A sudden epidemic of HIV type 1 among injecting drug users in the former Soviet Union: identification of subtype A, subtype B, and novel gagA/envB recombinants

OBJECTIVES: The choice of cisatracurium, especially for patients with organ dysfunction, seems to be beneficial, because of organ-independent Hofmann-elimination and less histamine release propensity. This study was designed to investigate pharmacodynamics and intubating conditions after bolus administration of 0.15 mg/kg cisatracurium (3 x ED95) in patients with renal failure and maintained with isoflurane/N2O in oxygen. METHODS: 20 patients with renal failure and 19 patients with normal renal function were studied. Anaesthesia was induced with fentanyl (2-3 micrograms/kg) and thiophentone (4-7 mg/kg). After rapid bolus administration of 0.15 mg/kg cisatracurium (3 x ED95), onset time and intubating conditions were assessed. Clinical duration (DUR 25%), recovery index and duration 90% were investigated by acceleromyography. Changes of mean arterial blood pressure and/or heart rate > or = 20% were defined as clinically significant. RESULTS: The onset time (3.1 +/- 0.8 min) was shorter in patients without renal failure (Cis-1) than in patients with normal renal function (3.6 +/- 0.8 min), but without statistical significance. Intubating conditions, scored according to a 3-step scale, were slightly better in patients with normal renal function. Other pharmacodynamic parameters did not differ significantly. However, a small tendency to a prolonged recovery with a wide inter-individual variety was characteristic for patients with renal failure. Regarding the hemodynamic actions, only minor individual cardiovascular changes occured. No clinical evidence of histamine release was observed in any patient. CONCLUSIONS: The result of this clinical study suggest, that cisatracurium is a suitable choice for patients with renal failure. The necessity for an intraoperative neuromuscular monitoring is given by the marked heterogeneity in the recovery parameters in patients with renal failure.     

Bone morphogenetic protein 2 suppresses the transformed phenotype and restores actin microfilaments of human lung carcinoma A549 cells

We compared the endotracheal intubating conditions after rocuronium, using the "timing principle," with those after succinylcholine. 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. Forty-five patients were randomly assigned to three groups. Patients allocated to Groups 1 and 2 received rocuronium 0.6 mg/kg. At the onset of clinical weakness (onset of ptosis), anesthesia was induced with thiopental 4-6 mg/kg; intubation was accomplished after 45 s in Group 1 and after 60 s in Group 2. Patients in Group 3 received vecuronium (0.01 mg/kg) 3 min before the administration of thiopental and succinylcholine 1.5 mg/kg, and their tracheas were intubated 60 s later by a blind anesthesiologist. Intubating conditions were assessed according to a grading scale and were either good (5 patients in Groups 1 and 2, 4 patients in Group 3) or excellent (10 patients in Groups 1 + 2, 11 patients in Group 3) in all patients. Patients were interviewed postoperatively, and all were satisfied with the induction of anesthesia. We conclude that rocuronium 0.6 mg/kg provides good to excellent intubating conditions 45 and 60 s after the induction of anesthesia using the timing principle. Implications: We compared the ease with which a breathing tube could be placed in patients using three techniques. The standard technique (succinylcholine) was compared with two others in which a muscle-relaxing drug (rocuronium) was administered just before the anesthetic drug (so-called timing principle). No difference among the techniques was observed.     

Writing for a medical journal

Cisatracurium (51W89) is one of the ten stereoisomers of atracurium, accounting for about 15% of the racemate. The ED95 of cisatracurium was determined to be about 50 micrograms/kg (cation, molecular weight 929), while the ED95 of atracurium (besylate salt, molecular weight 1245) was 250 micrograms/kg. Thus, on a molar basis in adult patients, cisatracurium is about 3.5 times as potent as the racemic atracurium mixture. We compared atracurium with cisatracurium in healthy adult patients and found an almost identical pharmacodynamic profile. In children, an ED95 of about 40 micrograms/kg was determined, while a 1-min-longer onset of cisatracurium was found in geriatric than in young adult patients. The presence of chronic renal failure did not prolong the duration of action of cisatracurium. The recovery of neuromuscular transmission from a cisatracurium infusion of up to 145 h was investigated in intensive care unit patients. Their time from the end of infusion to a train-of-four ratio > 0.7 (68 +/- 18 min) was on average only some 70% longer than after an infusion of cisatracurium for 2 h in normal surgical patients. In another study, no signs of histamine release nor any clinically relevant cardiovascular effects of cisatracurium were found in doses up to eight times ED95.     

