Cortisol deficiency in metomidate anesthetized bacteremic pigs: results in circulatory failure — beneficial effect of cortisol substitution

Etomidate and the closely related metomidate are known to inhibit cortisol synthesis. We studied the influence of metomidate on hemodynamic performance and survival time of bacteremic pigs. Thirty pigs, 30.2 +/- 0.8 kg, were anesthetized with intravenous metomidate (2.5 mg.kg-1.h-1) plus ketamine (3.0 mg.kg-1.h-1), and were then mechanically ventilated. The animals were randomly allocated to three groups of 10 pigs each. Group A received an infusion of live Pseudomonas aeruginosa bacteria (2.5.10(9).kg-1.h-1 organisms until death), Group B additionally received a bolus of 1 mg.kg-1 cortisol (followed by an infusion of 0.1 mg.kg-1.h-1) starting 1 h prior to the bacterial infusion, and Group C served as anesthesia control without receiving bacteria or cortisol. The experiments in Group C were terminated after 10 h. In Group A the cortisol level was severely suppressed from the very beginning. The animals died of circulatory failure after 4.3 +/- 0.4 h. In contrast, Group B exhibited fairly stable hemodynamics, but the animals died due to pulmonary edema after 11.1 +/- 1.3 h. Cortisol deficiency in metomidate anesthetized pigs facilitates the development of circulatory failure in the course of Pseudomonas bacteremia, which does not occur if cortisol is infused to reconstitute a physiological level. However, this cortisol substitution did not prevent the development of pulmonary edema caused by Pseudomonas aeruginosa. Possible mechanisms of the deleterious effect of cortisol deficiency and implications in regard to the clinical use of metomidate/etomidate are discussed.     

The changes in hemodynamics and dose requirements in total intravenous anesthesia using propofol and buprenorphine

A retrospective study was performed to evaluate the changes in hemodynamics and dose requirements in total intravenous anesthesia (TIVA) using propofol and buprenorphine without (Group S: spinal surgery (3-6 h), n = 8, 28-79 Y) or with (Group A: abdominal surgery (5-10 h), n = 15, 36-83 Y) epidural anesthesia. All patients were premedicated with midazolam i.m. (2-5 mg). Anesthesia was maintained with a single dose of buprenorphine (Group S: 1.9 +/- 0.4 micrograms.kg-1, Group A: 2.0 +/- 0.5 micrograms.kg-1), propofol infusion and vecuronium with 40% oxygen in air. Group A was supplemented with continuous epidural anesthesia using 2% mepivacaine. In Group A, mean arterial pressure (MAP) and heart rate remained stable after the start of surgery. However, in Group S, 2 hours after the start of surgery MAP increased (P < 0.05) and remained elevated (P < 0.05) at higher levels than those in Group A. The maintenance dose of propofol in Group A (4.0 +/- 1.1 mg.kg-1.h-1) was significantly smaller than in Group S (6.5 +/- 0.9 mg.kg-1.h-1). In both groups, infusion rates of propofol were unchanged from 1 hour after the start to the end of surgery. Infusion rates of mepivacaine (5.2 +/- 0.9 ml.h-1) were unchanged following the increase 2 hours after the start of surgery. Awakening times were within 25 min (Group S 11.3 +/- 7.2 min vs Group A 14.7 +/- 7.3 min). There was no awareness during anesthesia in either group. The results suggest that additional continuous epidural anesthesia in TIVA would be useful to reduce propofol dose, to stabilize hemodynamic state and to obtain rapid recovery in anesthesia of long duration.     

The effect of ketamine on clinical endpoints of hypnosis and EEG variables during propofol infusion

