Enhancement by hyponatremia and hyperkalemia of ventricular conduction and rhythm disorders caused by bupivacaine

Intraventricular conduction disorders and reentrant arrhythmias in dogs can be produced by high plasma bupivacaine concentrations. The authors' aim was to determine if these conduction disturbances also occurred at moderate plasma bupivacaine concentrations (2.2-3.7 micrograms/ml) when in association with other factors which affect intracardiac conduction, such as hyponatremia and hyperkalemia. Thus, duration of the QRS complex, ventricular conduction time, and effective refractory period (ERP) was measured during ventricular pacing at 180 beats per min in 46 anesthetized, closed-chest dogs separated into five treatment groups as follows: group I, an iv bolus of 4 mg/kg of bupivacaine plus an infusion of 0.1 mg.kg-1.min-1 of bupivacaine followed in 50-60 min by 10 ml.kg-1.min-1 of 1.5% glycine iv to produce dilutional hyponatremia; group II, 1.5% glycine alone, as above; group III, bupivacaine, as above, followed in 50-60 min by 0.05 mmol.kg-1.min-1 of KCl iv to produce hyperkalemia; group IV, KCl alone, as above; and group V, bupivacaine, as above, except that the duration of infusion was 90 min. QRS duration and ventricular conduction time, which were prolonged approximately 33% and 61%, respectively, by bupivacaine alone were additionally prolonged 29% and 44%, respectively, when serum sodium concentration was lowered to 114 mmol/l and potassium concentration was raised to 7.7 mmol/l. The combinations of bupivacaine and hyponatremia, and bupivacaine and hyperkalemia tended to increase ERP more than did bupivacaine alone, although these changes were not statistically significant. Wave burst arrhythmias and episodes of ventricular tachycardia occurred spontaneously or were triggered by pacing in those dogs in which conduction time was most prolonged.(ABSTRACT TRUNCATED AT 250 WORDS)     

胃肠手术中右旋美托咪定对全麻复苏期的影响

目的 探讨全身麻醉中全程复合应用右旋美托咪定对患者复苏期拔管时间、睁眼时间和血流动力学等指标的影响.方法 90例入选患者被随机分成试验Ⅰ组（T1）、试验Ⅱ组（T2）和对照组（C）3组.试验Ⅰ组患者15 min内输注0.5 μg/kg右旋美托咪定,以0.25 μg· kg-1· h-1右旋美托咪定维持至拔管;试验Ⅱ组15 min内输注0.5 μg/kg右旋美托咪定,以0.5 μg· kg-1· h-1右旋美托咪定维持至拔管;对照组（C） 输注生理盐水.记录复苏期拔管时间、睁眼时间和血流动力学变化.结果 麻醉复苏期停止输注丙泊酚至拔出气管导管时间分别为C 组（26.6 ± 8.8）min、T1组（36.0 ± 12.9）min和T2 组（33.0 ± 7.7）min,3组间比较差异无统计学意义.停止瑞芬太尼输注到拔出气管导管时间分别为 C 组（12.4 ± 7.4） min,T1 组（17.2 ± 9.9） min和T2 组（16.1 ± 7.9） min,3组间比较无统计学差异（P 〉 0.05）.睁眼时间T1为（22.1 ± 9.5）min、T2为（37.3 ± 7.4） min,均较对照组C（13.2 ± 4.8）min明显延长（P 〈 0.05）.麻醉复苏期血压、心率变化试验组较对照组稳定,T2组尤为明显.结论 成人胃肠手术全凭静脉麻醉全程复合较大剂量（0.5 μg· kg-1· h-1）右旋美托咪定对麻醉复苏期气管拔管时间无明显影响,但可延长睁眼时间并与剂量相关;复苏期血流动力学指标更平稳.     