cAMP analogues downregulate the expression of granulocyte macrophage colony-stimulating factor (GM-CSF) in human bone marrow stromal cells in vitro

STUDY OBJECTIVE: To determine the neuromuscular blocking effect and recovery profile of cisatracurium besylate in children after administration of a bolus dose that was twice the estimated dose required to produce 95% of the maximum effect (2 x ED95; 0.08 mg/kg) followed by an infusion during halothane-nitrous oxide anesthesia. STUDY DESIGN: Open-label study. SETTING: Teaching hospital. PATIENTS: 30 male and female (ASA physical status I and II) patients, 2 to 10 years of age, scheduled for elective surgery of low to moderate risk. INTERVENTIONS: After induction of general anesthesia, patients received cisatracurium 0.08 mg/kg administered over 5 to 10 seconds. For surgical procedures requiring neuromuscular block for at least 60 minutes, a second bolus dose of cisatracurium 0.02 mg/kg was administered after the first response to a train-of-four stimuli (T1) recovered to 25% of baseline. When T1 was 5% of baseline after the second dose, a 3 microg/kg/min infusion of cisatracurium was initiated and titrated to maintain 89% to 99% block for the duration of the surgery. For procedures requiring neuromuscular block of less than 60 minutes, one or more maintenance doses of 0.02 mg/kg cisatracurium were administered when T1 was 25% of baseline after the preceding dose. In 10 patients, recovery was facilitated with edrophonium 1.0 mg/kg administered when T1 was 26% to 48% of the final baseline. MEASUREMENTS AND MAIN RESULTS: Evoked muscular response at the adductor pollicis was measured by electromyography. With 0.08 mg/kg, onset time (mean +/- SEM) was 4.1 +/- 0.4 minutes, and clinically effective duration was 27.3 +/- 0.9 minutes. Mean 5% to 95% and 25% to 75% recovery indices were 28.4 +/- 2. 7 minutes and 11.2 +/- 0.8 minutes, respectively. The mean infusion rate necessary to maintain 89% to 99% T1 suppression for 17 to 145 minutes was 1.7 microg/kg/min. After termination of infusion, the mean 5% to 95% and 25% to 75% recovery indices were similar to those after a single bolus dose, and time to 95% recovery was 30.4 +/- 3.0 minutes. After administration of edrophonium, full recovery (T4:T1 > or = 70%) occurred in 1.5 +/- 0.4 minutes. No clinically significant changes in heart rate or blood pressure were noted during the first 5 minutes after administration of cisatracurium 0.08 mg/kg. CONCLUSIONS: Cisatracurium provided maximal neuromuscular block, cardiovascular stability, and predictable recovery at the doses tested. In view of this finding, cisatracurium should be a useful intermediate-duration neuromuscular blocking drug for children during general anesthesia.     

The acute effect of minocycline on the pericardium: experimental and clinical findings