BACKGROUND: We studied the effect of variable doses of ketamine on the endpoints of hypnosis, e.g., unresponsiveness to verbal commands (UVC), loss of eyelash reflex (LER), and inhibition of body movement response with or without sneezing to nasal membrane stimulation (INBMR), and processed EEG variables, e.g., bispectral index (BIS), 95% spectral edge frequency (SEF) and median frequency (MF) during propofol infusion. METHODS: Forty-eight patients received either propofol infusion, 30 mg.kg-1.h-1 (Group P; n = 12) or ketamine bolus, 0.25, 0.5 or 0.75 mg i.v., followed by propofol infusion, 30 mg.kg-1.h-1 + variable dose ketamine infusion, 0.25, 0.5 or 0.75 mg.kg-1.h-1 (Groups PK0.25, PK0.5 and PK0.75; n = 12 each) until UVC, LER and INBMR. BIS, 95% SEF and MF values were monitored and recorded at the endpoints of hypnosis. Propofol and ketamine concentrations were measured at INBMR. RESULTS: Propofol infusion, 30 mg.kg-1.h-1, induced UVC, LER and INBMR at BIS: 65 +/- 2, 63 +/- 9 and 33 +/- 7; 95% SEF: 17 +/- 3, 17 +/- 4 and 14 +/- 3; and MF values of 5 +/- 2, 5 +/- 3 and 3 +/- 2, respectively. With adjunctive ketamine (Groups PK0.5 and PK0.75), the hypnotic endpoints were achieved at higher BIS and 95% SEF values and lower propofol doses and concentrations as compared to Groups P and PK0.25 (9.9 +/- 5.8 and 9.4 +/- 3.4 vs. 13.4 +/- 4.5 and 14 +/- 5.8 micrograms.ml-1). CONCLUSIONS: Our results suggest additive interaction between propofol and ketamine (Groups PK0.5 and PK0.75) for achieving the hypnotic endpoints; however, ketamine did not depress the EEG variables in proportion to its hypnotic effect. The paradoxically higher BIS and 95% SEF values at the hypnotic endpoints may be due to lower propofol concentrations and/or no effect of ketamine on the EEG variables.     

Choice of anesthetic alters the circulatory shock pattern as gauged by conscious rat endotoxemia

A standardized rat endotoxin shock model was used to assess the differential effects of four commonly used anesthetics upon hemodynamics before and during endotoxin shock. Forty-nine male Sprague-Dawley rats weighing 307 +/- 4 g were divided into five groups:freely-moving conscious, enflurane (2%), isoflurane (1.4%), pentobarbital (6 mg.kg-1.h-1 i.v.), and ketamine (45 mg.kg-1.h-1 i.v.). Anesthetic doses were chosen as 1.0 MAC equivalent. Anesthetized rats were intubated and ventilated with oxygen. The right carotid artery was cannulated with a thermocouple-catheter for aortic blood pressure, heart rate, and thermodilution cardiac output measurements. The right jugular vein was cannulated for measurement of central venous pressure and for i.v. injections. Data were collected over a 30-min baseline period and for 4 h after an i.v. bolus of endotoxin (40 mg.kg-1, LD100 within 24 h). Gross small intestinal pathology was rated on a 0-4 scale. Anesthetic effects were judged in terms of significant deviations from the awake data on each parameter. Despite differing patterns, total deviations were similar for enflurane, ketamine, and pentobarbital, although the latter drug was the least preferable due to particularly high systemic vascular resistance. Significantly less hemorrhagic small intestinal pathology occurred with enflurane. Ketamine offered no advantage over the inhalation anesthetics. Among the four anesthetics tested, results were closest to the awake pattern with isoflurane anesthesia, thus making it the logical choice for hemodynamic studies in experimental shock research.     

Differential Protective Effects of Volatile Anesthetics against Renal Ischemia-Reperfusion Injury In Vivo

Background: Volatile anesthetics protect against cardiac ischemia-reperfusion injury via adenosine triphosphate-dependent potassium channel activation. The authors questioned whether volatile anesthetics can also protect against renal ischemia-reperfusion injury and, if so, whether cellular adenosine triphosphate-dependent potassium channels, antiinflammatory effects of volatile anesthetics, or both are involved.

Methods: Rats were anesthetized with equipotent doses of volatile anesthetics (desflurane, halothane, isoflurane, or sevoflurane) or injectable anesthetics (pentobarbital or ketamine) and subjected to 45 min of renal ischemia and 3 h of reperfusion during anesthesia.

Results: Rats treated with volatile anesthetics had lower plasma creatinine and reduced renal necrosis 24-72 h after injury compared with rats anesthetized with pentobarbital or ketamine. Twenty-four hours after injury, sevoflurane-, isoflurane-, or halothane-treated rats had creatinine (+/- SD) of 2.3 +/- 0.7 mg/dl (n = 12), 1.8 +/- 0.5 mg/dl (n = 6), and 2.4 +/- 1.2 mg/dl (n = 6), respectively, compared with rats treated with pentobarbital (5.8 +/- 1.2 mg/dl, n = 9) or ketamine (4.6 +/- 1.2 mg/dl, n = 8). Among the volatile anesthetics, desflurane demonstrated the least reduction in plasma creatinine after 24 h (4.1 +/- 0.8 mg/dl, n = 12). Renal cortices from volatile anesthetic-treated rats demonstrated reduced expression of intercellular adhesion molecule 1 protein and messenger RNA as well as messenger RNAs encoding proinflammatory cytokines and chemokines. Volatile anesthetic treatment reduced renal cortex myeloperoxidase activity and reduced nuclear translocation of proinflammatory nuclear factor [kappa]B. Adenosine triphosphate-dependent potassium channels are not involved in sevoflurane-mediated renal protection because glibenclamide did not block renal protection (creatinine: 2.4 +/- 0.4 mg/dl, n = 3).     

