Plasma Concentrations Of Bupivacaine Research Articles

Total plasma concentrations of bupivacaine, levobupivacaine and ropivacaine after combined psoas compartment–sciatic nerve block

Total plasma concentrations of bupivacaine, levobupivacaine and ropivacaine after combined psoas compartment–sciatic nerve block

A Comparison of the Pharmacodynamics and Pharmacokinetics of Bupivacaine, Ropivacaine (with Epinephrine) and Their Equal Volume Mixtures with Lidocaine Used for Femoral and Sciatic Nerve Blocks: A Double-Blind Randomized Study

Mixtures of lidocaine with a long-acting local anesthetic are commonly used for peripheral nerve block. Few data are available regarding the safety, efficacy, or pharmacokinetics of mixtures of local anesthetics. In the current study, we compared the effects of bupivacaine 0.5% or ropivacaine 0.75% alone or in a mixed solution of equal volumes of bupivacaine 0.5% and lidocaine 2% or ropivacaine 0.75% and lidocaine 2% for surgery after femoral-sciatic peripheral nerve block. The primary end point was onset time. In a double-blind, randomized study, 82 adults scheduled for lower limb surgery received a sciatic (20 mL) and femoral (20 mL) peripheral nerve block with 0.5% bupivacaine (200 mg), a mixture of 0.5% bupivacaine 20 mL (100 mg) with 2% lidocaine (400 mg), 0.75% ropivacaine (300 mg) or a mixture of 0.75% ropivacaine 20 mL (150 mg) with 2% lidocaine (400 mg). Each solution contained epinephrine 1:200,000. Times to perform blocks, onset times (end of injection to complete sensory and motor block), duration of sensory and motor block, and morphine consumption via IV patient-controlled analgesia were compared. Venous blood samples of 5 mL were collected for determination of drug concentration at 0, 5, 15, 30, 45, 60, and 90 min after placement of the block. Patient demographics and surgical times were similar for all four groups. Sciatic onset times (sensory and motor block) were reduced by combining lidocaine with the long-acting local anesthetic. The onset of bupivacaine-lidocaine was 16 +/- 9 min versus 28 +/- 12 min for bupivacaine alone. The onset of ropivacaine-lidocaine was 16 +/- 12 min versus 23 +/- 12 for ropivacaine alone. Sensory blocks were complete for all patients within 40 min for those receiving bupivacaine-lidocaine versus 60 min for those receiving bupivacaine alone and 30 min for those receiving ropivacaine-lidocaine versus 40 min for those receiving ropivacaine alone (P < 0.05). Duration of sensory and motor block was significantly shorter in mixture groups. There was no difference among groups for visual analog scale pain scores and morphine consumption during the 48 h postoperative period, except for bupivacaine alone (median: 9 mg) versus bupivacaine-lidocaine mixture (15 mg), P < 0.01. There was no difference in the incidence of adverse events among groups. Plasma concentrations of bupivacaine and ropivacaine were higher, and remained elevated longer, in patients who received only the long-acting local anesthetic compared to patients who received the mixture of long-acting local anesthetic with lidocaine (P < 0.01). Mixtures of long-acting local anesthetics with lidocaine induced faster onset blocks of decreased duration. Whether there is a safety benefit is unclear, as the benefit of a decreased concentration of long-acting local anesthetic may be offset by the presence of a significant plasma concentration of lidocaine.

Midazolam dose for loss of response to verbal stimulation during the unilateral or bilateral spinal anesthesia

We have conducted this study to investigate whether unilateral or bilateral spinal anesthesia with bupivacaine induces different sensitivity to intravenous (i.v.) midazolam for sedation. Forty-two patients undergoing various elective unilateral lower extremity surgeries were allocated into two groups: (1) unilateral spinal anesthesia group (Group US, n=21; heavy bupivacaine 5 mg/ml, 9 mg) and (2) bilateral spinal anesthesia group (Group BS, n=21; heavy bupivacaine 5 mg/ml, 9 mg). One milligram of midazolam was injected i.v. at 30-s intervals until the patients did not respond to the hand grasp test beginning 15 min after spinal anesthesia. The concentration of plasma bupivacaine was evaluated every 15 min for the first 75 min after the start of the spinal anesthesia, and the bispectral index was monitored continuously. The mean venous plasma concentration of bupivacaine was not significantly different between Group US and BS. The dose of midazolam required to abolish responses to verbal commands was significantly lower in Group BS (mean 5.9+/-1.2 mg) vs. Group US (mean 9.0+/-1.4 mg). A higher dosage of midazolam is required for loss of response to verbal stimulation during unilateral spinal anesthesia than during bilateral spinal anesthesia.

