Thiopental Group Research Articles

In Vitro Proton Magnetic Resonance Spectroscopy Detected a Differential Neurochemical Response in Rabbit Brain Administered Thiopental or Ketamine

Background: Cellular target sites and the neurochemical compounds responsible for anesthetic action remain unclear. This study was designed to detect regional changes in neurochemical compounds by NMR spectroscopy of extracted rabbit brain tissue after anesthetizing with thiopental or ketamine. Methods: Nine healthy white New Zealand rabbits (2.5-3.0 kg) were studied. A marginal ear vein was punctured for continuous intravenous infusion. Controlled breathing was maintained using a Jackson-Ree circuit after intubation during thiopental (n = 3) or ketamine (n = 3) anesthesia. After maintaining anesthesia for 30 minutes, brains were extracted and placed in liquid nitrogen. Rabbits in the control group (n = 3) were sacrificed using KCl and processed in the same manner. Extracted brain tissues were divided into frontal lobe, temporal lobe, occipital lobe, parietal lobe, pons, midbrain, basal ganglia and spinal cord. The H-NMR spectra of extracted regional brain tissues were obtained, and neurochemical compounds such as gamma-aminobutyric acid (GABA), N-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine (Cr) were compared with those of normal control tissues. Results: In the thiopental group, the GABA/Cr and NAA/Cr ratios of brain regions were not significantly different from those of the control group. The Cho/Cr ratios of the frontal lobe, parietal lobe, and basal ganglia were significantly higher than those of the control group. In the ketamine group, the GABA/Cr ratio of the midbrain was significantly lower than that of the control group. However, Cho/Cr ratios of the parietal lobe, temporal lobe, and midbrain were significantly higher than those of the control group, though the NAA/Cr ratio was similar to that of the control. Conclusions: These results suggest that the anesthetic actions of thiopental, such as, its sedative and hypnotic effects are due to increased GABA activity. Inhibition of acetylcholine induced neurotransmission was observed particularly in the frontal lobe, parietal lobe, and basal ganglia in thiopental anesthesia and in the parietal lobe, temporal lobe and midbrain in ketamine anesthesia. Neurotoxicity was not observed for either drug in anesthetized brain tissue.

The Effects of Transcranial Electrical Stimulation on Anaesthesia and Analgesia in Rats

In this study, we determined the effects of transcranial electrical stimulation (TCES) on the anaesthetic requirements of thiopental and the analgesic requirements of remifentanil, in rats. The experiments were performed on 120 albino male Wistar rats, which were randomly allocated to four groups (n=30). (Thiopental, Thiopental+TCES, Thiopental+Remifentanil, and Thiopental+Remifentanil+TCES). Animals were anaesthetized with thiopental, and 15 min later, remifentanil was injected to rats in the Remifentanil groups. TCES was started in the stimulated groups 20 min after thiopental administration. Rats were stimulated 5 times for this experiment. The times for recovery, herein called Cognition Recovery Time and Motion Recovery Time were measured. Cognition Recovery and Motion Recovery Times were not affected by the stimulation. Analgesia was assessed using the wet tail-flick latency (TFL). In the Thiopental group, the analgesia level returned to control values on the 35th min. In the Thiopental+Remifentanil group, the analgesia level returned to control values on the 50th min. In the Thiopental+ TCES group, the analgesia level reached the peak value on the 65th min. In the Thiopental+Remifentanil+TCES group, the analgesia level reached the peak value on the 35th min and analgesia remained high during the 90 min after cessation of the stimulation. The analgesic potency for the Thiopental+Remifentanil+TCES group was increased by 30-40% when compared with the prior TFL values, 160% when compared with the control group, and 50-75% when compared with Thiopental+TCES group on the 35th min (P<0.001). In conclusion, TCES markedly decreases the anaesthetic and analgesic requirements for thiopental and remifentanil in rats.