Interaction of fentanyl and pentobarbital on peripheral and cerebral hemodynamics in newborn lambs

The effects of 3.0 mg.kg-1 fentanyl on cerebral and peripheral hemodynamics alone and when combined with subanesthetic doses of pentobarbital (4.0 mg.kg-1), were studied in 11 unanesthetized, newborn lambs, in whom catheters had been previously inserted. After a control period, drugs were administered at 20-min intervals by intravenous bolus injection. Group 1 animals (n = 5) received fentanyl, pentobarbital, and naloxone (0.01 mg.kg-1), whereas Group 2 animals (n = 6) had the order of fentanyl and pentobarbital reversed. All animals responded to pain (withdrawal to tail clamping) and appeared conscious (eyes open, alert to sound) when either fentanyl or barbiturate was given alone. The combination of drugs, however, produced complete unresponsiveness. All of these effects were reversed by naloxone. Cardiac output did not change after either fentanyl or pentobarbital was administered individually but decreased significantly (29% in Group 1, 21% in Group 2) after administration of the combination of both. Mean arterial pressure and heart rate were unchanged. Cerebral blood flow, oxygen (O2) transport, and O2 consumption did not change after either administration of fentanyl or pentobarbital alone but decreased significantly after both (22%, 30%, 19%, respectively, in Group 1 and 35%, 40%, 38%, respectively, in Group 2). The decrease in cerebral O2 transport nearly paralleled the decrease in cerebral O2 consumption such that the ratio, the fractional O2 extraction, increased slightly. Fentanyl decreased kidney blood flow alone (24%) and in combination with pentobarbital (25%), although pentobarbital did so only when combined with fentanyl.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prophylactic and Delayed Treatment with High-Dose Methylprednisolone in a Porcine Model of Early ARDS Induced by Endotoxaemia

The effects of prophylactic and delayed treatment with high-dose methylprednisolone were evaluated in a porcine model of early adult respiratory distress syndrome induced by endotoxaemia. Spontaneously breathing pigs under ketamine anaesthesia were infused i.v. with E. coli endotoxin (10 micrograms . h-1 . kg-1) over 6h. Twenty animals received endotoxin without treatment. Eight animals were pretreated with methylprednisolone i.v., 60 mg . kg-1, followed by an i.v. infusion at a rate of 10 mg . h-1 . kg-1. Ten animals received the same dosage of methylprednisolone beginning 2 h after the start of endotoxin infusion. Pretreatment with methylprednisolone prevented the endotoxin-induced impairment in pulmonary gas exchange and the development of pulmonary oedema. The pulmonary hypertension was counteracted. Cardiac output (Qt) and O2 delivery were improved. Mean arterial blood pressure (MAP) increased and was higher than in the untreated endotoxin group. The profound fall in PMN count was inhibited, while the accumulation of these cells in the lung was still substantial. Survival was improved. Delayed methylprednisolone treatment prevented further deterioration in pulmonary gas exchange and tended to restore it towards baseline. The pulmonary oedema and pulmonary hypertension were reduced. Qt and O2 delivery did not improve. MAP was higher than in the untreated endotoxin group towards the end of the observation period. The decline in PMN count and the pulmonary accumulation of these cells were not significantly influenced. Survival was improved. These results indicate that high-dose methylprednisolone, when given early in the course of sepsis, might be of clinical value in prevention of the devastating pulmonary and circulatory complications of this disease.     