Potentiation by mild hypothermia of ventricular conduction disturbances and reentrant arrhythmias induced by bupivacaine in dogs

High concentrations of bupivacaine and profound hypothermia individually cause intraventricular conduction disturbances and reentrant arrhythmias. The effects of the combination of relatively low concentrations of bupivacaine and mild hypothermia are unknown and are the subject of this study. Three groups (n = 10-12) of dogs anesthetized with thiopental-chloralose were treated as follows: group 1, bupivacaine + hypothermia; group 2, bupivacaine alone; group 3, hypothermia alone. Bupivacaine was administered as a 4 mg/kg iv bolus followed by an iv infusion of 0.1 mg.kg-1.min-1. Hypothermia, i.e., a 4 degrees C reduction in core temperature, was produced by cooling the blood with an extracorporeal circuit. The peripheral ECG was recorded to determine the duration of QRS complexes and the QT interval. Conduction time and effective refractory period (ERP) of ventricular contractile tissue were measured with right ventricular endocavitary electrodes. Measurements were made with the heart paced at 180 beats/min and without pacing. In group 1 dogs, bupivacaine (plasma level, 2.8 +/- 0.3 microgram/ml) initially caused a prolongation of conduction time and QRS duration, which were further lengthened (approximately doubled) by a temperature decrease of 4 degrees C from baseline. The QT interval and ERP also were increased but to a lesser degree. In dogs in which the effects were most pronounced, rhythm disorders, such as wave burst arrhythmias (most common), premature systoles, ventricular tachycardia, and even ventricular fibrillation, occurred either spontaneously or during pacing. Bupivacaine alone (group 2) increased QRS duration and conduction time significantly, whereas hypothermia alone (Group 3) did not cause changes in any conduction variables. In neither group were dysrhythmias observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of propofol anesthesia on local cerebral glucose utilization in the rat

The autoradiographic 14C-2-deoxy-D-glucose method was used to determine local cerebral glucose utilization (LCGU) during propofol anesthesia and recovery in 52 regions of the rat brain. Control rats intravenously received 5 ml.kg-1.h-1 of the egg-oil-glycerol emulsion that constitutes the vehicle for propofol. Anesthetized animals received an iv bolus of propofol (20 mg/kg) followed by continuous infusion of the anesthetic at 12.5, 25, or 50 mg.kg-1.h-1 for 1 h prior to injection of 14C-2-deoxy-D-glucose and for the following 45 min. In addition, a fifth group of animals were studied immediately after awakening from a 20 mg/kg bolus of propofol as indicated by the first reappearance of head lift. All rats were spontaneously breathing room air throughout the experimental procedure. The general pattern of the cerebral metabolic response to propofol anesthesia was a dose-related, widespread depression of LCGU. At the three infusion rates of propofol tested, overall mean LCGU was reduced by 33%, 49%, and 55%, respectively, and significant decreases were observed in 60%, 85%, and 90% of the regions assayed. These effects were rapidly reversible, since in the recovery group, LCGU returned to near control values in the majority of the brain areas. Although all of the anatomofunctional systems (sensorimotor, extrapyramidal, limbic, and reticular) were involved, forebrain structures showed a greater sensitivity to the depressant action of propofol than did hindbrain regions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of continuous epidural bupivacaine infusion plus either continuous epidural infusion or patient-controlled epidural injection of fentanyl for postoperative analgesia.

We compared the postoperative epidural analgesia provided by the continuous epidural infusion of bupivacaine supplemented with patient-controlled injection (PCA) of epidural fentanyl with that provided by a continuous infusion of bupivacaine supplemented with a continuous epidural infusion of fentanyl. Our patient population comprised 16 ASA physical status I or II patients undergoing laparotomy with a midline incision under general anesthesia combined with bupivacaine epidural analgesia. Post-operatively, a continuous epidural infusion of bupivacaine (0.1 mg.kg-1.h-1) was combined with epidural fentanyl given by either (a) PCA (15-micrograms bolus with a lockout interval of 12 min, n = 8) or (b) continuous infusion (1 microgram.kg-1.h-1, n = 8). In the case of inadequate pain relief in the latter group, the fentanyl infusion rate was increased by 10 micrograms/h. Analgesia evaluated by a visual analogue pain score and by a verbal pain score was similarly effective in both groups. The sedation score was also similar in both groups. The total dose of epidural fentanyl administered during the first 24 h was significantly lower in the PCA group than in the continuous infusion group (405 +/- 110 micrograms vs 1600 +/- 245 micrograms, P less than 0.001). The dose of fentanyl given during each 4-h interval ranged between 40 and 160 micrograms in the PCA group and 251 and 292 micrograms in the continuous infusion group. Clinically detectable respiratory depression was not observed in either group. In conclusion, epidural administration of 0.1 mg.kg-1.h-1 bupivacaine combined with fentanyl provides effective postoperative analgesia with a total dose of fentanyl required that is lower when fentanyl is administered by epidural PCA rather than by continuous epidural infusion.     