The Effect of Pretreatment with Thiopental on Reducing Pain Induced by Rocuronium Injection

We examined whether pretreatment with a small dose of thiopental was effective in reducing pain induced by the intravenous injection of rocuronium. Withdrawal movement was used to assess pain reduction. Ninety patients were randomly assigned to one of two groups: patients in the control group were pretreated with 2 mL saline, and those in the thiopental group were pretreated with 2 mL (50 mg) thiopental. Thiopental 5 mg/kg was injected intravenously. After a loss of consciousness, the upper arm was compressed with a rubber tourniquet, and the pretreatment drugs were administered. Thirty seconds later the tourniquet was removed and 0.6 mg/kg rocuronium was administered. Withdrawal movement was assessed using a four-grade scale: no movement, movement limited to the wrist, to the elbow or to the shoulder. The frequency of withdrawal movement in the group pretreated with thiopental was lower than in the control group (34 vs. 13, p < 0.05). We concluded that pretreatment with 2 mL (50 mg) thiopental is effective in reducing pain caused by the intravenous injection of rocuronium.

Comparación de la eficacia del pentobarbital y el tiopental en el control de la hipertensión intracraneal refractaria. Resultados preliminares en una serie de 20 pacientes

To assess the effectiveness of pentobarbital and thiopental to control raised intracranial pressure (ICP), refractory to first level measures, in patients with severe traumatic brain injury.Prospective, randomized study to compare the effectiveness between two treatments: pentobarbital and thiopental. The patients will be selected from those admitted to the Intensive Care Unit with a severe traumatic brain injury (postresuscitation Glasgow Coma Scale equal or less than 8 points) and raised ICP (ICP>20 mmHg) refractory to first level measures according to the Brain Trauma Foundation guidelines. The adverse effects of both treatments were also collected.We present the results of the first 20 patients included. Ten received pentobarbital and the other ten thiopental. There were no statistically significance differences in patients'characteristics (age, sex, severity of the trauma at admission and comorbilities). There were no differences between both groups neither in the Glasgow Coma Scale at admission (thiopental six points; pentobarbital seven points; P=0.26) nor in the admission Cranial Tomography, according to the Traumatic Coma Data Bank Classification. Thiopental treatment controlled raised ICP in five cases and pentobarbital in two cases (P=0.16). Five patients in the thiopental group died and eight in the pentobarbital group (P=0.16). There were no statistically differences between both groups regarding to the presence of hypotension (P=1) or infectious complications.These preliminary results indicate that thiopental could be more effective than pentobarbital in patients with refractory intracranial hypertension. These results support previous experimental findings that show that both treatments are not equal and justify to continue this study.

Enhanced visual memory effect for negative versus positive emotional content is potentiated at sub-anaesthetic concentrations of thiopental

Emotional information has the ability to alter the formation and strength of a memory ('memory modulation'). Memory modulation by negative emotion is mediated by the amygdala. It is not known how gamma aminobutyric acid (GABA)ergic drugs affect the processes involved in memory modulation. This study investigates whether memory for negative emotional stimuli is more refractory to the effects of GABAergic drugs. Eighty-three healthy volunteers were shown a randomized sequence of 60 visual stimuli consisting of negative, positive and neutral emotive pictures, while receiving a controlled infusion of thiopental (n=31), propofol (n=31), dexmedetomidine (n=10) or placebo (n=11). After a 5 h retention interval, when drug concentration was negligible, subjects performed a recognition task with 'old' pictures randomly mixed with 'new' pictures. Drug effect was calculated as the proportionate reduction in recognition for images of each emotional valence. Forty-eight subjects were included in a within-subject logistic dose-response model analysis. In the thiopental group there was a smaller drug effect seen for negative vs positive images (proportional memory reduction from baseline 0.27 (SD 0.20) vs 0.56 (0.25), P<0.001, n=20 included in analysis). A similar trend was seen in the propofol group (0.25 (0.28) vs 0.54 (0.30), n=10), but this did not attain statistical significance. No trend was seen in the dexmedetomidine group (0.33 (0.26) vs 0.24 (0.22), n=7). Over a specific dose range of thiopental (target serum concentration 2-7 micro g ml(-1)), impairment of explicit memory for images with negative emotional valence is less than that for images with positive emotional valence. There is a strong possibility that propofol (target serum concentration 0.3-2.4 micro g ml(-1)) causes a similar effect. Modulation of visual memory by negative emotional content continues at sub-anaesthetic concentrations of GABAergic drugs associated with explicit memory impairment.

