Summary

Background and objective: This study clarifies the relationship between the neuromuscular blocking effects of rocuronium 0.6 mg kg−1 and its pharmacokinetics in patients with renal failure.

Methods: Seventeen healthy patients and 17 patients with renal failure were studied under propofol anaesthesia in this prospective open label study. Rocuronium 0.6 mg kg−1 was given after induction of anaesthesia. The train-of-four mechano-myographic response of the thumb to supramaximal stimulation of the ulnar nerve at 2 Hz every 12 s was measured. Venous blood samples (4 mL) were obtained at 0, 2, 4, 7, 10, 15, 20, 30, 60, 120, 180, 240 and 360 min after relaxant administration. Samples were centrifuged, separated and stored at −20°C until plasma levels of rocuronium and its metabolites were measured. Two- and three-exponential equations were used to describe the pharmacokinetic data in each group and these were compared to each other using the Wilcoxon signed rank sum test as was the pharmacodynamic data. P < 0.05 was significant.

Results: Onset of block was similar in both groups. Clinical duration and the time to recovery of the train-of-four to 70% were prolonged in the renal failure group compared to control; 49 vs. 32 min (P < 0.004, 95% confidential interval 17, difference 5–28) and 88 vs. 55 min (P < 0.001, 95% confidential interval 33, difference 17–50), respectively. Clearance of rocuronium was reduced by 39% in the renal failure patients compared to control, with an 84% increase in the mean residence time. The volume of distribution was unaffected by renal failure.

Conclusions: The duration of action of a bolus dose of 0.6 mg kg−1 rocuronium is increased significantly in patients with end-stage renal failure compared to healthy controls. This increase may be due to a decreased clearance of rocuronium, the disease process causing the renal failure and/or the medication which patients with renal failure need in their treatment.

Summary

Background: We have evaluated the use of the TOF-Guard® (TOF, train-of-four) acceleromyographic thumb responses to ulnar nerve stimulation in neonates and infants and the return of the responses after neuromuscular blockade.

Methods: Baseline acceleromyographic recording of thumb adduction to ulnar nerve stimulation during volatile anaesthesia was performed in 22 babies aged less than 30 weeks. At the start of stimulation the automatic set-up procedure of the TOF-Guard® was used to see if a 100% control twitch height could be achieved. Irrespective of the ability to achieve a 100% control twitch height, TOF stimulation was used thereafter. When no automatic 100% control twitch could be reached, the transducer signal gain factor was set manually to obtain a 100% value. In 14 of the 22 children the recovery after neuromuscular blockade with rocuronium 0.3 mg kg−1 was recorded.

Results: In nine of 22 patients a 100% baseline twitch height was obtained with the automatic set-up. In the other 13 babies the TOF-Guard® display indicated that the transducer signal was too low. The mean time to recovery of control twitch to 75% of baseline after rocuronium 0.3 mg kg−1 was 51 min (SD = 21) and the time to recovery of the TOF ratio to 70% was 49 min (SD = 19). The mean final twitch height and TOF after recovery from rocuronium blockade were 101% (SD = 15) and 92% (SD = 12), respectively.

Conclusion: The recovery of the responses after neuromuscular blockade to near baseline values shows that acceleromyography can be used to measure neuromuscular block and recovery in neonates and infants.

Summary

Background and objective: Cisatracurium is an intermediate acting, non-depolarizing neuromuscular blocking agent. Previous reports have indicated a growth-inhibitory effect of the isoforms cisatracurium and atracurium on two human cell lines in vitro. These effects were ascribed to oxidative stress elicited by acrylate esters formed during cisatracurium breakdown. Oxidative stress is a potent precipitator of apoptosis. Therefore, the aim of the present study was to investigate whether the growth-inhibitory effects of cisatracurium could be explained by initiation of apoptosis.

Methods: Human umbilical vein endothelial cells were incubated with cisatracurium at concentrations of 0.96, 3.2, 9.6, 32 and 96 μmol for 24 h. DNA fragmentation was measured using the Cell Death Detection ELISA Plus assay (Roche Diagnostics, Mannheim, Germany).

Results: There was a dose dependency of cisatracurium with respect to the rate of apoptosis in human umbilical vein endothelial cells. Programmed cell death could be demonstrated at concentrations encountered in human plasma after single-bolus injections of cisatracurium. Apoptosis was attenuated by the concomitant administration of glutathione.

Conclusions: These findings strongly support the hypothesis that acrylate esters, breakdown products of cisatracurium, induce oxidative stress and, subsequently, apoptosis.