Differential protective effects of volatile anesthetics against renal ischemia-reperfusion injury in vivo

BACKGROUND: Volatile anesthetics protect against cardiac ischemia-reperfusion injury via adenosine triphosphate-dependent potassium channel activation. The authors questioned whether volatile anesthetics can also protect against renal ischemia-reperfusion injury and, if so, whether cellular adenosine triphosphate-dependent potassium channels, antiinflammatory effects of volatile anesthetics, or both are involved. METHODS: Rats were anesthetized with equipotent doses of volatile anesthetics (desflurane, halothane, isoflurane, or sevoflurane) or injectable anesthetics (pentobarbital or ketamine) and subjected to 45 min of renal ischemia and 3 h of reperfusion during anesthesia. RESULTS: Rats treated with volatile anesthetics had lower plasma creatinine and reduced renal necrosis 24-72 h after injury compared with rats anesthetized with pentobarbital or ketamine. Twenty-four hours after injury, sevoflurane-, isoflurane-, or halothane-treated rats had creatinine (+/- SD) of 2.3 +/- 0.7 mg/dl (n = 12), 1.8 +/- 0.5 mg/dl (n = 6), and 2.4 +/- 1.2 mg/dl (n = 6), respectively, compared with rats treated with pentobarbital (5.8 +/- 1.2 mg/dl, n = 9) or ketamine (4.6 +/- 1.2 mg/dl, n = 8). Among the volatile anesthetics, desflurane demonstrated the least reduction in plasma creatinine after 24 h (4.1 +/- 0.8 mg/dl, n = 12). Renal cortices from volatile anesthetic-treated rats demonstrated reduced expression of intercellular adhesion molecule 1 protein and messenger RNA as well as messenger RNAs encoding proinflammatory cytokines and chemokines. Volatile anesthetic treatment reduced renal cortex myeloperoxidase activity and reduced nuclear translocation of proinflammatory nuclear factor kappaB. Adenosine triphosphate-dependent potassium channels are not involved in sevoflurane-mediated renal protection because glibenclamide did not block renal protection (creatinine: 2.4 +/- 0.4 mg/dl, n = 3). CONCLUSION: Some volatile anesthetics confer profound protection against renal ischemia-reperfusion injury compared with pentobarbital or ketamine anesthesia by attenuating inflammation. These findings may have significant clinical implications for anesthesiologists regarding the choice of volatile anesthetic agents in patients subjected to perioperative renal ischemia.     

Differential effect of oncotic pressure on cerebral and extracerebral water content during cardiopulmonary bypass in rabbits

To study the effect of oncotic pressure on brain water content during cardiopulmonary bypass (CPB), 14 anesthetized New Zealand White rabbits underwent 60 min of nonpulsatile CPB at normothermia. Animals were grouped according to the composition of the circuit priming fluid. Group 1 animals (n = 7) received a priming fluid (6.5% hydroxyethyl starch in 0.72 N NaCl; 323 +/- 13 mOsm/kg [mean +/- SD]) that maintained normal colloid oncotic pressure (COP) during CPB (19.0 +/- 1.5 mmHg). Group 2 animals (n = 7) received a priming fluid (0.9 N NaCl; 324 +/- 23 mOsm/kg) that led to a hypooncotic state (COP = 6.2 +/- 1.2 mmHg). Blood chemistries and hemodynamics were recorded every 15 min during CPB. Animals were given additional priming fluid and sodium bicarbonate during CPB to maintain a circuit flow of 85 ml.kg-1.min-1 and arterial pH greater than 7.35. There were no significant differences between groups 1 and 2 with respect to temperature, central venous pressure, mean arterial pressure, PaO2, PaCO2, plasma sodium concentration, or osmolality at any time during CPB, although osmolality increased in both groups. After 60 min of bypass, animals were killed and organ water contents were determined by wet/dry weight ratios. A separate group of nine similarly prepared and anesthetized animals that did not undergo cannulation or CPB also underwent measurement of plasma chemistries and tissue water contents and served as nonbypass controls (group 3). Brain and kidney water contents were unaffected by oncotic pressure, whereas duodenum and skeletal muscle had significantly greater water content (P = 0.003 and P = 0.008, respectively) after hypooncotic CPB.(ABSTRACT TRUNCATED AT 250 WORDS)     