右美托咪啶混合舒芬太尼用于剖宫产术后病人自控静脉镇痛的效果

目的 评价右美托咪啶混合舒芬太尼用于剖宫产术后病人自控静脉镇痛(PCIA)的效果.方法 择期脊椎-硬膜外麻醉下行剖宫产术病人120例,年龄18～40岁,身高155～170 cm,采用随机数字表法,将病人随机分为3组(n=40):Ⅰ组于胎儿娩出后静脉注射生理盐水20 ml,术后采用舒芬太尼进行PCIA(背景输注速率0.015μg·kg-1·h-1,PCA量0.023 μg/kg,锁定时间8 min);Ⅱ组于胎儿娩出后静脉注射右美托咪啶0.5 μg/kg,术后PCIA同Ⅰ组;Ⅲ组术中处理同Ⅱ组,术后采用舒芬太尼混合右美托咪啶进行PCIA(舒芬太尼背景输注速率0.015 μg·kg-1·h-1,右美托咪啶背景输注速率0.045 μg·kg-1·h-1,舒芬太尼PCA量0.023 μg/kg、右美托咪啶PCA量0.07 μg/kg,锁定时间8 min).于麻醉前和输注右美托咪啶1 h时测定痛阈和耐痛阈,于术后4、8、24 h时记录VAS评分、警觉/镇静评分和舒芬太尼用量,于术后3 h时记录恶露排出量,记录泌乳发动时间,于术后24 h时行病人满意度评价,于麻醉前和输注右美托咪啶1 h、术后24 h时采集外周静脉血样,采用双抗体夹心酶联免疫吸附法测定血清皮质醇浓度,记录不良反应的发生情况.结果 与Ⅰ组比较,Ⅱ组和Ⅲ组输注右美托眯啶1 h时痛阈和耐痛阈升高,Ⅲ组术后4、8、24 h时VAS评分和舒芬太尼用量降低,病人满意度升高(P＜0.05);与Ⅱ组比较,Ⅲ组术后4、8、24 h时VAS评分和舒芬太尼用量降低,Ⅲ组病人满意度升高(P＜0.05);其余指标组间比较差异无统计学意义(P＞0.05).结论 右美托咪啶混合舒芬太尼用于剖宫产术后PCIA的效果优于单独应用舒芬太尼.

Abstract：

Objective To evaluate the efficacy of dexmedetomidine combined with sufentanil for patientcontrolled intravenous analgesia (PCIA) after caeserean section. Methods One hundred and twenty parturients aged 18-40 yr undergoing caeserean section under spinal-epidural anesthesia were randomly assigned to one of 3 groups( n=40 each):group Ⅰ , group Ⅱ and group Ⅲ . During operation as soon as the baby was bom a bolus of dexmedetomidine 0.5 μg/kg was given iv in Ⅱ and Ⅲ groups while in group Ⅰ normal saline (NS) was given instead. Ⅰ and Ⅱ groups received PCIA with sufentanil (background infusion 0.015 μg·kg-1·h-1;bolus dose 0.023 μg/kg;lockout interval 8 min). Group Ⅲ received PCIA with sufentanil + dexmedetomidine (background infusion sufentanil 0.015 μg·kg-1 ·h-1 + dexmedetomidine 0.045 μg·kg· h-1;bolus dose sufentanil 0.023 μg/kg + dexmedetomidine 0.07 μg/kg;lockout interval 8 min) . Pain threshold and pain tolerance threshold were measured before caeserean section and 1 h after bolus dose of dexmedetomidine or NS. VAS, OAA/S and satisfaction scores and sufentanil consumption were recorded at 4, 8 and 24 h after operation.Blood samples were obtained before anesthesia,1 h after bolus injection of dexmedetomidine, and 24 h after operation for determination of serumcortisol concentration. Results Pain threshold and pain tolerance threshold at 1 h after bolus injection of dexmedetomidine were significantly increased as compared with the baseline before anesthesia in Ⅱ and Ⅲ groups and were significantly higher in Ⅱ and Ⅲ groups than in group Ⅰ . VAS scores and the consumption of sufentanil were significantly lower while the satisfactory score was significantly higher in group Ⅲ than in Ⅰ and Ⅱ groups. Serum cortisol concentrations were significantly increased at 1 h after iv dexmedetomidine or NS injection as compared with the baseline before anesthesia in all 3 groups, but there was no significant difference in serum cortisol levels among the 3 groups. Conclusion Addition of dexmedetomidine to sufentanil for PCIA can significantly reduce the consumption of sufentanil and improve parturient's satisfaction.     