Summary

Background and objective: To test the hypothesis that gabexate mesilate, a protease inihibitor, hastens recovery from neuromuscular blockade, we examined the effect of gabexate mesilate on the recovery of vecuronium-induced neuromuscular blockade in anaesthetized patients in a double-blind, randomized fashion.

Methods: Thirty adult patients were divided into two groups of 15. In the gabexate mesilate group, immediately after administration of vecuronium 0.1 mg kg−1, a continuous infusion of gabexate mesilate was started at a speed of 1.5 mg kg−1 h−1. In the control group, normal saline was administered instead of gabexate mesilate. Times to the return of T1, T2, T3 or T4 (first, second, third and fourth response of train-of-four (TOF)), times to the recovery of T1/control to 0.25 (T25) or 0.5 (T50), recovery of T1/control or TOF ratio (T4/T1) were compared between the two groups.

Results: Times to the returns of T1, T2, T3 and T4 in the gabexate mesilate group were significantly shorter than in the control group (19.4 ± 6.8 vs. 25.7 ± 7.2 min for T1; mean ± SD, P = 0.020). Times to T25 and T50 were significantly shorter in the gabexate mesilate group than in the control group (34.0 ± 9.9 vs. 51.3 ± 10.2 min for T25, P < 0.001). T1/control and TOF ratio in the gabexate mesilate group were significantly higher than in the control group 40–80 min and 40–120 min after administration of vecuronium, respectively (P < 0.05).

Conclusion: Gabexate mesilate hastens recovery from neuromuscular block in anaesthetized patients receiving vecuronium.

Summary

Background and objective: We investigated whether a high bolus dose of cisatracurium (8× ED95) given at induction can provide muscle relaxation for the major part of a cardiac procedure with hypothermic cardiopulmonary bypass, avoid important postoperative residual curarization and cause no waste of product.

Methods: Twenty patients were randomly assigned either to Group 1 (n = 10) or Group 2 (n = 10). Those in Group 1 were given cisatracurium in a high bolus dose (0.4 mg kg−1). Those in Group 2 received cisatracurium 0.1mg kg−1 at induction followed after 30 min by a continuous infusion of cisatracurium. As an escape medication in case of patient movement, a bolus dose of cisatracurium 0.03 mg kg−1 was given.

Results: In Group 1 (large cisatracurium bolus dose), the clinical duration of effect (until T1/T0 = 25%) was 110 min. Six of 10 patients in Group 1 required additional boluses of cisatracurium intraoperatively. Four of these six had received an additional bolus near the end of surgery and had a train-of-four (TOF) ratio = 0 at the end. The other four patients in Group 1 had a final TOF ratio >0.9. In Group 2 (continuous cisatracurium infusion), only two patients had a TOF ratio >0.9 at the end of surgery, no patient moved and none received additional boluses. The total amount of cisatracurium used in the bolus and infusion Groups was 34.5 ± 7.8 and 21.3 ± 5.7 mg, respectively (P = 0.0004).

Conclusions: For continued neuromuscular block during hypothermic cardiac surgery, a high bolus dose of cisatracurium appears to be safe, although it is not an alternative to a continuous infusion, as its neuromuscular blockade does not cover the intraoperative period and a high incidence of movements occurs. In the patients who received a high bolus dose of cisatracurium, postoperative residual curarization appeared after additional boluses had been given. The consumption of cisatracurium by high bolus was significantly greater than with continuous infusion.

Summary

Background and objectives: This study compares three modes of patient-controlled epidural analgesia in parturients during labour.

Methods: Eighty-four women were randomized to one of three groups. The epidural solution used in all the three groups was 0.1% bupivacaine with fentanyl 2 μg mL−1. Patients were able to self administer a demand dose of 3 mL with a lockout interval of 6 min in Group A, 6 mL with a lockout interval of 12 min in Group B and 9 mL with lockout interval of 18 min in Group C. All patients received a background infusion at a rate of 6 mL h−1. Visual analogue pain scores, pinprick analgesia and motor block were assessed hourly by a blinded observer. The physician-administered supplementation and the cumulative dose of bupivacaine were also compared between the three groups.

Results: Pain scores, sensory level and motor block were not different among the study groups. Patients' satisfaction was rated good to excellent with no difference among groups. The cumulative dose of bupivacaine was not significantly different. However, there was a trend towards a decreased need for rescue analgesia in Group C. Within each group, the physician-administered supplementations were significantly higher during the second stage of labour than during the first stage (P < 0.05).