腰椎内固定术后小剂量氯胺酮对舒芬太尼皮下镇痛的影响

目的评价氯胺酮持续皮下输注对舒芬太尼皮下自控镇痛(PCSA)效应的影响,探讨氯胺酮皮下辅助镇痛的最佳剂量。方法拟行腰椎内固定术患者200例,按照随机双盲原则均分为四组:K1、K2、K3组分别以0.5、1、2μg·kg-1·min-1持续输注氯胺酮,C组输注等量生理盐水。术后均行舒芬太尼皮下自控镇痛。比较术后8、24、48h舒芬太尼用量、静息时VAS评分及不良反应情况。结果术后8～48h,C组静息VAS评分均显著高于其它三组(P<0.05或P<0.01),而K3组显著低于K1、K2(P<0.01);K2、K3组舒芬太尼累积用量显著少于C组和K1组,且K3组显著少于K2组(P<0.01)。术后四组PONV发生率差异无统计学意义。K3组嗜睡发生率显著高于其它三组(P<0.05);K3组有8例(16%)复视,2例(4%)幻觉。结论氯胺酮1μg·kg-1·min-1可增强舒芬太尼PCSA效应,降低舒芬太尼需求量,且不良反应未有明显增加。     

The effects of intravenous anesthetics, propofol, fentanyl and ketamine on the excitability of spinal motoneuron in human: an F-wave study

We have investigated the effects of various intravenous anesthetics, propofol, fentanyl and ketamine on the excitability of spinal motoneuron using an F-wave analysis in a total of 28 patients. All patients were divided randomly into three groups as follows; 2 mg.kg-1 intravenous bolus injection followed by 6 mg.kg-1.h-1 infusion of propofol (P group), 1 mg.kg-1 intravenous bolus injection followed by 1 mg.kg-1.h-1 infusion of ketamine (K group), and 5 micrograms.kg-1 injection of fentanyl (F group). The F-wave was determined after supramaximal electrostimulation of the median nerve in distal point. After establishing stable baseline values, intravenous injection of one of the three anesthetics was applied. The F-wave was recorded 3 minutes after the time of bolus administration. We found a significant (P = 0.018) reduction of the persistence from 77.5 +/- 15.2 to 40.9 +/- 16.8% in the propofol group. On the other hand, no significant changes in F-wave parameters were found in ketamine, or fentanyl group. These results suggested that motoneuron excitability in spinal cord could be inhibited by anesthetic dose of propofol, but not by ketamine or fentanyl.     

Continuous-flow apneic ventilation during thoracotomy

Continuous-flow apneic ventilation (CFAV) by endobronchial insufflation of conditioned gas was evaluated in dogs during thoracotomy. In Group 1 (n = 6), dogs were anesthetized with pentobarbital (25 mg/kg). An endobronchial catheter (2.5 mm ID) was introduced into each mainstem bronchus using a fiberoptic bronchoscope and held in place by an endotracheal tube. Before the onset of CFAV (total flow 1.01 X kg-1 X min-1, the animals were paralyzed with pancuronium bromide and muscle relaxation was monitored with a peripheral nerve stimulator. The CFAV delivery system consisted of a flow meter, air/oxygen blender, oxygen analyzer, heated humidifier, and ultrasonic spirometer. Blood gas values were measured after 30 min of spontaneous ventilation, and CFAV with: 1) closed chest, fractional inspired O2 concentration (FIO2) 0.21; 2) open chest, FIO2 0.21; 3) open chest, FIO2 0.21, continuous positive airway pressure (CPAP) 5 mmHg; and 4) open chest FIO2 0.4, CPAP 5 mmHg. This last combination resulted in a mean PaO2 of 113.1 +/- 5.5 (SEM) mmHg and a PaCO2 of 35.0 +/- 2.1 (SEM) mmHg. In Group 2 (n = 6), animals with open chests were ventilated with CFAV (FIO2 0.4 and CPAP 5 mmHg) for 5 h. Adequate oxygenation and ventilation were achieved. PaCO2 after 5 h of CFAV was 41.8 +/- 1.9 (SEM) mmHg compared with 40.8 +/- 1.9 (SEM) mmHg during spontaneous breathing. PaO2 after 5 h of CFAV was 138.1 +/- 11.7 (SEM) mmHg. There were no significant changes observed in vascular pressures. Significant differences in other hemodynamic parameters were probably due to pentobarbital anesthesia. Adequate gas exchange can be achieved during CFAV in dogs with open chests for 5 h.     