右美托咪啶与丙泊酚用于小儿心导管术麻醉维持的比较

目的 右美托咪啶(dexmedetomidine,DEX)为α2肾上腺素受体激动剂,目前较多研究正在探索其用于小儿麻醉的可行性.研究比较了DEX与丙泊酚用于小儿心导管术的维持麻醉的药效学.方法 选择40例ASA Ⅱ～Ⅲ级、22月～67月、体重11 kg～28 kg导管介入治疗患儿,进入导管室后静注氯胺酮2 mg/kg,...     

Total intravenous anaesthesia with propofol or etomidate

In combination with fentanyl, propofol was compared with etomidate for total intravenous anaesthesia in 21 women (ASA Grades I-II) admitted for elective hysterectomy. They received either propofol (bolus 1.5 mg kg-1, infusion 9 mg kg-1 h-1 for 10 min thereafter 6 mg kg-1 h-1) or etomidate (bolus 0.10 mg kg-1, infusion 3 mg kg-1 h-1 reduced to 0.6 mg kg-1 h-1). Fentanyl 10 micrograms kg-1 was given for induction followed by an infusion of 30 micrograms kg-1 h-1 for 10 min reduced to 6 micrograms kg-1 h-1 for the first hour and successively reduced over time. Induction was smooth and maintenance easy to manage in both groups. There was no difference in time from end of infusion until extubation, but the time until the patients could report their date of birth was significantly shorter in the propofol group. Nausea and vomiting were more pronounced in the etomidate group, and mental side-effects were only seen after etomidate. After 3 months, more patients in the etomidate group complained of reduced power of concentration. We conclude that total intravenous anaesthesia with either propofol or etomidate is equally easy to manage, but in the recovery situation propofol was advantageous in time and quality.     

Thiopental pharmacokinetics under conditions of long-term infusion

Thiopental was used in long-term infusion (3-4.5 mg . kg-1 . h-1 during 4-8 days) to protect the brain from injury following trauma. Thiopental plasma concentrations were measured during infusion (48 patients) and after infusion (14 patients) to determine the kinetics of the drug in continuous infusion. All mean values were mean +/- SD. Steady state concentrations (Css) were 31.8 +/- 10.7 mg/l for an infusion rate of 3.05 +/- 0.37 mg . kg-1 . h-1 and 48.9 +/- 14.6 mg/l for a rate of 4.2 +/- 0.3 mg . kg-1 . h-1. Corresponding steady state clearance decreased when Css increased, indicating possible saturation of the metabolic enzymatic system. Michaelis-Menten kinetics were confirmed by postinfusion data that give, for higher Css, a nonlinear decay of log C versus time. First-order kinetics were only obtained with Css below 30 mg/l. The maximum rate of elimination (Vm) was 1.76 +/- 1.15 mg . l-1 . h-1 (n = 11), and the Michaelis constant (Km) was 26.7 +/- 22.9 mg/l (n = 11). Hepatic enzyme saturation was between 35 and 85%. The volume of distribution at steady state was 4.35 +/- 1.83 l/kg (n = 11). Apparent half-lives of elimination were between 18 and 36 h at the end of infusion, and predicted terminal half-lives were 10.15 +/- 5.43 h (n = 11). Phases of burst-suppression were observed on electroencephalographic traces for concentrations greater than 40 mg/l. The authors' results suggest that a continuous infusion at a dose of 4 mg . kg-1 . h-1 induces EEG changes consistent with a near-maximum reduction in cerebral metabolism. Because of the thiopental Michaelis-Menten kinetics at doses above 4 mg . kg-1 . h-1, the authors suggest that thiopental plasma concentrations be measured and/or the drug effect be measured with the EEG to prevent excessive thiopental overdosage, causing a prolonged recovery time.     