Rapid sevoflurane induction compared with thiopental

Study objectives To examine whether the speed of induction of anesthesia with sevoflurane/nitrous oxide (N 2O) utilizing a 10-second vital capacity rapid inhalation induction (VCRII) followed by tidal breathing was similar or faster than cautious intravenous (IV) thiopental induction with inhaled N 2O. Design Prospective, randomized, double-blinded study. Setting Veterans Affairs Medical Center. Patients 50 male ASA physical status I, II, and III patients scheduled for general anesthesia. Interventions Patients were randomized to receive either 8% sevoflurane or IV thiopental. Patients were allocated to one of two groups of 25 patients each. In both groups, the breathing circuit was initially primed for 5 minutes with (4 L/min) and O 2 (2 L/min), while the Y-piece was occluded. In the sevoflurane group, the circuit was additionally primed with 8% sevoflurane. Patients were trained to perform a vital capacity breath. After maximal exhalation, the occluding plug was rapidly removed from the Y-piece and connected to the facemask. The patient then inspired to vital capacity, held his breath for 10 seconds, and then was allowed to breathe normally. At the end of the 10-second breathhold, and as the patient started normal breathing, either thiopental (thiopental group) or normal saline (sevoflurane group) was injected at a rate of 4 mL every 10 seconds. Measurements A study-blinded observer recorded the time to induction, as defined by the time to loss of eyelash reflex, and noted the occurrence of side effects. Main results The speed of induction was the same for both groups ( p > 0.05). An average of eight breaths was required before loss of eyelash reflex. Side effects occurred in 36% of the patients in the thiopental group, and 32% in the sevoflurane group ( p > 0.05); these were minor and did not affect induction. Conclusion Sevoflurane/N 2O VCRII as used in this investigation is an effective inhalation technique; it resulted in an induction time similar to that of slow IV thiopental with inhaled N 2O.

Effect of Thiopental Sodium on Hearing Outcomes Following Microvascular Decompression Surgery

Background: The use of intraoperative brainstem auditory evoked potential (BAEP) has reduced the incidence of sensorineural hearing loss (SNHL) after microvascular decompression (MVD). This complication occurs due to direct compressive and/or stretching injury of the cochlear nerve or to indirect compression of the perineural vasculature during cerebellar retraction. The aim of this study was to evaluate the effect of thiopental sodium on SNHL after MVD for hemifacial spasm. Methods: 94 hemifacial spasm patients with normal hearing function preoperatively and who underwent MVD under intraoperative BAEP monitoring were enrolled in this study. Patients were randomly divided into two groups. 52 patients were administered placebo (control group) and 42 patients were administered thiopental sodium 5 mg/kg intravenously 5 minutes before cerebellar retraction (thiopental group). The effects of thiopental on intraoperative BAEP changes and postoperative hearing functional outcomes were sought. Incidence and degree of postoperative SNHL were evaluated by pure tone audiometry threshold analysis. Results: Maximal changes in intraoperative BAEP parameters did not differ between the two groups, and neither did the incidence nor degree of SNHL. In the control group, 4 transient and 4 permanent postoperative SNHL, including 2 deaf patients, occurred with an overall incidence of 15.4%. In the thiopental group, 2 transient and 1 permanent postoperative SNHL occurred, with an overall incidence of 7.1%. Conclusions: Thiopental sodium administered prior to cerebellar retraction might reduce the incidence of postoperative hearing loss.