Conclusion: The three modes of patient-controlled epidural analgesia supplemented by a background infusion of 6 mL h−1 were equally effective for labour analgesia with a trend for decreased rescue analgesia in the group with a larger bolus dose and a longer lockout interval.

Summary

Background and objective: Although lidocaine has been used extensively for spinal anaesthesia since 1949, it has been associated with transient neurological symptoms only in the past 10 yr. It has been suggested that early ambulation after spinal anaesthesia, as opposed to traditional 24 h recumbency, might be the causative factor for the development of transient neurological symptoms. The purpose of this study was to examine the effect of early ambulation on the incidence of transient neurological symptoms after single injection spinal anaesthesia with lidocaine 2%.

Methods: Sixty patients undergoing minor surgery under spinal anaesthesia were included. All patients received lidocaine 60 mg. After the establishment of successful subarachnoid block, patients were randomly allocated to two groups of 30 patients. Patients in Group 1 were ambulated as soon as possible, whereas patients in Group 2 were kept recumbent until 6 h after subarachnoid injection. Two days after surgery patients were contacted by a blinded observer and interviewed of transient neurological symptoms using a standardized questionnaire. Patients were asked to express the intensity of pain/discomfort on a verbal rating scale from 0 (no pain) to 10 (worst pain imaginable).

Results: There was no significant difference in the incidence of transient neurological symptoms (23% vs. 27%). In all patients, symptoms resolved completely within 6–24 h. The median pain score was 5 (range 2–8) in Group 1 and 7 (range 1–8) in Group 2.

Conclusions: Under the conditions of this study, there is no correlation between the time of ambulation after spinal anaesthesia with lidocaine and the incidence of transient neurological symptoms.

Summary

Background and objectives: Patients undergoing eye surgery under regional anaesthesia often require concomitant medication for analgesia and comfort. Remifentanil, with its ultra-short acting-profile, may be useful to reduce pain during retrobulbar nerve block for cataract surgery.

Methods: We performed a prospective, randomized, double-blind study to compare the efficacy of remifentanil for analgesia during retrobulbar nerve block placement. Ninety patients undergoing cataract surgery were randomly divided to receive either remifentanil 0.3 μg kg−1 (n = 45) or an equivalent volume of saline (n = 45). The injection was administered within 30 s in both groups. Patients rated their amount of pain on a 10 cm visual analogue scale. Respiratory frequency, oxygen saturation, cardiac rhythm and postoperative nausea and vomiting (PONV) were recorded.

Results: The mean visual analogue score in the Remifentanil group was 2.56; it was 5.51 in the Saline group (P = 0.001, U-test). Three patients developed bradycardia and three had PONV in the Remifentanil group. Two patients developed tachycardia and one had PONV in the Saline group. No patient developed respiratory depression.

Conclusion: In patients undergoing retrobulbar block placement for eye surgery, 0.3 μg kg−1 remifentanil over 30 s significantly reduced their reported pain. In addition, remifentanil did not increase the risk of untoward side-effects.

Summary

Background and objective: This prospective, double-blind, randomized, placebo-controlled study compares the effects of ephedrine and ketamine on injection pain, and hypotension from propofol.

Methods: After obtaining the approval of the Ethics Commitee, 75 patients (ASA I–II) scheduled for elective operations with general anaesthesia were divided into three groups. Saline 2 mL (Group S, n = 25), ketamine 0.5 mg kg−1 (Group K, n = 25) or ephedrine 70 μg kg−1 (Group E, n = 25) were administered over 5 s after tourniquet application. After releasing the tourniquet, propofol 2 mg kg−1 was injected in 30 s. Pain was evaluated on a numerical scale (0–10) where 0 represented no pain and 10 the most severe pain possible. Systolic, diastolic blood pressures and heart rates were recorded preoperatively, 1 min after propofol injection, before intubation and 1, 2 and 3 min after intubation in all patients.

Results: The incidences of pain in Groups S, E and K were similar (84%, 80% and 72%, respectively). The mean pain score in Group K (2.1, SD 3.1) was significantly lower than those of Groups S and E (4.9, SD 2.6 and 4.6, SD 3.3, respectively) (P < 0.05). The systolic and diastolic blood pressure values in Group K (120 ± 27 mmHg) and Group E (123 ± 21 mmHg) before intubation were significantly higher than that of Group S (104 ± 25 mmHg) (P < 0.05). There was no significant difference between the mean heart rate values of the groups.

Conclusions: Low dose ketamine or ephedrine pretreatment may prevent hypotension due to propofol induction. Despite the reduction in injection pain intensity after ketamine, the study drugs were found to be ineffective in lowering the injection pain incidence.