To evaluate the influence of acute isovolemic hemodilution on the dose-response and time course of action of vecuronium, we studied 60 adult patients with and without hemodilution during surgery. The patients with hemodilution underwent major elective plastic surgery with an anticipated surgical loss of more than 600 mL. Anesthesia was induced with thiopental 4-6 mg/kg and fentanyl 2-4 microg/kg i.v. and was maintained with 60% nitrous oxide in oxygen. Further increments of thiopental 2 mg/kg or fentanyl 2 microg/kg were given as required. Acute isovolemic hemodilution in the hemodilution group was induced by drainage of venous blood and an i.v. infusion of lactated Ringer's solution and 6% dextran, during which hematocrit and hemoglobin decreased from 45.7% to 26.2% and from 148.5 g/L to 90.2 g/L, respectively. Neuromuscular function was assessed mechanomyographically with train-of-four stimulation at the wrist every 12 s, and the percent depression of T1 response was used as the study parameter. The dose-response relationships of vecuronium in the two groups were determined by using the cumulative dose-response technique. The results showed that during hemodilution, the dose-response curve of vecuronium was shifted to the left in a parallel fashion, and the potency of vecuronium was increased. There were significant differences in the 50%, 90%, and 95% effective doses between the two groups. After the i.v. administration of vecuronium 80 microg/kg, vecuronium-induced neuromuscular block was significantly longer in the patients with hemodilution than in the control patients. The duration of peak effect, clinical duration, recovery index, and total duration in the hemodilution patients were significantly different from those in the control patients. We conclude that hemodilution induces significant changes in the pharmacodynamics of vecuronium. Implications: We found that patients with hemodilution were 20% more sensitive to vecuronium and had a longer duration of action after the administration of the same dose than the controls. This should be taken into account when vecuronium is used as a muscle relaxant during acute hemodilution.     

The onset of rocuronium, but not of vecuronium or mivacurium, is modified by tourniquet inflation

A previous investigation showed that inflation of a tourniquet did not interrupt onset of vecuronium neuromuscular block. To test the hypothesis that this effect depended on potency, twitch tension was measured in an arm with a tourniquet inflated during onset and compared with a control arm in 30 patients under fentanyl-thiopental-nitrous oxide-isoflurane anesthesia. Patients were randomly allocated to receive either vecuronium 0.1 mg/kg (n = 10), rocuronium 0.6 mg/kg (n = 10), or mivacurium 0.2 mg/kg (n = 10). The electromyographic response of the first dorsal interosseus to single twitch stimulation of the ulnar nerve every 10 s was recorded in both arms. When neuromuscular block was 20% (i.e., twitch tension was 80% of control), the tourniquet was inflated to a pressure of 300 mm Hg. It was deflated 5 min later. In the vecuronium and mivacurium groups, the tourniquet did not influence onset of block. In the rocuronium group, maximum neuromuscular block was (mean +/- SD) 79% +/- 10% in the tourniquet arm, compared with 96% +/- 4% in the perfused arm (P < 0.05). The maximum rate of onset was half that of the perfused arm. The difference in maximum neuromuscular block between arms was 17% +/- 7%, 5% +/- 5%, and 0% +/- 2% in the rocuronium, vecuronium, and mivacurium groups (P < 0.05). To explain that onset of block continues in spite of interruption of blood flow, drug molecules must gain access to the neuromuscular junction via routes other than the circulation. The results of this investigation are consistent with the hypothesis that there is redistribution of drug from extrajunctional to junctional areas during onset of action of muscle relaxants and this process is more important for the more potent drugs (vecuronium and mivacurium) than for rocuronium.     

The effects of age on onset and recovery from atracurium, rocuronium and vecuronium blockade

Elderly patients may show an age-related decline in physiologic functions, which may be responsible for the prolonged duration of some neuromuscular blocking agents. Previous studies have yielded conflicting results as to the effects of these drugs in the elderly. METHODS: After obtaining informed consent and approval of the Ethics Committee, we compared onset and recovery times of single IV doses of atracurium, rocuronium, and vecuronium given to 108 patients divided into three groups according to age (18-50, 51-64, > or = 65 years). Following oxazepam premedication and fentanyl and thiopentone induction, patients were randomly allocated to receive atracurium, rocuronium or vecuronium (0.5, 0.6, or 0.1 mg/kg, respectively) in < or = 0.8 vol.% enflurane (end-tidal)-nitrous oxide anaesthesia. Muscular relaxation was assessed by electromyographic (EMG) recording of the adductor pollicis muscle after supramaximal single-twitch stimulation of the ulnar nerve every 10 s. Onset time and recovery to 25%, 75% and 90% of twitch control values (DUR25, 75, 90) were recorded. Creatinine clearance predicted from serum creatinine (Ccr) was correlated with recovery from neuromuscular block. RESULTS: Onset time was not different among groups or relaxants. The results showed a prolonged duration of action for atracurium (DUR75, DUR90), rocuronium (DUR25, DUR75), and vecuronium (DUR25) in the elderly. A number of patients did not reach DUR75 or DUR90. There was a significant relationship between age and failure to return to control values during recovery from neuromuscular block, especially after atracurium and rocuronium. Ccr showed a negative correlation with age for all relaxants, but a negative significant correlation between Ccr and recovery was found only for rocuronium. CONCLUSIONS: This study suggests that onset time for atracurium, rocuronium and vecuronium is not age-dependent. Recovery was prolonged in the elderly for all three relaxants. This effect appears to be secondary to changes in body composition and function accompanying the aging process. Neither atracurium nor vecuronium depends significantly on the kidney for elimination, but the negative correlation between Ccr and rocuronium suggests an appreciable role for the kidney in the elimination of this relaxant. The long recovery times observed in this study could also be related to enflurane anaesthesia. We suggest that failure of EMG responses to return to baseline values during recovery from neuromuscular block may be related to age, especially for atracurium and rocuronium.     