异丙酚对氯胺酮致老龄大鼠认知功能障碍的影响

目的 探讨异丙酚对氯胺酮致老龄大鼠认知功能障碍的影响.方法 健康雄性SD老龄大鼠32只,月龄18～24月龄,体重380～470 g,随机分为4组(n=8):对照组(C组)、异丙酚组(P组)、氯胺酮组(K组)和异丙酚+氯胺酮组(PK组).P组静脉输注异丙酚30 mg·kg-1·h-1,K组静脉输注氯胺酮40 mg·kg-1·b-1,PK组静脉输注异丙酚30 mg·kg-1·h-1+氯胺酮40 mg·kg-1·h-1,C组给予等容量生理盐水,每天2 h,连续7 d.给药结束后测定大鼠认知功能,记录逃避潜伏期和穿越平台次数.认知功能测试完毕后,处死大鼠,取海马组织,检测CA1区神经元凋亡情况,计算神经元凋亡率;测定CA1区caspase-3的表达水平.结果 与C组比较,P组逃避潜伏期、穿越平台次数、海马CA1区神经元凋亡率和caspase-3表达差异无统计学意义(P＞0.05),K组和PK组逃避潜伏期延长,穿越平台次数减少,海马CA1区神经元凋亡率升高,caspase-3表达上调(P＜0.05);与K组比较,PK组逃避潜伏期缩短,穿越平台次数增加,海马CA1区神经元凋亡率降低,caspase-3表达下调(P＜0.05).结论 异丙酚可减轻氯胺酮致老龄大鼠认知功能障碍,其机制可能与异丙酚可在一定程度上抑制氯胺酮所致caspase-3表达上调,从而抑制氯胺酮诱发的神经元凋亡有关.     

Effect of halothane, fentanyl and ketamine on the threshold for the passage of venous air embolism through lungs in dogs

Effect of halothane, fentanyl and ketamine on the passage of air injected bolus across the pulmonary circulation was studied in dogs using transesophageal M-mode echocardiography. Dogs in Group 1 (N = 5) were anesthetized with halothane and then halothane with fentanyl. At least 3 weeks later the dogs were anesthetized with fentanyl and then fentanyl with halothane. The same procedure was utilized in group 2 (N = 4) using halothane and ketamine. The doses of halothane, fentanyl and ketamine were 1% inspired concentration, 100 micrograms.kg-1 followed by 1 microgram.kg-1.min-1 iv, and 10 mg.kg-1 followed by 0.1 mg.kg-1.min-1 iv, respectively. The threshold for bolus air detection during halothane, fentanyl and ketamine alone were 0.05, 0.5 and 0.2 ml.kg-1, respectively. The threshold during fentanyl administration, but not during ketamine administration, was significantly higher than that during halothane. The addition of halothane to fentanyl or ketamine lowered the threshold to the same level as with halothane alone, and the addition of either fentanyl or ketamine to halothane made no difference. Although there was no difference in baseline shunt fraction resistance index [PVRI/(Qs/Qt)] during administration of each anesthetic, every air injection decreased shunt fraction resistance index during halothane without fentanyl or during halothane with or without ketamine, and increased it during fentanyl administration.     

Positive effects of prophylactic ventilator treatment on gas exchange and extravascular lung water in a porcine model of adult respiratory distress syndrome induced by endotoxaemia

The influence of prophylactic ventilator treatment was evaluated in a porcine model of early adult respiratory distress syndrome (ARDS) induced by endotoxaemia. Sixteen animals, controls, under continuous i.v. ketamine anaesthesia were either mechanically ventilated using intermittent positive pressure ventilation (IPPV; n = 6) with air or breathed air spontaneously (n = 10). Twenty animals under continuous i.v. ketamine anaesthesia and spontaneously breathing air were infused i.v. with E. coli endotoxin (10 micrograms X kg-1 X h-1) over 6 h. Fifteen animals under continuous i.v. ketamine anaesthesia were given IPPV with air and were infused i.v. with E. coli endotoxin in the same dosage regimen. In the controls, cardiac output decreased slightly. Otherwise there were no changes in pulmonary gas exchange, pulmonary haemodynamics or extravascular lung water. In spontaneously breathing and IPPV animals given endotoxin there was a profound deterioration in pulmonary gas exchange, a marked rise in pulmonary vascular resistance and a moderate increase in extravascular lung water. Animals given IPPV showed a significantly less pronounced impairment in pulmonary gas exchange and a significantly smaller increase in extravascular lung water than in animals breathing spontaneously, whereas the changes in pulmonary haemodynamics were fairly similar in both groups. Animals with IPPV also had an improved survival rate. The beneficial effects of mechanical ventilation on pulmonary gas exchange are not due to changes in extravascular lung water, but are caused by its influence in counteracting terminal airway and alveolar closure. These results indicate that mechanical ventilation, when instituted early in the course of human ARDS induced by septicaemia, might be of potential value in the prevention of severe pulmonary failure and death.     