Summary

Background and objective: Isoflurane has been shown to mimic ischaemic preconditioning (IPC). The protective effect of IPC, or applying isoflurane or perfusion with the ‘push-pull’ complex zinc–desferrioxamine (Zn–DFO) in the canine heart, was investigated.

Methods: Thirty minutes after salicylate administration (100 mg kg−1) the heart was exposed. All dogs were subjected to a 10 min left anterior descending artery occlusion followed by 2 h of reperfusion. In Group I (n = 9) isoflurane (2.5%) was administered 10 min prior to and during ischaemia. In Group II (n = 8), IPC was elicited by 5 min coronary artery occlusion, followed by 5 min of reperfusion, prior to the 10 min ischaemia. In Group III (n = 9) Zn–DFO (2.5 mg kg−1) was given 10 min prior to ischaemia. The effects of these interventions were compared to control (n = 10). Coronary sinus blood concentrations of salicylate, 2,3-dihydroxybenzoic acid (DHBA), lactate, pH and oxygen content were monitored.

Results: In the control group, 2,3-DHBA increased by 32% above the pre-ischaemic value (P < 0.05). In contrast, in the IPC hearts, a significant decrease in the production of 2,3-DHBA was observed (40% lower than baseline, P < 0.01). In the isoflurane group only a 13% (and non-significant) decrease was noticed. In the Zn–DFO group a 33% decrease was found (P < 0.01). The increase in lactate concentrations in the IPC and Zn–DFO groups was significantly smaller than that of control and isoflurane groups.

Conclusions: IPC protected the heart against the deleterious effects of reperfusion, possibly by amelioration of the level of oxygen-derived reactive species, and the complete inhibition of reactive hydroxyl radical production. Isoflurane did not prove to be as effective in reducing the free radical damage.

Summary

Background and objective: Target-controlled infusions (TCIs) of remifentanil and fentanyl in conscious sedation regimes for extra-corporeal shock-wave lithotripsy have not been reported. We estimated the effect site concentrations of remifentanil and fentanyl needed to obtain adequate analgesia in 50% of patients (EC50) and compared both drugs in terms of intra- and post-procedure complications.

Methods: Forty-four adult patients were randomly distributed into two groups: Group R received remifentanil and Group F received fentanyl TCI with initial effect site concentrations of 1.5 and 2 ng mL−1, respectively. Pain was assessed using a 10-point verbal analogue scale and <3 was considered adequate analgesia. Increments or decrements of 0.5 ng mL−1 were then introduced for subsequent patients according to Dixon's up and down method. During the rest of the procedure, TCI was adjusted to maintain verbal analogue scale <3.

Results: Remifentanil and fentanyl EC50 were 2.8 ng mL−1 (95% confidence interval (CI): 1.8–3.7 ng mL−1) and 2.9 ng mL−1 (95% CI: 1.7–4.1 ng mL−1), respectively (n.s.). At EC50, the probability of having a respiratory rate <10 was 4% (95% CI: 0–57%) for remifentanil and 56% (95% CI: 13–92%) for fentanyl. Hypoxaemia, vomiting and sedation were more frequent in Group F during and after the procedure (P < 0.05).

Conclusions: A similar EC50 but more respiratory depression, sedation and PONV were found with fentanyl TCI than with remifentanil TCI.

Summary

Background and objective: The aim of the present study was to investigate the impact of arginine vasopressin (AVP), a drug currently under investigation for use during cardiopulmonary resuscitation, on cerebral oxygenation and cerebral blood volume (CBV) in pigs with intact systemic circulation using near infrared spectroscopy.

Methods: Nine healthy pigs were anaesthetized and subjected to invasive haemodynamic monitoring as well as to non-invasive determination (with near infrared spectroscopy) of changes in the Tissue Oxygenation Index (TOI is the ratio of oxygenated to total tissue haemoglobin), Tissue Haemoglobin Index (THI, representing CBV) and cytochrome oxidase (ΔCytOx, representing the balance of intracellular oxygen supply).

Results: At both 3 and 5 min after AVP administration, TOI, THI and ΔCytOx were significantly (P < 0.001) reduced compared to baseline, while cerebral perfusion pressure increased significantly (P < 0.001). The effects of AVP on TOI and THI lasted longer than on ΔCytOx. There were no significant changes with respect to the intracranial pressure throughout the study period.

Conclusions: No improvement of cerebral oxygenation was detected after AVP administration in swine with an intact systemic circulation. In contrast to recently published investigations, AVP provoked a sustained drop in indices of cerebral oxygenation and CBV.