Esophageal cyst--a rare cause of backache

BACKGROUND: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. METHODS: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg.kg-1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg.kg-1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg.kg-1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. RESULTS: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). CONCLUSION: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

The effect of stabilization on the onset of neuromuscular block when assessed using accelerometry

Accelerometry is increasingly being used for neuromuscular monitoring. We sought to determine whether this system is sensitive to the period of stabilization of muscle twitch prior to the administration of neuromuscular relaxant. We recruited 20 patients. No premedication was given, and anesthesia was induced with propofol and alfentanil and maintained by a propofol infusion. An accelerometer was attached to each wrist. One of the ulnar nerves was stimulated for 20 min and the other for 3 min using a train-of-four pattern at 15-s intervals. Ten patients then received vecuronium 0.1 mg/kg and a subsequent 10 received atracurium 0.5 mg/kg. The time to onset of maximum block was recorded. The data collected was subjected to a paired t-test with P < 0.05 taken as significant. The mean onset times for patients who received vecuronium was 148.5s for the arms stabilized for 3 min and 151.5s for the arms stabilized for 20 min, and in those who received atracurium it was 138.0s and 130.5s, respectively. We conclude that there is no significant difference in the onset of neuromuscular block with either vecuronium or atracurium after stabilization periods of 3 or 20 min when assessed by accelerometry.     

Pharmacodynamic dose-response and safety study of cisatracurium (51W89) in adult surgical patients during N2O-O2-opioid anesthesia

After administration of doses ranging from 0.025 to 0.25 mg/kg, the neuromuscular blocking effect of cisatracurium was assessed in 119 adult surgical patients receiving N2O-opioid-midazolam-thiopental anesthesia. The calculated 95% effective dose (ED95) for inhibition of adductor pollicis twitch evoked at 0.1 Hz was 0.053 mg/kg. With 0.10 mg/kg injected over 5-10 and 20-30 s, median onset times (range) were 5.8 (3.0-7.7) and 4.8 (1.2-10.2) min, respectively, and median times to 5% and 95% recovery (range) were 27 (19-46) and 48 (25-68) min, respectively. For doses of 0.10, 0.20, and 0.25 mg/kg, median 5%-95% and 25%-75% recovery indexes ranged from 48 to 90 min and 8 to 9 min, respectively. After administration of neostigmine (0.06 mg/kg) at 10%-15% or 16%-30% recovery, the median times to 95% recovery (range) were 6 (2-22) and 4 (2-5) min, respectively. There were no changes in heart rate, blood pressure, or plasma histamine concentrations during the first 5 min after administration of cisatracurium at doses up to 5 x ED95 injected over 5-10 s. No cutaneous flushing or bronchospasm was noted. In summary, cisatracurium is a potent neuromuscular blocking drug with an intermediate duration of action, characterized by excellent cardiovascular stability, with no apparent histamine release.     

