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.
Rocuronium; Vecuronium; Timing Principle; Nerve stimulator
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.
Endotracheal intubation; intubating conditions; priming; rocuronium
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.
Intratracheal; Intubation; Rocuronium; Succinylcholine
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.
neuromuscular relaxants, mivacurium; pharmacodynamics; trauma, burns
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.
ClinicalTrials.gov NCT01152905; European Clinical Trials Database at http://eudract.emea.eu.int/2006-006037-41.
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.
Anaphylactoid reaction; Anaphylaxis; Muscle relaxant; Pediatrics; Rocuronium
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.
Nitrous oxide; pain; rocuronium
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.
Neuromuscular junction; Rocuronium; Ulinastatin
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.
Hand dominance; Neuromuscular blockade; Neuromuscular monitoring
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.
BIS; Intubation; Nicardipine; Nimodipine
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.
Onset time; Phenylephrine; Rocuronium
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.
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.
Intubation condition; Rapid sequence induction; Rocuronium; Timing principle
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.
ClinicalTrials.gov, number NCT00355368.
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.
Cisatracurium; Isoflurane; Propofol; Remifentanil
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.
Propofol; rocuronium; thiopentone sodium; train of four ratio
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.
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.
Drug administration technique; Lung 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.
Endotoxin; priming; acute lung injury; neutrophils
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.
Steroidal neuromuscular blocking agents (NMBAs), such as rocuronium, are widely used in clinical anesthesia and emergency medicine to facilitate endotracheal intubation and artificial ventilation and to allow surgical access to body cavities. Reversal of neuromuscular blockade is important for the acceleration of patient recovery and prevention of postoperative residual neuromuscular blockade and reduces the incidence of severe morbidity and mortality associated with anesthesia management. Sugammadex is the first selective relaxant binding agent (SRBA) and has been designed to reverse the steroidal neuromuscular blocking drug rocuronium. Encapsulation of the rocuronium molecule by sugammadex results in a rapid decrease in free rocuronium in the plasma and subsequently at the nicotinic receptor at the motor endplate. After encapsulation, rocuronium is not available to bind to the nicotinic receptor in the neuromuscular junction. This promotes the liberation of acetylcholine receptors, and muscle activity reappears. This new concept of reversal of neuromuscular block induced by rocuronium (or vecuronium) led to impressive results in animal and phase 1 and 2 studies. Sugammadex is currently in phase 3 clinical studies and may be commercially available by 2008.
neuromuscular block; rocuronium; neuromuscular blocking agent; sugammadex; reversal agent
To compare the effectiveness of single bolus dose of esmolol or fentanyl in attenuating the hemodynamic responses during laryngoscopy and endotracheal intubation.
Ninety adult ASA I and ASA II patients were included in the study who underwent elective surgical procedures. Patients were divided into three groups. Group C (control) receiving 10 ml normal saline, group E (esmolol) receiving bolus dose of esmolol 2 mg/kg and group F (fentanyl) receiving bolus dose of fentanyl 2 µg/kg intravenously slowly. Study drug was injected 3 min before induction of anesthesia. Heart rate, systemic arterial pressure and ECG were recorded as baseline and after administration of study drug at intubation and 15 min thereafter.
Reading of heart rate, blood pressure and rate pressure product were compared with baseline and among each group. The rise in heart rate was minimal in esmolol group and was highly significant. Also the rate pressure product at the time of intubation was minimal and was statistically significant rate 15 min thereafter in group E.
Esmolol 2 mg/kg as a bolus done proved to be effective in attenuating rises in heart rate following laryngoscopy and intubation while the rise in blood pressure was suppressed but not abolished by bolus dose of esmolol.
Esmolol; fentanyl; laryngoscopy endotracheal intubation; pressure response
Remifentanil has been shown to be effective at treating potentially adverse hemodynamic responses to tracheal intubation even at low doses (< 1 µg/kg/min), which needs to be evaluated in patients with diverse cardiovascular conditions.
A low-dose regimen of remifentanil (continuous infusion of 0.1 µg/kg/min, preceded by 0.5 µg/kg bolus) was given before induction with bolus propofol and rocuronium, and heart rate as well as systolic, diastolic, and mean arterial pressures were measured at 1 min intervals from before induction to 5 min after tracheal intubation in normotensive patients, untreated hypertensive patients, and patients with known hypertension.
The low-dose regimen of remifentanil resulted in parallel hemodynamic responses in all three groups, and was effective at limiting hemodynamic responses to tracheal intubation without excessive cardiovascular depression. Hemodynamic responses in our study showed a similar pattern to that reported in previous investigations, except for elevations in heart rate and arterial pressures over the baseline values immediately after intubation.
We suggest that the low-dose regimen of remifentanil in our study could be routinely used to modify hemodynamic responses to tracheal intubation in patients with diverse hemodynamic characteristics. However, the development of supplementary regimens is still needed to control the brief, but exaggerated responses to tracheal intubation, especially in untreated hypertensive patients.
Hemodynamics; Hypertension; Remifentanil; Tracheal intubation
The effect of intravenous captopril was studied in 26 patients with severe chronic heart failure. Fourteen patients received a 25 mg intravenous bolus dose and 12 patients were given a series of incremental intravenous doses over the range 0.3125-45 mg. After the 25 mg bolus dose there was a rapid reduction in systemic vascular resistance and systemic blood pressure. The effect was greatest five minutes after the dose when cardiac output was increased by 20%. Mean right atrial pressure and pulmonary end diastolic pressure fell more slowly and reached their nadir 60 minutes after administration. Plasma free captopril concentration was significantly correlated with percentage reduction in systemic vascular resistance 15 minutes after the bolus injection, but was not correlated with either changes in right atrial or pulmonary artery pressures. With the series of incremental doses there was a progressive fall in systemic vascular resistance until a cumulative dose of 5.0 mg was reached; beyond this there was no further significant change. The rapid response to intravenous captopril indicates that it may be useful in the treatment of patients with severe heart failure who require intensive treatment. After intravenous injection of captopril haemodynamic responses in patients with heart failure were greatest at plasma concentrations of 100 g/ml to 150 ng/ml. This is considerably higher than the plasma free captopril concentrations found after conventional oral doses of captopril.
Anesthesiologists perceive that the ideal muscle relaxant is not yet available, particularly the nondepolarizing one with a rapid onset and a short duration of action. There is also a need for relaxants with different durations of action but which would be free from side effects. During the process of this development several new compounds have been tested and four have reached an advanced state of study; three of these, doxacurium, pipecuronium, and mivacurium are already licensed and rocuronium is likely to be licensed in the near future. Doxacurium and pipecuronium are slow onset and long duration of action compounds but singularly free from cardiovascular side effects. Mivacurium has an onset comparable to that of atracurium and vecuronium but with a duration of action which is intermediate in duration between these drugs and succinylcholine. Rocuronium is a drug with a fast onset of action capable of being used in place of succinylcholine but with a duration of action which is similar to that of vecuronium.