Effects of Intravenous Induction Drugs on Intubation Conditions Using Rocuronium for Rapid Sequence Induction

Background: We assessed the effect of intravenous induction agents on intubation conditions and hemodynamic changes when using rocuronium 0.7 mg/kg for rapid sequence induction. Methods: Sixty ASA class I or II patients undergoing elective surgery were divided into a thiopental group (5 mg/kg, n = 20), a propofol group (2 mg/kg, n = 20) and an etomidate group (0.2 mg/kg, n = 20). Anesthesia was induced with intravenous induction agents. After loss of consciousness, rocuronium 0.7 mg/kg was injected. Intubation was attempted at 60 seconds after rocuronium administration. Arterial blood pressure and heart rate were measured before induction, immediately after intubation, and 1, 3, 5, and 10 minutes after intubation. Intubation conditions were assessed by jaw relaxation, vocal cord movement, response to tracheal intubation, and were evaluated as excellent, good, fair, and poor. Results: Excellent intubation conditions were obtained 55% (n = 11) in the thiopental group, 60% (n = 12) in the propofol group, and 45% (n = 9) in the etomidate group. Systolic and diastolic arterial blood pressures were elevated after intubation in all three groups. But these changes were minimal in the propofol group. Conclusions: Intubation conditions were not significantly different after the intravenous injection of thiopental 5 mg/kg, propofol 2mg/kg, or etomidate 0.2 mg/kg when using rocuronium 0.7 mg/kg for rapid sequence induction.

ED50 of Nicardipine for Preventing Hypertensive Response to Tracheal Intubation during Induction with Thiopental, Propofol or Etomidate

Background: Laryngoscopy and tracheal intubation often provoke an undesirable increase in blood pressure and heart rate. This study was done to determine median effective dose (ED50) of nicardipine for prevention of hemodynamic response to tracheal intubation during induction of anesthesia with thiopental, propofol, or etomidate. Methods: Fourty-five ASA physical status 1 adult patients were allocated into three group; thiopental group (n = 15), propofol group (n = 15), and etomidate group (n = 15). The first patient of each groups received 10/kg of nicardipine 1 minute before induction. Subsequent dose was determined by the hemodynamic response of the previous patient to tracheal intubation based on Dixon's up and down sequential allocation. The test dosing interval was set at 3/kg. If mean arterial pressure increased more than 20% after tracheal intubation, dose of the subsequent patient was increased by 3/kg. If not, it was decreased by 3/kg. Blood pressure was measured after arrival at the operating room, before tracheal intubation, and 1, 2, 3, 4, and 5 minutes following intubation by non invasive method. Results: ED50 of nicardipine for attenuation of hypertensive response after tracheal intubation were 18.0/kg (95% Confidence Limit [CL], 14.8-22.0/kg), 6.2/kg (CL, 2.6-9.5/kg), and 16.7/kg (CL, 13.6-20.7/kg) in thiopental group, propofol group and etomidate group, respectively. Conclusions: We concluded that less nicardipine dose in propofol group was needed to prevent hypertensive response after tracheal intubation (P

Effect of Thiopental and Ketamine on Endothelium-Dependent Relaxation Induced by Reactive Oxygen Species in Rabbit Thoracic Aorta

Background: Reactive oxygen species (ROS) are free radicals that induce lipid peroxidation and cause tissue damage. ROS are frequently produced by ischemia and subsequent reperfusion in clinical situation and like coronary artery bypass graft surgery and transplantation. More over, some anesthetics are known to act as an antioxidants and free radical scavenger and, the aim of this study was to explore the scavenging effects of thiopental and ketamine against ROS induced by isolated rabbit thoracic aortic endothelial damage. Methods: Twenty white male rabbits (weighing 2.0-2.5 kg) were used. Thoracic aorta and were dissected free, cut into rings (3-4 mm), and suspended in an organ bath filled with 10 ml Krebs solution bubbled with 5% and 95% at $37^{\circ}C$. The rings were equilibrated for 90 min and the solution changed every 15 min, and then a resting tension of 1.5 g was applied to the rings. Isometric tensions were recorded using a transducer connected to a data acqusition system (Biopac Inc. USA). Aortic rings were precontracted with norepinephrine (NE, M), and changes in tension were measured after the cumulative administration of acetylcholine (ACh M) and nitroglycerin (NTG M). Data are expressed as percentages of the M NTG-induced relaxation (ACh/NTG). Percentages of ACh/NTG, before and after ROS exposure by electrolysis were noted for control and experimental groups. Aortic rings were pretreated with thiopental ( M, n = 9, 13, 17), ketamine ( M, n = 8), catalase (1000 U/ml, n = 12), mannitol ( M, n = 5) or not pretreated (free, n = 6). After 30 minutes, with the rings were exposed to ROS by electrolysis (DC 9 V, 20 mA, aortic rings 1 cm removed from the anode) in Krebs solution for 2 minutes. After electrolysis, the organ bath fluid was replaced with fresh Krebs solution, and the aortic rings were precontracted with NE and was vasorelaxation with ACh and NTG as above mentioned concentrations. Results: Endothelium-dependent vasorelaxation was induced in all concentrations of thiopental groups in a dose-dependent fashion (P