Monitoring orbicularis oculi predicts good intubating conditions after vecuronium in children

PURPOSE: The aim of the study was to compare visual estimation of onset of neuromuscular blockade at both the adductor pollicis (AP) and the orbicularis oculi (OO) in children and to determine if monitoring the OO could predict good intubating conditions during vecuronium-induced neuromuscular blockade. METHODS: Thirty ASAI--II children (1.5-9 yr) were studied. Anaesthesia was induced with 6-8 mg.kg-1 thiopentone. The ulnar nerve at the wrist and the temporal branch of the facial nerve were stimulated every 10 sec using train-of-four (TOF) stimuli. Vecuronium, 0.15 mg.kg-1, was administered as a bolus. The responses at both the OO and the AP were evaluated visually. Patients were randomly divided into two groups. In the AP group (n = 15), the trachea was intubated when the AP was completely blocked. In the OO group (n = 15), intubation was performed when the OO was completely blocked. Intubating conditions were scored on a scale of 1 to 4. RESULTS: All the patients had complete blockade at both the orbicularis oculi and the adductor pollicis. In the two group, time from injection of vecuronium to complete neuromuscular blockade was shorter at the orbicularis oculi than at the adductor pollicis, 1.5 +/- 0.5 min vs 2.3 +/- 0.7 min, respectively, (P < 0.05; mean +/- SD) in the AP group, 1.7 +/- 0.3 min vs 2.3 +/- 0.8 min, respectively in the OO group (P < 0.05). Intubating conditions were excellent in all patient except one, where it was rated as good. They did not differ between groups. CONCLUSION: Following administration of 0.15 mg.kg-1 vecuronium in children, monitoring of the OO can detect good intubating conditions 0.7 min earlier than with monitoring of the AP.     

Simple strategy for sequencing cDNA clones

This randomized, open-label study compared the investigational inhalational anesthetic sevoflurane with isoflurane in 47 healthy women undergoing elective ambulatory surgery. The women were randomized to receive either sevoflurane or isoflurane in 60% nitrous oxide-oxygen. Induction with thiopental 3-6 mg/kg was followed by vecuronium 0.1 mg/kg and fentanyl 0-200 micrograms. Duration of anesthesia, time to emergence, orientation, length of stay in the surgical unit, and hospital discharge were recorded. The emergence, length of stay, and discharge times after discontinuation of sevoflurane were 9.7 +/- 0.7, 120.6 +/- 8.0, and 244 +/- 15 minutes, respectively, and for isoflurane were 11.9 +/- 1.4, 106.8 +/- 7.1, and 282 +/- 24 minutes, respectively (NS). The isoflurane group had a higher frequency of postoperative cough. At the end of surgery, the sevoflurane group received a deeper level of anesthesia (minimum alveolar concentration 1.5 vs 1.3), however, these patients were oriented earlier (13.6 +/- 1.1 min vs 17.0 +/- 1.5 min isoflurane; p = 0.02) after discontinuation of anesthesia, although this difference is of little clinical significance.     

Cisatracurium

Cisatracurium is one of ten isomers that form the racemic mix of atracurium (51W89 or 1 R-cis, 1'R-cis atracurium). It is three times more potent than atracurium itself and hemodynamically stable thanks to its scarce release of histamine. Cisatracurium is hydrolyzed mainly by the pathway of Hofmann (77%) and to a lesser degree it is metabolized by organ-dependent modes (mainly by the kidney (16%)). Dose therefore hardly needs to be changed for elderly patients or those with liver, kidney or cardiovascular disease. The calculated ED95 is 0.05 mg.kg-1 (0.04 mg.kg-1 in children), although a dose two to four times greater is used under clinical conditions to shorten tracheal intubation time because of low onset of blockade, particularly in comparison with rocuronium. The period of deep blockade (lack of response to neurostimulation) is prolonged by the higher dose, but recovery is dose-independent and recovery indices are similar. Cisatracurium has proven useful in intensive care because of its hemodynamic stability, which is comparable to that of steroid derivatives but with faster recovery from blockade once administration is discontinued. Its metabolism predominantly through Hofmann's pathway, with less laudanosine formation than is produced by atracurium, is also appreciated. Cisatracurium is described as the nondepolarizing muscle relaxant of choice for medium-to-long-term surgery on hemodynamically unstable patients or those with kidney or liver disease, and for neuromuscular blockade in intensive care.     