The effects of nitrous oxide and ketamine on the bispectral index and 95% spectral edge frequency during propofol-fentanyl anaesthesia

In this study, we have sought to establish whether N2O and ketamine alter the bispectral index during propofol-fentanyl anaesthesia. Fourteen surgical patients were randomly assigned to one of two groups: the N2O group (n = 7) and the ketamine group (n = 7). In both groups, anaesthesia was induced with propofol 1.5-2 mg kg-1 and fentanyl 2 micrograms kg-1 and maintained with propofol 5-7 mg kg-1 hr-1 to target the bispectral index between 40 and 50. After the bispectral index value had stabilized the propofol infusion rate was fixed. In the N2O group, the following concentrations of N2O were subsequently inhaled at 20-min intervals; 20, 40, 60 and 70%, and then N2O was terminated. In the ketamine group, ketamine (0.4 mg kg-1 + 1.0 mg kg-1h-1) was given. The bispectral index and 95% spectral edge frequency were recorded 20 min after each change in concentration of N2O or ketamine infusion. The bispectral index and 95% spectral edge frequency did not change significantly in the N2O group, but increased significantly from 44.1 +/- 0.7 and 16.0 +/- 0.5 to 58.6 +/- 1.4 and 19.5 +/- 0.3 (P < 0.01), respectively, in the ketamine group. Additional N2O or ketamine did not decrease the bispectral index and 95% spectral edge frequency values. The depth of sedation should be assessed carefully using a bispectral index monitor when these anaesthetic agents are used together.     

Comparison of halothane, isoflurane, alfentanil, and ketamine in experimental septic shock

The effects of four commonly used anesthetic agents, halothane, isoflurane, alfentanil, and ketamine, on cardiovascular function and oxygen balance were studied in a dog model of septic shock. After initial pentobarbital administration, the dogs were given Escherichia coli endotoxin (3 mg/kg) and, after 30 min, fluids to restore cardiac filling pressures to baseline levels. This resulted in a low resistance shock in all animals. Dogs were then given for 2 h either halothane (n = 9, 0.5 MAC), isoflurane (n = 9, 0.5 MAC), or alfentanil (n = 9, 150 micrograms/kg IV plus 2 micrograms.kg-1.min-1) or ketamine (n = 9, 2 mg/kg IV plus 0.2 mg.kg-1.min-1) or no anesthetic (control: n = 9). Mean arterial pressure increased in the control group (+11 +/- 18 mm Hg) and with ketamine (+10 +/- 20 mm Hg), remained unchanged with isoflurane (-2 +/- 11 mm Hg), and decreased with halothane (-22 +/- 23 mm Hg) and alfentanil (-9 +/- 23 mm Hg). Heart rate tended to increase in the control group but decreased with the four anesthetic agents, especially with alfentanil and halothane. Cardiac index and left ventricular stroke work index increased in the control group and in each anesthetic group except the halothane group. Systemic vascular resistance decreased in all groups except in the ketamine group. In the control group, the increase in cardiac index was associated with significant increases in oxygen delivery and consumption, and with a significant decrease in blood lactate levels. There was a dramatic decrease in oxygen consumption in all anesthetic groups, whereas oxygen delivery failed to increase only with halothane. Blood lactate increased significantly with halothane (5.0 +/- 1.5 to 6.3 +/- 1.4 mM/L) and isoflurane (4.8 +/- 1.1 to 5.3 +/- 1.2 mM/L), remained unchanged with alfentanil (4.5 +/- 1.5 and 4.6 +/- 0.8 mM/L), and tended to decrease with ketamine (4.9 +/- 1.4 to 4.5 +/- 1.4 mM/L). In conclusion, among the four anesthetic agents tested, halothane had the least desirable effects. Ketamine best preserved cardiovascular function and appeared to have the least deleterious effects on the hypoxic tissues. Thus, ketamine could be the anesthetic agent of choice in septic shock.     

Differential Effects of Anesthetic Agents on Outcome from Near-complete but Not Incomplete Global Ischemia in the Rat

Background: It has been postulated that anesthetic agents that reduce cerebral metabolic rate will protect the brain against ischemia when electroencephalographic (EEG) activity is persistent, but will provide no protection when ischemia is severe enough to cause EEG isoelectricity. No outcome studies have addressed this issue. The authors studied anesthetic agents to determine if they provide differential effects on outcome from global cerebral ischemic insults that cause either an attenuated or isoelectric EEG.