QT interval and QT dispersion during the induction of anaesthesia in patients with subarachnoid haemorrhage: a comparison of thiopental and propofol

Background and objective: Thiopental prolongs the QT interval more than propofol, and the two induction agents were compared in patients with subarachnoid haemorrhage predisposed to electrocardiographic abnormalities and cardiac dysrhythmias. Methods: Twenty-nine patients were studied randomly. Anaesthesia was induced with either thiopental or propofol and fentanyl; vecuronium was used as a neuromuscular blocking agent. The electrocardiogram and arterial blood pressure were monitored from before the induction of anaesthesia to 2 min after endotracheal intubation. Results: The median QT interval was at baseline 423 ms in the thiopental group and at 432 ms in the propofol group, and it increased in the thiopental group to 446 ms and decreased in the propofol group to 425 ms (P < 0.01 between groups). After induction and endotracheal intubation, the number of patients with increased QT dispersion was greater in the propofol group (P < 0.05). The incidence of cardiac dysrhythmias was similar in the study groups. Conclusions: Thiopental and propofol are equally suitable for the induction of anaesthesia in patients with subarachnoid haemorrhage.

AnaesthesiaJournal of the Association of Anaesthetists of Great Britain and Ireland

AnaesthesiaJournal of the Association of Anaesthetists of Great Britain and Ireland

Thiopental and phenytoin by aortic arch flush for cerebral preservation during exsanguination cardiac arrest of 20 minutes in dogs. An exploratory study

We are systematically exploring in our exsanguination cardiac arrest (CA) outcome model in dogs suspended animation (SA), i.e. immediate preservation of brain and heart for resuscitative surgery during CA, with delayed resuscitation. We have shown in dogs that inducing moderate cerebral hypothermia with an aortic arch flush of 500 ml normal saline solution of 4°C, at start of CA 20 min no-flow, leads to normal functional outcome. We hypothesized that, using the same model, adding thiopental (or even better thiopental plus phenytoin) to the flush at ambient temperature (24°C), which would be more readily available in the field, will also achieve normal functional outcome. Thirty dogs (20–28 kg) were exsanguinated over 5 min to CA of 20 min no-flow, and resuscitated by closed-chest cardiopulmonary bypass. They received assisted circulation to 2 h, 34°C post-CA to 12 h, controlled ventilation to 20 h, and intensive care to 72 h. At CA 2 min, the dogs received an aortic arch flush of 500 ml saline at 24°C by a balloon-tipped catheter, inserted through the femoral artery (control group 1, n=14). In group 2 ( n=9), thiopental (variable total doses of 15–120 mg/kg) was added to the flush and given with reperfusion. In group 3 ( n=7), thiopental (15 or 45 mg/kg) plus phenytoin (10, 20, or 30 mg/kg) was given by flush and with reperfusion. Outcome was assessed in terms of overall performance categories (OPC 1, normal; 2, moderate disability; 3, severe disability; 4, coma; 5, brain death), neurologic deficit scores (NDS 0–10%, normal; 100%, brain death), and histologic deficit scores (HDS, total and regional). The flush reduced tympanic temperature to about 36°C in all groups. In control group 1, one dog achieved OPC 1, three OPC 2, six OPC 3, and four OPC 4. In thiopental group 2, two dogs achieved OPC 1, two OPC 3, and five OPC 4. In thiopental/phenytoin group 3, one dog achieved OPC 1, two OPC 3, and four OPC 4 ( p=0.5). Median NDS were 36% (IQR 22–62%) in group 1; 51% (IQR 22–56%) in group 2; and 55% (IQR 38–59%) in group 3 ( p=0.7). Median total HDS were 67 (IQR 56–127) in group 1; 60 (IQR 52–138) in group 2; and 76 (IQR 48–132) in group 3 ( p=1.0). Thiopental and thiopental/phenytoin dogs achieved significantly lower HDS only in the putamen. Thiopental in large doses caused side effects. We conclude that neither thiopental alone nor thiopental plus phenytoin by flush, with or without additional intravenous infusion, can consistently provide ‘clinically significant’ cerebral preservation for 20 min no-flow. Other drugs and drug-combinations should be tested with this model in search for a breakthrough effect.

