous nicardipine or nimodipine could attenuate blood pressure increases but not affect BIS increases in rapid sequence intubation.
PMCID: PMC2966706  PMID: 21057615
BIS; Intubation; Nicardipine; Nimodipine
15.  The effect of hand dominance on neuromuscular monitoring at the adductor pollicis muscle 
Neuromuscular blockade of the adductor pollicis muscle may be influenced by hand dominance resulting in conflicting results of several studies. The current study examined whether hand dominance could influence the measurements of neuromuscular blockade with acceleromyography at the adductor pollicis.
The acceleromyographic responses from 0.6 mg/kg of rocuronium were monitored supramaximally in both hands in 31 patients after induction of anesthesia. Onset, maximum effect, and offset of rocuronium were measured and compared in both hands. The train-of-four (TOF) ratios to 0.9 were recorded in all patients.
In total, 27 patients were right-handed and 4 patients were left-handed. The mean supramaximal threshold or initial TOF ratio was not different between dominant and nondominant hands. No statistically significant differences were found between 716 paired TOF ratios in both hands. A correlation was seen between the dominant and nondominant hand (Nondominant = 0.931·Dominant + 1.714, R = 0.929). The analysis by the Bland-Altman plot showed an excellent agreement with a bias of 1.6% and limits of agreement of -21.2 to 24.5%.
Dominant and nondominant hands can be used interchangeably for neuromuscular monitoring at the adductor pollicis.
PMCID: PMC3726843  PMID: 23904936
Hand dominance; Neuromuscular blockade; Neuromuscular monitoring
16.  The effect of phenylephrine on the onset time of rocuronium 
Korean Journal of Anesthesiology  2010;59(4):244-248.
Several studies have demonstrated that ephedrine shortens the onset time of muscle relaxants, and it does so probably by increasing the cardiac output. However, elevation of the systemic blood pressure through α adrenergic stimulation via ephedrine may affect the onset of muscle relaxants during the induction of anesthesia. We investigated the effect of phenylephrine, which is a selective α-1 agonist, on the onset time of rocuronium and the intubating conditions in adults after the administration of propofol.
Sixty-four patients were randomly assigned to two groups. Phenylephrine (0.9 µg/kg) (P group) or the same volume of saline (S group) was injected before rocuronium (0.6 mg/kg) administration. Anesthesia was induced with fentanyl 2 µg/kg and propofol 2 mg/kg. The onset time was defined as the time from the end of rocuronium injection to the time when a single twitch height gets to 0% or the minimum level. A well-trained anesthesiologist who was 'blinded' to the treatment groups evaluated the intubating conditions. The mean arterial pressure and heart rate were recorded before induction, before intubation, immediately after intubation and 1 minute and 2 minutes after intubation.
The onset time was 84 ± 18 sec in the P-group and 72 ± 14 sec in the S-group. There was no difference of the intubating conditions, the mean arterial pressure and the heart rate between the two groups.
A small dose of phenylephrine, which has a limited effect on blood pressure, delayed the onset time of rocuronium after the administration of propofol, and the vasoconstriction effect of phenylephrine may affect the prolongation of the rocuronium onset time at the induction of anesthesia with using propofol.
PMCID: PMC2966704  PMID: 21057613
Onset time; Phenylephrine; Rocuronium
17.  Is the rapid sequence induction possible with 0.6 mg/kg rocuronium in pediatric patient? 
We have investigated the possibility of rocuronium 0.6 mg/kg and timing principle application with the same dose for rapid sequence induction (RSI) in 65 children, aged 4-8 yr.
Sixty five patients were randomly assigned to one of two groups; Group A (n = 31, timing principle application) received rocuronium (0.6 mg/kg) followed by administration of propofol (2.5 mg/kg), and group B (n = 36) received rocuronium (0.6 mg/kg) after administration of propofol. Intubation was assessed at 60 seconds just after administration of last injectants. Intubating conditions (jaw relaxation, vocal cord movement, and response to tracheal intubation) were evaluated as excellent, good, fair and poor.
Excellent intubation conditions were obtained in 87% in group A and 61% in group B. However, clinically acceptable intubation conditions which means excellent and good did not show any significant difference as 100% (group A) and 99% (group B).
In cases of pediatiric patients undergoing elective surgery, RSI was possible irrespective of the use of timing principle.
PMCID: PMC2872890  PMID: 20498807
Intubation condition; Rapid sequence induction; Rocuronium; Timing principle
18.  Effect of isoflurane versus propofol-remifentanil anesthesia on neuromuscular blockade and hemodynamic responses by cisatracurium bolus injection 
Korean Journal of Anesthesiology  2011;61(4):297-301.