A Comparison of the Combination of Epinephrine and Vasopressin with Lipid Emulsion in a Porcine Model of Asphyxial Cardiac Arrest After Intravenous Injection of Bupivacaine

In a porcine model, we compared the effect of the combination of vasopressin/epinephrine with that of a lipid emulsion on survival after bupivacaine-induced cardiac arrest. After administration of 5 mg/kg of a 0.5% bupivacaine solution i.v., ventilation was interrupted for 2 +/- 0.5 (mean +/- SD) min until asystole occurred. Cardiopulmonary resuscitation (CPR) was initiated after 1 min of untreated cardiac arrest. After 2 min of CPR, 10 animals received, every 5 min, either vasopressin combined with epinephrine or 4 mL/kg of a 20% lipid emulsion. Three minutes after each drug administration, up to three countershocks (4, 4, and 6 J/kg) were administered; all subsequent shocks with 6 J/kg. Blood for determination of the plasma bupivacaine concentration was drawn throughout the experiment. In the vasopressor group, all five pigs survived, whereas none of five pigs in the lipid group had restoration of spontaneous circulation (P < 0.01). There was no significant difference between groups in the plasma concentration of total bupivacaine. In this model of a bupivacaine-induced cardiac arrest, the vasopressor combination of vasopressin and epinephrine compared with lipid emulsion resulted in higher coronary perfusion pressure during CPR and survival rates.

Estimated Plasma Bupivacaine Concentration After Single Dose and Eight‐Hour Continuous Intra‐Articular Infusion of Bupivacaine in Normal Dogs

To estimate maximum plasma concentration (C(max)) and time to maximum plasma (t(max)) bupivacaine concentration after intra-articular administration of bupivacaine for single injection (SI) and injection followed by continuous infusion (CI) in normal dogs. Cross-over design with a 2-week washout period. Healthy Coon Hound dogs (n=8). Using gas chromatography/mass spectrometry, canine plasma bupivacaine concentration was measured before and after SI (1.5 mg/kg) and CI (1.5 mg/kg and 0.3 mg/kg/h). Software was used to establish plasma concentration-time curves and estimate C(max), T(max) and other pharmacokinetic variables for comparison of SI and CI. Bupivacaine plasma concentration after SI and CI best fit a 3 exponential model. For SI, mean maximum concentration (C(max), 1.33+/-0.954 microg/mL) occurred at 11.37+/-4.546 minutes. For CI, mean C(max) (1.13+/-0.509 microg/mL) occurred at 10.37+/-4.109 minutes. The area under the concentration-time curve was smaller for SI (143.59+/-118.390 microg/mL x min) than for CI (626.502+/-423.653 microg/mL x min, P=.02) and half-life was shorter for SI (61.33+/-77.706 minutes) than for CI (245.363+/-104.415 minutes, P=.01). The highest plasma bupivacaine concentration for any dog was 3.2 microg/mL for SI and 2.3 microg/mL for CI. Intra-articular bupivacaine administration results in delayed absorption from the stifle into the systemic circulation with mean C(max) below that considered toxic and no systemic drug accumulation. Intra-articular bupivacaine can be administered with small risk of reaching toxic plasma concentrations in dogs, though toxic concentrations may be approached. Caution should be exercised with multimodal bupivacaine administration because plasma drug concentration may rise higher than with single intra-articular injection.

Plasma concentrations of levobupivacaine, ropivacaine and bupivacaine after combined psoas compartment - sciatic nerve block: 175.

Plasma concentrations of levobupivacaine, ropivacaine and bupivacaine after combined psoas compartment - sciatic nerve block: 175.