Effects of thiopental on transport and metabolism of glutamate in cultured cerebellar granule neurons

This study was performed to analyze the effects of the barbiturate thiopental on neuronal glutamate uptake, release and metabolism. Since barbiturates are known to bind to the GABA A receptor, some experiments were carried out in the presence of GABA. Cerebellar granule neurons were incubated for 2 h in medium containing 0.25 mM [U- 13C]glutamate, 3 mM glucose, 50 μM GABA and 0.1 or 1 mM thiopental when indicated. When analyzing cell extracts, it was surprisingly found that in addition to glutamate, aspartate and glutathione, GABA was also labeled. In the medium, label was observed in glutamate, aspartate and lactate. Glutamate exhibited different labeling patterns, indicating metabolism in the tricarboxylic acid cycle, and subsequent release. A net uptake of [U- 13C]glutamate and unlabeled glucose was seen under all conditions. The amounts of most metabolites synthesized from [U- 13C]glutamate were unchanged in the presence of GABA with or without 0.1 mM thiopental. In the presence of 1 mM thiopental, regardless of the presence of GABA, decreased amounts of [1,2,3- 13C]glutamate and [U- 13C]aspartate were found in the medium. In the cell extracts increased [U- 13C]glutamate, [1,2,3- 13C]glutamate, labeled glutathione and [U- 13C]aspartate were observed in the 1 mM thiopental groups. Glutamate efflux and uptake were studied using [ 3H] d-aspartate. While efflux was substantially reduced in the presence of 1 mM thiopental, this barbiturate only marginally inhibited uptake even at 3 mM. These results may suggest that the previously demonstrated neuroprotective action of thiopental could be related to its ability to reduce excessive glutamate outflow. Additionally, thiopental decreased the oxidative metabolism of [U- 13C]glutamate but at the same time increased the detectable metabolites derived from the TCA cycle. These latter effects were also exerted by GABA.

Anesthetic and cardiorespiratory effects of a 1:1 mixture of propofol and thiopental sodium in dogs

Objective To compare anesthetic and cardiorespiratory effects of a 1:1 (vol:vol) mixture of propofol and thiopental sodium with either drug used alone in dogs. Design Randomized crossover study. Animals 10 healthy Walker Hounds. Procedure Dogs received propofol (6 mg/kg [2.7 mg/lb] of body weight), thiopental (15 mg/kg [6.8 mg/lb]), or a mixture of propofol (6 mg/kg) and thiopental (15 mg/kg) at 1-week intervals. Drugs were slowly administered IV over 90 seconds or until dogs lost consciousness. Increments of 10% of the initial dose were administered until intubation was possible. Amount of drug required for intubation, quality of induction and recovery, times from induction to intubation and to walking with minimal ataxia, and duration of intubation and lateral recumbency were recorded. Heart and respiratory rates, mean, systolic, and diastolic blood pressure, hemoglobin saturation of oxygen (Spo2), and end-tidal CO2 concentration (ETco2) were determined before and after intubation. Results Amounts of propofol and thiopental required to permit intubation were less, but not significantly so, when administered in combination than when administered alone. Duration of lateral recumbency and time from induction to walking were greater and recovery quality was worse in the thiopental group, compared with the other groups. Dogs in all groups remained normotensive. Respiratory rate, heart rate, ETsco2, and Spo2 did not differ among groups. Conclusions and Clinical Relevance A 1:1 mixture of propofol and thiopental induced anesthesia of similar quality to propofol or thiopental alone. Recovery quality and recovery times were similar to those of propofol and superior to those of thiopental. (J Am Vet Med Assoc 1999;215:1292–1296)