Inhalational anesthetics potentiate nondepolarizing muscle relaxants. Cisatracurium is a recently introduced neuromuscular blocker in Korea. We studied the effect of inhalational anesthesia and total intravenous anesthesia (TIVA) on neuromuscular blockades and hemodynamic responses by cisatracurium bolus injection.
Forty patients undergoing elective surgery were randomly divided into isoflurane and propofol-remifentanil groups. A bolus dose of cisatracurium of 0.15 mg/kg (3 × ED95) was administered after induction and the onset time and clinical duration of action were recorded. The nueromuscular blockade was monitored using train-of-four (TOF) stimulation. Hemodynamic parameters were also recorded.
Onset time was 194.0 ± 39.1 sec in the isoflurane group and 226.5 ± 62.2 sec in the propofol-remifentanil group. Clinical duration of action was 49.2 ± 9.0 min in the isoflurane group and 43.0 ± 9.2 min in the propofol-remifentanil group. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) immediately before intubation decreased in the propofol-remifentanil group. Heart rate (HR), SBP and DBP 1 and 3 min after tracheal intubation increased in the isoflurane group.
Onset time was similar between isoflurane and propofol-remifentanil anesthesia. Clinical duration of action was significantly longer in isoflurane anesthesia. SBP and DBP immediately before intubation and HR, SBP and DBP 1 and 3 min after tracheal intubation were significantly different between the two groups.
PMCID: PMC3219775  PMID: 22110882
Cisatracurium; Isoflurane; Propofol; Remifentanil
19.  Succinylcholine versus rocuronium for rapid sequence intubation in intensive care: a prospective, randomized controlled trial 
Critical Care  2011;15(4):R199.
Succinylcholine and rocuronium are widely used to facilitate rapid sequence induction (RSI) intubation in intensive care. Concerns relate to the side effects of succinylcholine and to slower onset and inferior intubation conditions associated with rocuronium. So far, succinylcholine and rocuronium have not been compared in an adequately powered randomized trial in intensive care. Accordingly, the aim of the present study was to compare the incidence of hypoxemia after rocuronium or succinylcholine in critically ill patients requiring an emergent RSI.
This was a prospective randomized controlled single-blind trial conducted from 2006 to 2010 at the University Hospital of Basel. Participants were 401 critically ill patients requiring emergent RSI. Patients were randomized to receive 1 mg/kg succinylcholine or 0.6 mg/kg rocuronium for neuromuscular blockade. The primary outcome was the incidence of oxygen desaturations defined as a decrease in oxygen saturation ≥ 5%, assessed by continuous pulse oxymetry, at any time between the start of the induction sequence and two minutes after the completion of the intubation. A severe oxygen desaturation was defined as a decrease in oxygen saturation ≥ 5% leading to a saturation value of ≤ 80%.
There was no difference between succinylcholine and rocuronium regarding oxygen desaturations (succinylcholine 73/196; rocuronium 66/195; P = 0.67); severe oxygen desaturations (succinylcholine 20/196; rocuronium 20/195; P = 1.0); and extent of oxygen desaturations (succinylcholine -14 ± 12%; rocuronium -16 ± 13%; P = 0.77). The duration of the intubation sequence was shorter after succinycholine than after rocuronium (81 ± 38 sec versus 95 ± 48 sec; P = 0.002). Intubation conditions (succinylcholine 8.3 ± 0.8; rocuronium 8.2 ± 0.9; P = 0.7) and failed first intubation attempts (succinylcholine 32/200; rocuronium 36/201; P = 1.0) did not differ between the groups.
In critically ill patients undergoing emergent RSI, incidence and severity of oxygen desaturations, the quality of intubation conditions, and incidence of failed intubation attempts did not differ between succinylcholine and rocuronium.
Trial Registration, number NCT00355368.
PMCID: PMC3387641  PMID: 21846380
20.  Proinflammatory cytokine expression contributes to brain injury provoked by chronic monocyte activation. 
Molecular Medicine  2001;7(4):219-229.