Evaluation of the usefulness of intrathecal bupivacaine infusion for analgesia after hip and knee arthroplasty

Spinal anaesthesia in 47 ASA I-III patients was induced with 0.5% bupivacaine 2 ml via a 28-gauge spinal catheter (L3-4 interspace) and 0.5-ml increments were given if needed before or during hip or knee arthroplasty. Intrathecal 24-h infusions consisted of 0.5% bupivacaine 0.4 ml h-1 (2 mg h-1) (n = 12), 0.5% bupivacaine 0.2 ml h-1 (1 mg h-1) (n = 12) or saline (n = 11) (12 exclusions). Patients received oxycodone 0.1-0.14 mg kg-1 i.m. for rescue analgesia. Infusion of bupivacaine 2 mg h-1 provided significantly better postoperative analgesia (19 oxycodone doses per group in 24 h) compared with bupivacaine 1 mg h-1 (36 doses of oxycodone per group) and saline (52 doses per group) (P < 0.05). Five patients in the bupivacaine 2-mg h-1 group and none in the other groups had measurable sensory block 24 h after the infusion was started. Three patients in the bupivacaine 2-mg h-1 group, two with concomitant arterial hypotension, and one patient in the bupivacaine 1-mg h-1 group experienced an increase in block on the ward. The incidence of nausea and vomiting was similar in all groups. Although an effective analgesic, intrathecal infusion of bupivacaine 2 mg h-1 cannot be recommended for routine pain relief because of the risk of increasing spinal block. Technical problems (19%) also reduced the overall efficacy of the continuous intrathecal analgesic regimen.      

Continuous epidural butorphanol relieves pruritus associated with epidural morphine infusions in children

We examined the efficacy of epidural butorphanol to either prevent or relieve pruritus associated with epidural morphine infusion in children. Forty-six children were randomized to receive either epidural morphine (M) or epidural M with butorphanol (B) for postoperative analgesia. They received bupivacaine and either M 50 microg.kg-1 or the same dose of M plus B 10 microg.kg-1. Following surgery, a continuous infusion of 0.1% bupivacaine with either M 20 microg.ml-1 or M 20 microg.ml-1 + B 4 microg.ml-1 was given at a rate of 0.3 ml.kg-1.h-1. Pain scores and pruritus scores were recorded every 4 h during epidural infusion. Subjects with a pruritus score=2 received diphenhydramine 0.5 mg.kg-1 i.v. and were switched to an alternate epidural infusion; subjects receiving M (group M) were switched to M+B while subjects receiving M+B (group B) were switched to hydromorphone (H) 4 microg.ml-1. There was no difference in the initial incidence of pruritus (group M 11/18; group B 13/28). No subject in group M required a second change of epidural infusion because of continued pruritus after being switched to M+B; five of 13 subjects in group B continued to experience pruritus after being switched to H and required a second change of epidural infusion or an alternate analgesic modality (P=0.038). The median pruritus score in the first 24 h after changing epidural infusions was 0 in subjects in group MDelta (changed from M to M+B) and 1 in subjects in group BDelta (changed from M+B to H; P=0.012). While the median sedation score in the first 24 h was 1 in both groups, there was a greater incidence of sedation scores of 2 in group B than group M (28% vs 12.3%; P=0.021). B 10 microg.kg-1 was not effective in preventing pruritus associated with bolus epidural administration of M 50 microg.kg-1 in children. B 1.2 microg.kg-1. h-1 was effective in relieving pruritus associated with continuous epidural infusion of M 6 microg.kg-1.h-1.     

静注利多卡因对行腹腔镜胆总管探查术患者镇痛和肠蠕动的影响

目的观察静脉输注利多卡因对行腹腔镜胆管探查术患者术后镇痛和肠功能的影响。方法择期腹腔镜胆总管探查术患者80例,年龄23～55岁,ASAⅠ或Ⅱ级,随机均分为治疗组和对照组。治疗组诱导期静注利多卡因1.5mg/kg,术中以2mg·kg-1·h-1持续输注,术后24h内改为1.2mg·kg-1·h-1持续静脉输注。对照组给予等剂量的生理盐水。记录两组患者术中七氟醚总量,术后抽取静脉血检测利多卡因浓度并记录术后2h(T1)、4h(T2)、8h(T3)、12h(T4)、24h(T5)、术后第2天(T6)和第3天(T7)两组VAS评分以及术后首次排气、排便时间,住院天数和恶心呕吐发生率。结果与对照组比较,T1～T5时治疗组VAS评分均明显下降(P<0.05);治疗组术中七氟醚总量降低,术后首次排气时间、排便时间以及住院天数均缩短(P<0.05)。结论小剂量利多卡因静注可促进腹腔镜胆管探查术患者肠蠕动恢复,缩短患者住院时间,有利于术后康复。     

L-644,711, a novel anion transport inhibitor, increases isoflurane MAC in rats.