175: Plasma concentrations of levobupivacaine, ropivacaine and bupivacaine after combined psoas compartment – sciatic nerve block

175: Plasma concentrations of levobupivacaine, ropivacaine and bupivacaine after combined psoas compartment – sciatic nerve block

Plasma Bupivacaine Concentrations Are Too Low to Explain Reduced Vecuronium Requirement with an Epidural

Plasma Bupivacaine Concentrations Are Too Low to Explain Reduced Vecuronium Requirement with an Epidural

The number of injections does not influence absorption of bupivacaine after cervical plexus block for carotid endarterectomy

Study ObjectiveTo investigate the efficacy and kinetics of bupivacaine when used for deep cervical plexus block (CPB), using either a single-injection or multiple-injections technique. DesignProspective, randomized, double-blind study. SettingOperating room of a university hospital. PatientsTwenty-four adult patients (16 men, 8 women) scheduled for carotid endarterectomy. InterventionsPatients were randomly assigned to receive CPB either by a single injection or after 3 injections. Patients in the multiple-injections group received a total dose of 15 mL of 0.5% bupivacaine (5 mL each deposited at C2, C3, and C4 over 2 minutes). Patients in the single-injection group received a single 15-mL injection of 0.5% bupivacaine. After the deep CPB, a superficial CPB was performed with 20 mL of 0.5% bupivacaine in all patients. MeasurementsAn anesthesiologist and a surgeon graded the success of the block. Arterial plasma concentrations of bupivacaine were measured using liquid chromatography–mass spectroscopy. Main ResultsNo significant differences were seen between the 2 groups with respect to the mean peak concentration of bupivacaine (single injection 2314 ± 1385 ng/mL vs multiple injections 2255 ± 1105 ng/mL) or time to reach the maximal concentration (time to maximum concentration [single injection 12.1 ± 7.2 minutes vs multiple injections 12.5 ± 3.9 minutes]). Furthermore, there were no significant differences in mean block scores between the single-injection and the multiple-injections groups, evaluated either by the anesthesiologists or the surgeon. ConclusionsThe results of this study showed that the absorption of bupivacaine is independent of the number of injections after CPB, and that anesthesia for carotid endarterectomy may be accomplished successfully using either technique.

Interscalene Brachial Plexus Block with Bupivacaine and Ropivacaine in Patients with Chronic Renal Failure: Diaphragmatic Excursion and Pulmonary Function Changes

In this randomized, double-blind study, we compared the anesthetic characteristics and pulmonary function changes of 0.33% bupivacaine and 0.33% ropivacaine used for interscalene brachial plexus (IBP) anesthesia in patients with chronic renal failure. Forty-two patients undergoing IBP anesthesia for creation of arteriovenous fistulas were randomly allocated to receive either 30 mL of 0.33% bupivacaine (Group B) or 0.33% ropivacaine (Group R). Block onset time, diaphragmatic excursion (ultrasonographic evaluation), and free plasma concentrations of bupivacaine and ropivacaine were evaluated. Negative motion or immobility of the ipsilateral hemidiaphragm and a decrease of >10 mm in positive motion were defined as diaphragmatic paresis. The pulmonary function variables were measured by bedside spirometry equipment. Seven patients needed supplemental local anesthetic, one with total spinal block; these patients were excluded from the study. The success rate was 80.9%. Block quality was similar in the two groups. Ipsilateral hemidiaphragmatic excursion was decreased in both groups compared with baseline values (P < 0.05). Diaphragmatic paresis was identified in 10 of 16 patients and 8 of 18 patients in Groups B and R, respectively (P > 0.05). Pulmonary function significantly decreased from baseline in both groups (forced vital capacity (FVC) 30%, forced expiratory volume at 1 second (FEV(1)) 32%, and peak expiratory flow (PEF) 31% in Group B and FVC 17%, FEV(1) 17%, and PEF 5% in Group R) (P < 0.001). The decreases in Group B were larger than those in Group R (P < 0.05). Three patients in Group B and one in Group R had mild respiratory problems (P > 0.05). Concentrations of bupivacaine and ropivacaine were below toxic levels rather than "normal range." We conclude that pulmonary function decreased more after IBP with 0.33% bupivacaine than with 0.33% ropivacaine.