BACKGROUND: We have proposed that an increased interaction between monocyte/macrophages and blood vessel endothelium predisposes subjects to strokes. The effect of chronic monocyte activation on the development of cerebral infarcts was thus studied in rats after provocation of a modified local Swartzman reaction, in brain vasculature. MATERIALS AND METHODS: Two weeks after an IV bolus of bacillus Calmette-Guérin (BCG), we studied spontaneous superoxide production, integrin expression, endothelial adhesion of monocytes and the neurological symptoms, brain histology, and cytokine immunoreactivity after a provocative dose of LPS (30-300 microg/rat i.c.v.). RESULTS: Monocyte migration into the brain was stimulated by BCG priming. The incidence of paralysis and death in response to LPS was markedly increased in BCG-primed rats. Histological evaluation of the brains of neurologically impaired and moribund animals revealed intravascular thrombosis and pale and hemorrhagic infarcts. Infiltrates of leukocytes expressing immunoreactive IL-1:, IL-6, and TNF-alpha were found around blood vessels, cerebral ventricles, and meninges, and were accompanied by a profound microglial expression of IL1P, endothelial expression of IL-6, and expression of TNF-alpha and TNF-R 1 in glia and neurons of cortex and hippocampus. Treatment (2 x 100 microg/10 ,I, i.c.v.) with recombinant human (rh-)TNF 55kDa receptor completely prevented, and treatment with rh-IL- I receptor antagonist significantly decreased the incidence of paralysis and death in response to BCG + LPS. The improvement of neurological symptoms was accompanied by reduced histological damage and supppression of IL-1P/ expression in the brain tissue. CONCLUSIONS: The data demonstrate that chronic monocyte activation predisposes subjects to thrombosis and hemorrhage via an exaggerated release of proinflammatory cytokines.
PMCID: PMC1950036  PMID: 11471566
21.  Evaluation of Pharyngeal Function between No Bolus and Bolus Propofol Induced Sedation for Advanced Upper Endoscopy 
This study aimed to assess pharyngeal function between no bolus and bolus propofol induced sedation during gastric endoscopic submucosal dissection. A retrospective study was conducted involving consecutive gastric cancer patients. Patients in the no bolus group received a 3 mg/kg/h maintenance dose of propofol after the initiation of sedation without bolus injection. All patients in the bolus group received the same maintenance dose of propofol with bolus 0.5 mg/kg propofol injection. Pharyngeal functions were evaluated endoscopically for the first 5 min following the initial administration of propofol. Fourteen patients received no bolus propofol induction and 13 received bolus propofol induction. Motionless vocal cords were observed in 2 patients (14%) in the no bolus group and 3 (23%) in the bolus group. Trachea cartilage was not observed in the no bolus group but was apparent in 6 patients (46%) in the bolus group (P < 0.01). Scope stimulated pharyngeal reflex was observed in 11 patients (79%) in the no bolus group and in 3 (23%) in the bolus group (P < 0.01). Propofol induced sedation without bolus administration preserves pharyngeal function and may constitute a safer sedation method than with bolus.
PMCID: PMC3958785  PMID: 24723747
22.  Priming with endotoxin increases acute lung injury in mice by enhancing the severity of lung endothelial injury 
Endotoxin induced acute lung injury is a commonly used model. However, the effect of a priming dose of endotoxin on lung fluid balance has not been well studied. We hypothesized that endotoxin induced acute lung injury in mice would be enhanced under a priming condition. Mice were intratracheally (IT) instilled with either a priming dose of endotoxin from E. coli (0.5 mg/kg) or equal volume of PBS. 18 h later, a larger challenge dose of endotoxin (5 mg/kg) was given IT. Control mice received PBS only. After 24 h, the mice were sacrificed and the degree of lung injury and inflammation were measured. Endotoxin priming increased body weight loss and worsened hypothermia. Extravascular lung water and lung endothelial permeability were higher in the primed group. Priming with endotoxin reduced alveolar fluid clearance, but, there was no effect on bronchoalveolar lavage (BAL) levels of RAGE (receptor for advanced glycation end-products). The primed group had increased alveolar inflammation as demonstrated by increased numbers of neutrophils in the BAL. There was no significant difference in NF-κB p65 in the lung nuclear extract among the experimental groups. Taken together, priming with a small dose of endotoxin followed by a larger challenge dose of endotoxin induces more systemic illness and increased pulmonary edema in mice, largely due to increased lung endothelial permeability and lung inflammation. This model should be useful to investigators studying acute lung injury who want to simulate the clinical setting in which more than one insult often leads to greater clinical lung injury.
PMCID: PMC3072226  PMID: 21157927
Endotoxin; priming; acute lung injury; neutrophils
23.  Lavage Administration of Dilute Surfactant in a Piglet Model of Meconium Aspiration 
Lung  2004;182(4):227-240.