The effect of the anion transport inhibitor L-644,711 on isoflurane MAC was determined in rats (n = 24). After baseline MAC determination, each rat received one of the following drug protocols: (a) control, vehicle only; (b) L-644,711IT, a 3-mg/kg intrathecal bolus of L-644,711 followed by an infusion at 1.5 mg.kg-1.h-1; or (c) L-644,711IV, a 6-mg/kg intravenous bolus of L-644,711 followed by an infusion at 3 mg.kg-1.h-1. MAC was again determined. The baseline isoflurane MAC was not different between groups (control, 1.52% +/- 0.15%; L-644,711IT, 1.51% +/- 0.24%; L-644,711IV, 1.54% +/- 0.13% [mean +/- SD]). After drug or vehicle administration, isoflurane MAC was larger for the L-644,711IT group (2.25% +/- 0.17%) versus the control (1.38% +/- 0.13%) and L-644,711IV (1.39% +/- 0.15%) groups (P less than 0.05). These data are consistent with the hypothesis that isoflurane anesthesia is influenced by anion channels and that blocking these channels may reduce the pharmacodynamic potency of isoflurane.     

Epidural Clonidine Used as the Sole Analgesic Agent during and after Abdominal Surgery: A Dose-Response Study

Background: Many studies have shown the beneficial effect of epidural clonidine in postoperative pain management. In these studies, the patients received local anesthetics, opioids, or both in combination with clonidine. Due to the interactive potentiation of those drugs, the importance of the intrinsic analgesic properties of the alpha2 -adrenoceptor agonist is difficult to establish. The authors investigated the analgesic potency of epidural clonidine when used as the sole analgesic agent during and after major abdominal surgery.

Methods: Fifty young adult patients undergoing intestinal surgery under general anesthesia with propofol were studied. At induction, the patients received epidurally either an initial dose of 2 micro gram/kg clonidine followed by an infusion of 0.5 micro gram [center dot] kg-1 [center dot] h-1 (group 1, n = 10) or 4 micro gram/kg followed by 1 micro gram [center dot] kg-1 [center dot] h-1 (group 2, n = 20) or 8 micro gram [center dot] kg-1 [center dot] h-1 followed by an infusion of 2 micro gram [center dot] kg-1 [center dot] h-1 (group 3, n = 20). During the operation, increases in arterial blood pressure or heart rate that did not respond to a propofol bolus (0.5 mg/kg) were treated with a bolus of intravenous lidocaine (1 mg/kg). Three successive injections were allowed. When baseline values were not restored, opioids were added and the patient was removed from the study. After operation, the clonidine infusions were maintained for 12 h. During this period and at every 30 min, sedation scores and visual analog scale values at rest and at cough were noted. In case of subjective scores up to 5 cm at rest or up to 8 cm at cough, the patients were given access to a patient-controlled analgesia device that delivered epidural bupivacaine. The end point of the study was reached once the patient activated the analgesic delivery button.

Results: During surgery, 60% of patients in group 1 compared with 33% of patients in group 2 and only 5% of patients in group 3 were removed from the study protocol because of inadequate anesthesia (P < 0.05). After operation, epidural clonidine provided complete analgesia lasting 30 +/- 21 min in group 1 compared with 251 + 237 min in group 2 or 369 +/- 256 min in group 3 (P < 0.05 for group 1 vs. groups 2 and 3 and group 2 vs. group 3).     

Plasma bupivacaine concentrations associated with continuous extradural infusions in babies