Single-Injection Paravertebral Block Before General Anesthesia Enhances Analgesia After Breast Cancer Surgery With and Without Associated Lymph Node Biopsy

Paravertebral block (PVB) seems to decrease postoperative pain and postoperative nausea and vomiting (PONV) after breast surgery, but the studies have not been placebo controlled. We studied 60 patients scheduled for breast cancer surgery randomly given single-injection PVB at T3 with bupivacaine 5 mg/mL (1.5 mg/kg) or saline before general anesthesia. The patient and attending investigators were blinded; the PVB or the sham block was performed behind a curtain by an anesthesiologist not involved in the study. The patients given PVB with bupivacaine needed 40% less IV opioid medication (primary outcome variable) in the postanesthesia care unit, had a longer latency to the first opioid dose, and had less pain at rest after 24 h than the control patients (P < 0.01). They also had less PONV in the postanesthesia care unit (P < 0.05), were less sedated until 90 min (P < 0.05), and performed better in the digit symbol substitution test at 90 min and the ocular coordination test 60-120 min after surgery (P < 0.05). The average peak bupivacaine plasma concentration was 750 ng/mL. One patient had bilateral convulsions immediately after bupivacaine injection. We conclude that PVB before general anesthesia for breast cancer surgery reduced postoperative pain, opioid consumption, and occurrence of PONV and improved recovery from anesthesia.

Vasodilation increases the threshold for bupivacaine-induced convulsions in rats.

Bupivacaine affects the vascular resistance by peripheral and central nervous system (CNS) mechanisms. As vasoconstrictors increase the CNS toxicity of IV bupivacaine, vasodilators may decrease its CNS toxicity. We examined the hypothesis that vasodilators decrease the CNS toxicity of bupivacaine in awake, spontaneously breathing rats. Male Sprague-Dawley rats were randomly divided into control (C), nicardipine (N), and phentolamine (P) groups (n = 12 in each group). Racemic bupivacaine was administered IV at 1 mg/kg/min until tonic/clonic convulsions occurred. Saline, nicardipine (0.4 microg/min), and phentolamine (10 microg/min within 5 min, 50 microg/min thereafter) were simultaneously administered with bupivacaine in groups C, N, and P, respectively. Mean arterial blood pressure was significantly increased by infusion of bupivacaine in group C and was maintained at baseline levels before the onset of convulsions in groups N and P. The convulsive dose of bupivacaine in group C was 5.8 +/- 1.5 mg/kg, but was significantly larger in groups N and P (7.6 +/- 1.5 and 8.1 +/- 1.1 mg/kg, P = 0.02 and 0.001, respectively). However, there were no differences in total or protein-unbound plasma concentration of bupivacaine or in concentration of bupivacaine in the brain at the onset of convulsions among the 3 groups. We conclude that nicardipine and phentolamine increase the cumulative dose but do not affect the threshold plasma or brain concentrations required for bupivacaine-induced convulsions. Bupivacaine, a long-acting local anesthetic, induces central nervous system toxicity when its plasma concentration is increased. Nicardipine and phentolamine increased the cumulative dose but did not affect the threshold plasma concentrations, required for bupivacaine-induced convulsions, suggesting that both nicardipine and phentolamine inhibited the increase in the plasma concentration of bupivacaine by inducing peripheral vasodilation.

Kinetic and dynamic studies of liposomal bupivacaine and bupivacaine solution after subcutaneous injection in rats.

The pharmacodynamics and pharmacokinetics of bupivacaine in solution and in liposome preparations following subcutaneous administration were studied in rats. Multilamellar vesicles entrapping bupivacaine solution were prepared. The local anaesthetic effect was estimated by the tail-flick test in Wistar rats treated with 1 mg bupivacaine in 0.2-mL preparations. Plasma concentrations of bupivacaine were determined by high-performance liquid chromatography. The results showed that both bupivacaine solution and bupivacaine liposomes revealed local anaesthetic effects in the initial tail-flick test (15 min after injection). With bupivacaine liposomes, the duration of action was 5-fold (447+/-28.9 vs 87+/-6.7 min), the maximum possible effect was 2-fold (100+/-0 vs 47.6+/-13%), and the peak plasma concentration (Cmax) was less than one-fifth (0.12+/-0.04 vs 0.65+/-0.04 microg mL(-1)) that with bupivacaine solution. The sensory block effect of bupivacaine solution completely resolved at 90 min, while the plasma concentration of bupivacaine was still more than half the Cmax. Bupivacaine liposomes resulted in a low and relatively constant plasma level (approx. 0.1 microg mL(-1)) and a pronounced local anaesthetic effect throughout the experimental period (> 7 h). In conclusion, bupivacaine liposomes elevated the intensity and prolonged the duration of the local anaesthetic effect of bupivacaine, and suppressed the systemic absorption rate of encapsulated bupivacaine.