Maldistribution of exogenous surfactant may preclude any clinical response in acute lung injury associated with surfactant dysfunction. Our previous studies have shown the effectiveness of surfactant lavage after homogenous lung injury. The present study utilizes a histologically confirmed non-homogeneous lung injury model induced by saline lung-lavage followed by meconium injected into a mainstem bronchus. Piglets were then treated with Infasurf® or Exosurf® by lavage (I-LAVAGE, n = 7; E-LAVAGE, n = 5) or bolus (I-BOLUS, n = 8; E-BOLUS, n = 5), or went untreated (CONTROL, n = 4). Lavage administration utilized a dilute surfactant (35 ml/kg; 4mg phospholipid/ml) instilled into the lung, followed by gravity drainage. The retained doses of the respective surfactant in the lavage and bolus groups were similar. Results showed that the surfactant distribution was more uniform in the lavage groups compared to the bolus groups. Significant and consistent increases in PaO2 were observed in the lavage groups compared to the bolus groups and the controls. PaO2 (mmHg) at 240 min posttreatment: I-LAVAGE = 297 ± 54, E-LAVAGE =280 ± 57; I-BOLUS = 139 ± 31; E-BOLUS = 152 ± 29; C = 119 ± 73 (mean ± SEM). Other improved pulmonary function parameters favored lavage administration. We conclude that better surfactant distribution achieved by lavage administration can be more effective than bolus administration in this type of non-homogeneous lung injury.
PMCID: PMC1315299  PMID: 15636195
Drug administration technique; Lung injury
24.  Evaluation of intubating conditions after rocuronium bromide in adults induced with propofol or thiopentone sodium 
The aims of present study were to compare the propofol and rocuronium with thiopentone and rocuronium in terms of clinically satisfactory intubating conditions and to co-relate intubating conditions with degree of paralysis in adductor pollicis muscle using train of four ratio (TOFR). The intubating conditions were evaluated after rocuronium bromide 0.6 mg kg-1 at 60 s.
Materials and Methods:
60 patients of ASA grades I-II of either sex, age 18-50 years, undergoing various elective surgical procedures were randomly divided into two groups, propofol rocuronium (PR group) and thiopentone rocuronium (TR group) of 30 patients in each. In the PR group, patients received propofol 2.5 mg kg-1 and rocuronium 0.6 mg kg-1; in TR group, patients received thiopentone 5 mg kg-1 and rocuronium 0.6 mg kg-1. In all patients the intubating conditions were evaluated by the observer at 60 s. TOFR was measured at the time of intubation by an assistant.
In the PR group the number of the patients placed in intubating conditions grades I, II, III and IV were 40%, 36.67%, 13.33% and 10% and their mean TOFR were 31.8±17.9%, 61.8±;14.6%, 61.7±27.9%, and 78.3±5.7% respectively. While in theTR group the number of patients placed in intubating condition grade I, II, and III were 60%, 26.67%, and 13.33% and their mean TOFR , 41.2±28.3%, 68.0±10.9% and 78.7±6.8%, respectively. There was no patient in grade lV in theTR group.
The clinical intubating conditions and degree of paralysis of adductor pollicis muscle after rocuronium 0.6 mg kg-1 at 60 s in adults induced with propofol or thiopentone sodium are comparable.
PMCID: PMC3127302  PMID: 21772683
Propofol; rocuronium; thiopentone sodium; train of four ratio
25.  Previous Burn Injury Predisposes Mice to Lipopolysaccharide (LPS) Induced Changes in Glucose Metabolism 
In mice, it has been demonstrated that at 7 days after burn injury, injection of LPS is more lethal than the same dose at one day after injury. In the present study, we examined the effect of LPS injection to mice burned seven days previously on glucose metabolism (18FDG uptake) in vivo. CD-1 male mice (25-28 grams, Charles River breeding laboratories) were anesthetized, backs shaven, and subjected to dorsal full thickness burn on 25% total body surface area. Sham treated animals were used as controls. Six days after burn injury all mice were fasted overnight. One half of the burned and sham controls were subsequently injected i.p. with LPS (10 mg/kg, E. Coli). The remaining animals were injected with saline i.p. Two hours later all mice were injected i.v. with 50 μCi of 18F FDG. One hour later the animals were euthanized and biodistribution was measured. Tissues were weighed and radioactivity was measured with a well-type gamma counter. Results were expressed as %dose/gram tissue, mean ± SEM. The combination of burn 7 days previously and LPS significantly increased mortality compared animals with burn alone, LPS alone or sham controls. Burn injury seven days previously caused a significant reduction in 18FDG uptake by the brain compared to sham controls. The combination of LPS and burn injury seven days previously produced a significant increase in 18FDG uptake by brown adipose tissue (BAT) and heart compared with either treatment separately. LPS produced a significant increase in 18FDG uptake by lung, spleen and GI tract of the sham animals, changes that were different in mice burned 7 days previously and injected with LPS. The present results suggest that burn injury seven days previously predisposes mice to alterations in 18FDG uptake produced by LPS. These changes may relate in part, to the increased lethality of LPS injection in previously burned mice.
PMCID: PMC3441057  PMID: 22961012

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