Etomidate and the osteocalcin response to gynaecological surgery

Circulating osteocalcin is a good marker of osteoblastic activity and decreases significantly after stressful physiological states such as major surgery. Glucocorticoids are known to inhibit osteoblastic activity and result in a decline in circulating osteocalcin. We used etomidate to inhibit the cortisol response to routine gynaecological surgery to determine if this would prevent the postoperative decline in osteocalcin. Twenty-four patients were allocated randomly to receive either thiopental or etomidate for induction of anaesthesia; all other aspects of anaesthesia and perioperative management were standardized. In the thiopental group, circulating cortisol increased significantly at 2 and 6 h after the start of surgery and plasma osteocalcin concentrations decreased significantly to almost 50% of baseline values at 48 h. Etomidate abolished the cortisol response to surgery, and circulating osteocalcin concentrations did not change after operation. There was a significant difference in osteocalcin concentration between the groups at 48 h. We conclude that the cortisol response to surgery is associated with a postoperative decrease in circulating osteocalcin.

MIDAZOLAM IS A SAFE AGENT BY COMPARISON WITH THIOPENTONE ON ARRHYTHMIAS IN ISCHAEMIA AND REPERFUSION CONDITIONS IN ISOLATED PERFUSED RAT HEARTS

Arrhythmia due to ischaemia and/or reperfusion is an important problem, especially in open heart surgery and for patients with ischaemic heart diseases undergoing non-cardiac surgery. This experimental study is planned to evaluate the effects of midazolam on ischaemia and/or reperfusion-induced arrhythmias by comparison with thiopentone in two sets of experiments (n=20 for every group). In total ischaemia-reperfusion experiments, hearts were perfused in constant pressure conditions. In the control group, after a stabilisation period, perfusion was totally stopped for 30 min and the hearts were reperfused for 10 min. For the experimental groups, hearts were pretreated for 5 min with either 10−6mol l−1midazolam or 10−5mol l−1thiopentone before total ischaemia and reperfused for 10 min with the same concentrations of the drugs. In low-flow ischaemia-reperfusion experiments, hearts were perfused at a constant flow of 10 ml g−1heart per min initially. In the control group, after a stabilisation period, perfusion rate was decreased successively 1 ml g−1heart per min for 10 min (mild ischaemia) and to 0.2 ml g−1heart per min for another 10 min (severe ischaemia). The ischaemic hearts were then reperfused for an additional 10 min at a flow rate of 10 ml g−1heart per min. Electrogram recordings were evaluated before ischaemia and at the 5th and 10th min of mild ischaemia, severe ischaemia and reperfusion. Midazolam, 10−6mol l−1, or thiopentone, 10−5mol l−1, were added to the perfusion solution in the midazolam and thiopentone groups, respectively. In these two groups, hearts were perfused according to perfusion rates mentioned above in the control group. As a commonly used i.v. anaesthetic, thiopentone was arrhythmogenic for hearts exposed to ischaemia-reperfusion by increasing ventricular premature beat (% incidences for control, midazolam and thiopental groups in the 10th min of reperfusion were 25, 15 and 65 in total ischaemia-reperfusion experiments,P<0.01) and ventricular tachycardia (respective % incidences were 0, 5, 25,P<0.05) incidences, but in our experiments we found out that the new agent midazolam does not have more arrhythmia incidence than the respective control group in any criteria evaluated. None of the agents exerted atrioventricular conductance abnormalities. So we conclude that midazolam is a safe agent for ischaemic hearts and might also be antiarrhythmic and the mechanism of action of this effect remains to be further investigated.