The maximum recommended dose for extradural infusions of bupivacaine in children older than 1 month is 0.5 mg kg-1 h-1 but there are few specific reports of the associated blood concentrations during infusions in babies. Toxic symptoms can occur in children at plasma concentrations of bupivacaine as low as 2 micrograms ml-1. We attempted to measure venous plasma concentrations of total and free bupivacaine in babies aged 3-12 months during extradural infusions given at a rate commonly used in our hospital. We studied eight babies (mean age 33 weeks; mean weight 7.8 kg). After a mean initial dose of 1.2 mg kg-1 (range 1.1-1.3 mg kg-1), bupivacaine was infused at a mean rate of 0.38 (0.36-0.39) mg kg-1 h-1 for a mean of 31 (4-44) h. Blood was obtained at 4, 8, 16, 24, 32 and 40 h after starting the infusion and plasma separated by centrifugation. Total plasma bupivacaine concentration was measured using high pressure liquid chromatography (HPLC). Plasma concentrations of total bupivacaine were mostly less than 2 micrograms ml-1. One baby had a concentration of 2.02 micrograms ml-1 at 32 h and showed clear evidence of accumulation of bupivacaine. Babies can accumulate bupivacaine and achieve plasma concentrations above the threshold for toxic side effects, despite infusion rates below the currently accepted maximum. The samples size in our study was small but we believe an extradural infusion rate of 0.375 mg kg-1 h-1 is probably an absolute maximum for babies younger than 12 months.      

Thiopental sodium by single bolus dose compared to infusion for cerebral protection during cardiopulmonary bypass

The authors previously demonstrated that thiopental sodium infused throughout cardiopulmonary bypass (CPB) considerably reduced persistent but not transient neuropsychiatric complications after open-chamber cardiac operations. Based on the probability that emboli released at the time of aortic declamping cause most postoperative central nervous system (CNS) dysfunction, this study was designed to test whether administration of a single bolus dose of thiopental before aortic declamping provided cerebral protection equal to that of infusion throughout bypass as well as a decrease in unwanted side effects. One hundred adult patients undergoing open-chamber cardiac operations with CPB received either thiopental sodium by infusion throughout CPB (n = 52) or thiopental sodium 15 mg/kg by bolus before aortic declamping (n = 48). In 90% of the patients, thiopental sodium 15 mg/kg produced electroencephalographic (EEG) burst suppression, with more than 60 seconds between bursts. Postoperative CNS dysfunction occurred in 3 (6%) of the infusion group patients (thiopental sodium 36 +/- 10 mg/kg) and 2 (4%) of the bolus group patients (thiopental sodium 16 +/- 2 mg/kg). CNS dysfunction persisting to the tenth postoperative day occurred in only one patient, who was in the infusion group. Requirements for inotropic support on separation from CPB did not differ between groups, but average time to extubation was 2.7 hours shorter in the bolus group. The authors conclude that thiopental sodium 15 mg/kg given as a single bolus immediately before aortic declamping without the need for EEG monitoring provided the same brain protection as larger doses given by infusion titrated to burst suppression, but it did not reduce the need for inotropic support during separation from CPB.     

The effect of amrinone on recovery from severe bupivacaine intoxication in pigs.

Cardiovascular collapse following intravascular bupivacaine may be resistant to treatment. The effect of amrinone on recovery from bupivacaine-induced severe cardiovascular depression was evaluated in 20 pigs (13-26 kg) in a placebo-controlled randomized double-blind study. Under 0.7% isoflurane anesthesia at FIO2 0.21, 0.5% bupivacaine 2 mg.kg-1.min-1 was infused until mean arterial pressure was 40% of the baseline. Cardiac output and heart rate decreased 75% and 50% from the baseline, respectively. The total dose of bupivacaine was 17 +/- 6 (SD) mg.kg-1 in the control and 19 +/- 5 mg.kg-1 in the amrinone group, resulting in mean plasma concentrations of 42 +/- 6 and 53 +/- 19 micrograms.ml-1, respectively. A bolus of amrinone 4 mg.kg-1 (n = 10) was given immediately after cardiovascular depression, followed by an infusion of 0.6 mg.kg-1.min-1. The control animals received corresponding volumes of physiologic saline (n = 10). After cardiovascular depression, the lungs were ventilated with FIO2 1.0 without anaesthetics or sympathomimetic support. Electric activity of the heart ceased in all control animals in 3.9 +/- 2 min after cardiovascular depression despite atropine and external cardiac compression. All animals in the control group and 5 of 10 animals in the amrinone group were given atropine (P less than 0.01). The animals receiving amrinone survived without cardiac compression (P less than 0.0001). During bupivacaine infusion, all animals developed burst suppression in the electroencephalogram. At the time of cardiovascular depression, in 8 of 10 control and in 6 of 10 amrinone animals, the electroencephalogram was isoelectric.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intravenous Magnesium Sulfate Administration Reduces Propofol Infusion Requirements during Maintenance of Propofol-N2O Anesthesia: Part I: Comparing Propofol Requirements According to Hemodynamic Responses: Part II: Comparing Bispectral Index in Control and Magnesium Groups

Background: The authors investigated whether an intravenous administration of magnesium sulfate reduces propofol infusion requirements during maintenance of propofol-N2O anesthesia.