Pharmacokinetics of 0.75% ropivacaine and 0.5% bupivacaine after ilioinguinal–iliohypogastric nerve block in children

Blockade of the ilioinguinal and iliohypogastric nerves is a useful procedure in paediatric patients undergoing inguinal surgery. Bupivacaine 2 mg kg-1 has been recommended for this block. We compared the plasma concentrations of ropivacaine and bupivacaine following an ilioinguinal-iliohypogastric block. Forty children scheduled for elective inguinal surgery were randomized to receive 2 mg kg-1 of either 0.75% ropivacaine or 0.5% bupivacaine. Surgical anaesthesia was maintained with mask inhalation of oxygen, nitrous oxide and sevoflurane. Venous blood samples were drawn at regular intervals for up to 2 h and plasma was separated. Total venous plasma concentrations were determined by gas chromatography. The groups were similar with respect to age, weight and dose of local anaesthetic. The peak plasma concentration achieved was significantly higher in the bupivacaine group compared with the ropivacaine group (2.2 vs 1.2 micrograms ml-1, P = 0.025). The time to peak plasma concentration was significantly shorter in the bupivacaine group (24 vs 35 min, P = 0.024). The initial distribution half time of bupivacaine was significantly shorter (3.6 vs 6.5 min, P = 0.020) compared with that of ropivacaine. Bupivacaine is more rapidly absorbed from the injection site and leads to higher plasma concentrations than ropivacaine.

The P-Glycoprotein Inhibitor Quinidine Decreases the Plasma Concentration of Bupivacaine Required To Induce Convulsions

The P-Glycoprotein Inhibitor Quinidine Decreases the Plasma Concentration of Bupivacaine Required To Induce Convulsions

Bupivacaine inhibits human neuronal Kv3 channels in SH‐SY5Y human neuroblastoma cells

Information on molecular targets that may be involved in the neurotoxicity of bupivacaine is limited. Suppression of Kv3 channels has been demonstrated to result in abnormal patterns in the electroencephalogram and in seizures. Inhibition of Kv3 channels by bupivacaine may consequently contribute to its neuroexcitatory side-effects. Data on the effects of bupivacaine on these potassium channels are lacking. We therefore characterized the effects of bupivacaine on human Kv3 channels natively expressed in SH-SY5Y cells. Kv3 channels natively expressed in human SH-SY5Y cells were studied using a standard whole-cell patch-clamp protocol. Bupivacaine reversibly inhibited Kv3 channels in a concentration-dependent manner. The half-maximal inhibitory concentration (IC50) for conductance block was 57 microM and the Hill coefficient was close to unity. Bupivacaine accelerated macroscopic current decline by inducing inactivation-like behaviour. The midpoint of current activation was shifted to depolarized potentials in a concentration-dependent and reversible manner by a maximum of 26 mV. The IC50 was 47 microM and the Hill coefficient was 2.4. The free arterial plasma concentrations of bupivacaine that have been estimated to occur during convulsions in man would inhibit the Kv3 channels by at least 40% and would shift the midpoint of current activation by a minimum of 9 mV. Both inhibition of potassium channels and a depolarizing shift of their activation midpoint would increase neuronal excitability. The effects of bupivacaine on human Kv3 channels are thus compatible with a contributory role of Kv channel alteration in bupivacaine-induced neuronal excitation.

The pharmacokinetics and pharmacodynamics of bupivacaine-loaded microspheres on a brachial plexus block model in sheep.