Reduced progression-free survival in elderly patients receiving intensification with autologous peripheral blood stem cell reinfusion for multiple myeloma

The stability of cisatracurium besylate was studied. Cisatracurium (as besylate) 2 mg/mL in 5- and 10-mL unopened vials and 10 mg/mL in 20-mL unopened vials, as well as 3 mL of solution from additional 2-mg/mL vials, repackaged in 3-mL sealed plastic syringes, was stored at 4 and 23 degrees C in the dark and in normal fluorescent room light. Admixtures of cisatracurium (as besylate) 0.1, 2, or 5 mg/mL in polyvinyl chloride (PVC) minibags of 5% dextrose injection or 0.9% sodium chloride injection were stored at 4 and 23 degrees C in normal fluorescent room light. Triplicate samples for each storage condition were taken initially and at 1, 3, 5, 7, 14, 21, and 30 days; samples from vials were also removed at 45 and 90 days. Solutions were stored in sterile vials at -70 degrees C and then thawed at room temperature before analysis of chemical stability by high-performance liquid chromatography. Physical stability was assessed as well. Cisatracurium besylate was physically stable in all samples throughout the study. Cisatracurium (as besylate) 2 mg/mL exhibited drug losses at 23 degrees C in vials at 45 days and in syringes at 30 days. Cisatracurium (as besylate) 0.1, 2, and 5 mg/mL in 5% dextrose injection and in 0.9% sodium chloride injection was stable for at least 30 days at 4 degrees C, but substantial drug losses occurred at 23 degrees C. Admixtures prepared with cisatracurium (as besylate) 0.1 mg/mL and with 5% dextrose injection exhibited the greatest losses. Cisatracurium besylate was stable in most samples for at least 30 days at 4 and 23 degrees C; admixtures containing cisatracurium (as besylate) 0.1 or 2 mg/mL exhibited substantial drug loss at 23 degrees C.     

Comparative clinical pharmacology of rocuronium, cisatracurium, and their combination

BACKGROUND: The comparative clinical pharmacology of cisatracurium and rocuronium and their combinations has not been reported. In this study, the authors compared the relative potency and the clinical profile and characterized the interaction of both drugs. METHODS: Two hundred twenty adults classified as American Society of Anesthesiologists physical status I and anesthetized with propofol-fentanyl-nitrous oxide were studied. In part 1, the neuromuscular-blocking effects of cisatracurium and rocuronium were assessed after administration of bolus doses of 20-50 microg/kg and 100-300 microg/kg, respectively. In part 2, we compared the time course of 1xED50, 1, 1.5, and 2xED95 doses of both drugs (where ED50 and ED95 are, respectively, the doses producing 50% and 95% depression of the first twitch height [T1]). In part 3, equieffective combinations of both drugs were studied to characterize their interaction. RESULTS: The calculated ED50 values and their 95% confidence intervals were 111 (107-115) and 26.2 (25.8-26.5) microg/kg [corrected] for rocuronium and cisatracurium, respectively. Compared with equipotent doses of cisatracurium, rocuronium had a faster onset, and a faster spontaneous T1 and train-of-four recovery times that were significant except at maximum recovery with the 2xED95 dose. The interaction between rocuronium and cisatracurium was synergistic, and the time profile of the combination group was different from that of the single-dose groups. CONCLUSIONS: Cisatracurium is four to five times more potent than rocuronium. Rocuronium had a faster onset of action, a shorter clinical duration, and a faster spontaneous recovery rate compared with equipotent doses of cisatracurium.     