Methods: Part I study: 54 patients undergoing total abdominal hysterectomy were randomly divided into two groups (n = 27 per group). The patients in the control group received 0.9% sodium chloride solution, whereas the patients in the magnesium group received magnesium (50 mg/kg as a bolus, then 8 mg [middle dot] kg-1 [middle dot] h-1). To maintain mean arterial blood pressure (MAP) and heart rate (HR) at baseline value, the propofol infusion rate was changed when the MAP or the HR changed. The amount of propofol infused excluding the bolus dosage was divided by patient's body weight and total infusion time. Part II study: Another 20 patients were randomly divided into two groups (n = 10 per group). When the MAP and HR had been maintained at baseline value and the propofol infusion rate had been maintained at 80 [mu]g [middle dot] kg-1 [middle dot] min-1 (magnesium group) and 160 [mu]g [middle dot] kg-1 [middle dot] min-1 (control group), bispectral index (BIS) values were measured.

Results: Part I: The mean propofol infusion rate in the magnesium group (81.81 +/- 13.09 [mu]g [middle dot] kg-1 [middle dot] min-1) was significantly less than in the control group (167.57 +/- 47.27). Part II: BIS values in the control group (40.70 +/- 3.89) were significantly less than those in the magnesium group (57.80 +/- 7.32).     

Recovery characteristics using isoflurane or propofol for maintenance of anaesthesia: a double-blind controlled trial

We studied 114 female patients (ASA 1 or 2) who were within 20% of ideal body weight and who were scheduled to undergo gynaecological laparoscopy which required supplementation with an opioid (groups IA and PA), or dental procedures which did not require opioid supplementation (groups IO and PO). A computerised package of psychomotor tests was performed before surgery. Anaesthesia was induced with propofol 2.5 mg.kg-1 and all patients received atracurium 0.3 mg.kg-1 and 67% nitrous oxide in oxygen. Patients in group IA received isoflurane 1% (inspired), and alfentanil 10 micrograms.kg-1 as a bolus and 10 micrograms.kg-1.h-1 as an infusion. Patients in group PA received propofol 9 mg.kg-1.h-1 as an infusion, decreasing to 6 mg.kg-1.h-1 after 15 min, together with alfentanil 10 micrograms.kg-1.h-1. Patients in groups IO and PO received isoflurane and propofol in the regimens described for groups IA and PA, but without alfentanil. Recovery was assessed by a blinded observer who recorded times to awakening (eye opening) and orientation (giving date of birth), and who repeated the psychomotor tests at 1, 3 and 5 h. Linear analogue scales of mood, nausea and pain were obtained and other side effects were noted in the succeeding 48 h. A matched control group of 25 females (who were not anaesthetised) underwent psychomotor testing on four occasions in order to assess the 'learning effect' of repeated recovery testing. The analysis of recovery tests did not assume a normal distribution.(ABSTRACT TRUNCATED AT 250 WORDS)     

Continuous epidural infusion of bupivacaine and morphine for postoperative pain relief

Forty-five patients admitted to the intensive care unit following thoracic or abdominal surgery received continuous epidural infusion of bupivacaine and morphine for 48 hours. During the first 10 hours, the patients received 0.25% bupivacaine solution with 0.005% morphine at the rate of 4 ml.h-1, and bupivacaine concentration was decreased to 0.125% with the same morphine concentration. The mean infusion rate of bupivacaine during 48 hours was 0.12 +/- 0.03 (SD) mg.kg-1.h-1 and that of morphine was 4.0 +/- 1.0 micrograms.kg-1.h-1. Thirty-one patients (69%) complained no pain on deep breathing at 24 hours and 33 patients (74%) required no other type of analgesics during this study. The mean plasma bupivacaine concentration was 0.6 +/- 0.3 microgram.ml-1 at 48 hours. Hypotension defined as systolic arterial pressure below 90 mmHg and itching were observed in 15 patients (33%), but no other severe side effects were noted. Continuous epidural infusion of bupivacaine and morphine mixture for 48 hours postoperatively provided effective pain relief with a low incidence of side effects.