Methods: Fasted rats were subjected to either (1) incomplete ischemia (attenuated EEG; 20 min of mean arterial pressure [MAP] = 50 mmHg and bilateral carotid occlusion) or (2) near-complete ischemia (isoelectric EEG; 10 min of MAP = 30 mmHg and bilateral carotid occlusion) while anesthetized with 1.4% isoflurane, 1 mg [middle dot] kg-1 [middle dot] min-1 ketamine, or 25 [micro sign]g [middle dot] kg-1 [middle dot] h-1 70% nitrous oxide and fentanyl. The brain was maintained at normothermia during ischemia and for 22 h after ischemia. Five days later, hippocampal CA1 and cortical injury were measured.

Results: There was no difference among anesthetic agents during incomplete ischemia for mean +/- SD percentage dead CA1 neurons (fentanyl, 38% +/- 20%; isoflurane, 31% +/- 10%; ketamine, 40% +/- 19%; P = 0.38). During near-complete ischemia, there was a difference among anesthetic agents (fentanyl, 88% +/- 9%; isoflurane, 37% +/- 20%; ketamine, 70% +/- 28%; P = 0.00008). Isoflurane was protective compared with fentanyl (P = 0.00007) and ketamine (P = 0.0061). There was no difference between fentanyl and ketamine (P = 0.143). Similar observations were made in the cortex. Neurologic function correlated with histologic damage.     

The effect of ketamine on reducing postoperative agitation after sevoflurane anesthesia in pediatric strabismus surgery

We investigated the effect of ketamine on reducing postoperative agitation after sevoflurane anesthesia in children undergoing elective strabismus surgery. Fifty-five children, 3-9 years of age, were randomly assigned to the following three groups; ketamine (group K, n = 18), pentazocine (group P, n = 19), and flurbiprofen axetil(group F, n = 18). Group K received ketamine 1 mg.kg-1 intravenously, followed by infusion of ketamine 1 mg.kg-1.hr-1 during surgery, group P received pentazocine 0.2 mg.kg-1 intravenously after induction of anesthesia, and Group F received intravenous flurbiprofen axetil, 1 mg.kg-1 5 minutes before the end of surgery. Agitation (evaluated by Aono's four-point scale; AFPS) and awareness (evaluated by Steward score) were assessed just before tracheal extubation(T 1), 5 minutes after tracheal extubation(T 2), arrival at the ward(T 3), and 60 minutes after arrival at the ward(T 4). We considered AFPS > or = 3 patients as "agitated" and APFS < or = 2 patients as "not agitated". At T 1 and T 2, the incidence of agitation(AFPS > or = 3) in group K was less than that of group F and group P. However, in group K, more patients needed oxygen supplement after extubation. We concluded that coadministration of ketamine could be beneficial for reducing postoperative agitation after sevoflurane anesthesia in pediatric strabismus surgery.     

A comparison of fentanyl and buprenorphine in total intravenous anesthesia using propofol during spinal surgery

A retrospective study was performed to compare the hemodynamic effect and postoperative pain relief of fentanyl (Group F, n = 11) and buprenorphine (Group B, n = 11) in total intravenous anesthesia (TIVA) using propofol during spinal surgery. All patients were premedicated with midazolam (3-5 mg) i.m. Anesthesia was maintained with propofol infusion, and increments of fentanyl or single dose of buprenorphine with 40% oxygen in air. Total doses of fentanyl and buprenorphine were 7.6 +/- 1.0 micrograms.kg-1 and 2.0 +/- 0.4 micrograms.kg-1, respectively. Maintenance doses of propofol (Group F: 5.5 +/- 0.8 mg.kg-1.h-1, Group B: 5.9 +/- 1.1 mg.kg-1.h-1) and vecuronium were not significantly different. Mean arterial pressures from 2 hours after incision to the end of surgery were elevated significantly in Group F than in Group B. Recovery time (Group F 12.5 +/- 6.1 min vs Group B 11.8 +/- 6.1 min) and extubation time (Group F 19.5 +/- 10.3 min vs Group B 15.0 +/- 7.0 min) were not different. At the end of anesthesia, seven patients in Group F and one patient in Group B (P < 0.01) complained of severe pain. All patients in Group F, and only two in Group B (P < 0.02) received analgesics within 20 hours. Neither nausea nor respiratory depression was found in both groups. This study suggests that buprenorphine would provide a more stable hemodynamic state and better postoperative pain relief than fentanyl in TIVA using propofol.