Nephrotoxicity of acyclovir and ganciclovir in rats: evaluation of glomerular hemodynamics

Effects of pretreatment with thiopental on endothelium-dependent vasodilator responses elicited by drugs in rat aortic rings were investigated. The vasodilators employed were acetylcholine and histamine (endothelium- and receptor-dependent), A23187 (endothelium-dependent but receptor-independent) and sodium nitroprusside (endothelium-independent); they were tested 15 or 60 min after aortic preparations were exposed during 15 min to thiopental. Pretreatment with the barbiturate reversibly inhibited relaxation elicited by either acetylcholine and histamine, but a high concentration of the anesthetic was needed (3.1 mg/ml). On the contrary, thiopental did not modify the relaxation elicited by sodium nitroprusside or A23187. In addition, the barbiturate inhibited basal and acetylcholine-stimulated production of nitrites (an indicator of nitric oxide output) in aortic rings. In conclusion, thiopental inhibited the endothelium-dependent relaxation elicited by either acetylcholine or histamine. Although the barbiturate also inhibited nitric oxide production, the reduction in the relaxant response provoked by it does not seem to be the result of direct guanylate cyclase or nitric oxide synthase alterations, since thiopental did not modify the effect of sodium nitroprusside or A23187. Disturbances elicited by thiopental on endothelial receptors or on signal transduction elements may indirectly provoke nitric oxide synthase inhibition.     

Pharmacokinetics and pharmacodynamics of cisatracurium after a short infusion in patients under propofol anesthesia

Fourteen patients, ASA physical status I or II, were recruited to assess the pharmacokinetic-pharmacodynamic relationship of cisatracurium under nitrous oxide/sufentanil/propofol anesthesia. The electromyographic response of the abductor digiti minimi muscle was recorded on train-of-four stimulation of the ulnar nerve. A 0.1-mg/kg dose of cisatracurium was given as an infusion over 5 min. Arterial plasma concentrations of cisatracurium and its major metabolites were measured by using high-performance liquid chromatography. A nontraditional two-compartment pharmacokinetic model with elimination from central and peripheral compartments was used. The elimination rate constant from the peripheral compartment was fixed to the in vitro rate of degradation of cisatracurium in human plasma (0.0237 min(-1)). The mean terminal half-life of cisatracurium was 23.9+/-3.3 min, and its total clearance averaged 3.7+/-0.8 mL x min(-1) x kg(-1). Using this model, the volume of distribution at steady state was significantly increased compared with that obtained when central elimination only was assumed (0.118+/-0.027 vs 0.089+/-0.017 L/kg). The effect-plasma equilibration rate constant was 0.054+/-0.013 min(-1). The 50% effective concentration (153+/-33 ng/mL) was 56% higher than that reported in patients anesthetized with volatile anesthetics, which suggests that, compared with inhaled anesthetics, a cisatracurium neuromuscular block is less enhanced by propofol. IMPLICATIONS: The drug concentration-effect relationship of the muscle relaxant cisatracurium has been characterized under balanced and isoflurane anesthesia. Because propofol is now widely used as an IV anesthetic, it is important to characterize the biological fate and the concentration-effect relationship of cisatracurium under propofol anesthesia as well.     

The haemodynamic effects of rocuronium and vecuronium are different under balanced anaesthesia

BACKGROUND: Rocuronium has been reported to have minimal haemodynamic effects. However, this conclusion has been drawn primarily from investigations conducted under narcotic-based anaesthesia. This study was designed to evaluate the cardiovascular effects of rocuronium under isoflurane/N2O/fentanyl anaesthesia and to compare rocuronium's haemodynamic effects to those of vecuronium and pancuronium. METHODS: Anaesthesia was induced with fentanyl 2 micrograms/kg, thiopentone 4 mg/kg, and suxamethonium 0.5 mg/kg in 75 ASA I or II patients. After tracheal intubation, anaesthesia was maintained with isoflurane 0.5% and N2O 50% in oxygen. Five min after intubation (baseline), patients randomly received either vecuronium 100 micrograms/kg, rocuronium 600 micrograms/kg, rocuronium 900 micrograms/kg, rocuronium 1200 micrograms/kg, or pancuronium 140 micrograms/kg. One min after administration of muscle relaxant, mean arterial pressure (MAP) and heart rate (HR) were recorded and were subsequently measured at 1-min intervals for the next 4 min. RESULTS: HR decreased significantly (P < 0.05) at all times compared to baseline in patients receiving vecuronium. HR significantly (P < 0.05) increased in those receiving rocuronium 1200 micrograms/kg or pancuronium. Patients who received vecuronium had a significant (P < 0.05) decrease in MAP at all times compared to baseline. Comparing results between groups, patients who received rocuronium or pancuronium had significantly (P < 0.05) higher MAP compared to those administered vecuronium. CONCLUSION: The haemodynamic effects of rocuronium and vecuronium are different under balanced anaesthesia. Rocuronium may attenuate the fall in MAP that often occurs under balanced anaesthesia without surgical stimulation.     