We evaluated bupivacaine-loaded microspheres (B-Ms) using a brachial plexus block model in sheep. In the first step, pharmacokinetic characterization of 75 mg bupivacaine hydrochloride (B-HCl) (IV infusion and brachial plexus block) was performed (n = 12). In the second step, a brachial plexus block dose response study of B-HCl was performed with 37.5 mg, 75 mg, 150 mg, 300 mg, and 750 mg. As a comparison, evaluations were performed using a 750-mg bupivacaine base (B). In the third step, evaluations of brachial plexus block were performed with B-Ms (750 mg of B as B-Ms) using two formulations, 60/40 and 50/50 (w/w %); drug-free microspheres were also evaluated. Toxicity evaluations were also performed after IV administration of B-HCl (750 mg and 300 mg), B-Ms (750 mg), and drug-free microspheres (30 mL over 1 min). As the B-HCl dose increased, the time of onset of block decreased and the duration of complete motor blockade increased at the expense of an increase in bupivacaine plasma concentrations. The time of maximum concentration appeared to be independent of the B-HCl dose. In brachial plexus block, a 37.5-mg dose of B-HCl did not induce motor blockade whereas a dose of 750 mg of B-HCl was clinically toxic. In the case of IV administration, doses of 300 mg of B-HCl were as toxic as 750 mg of B-HCl. Compared with the 75 mg of B-HCl administration for brachial plexus block, administration of 750 mg of B as B-Ms increased the duration of complete motor blockade without significant difference in maximum concentration. No significant clinical difference between the two formulations of B-Ms was demonstrated. The IV administration of B-Ms was safe. We conclude that the controlled release of bupivacaine from microspheres prolonged the brachial plexus block without obvious toxicity. Administration of 750 mg of bupivacaine as loaded-microspheres resulted in prolongation of brachial plexus block in sheep. The peak plasma concentration was not significantly larger than that obtained with 75 mg of plain bupivacaine. The motor blockade was increased more than six times compared with 75 mg plain bupivacaine.

Pediatric caudal block with mepivacaine, bupivacaine or a mixture of both drugs: requirement for postoperative analgesia and plasma concentration of local anesthetics

Study Objectives: To assess the effects of pediatric caudal block using mepivacaine, bupivacaine, or a mixture of both drugs on postoperative analgesia, and to examine plasma concentrations of the local anesthetics after caudal injection. Design: Prospective, randomized, double-blind study. Setting: Operating room and pediatric surgical ward. Patients: 60 ASA physical status I children weighing 10 to 20 kg (26 females, 34 males), and scheduled for inguinal herniorrhaphy. Interventions: Patients randomly received caudal block with 1 mL/kg of mepivacaine 1% (Group M, n = 20), 1 mL/kg of bupivacaine 0.25% (Group B, n = 20), or a mixture of 0.5 mL/kg of mepivacaine 1% and 0.5 mL/kg of bupivacaine 0.25% (Group MB, n = 20) after induction of anesthesia with sevoflurane in 50% oxygen (O 2). Anesthesia was maintained with 66% nitrous oxide in O 2 supplemented with sevoflurane at an end-tidal concentration of less than 1%. Measurements and Main Results: Postoperative pain scores using a pediatric pain scale and plasma concentration of each local anesthetic were measured. In Group M, four patients required postoperative analgesics within the first 24 hours. However, no patients required postoperative analgesics in Groups B and MB. In Group M, the plasma concentration of mepivacaine of two patients exceeded 5 μg/kg of the level of toxicity. However, these patients did not show any toxic symptoms. Because a mixture of two local anesthetics halves the concentration of each local anesthetic, the plasma concentrations of mepivacaine and bupivacaine in Group MB were significantly lower than those of Groups M and B. Conclusions: Pediatric caudal block with a mixture of mepivacaine and bupivacaine is effective for intraoperative and postoperative analgesia.

Plasma concentrations of bupivacaine after combined spinal epidural anaesthesia in infants and neonates

Plasma concentrations of bupivacaine after combined spinal epidural anaesthesia in infants and neonates

Plasma concentrations of bupivacaine after combined spinal epidural anaesthesia in infants and neonates.

The unbound and bound plasma concentration of bupivacaine in 50 infants less than 55 weeks postconceptual age was determined following combined spinal and epidural anaesthesia (csea). Plasma concentrations were determined at 15-min intervals up to 60 min postspinal anaesthesia. Maximum plasma bupivacaine levels were recorded between 45 and 60 min post CseA. Total plasma concentrations above a toxic threshold level of 4 microg.ml(-1) were recorded in 4% of patients and above 2.5 microg.ml(-1) in 10% of patients. Unbound bupivacaine levels were greater than a presumed toxic level of 0.25 microg.ml(-1) in 16% of cases and above 0.3 microg. ml(-1) in 14% of cases. A wide range of protein binding was measured (varying from 53.8-98.2%) and could not be correlated with standard indicators of local anaesthetic binding. Two neonates had brief apnoeas in the immediate perioperative phase but no adverse cardiac or central nervous system events attributable to the performance of Csea were demonstrated.