Induction of Anesthesia by Titration of Eltanolone Compared with Thiopental and Etomidate for Coronary Artery Bypass Grafting

Study Objective: To evaluate whether induction of anesthesia with eltanolone in coronary artery bypass graft (CABG) patients is associated with greater hemodynamic stability than either thiopental sodium or etomidate. Design: Randomized, controlled study. Setting: University hospital. Patients: 75 ASA physical status III and IV patients scheduled for elective CABG over 18 years of age, with left ventricular ejection fraction over 30%. Interventions: The participants were prospectively randomized into three groups, each group consisting of 25 patients. Anesthesia was induced by titration of either eltanolone, thiopental sodium, or etomidate. The end point was “loss of verbal contact.” Measurements and Main Results: Hemodynamic variables were recorded in the awake state, 2 minutes after induction, after administration of fentanyl 0.01 mg/kg, and 2 and 5 minutes after intubation. After induction of anesthesia, cardiac index (CI) decreased from 2.6 ± 0.5 to 2.2 ± 0.5 Lxmin −1xm −2 in the eltanolone group and remained at this value throughout the study period in contrast to the control groups. After fentanyl was given, mean arterial pressure was significantly lower in the case of eltanolone (69 ± 15 mmHg) compared with thiopental (81 ± 19 mmHg) and etomidate (84 ± 18 mmHg). Mean arterial pressure remained significantly lower at the points of measurement after intubation. Two minutes after intubation, CI was likewise significantly lower in the eltanolone group (2.2 ± 0.4 Lxmin −1xm −2) compared with the thiopental group (2.7 ± 0.7 Lxmin −1xm −2). Conclusions: Eltanolone produces more hemodynamic depression compared with etomidate and thiopental when administered in combination with fentanyl 10 μg/kg.

The effects of anesthesia on the biodistribution of drugs in rats: a carboplatin study.

Anesthetics can alter the biodistribution profile of drugs and, consequently, the regional pharmacokinetics of antineoplastic drugs at the tumor site. The effect of coadministered anesthetics on the biodistribution profile of carboplatin was studied in rats. Female Wistar rats were used to compare the effects of ketamine/xylazine, thiopental and pentobarbital on the biodistribution of 30 mg/kg radiolabelled 195mPt-carboplatin administered intravenously, with conscious rats as the control group. Blood and urine samples were collected between 5 and 120 min. The percentage values of the injected dose of platinum per ml (%ID/ml) in plasma at the final time-point were respectively, 0.557%, 0.156%, 0.115% and 0.086%, in pentobarbital-, ketamine/xylazine- and thiopental-injected rats, and in conscious animals. Following the same sequence of groups, the %ID/ml values of platinum in the cumulative urine were 0.001%, 0.619%, 0.184% and 0.118%, respectively. Urine output varied from very little in the pentobarbital group, to several milliliters in the other groups. There was an increase of almost 100-fold in total platinum uptake in the kidneys, cerebrum and cerebellum of rats receiving pentobarbital over the uptake in the control rats, whereas the biodistribution profile of the thiopental group had the least variance. These results demonstrate the importance of anesthetic selection in animal pharmacokinetic studies, as it influences the biodistribution and pharmacokinetic profile of the drug being studied.

Thiopental-Rocuronium Versus Ketamine-Rocuronium for Rapid-Sequence Intubation in Parturients Undergoing Cesarean Section

We investigated the neuromuscular effects and conditions of tracheal intubation after administration of rocuronium in 40 parturients undergoing elective cesarean section.After preoxygenation, anesthesia was induced in 20 patients by thiopental 4 mg/kg and, in the other 20 patients, by ketamine 1.5 mg/kg. Rocuronium 0.6 mg/kg was then administered, and neuromuscular transmission was assessed using electromyographic response to train-of-four stimulation of the ulnar nerve at the wrist every 10 s. The time to T1/control ratio of 50% neuromuscular block (NMB) as well as the time to maximum NMB (onset time) were compared in the two groups. The time to 50% block was 45 +/- 10 s in the thiopental group and 42 +/- 14 s in the ketamine group, while the onset time was 105 +/- 35 s in the thiopental group and 101 +/- 35 s in the ketamine group. Neither the time to 50% NMB nor the onset time were significantly different between the two groups. Tracheal intubation at 50% NMB was easily performed in all patients in the ketamine-rocuronium group but was difficult in 75% of the thiopental-rocuronium group. We concluded that ketamine 1.5 mg/kg followed by rocuronium 0.6 mg/kg may be suitable for rapid-sequence induction of anesthesia in parturients undergoing cesarean section. (Anesth Analg 1997;84:1104-7)