A case report of complete inversion of the bladder in an old woman

BACKGROUND: The inhaled anaesthetic desflurane is characterized by a rapid wash-in and wash-out and may be useful for short paediatric ENT procedures. Therefore, this study was designed to compare the effects of desflurane or isoflurane on intubating conditions and recovery characteristics in paediatric ENT patients. METHODS: In this prospective, randomised investigation, we studied 44 children scheduled for ENT surgery, aged 4-12 yr and classified ASA I-II. After thiopentone induction (5-8 mg/kg) the lungs were ventilated by face mask and the vaporizer was dialed to 1 MAC (age-adapted) of desflurane of isoflurane. A reduced dose of vecuronium (0.05 mg/kg) was administered, and intubating conditions were rated 3 min later. Following tracheal intubation, 50% nitrous oxide were added, and the concentration of desflurane or isoflurane was adjusted according to clinical needs. At the end of surgery all anaesthetics were discontinued simultaneously and recovery times were recorded. RESULTS: Intubating conditions were rated significantly better for desflurane (excellent or good 20 of 22) than for isoflurane (12 of 22). Recovery times were significantly shorter for desflurane than for isoflurane (mean +/- SE): spontaneous ventilation 4.0 +/- 0.5 min vs. 6.0 +/- 0.7 min, extubation 8.4 +/- 0.7 vs. 11.4 +/- 1.1 min and arrival at PACU 11.5 +/- 0.8 vs. 16.6 +/- 1.5 min. No airway complications (coughing, laryngospasm, or desaturation < 97%) were noted for either anaesthetic. CONCLUSIONS: Following an intravenous induction improved intubating conditions, shorter recovery times and the lack of airway complications make desflurane a suitable alternative to isoflurane for paediatric ENT anaesthesia.     

An open-label study of the safety and tolerability of converting stable liver transplant recipients to neoral

STUDY OBJECTIVES: (1) To compare the dose-response relations of rocuronium and vecuronium in healthy adult patients anesthetized with nitrous oxide-oxygen-fentanyl-thiopental; and (2) to evaluate the time-course of action of two drugs following equipotent doses. DESIGN: Prospective, randomized, clinical comparison. SETTING: Operating room, Plastic Surgery Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College. PATIENTS: 60 ASA physical status I patients, aged 17-51 years, scheduled for elective plastic surgery. INTERVENTIONS: All patients were randomly assigned to either the rocuronium or vecuronium group. General anesthesia was induced with thiopental 4 to 6 mg/kg and fentanyl 2 to 4 micrograms/kg intravenously (i.v.), and maintained with 60% nitrous oxide (N2O) in oxygen. Further increments of thiopental or fentanyl were given as required. The dose-response relations of rocuronium and vecuronium were determined by the cumulative dose-response technique. MEASUREMENTS AND MAIN RESULTS: Neuromuscular function was assessed mechanomyographically with train-of-four (TOF) stimulation at the wrist every 12 seconds. The percentage depression of first twitch (T1) was used as the study parameter. The cumulative dose-response curve of vecuronium was shifted to the left in a parallel fashion compared with that of rocuronium. As assessed by linear regression, the potency ratio of vecuronium: rocuronium was 1:7.2. There were significant differences in the ED50, ED90, and ED95 between the two drugs. After i.v. administration of equipotent doses of both drugs (2 x ED90), the duration of peak effect, clinical duration, recovery index, and total duration were not significantly different between the two drugs. CONCLUSIONS: Compared with vecuronium, rocuronium is a low-potency, nondepolarizing relaxant, and its neuromuscular blocking potency is approximately 15% that of vecuronium in adult patients anesthetized with N2O and fentanyl. Following equipotent doses, the time-course of recovery for rocuronium is similar to that of vecuronium.