Dose Of Thiopental Research Articles

Don’t Use Thiopental to Decrease Propofol Injection Pain: In Response

We would like to thank Timothy et al. for their interest in our article and their valuable comments. We totally agree with them regarding postoperative nausea and vomiting (PONV) being a major cause of morbidity and its significance in terms of increased hospital stay and cost of treatment (1). But do these observations really apply to our study? All the studies quoted by Timothy et al. have observed the incidence of PONV following induction dose of thiopental or propofol (1–3). This does not hold true in our case, as we had administered 0.5 mg/kg of thiopental prior to induction with propofol (4). Propofol, even when administered in subhypnotic doses, has been reported to decreases the incidence of PONV (5). When an admixture of propofol and thiopental is used for induction, the incidence of PONV is the same as that with propofol alone (6,7). Therefore, we feel there should not be any increase in the incidence of PONV after thiopentone 0.5 mg/kg, which was followed by induction of anesthesia with propofol. Anil Agarwal, MD Mohammad F. Ansari, MD Sanjay Dhiraaj, MD Mehdi Raza, MD Department of Anesthesia, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India

Evaluation of intraperitoneal and incisional lidocaine or bupivacaine for analgesia following ovariohysterectomy in the dog

ObjectiveTo determine if intraperitoneal (IP) and incisional (SC) lidocaine or bupivacaine provide analgesia following ovariohysterectomy (OHE). Study DesignProspective, randomized, controlled, blinded clinical trial. AnimalsThirty dogs presenting to the Veterinary Teaching Hospital for elective OHE. MethodsDogs were pre-medicated with acepromazine and butorphanol, induced with thiopental and maintained with isoflurane. They were randomly assigned to three groups: 10 received 8.8 mg kg−1 2% lidocaine with epinephrine IP (LID); 10 received 4.4 mg kg−1 0.75% bupivacaine IP (BUP); and 10 received 0.9% saline IP (SAL) upon completion of OHE. All IP doses were standardized to 0.88 mL kg−1 with saline. An additional 2 mL of undiluted solution was placed SC prior to incisional closure. Dogs were scored at 0.5, 1, 2, 3, 6, 8 and 18 hours post-extubation by one observer. Dogs were evaluated using a visual analogue scale (VAS) for pain and sedation, and a composite pain scale (CPS) that included physiologic and behavioral variables. Dogs were treated with 0.22 mg kg−1 butorphanol + acepromazine if their VAS (pain) score was >50. Parametric variables were analyzed using Student's t-test or repeated measures anova as appropriate. Non-parametric variables were analyzed by χ2-test. ResultsThere were no significant differences in age, weight, incision length, surgery time, anesthesia time, or total thiopental dose among groups. Peak post-surgical pain scores for all groups occurred at 0.5 hours and returned to baseline by 18 hours. Dogs in the BUP group had significantly lower VAS-pain scores overall than dogs in the SAL group. Seven out of 10 dogs in the SAL group, 4/10 in the LID group and 2/10 in the BUP group were treated with supplemental acepromazine and butorphanol. No differences between groups were detected with the CPS. No adverse side-effects were observed. Conclusions and clinical relevanceOur findings support the use of IP and SC bupivacaine for post-operative analgesia following OHE in the dog.

Pharmacologic and physiologic influences affecting sensory evoked potentials: implications for perioperative monitoring.

Pharmacologic and physiologic influences affecting sensory evoked potentials: implications for perioperative monitoring.

Overdose, Coronary Artery Disease, or Both

In Reply:—Unfortunately, Dr. Via-Reque appears to have missed the main point of our case report, 1which was to alert anesthesiologists to the possibility that, in some rare cases, coronary angiography may grossly underestimate the true degree of coronary artery stenosis. As revealed at the autopsy, severe triple vessel atherosclerosis was unequivocally present in the patient described in this report and was the cause of his death.To specifically address the points raised by Dr. Via-Reque, the dose of thiopental was similar to that used for a previous, uneventful anesthetic. In both instances, the drug was given in fractionated doses. The blood pressure and heart rate after tracheal intubation (176/ 105 mmHg, 101 bpm) do not support Dr. Via-Reque's theory of exaggerated venodilation or decreased sympathetic output due to excessive induction agent. Indeed, the hyperdynamic response to intubation could be easily used to support the contention that more thiopental-fentanyl-lidocaine should have been used. As a final point, had the cardiac arrest been solely due to an anesthetic overdose, one would be hard pressed to explain the multiple subsequent episodes of cardiac arrest in the intensive care unit in the absence of any anesthetic agent having been administered.

A study of anesthetic drug utilization in different age groups

Study objective To determine anesthetic drug utilization in different age groups. Design Retrospective, automated, intraoperative database study. Setting Tertiary care medical center. Measurements 30,842 noncardiac general anesthesia case records between January 1991 and July 1997 were studied. We investigated the effect of age on anesthetic requirements for fentanyl (F), midazolam (M), thiopental sodium (T), propofol (P), isoflurane (I), and nitrous oxide (N). Because drugs are not given in isolation we looked at the most common drug combinations, IFNTM, IFNPM, INFT, and PFNM. Regression analyses on log-transformed drug dosages were used to test the significance of age on individual requirements. Results In each of the above anesthetic drug combinations, reduced doses of fentanyl, propofol, midazolam, thiopental, and isoflurane were used with increasing age. Fentanyl, propofol, thiopental, and isoflurane showed a 10%, 8%, 6%, and 4% reduction in dose per decade of age, respectively, from age of maximum dose to age 80 years. Conclusions In clinical practice, increasing age results in decreased anesthetic drug administration. The mechanism of this observation needs to be determined.

Pharmacological effects of intravenous melatonin: comparative studies with thiopental and propofol

Possible utility of high-dose i.v. melatonin as an anaesthetic adjuvant has not been studied. This study compared its effects with thiopental and propofol. Sprague Dawley rats were assigned to receive bolus or cumulative i.v. doses of melatonin, thiopental or propofol. Righting reflex, hindpaw withdrawal to a noxious stimulus, response to tail clamping and haemodynamic effects were assessed. Melatonin caused a dose-dependent increase in paw withdrawal threshold and the percent of rats displaying loss of the righting reflex. Melatonin was comparable to thiopental and propofol in terms of its rapid onset of hypnosis. The mean ED(50) values for loss of righting reflex were 5.4 (SEM 1.2), 12.5 (1.1) and 178 (1.1) mg kg(-1) for propofol, thiopental and melatonin, respectively. The percent of rats displaying loss of response to tail clamping was greater with propofol than with melatonin (P<0.05). Haemodynamic changes produced by melatonin or propofol were similar in onset and magnitude. I.V. melatonin can exert hypnotic effects similar to those observed with thiopental and propofol. Melatonin exhibited significant antinociceptive effects but was less effective in abolishing the response to tail clamping.

Evaluation of intraperitoneal and subcutaneous lidocaine and bupivacaine for analgesia following ovariohysterectomy in the dog

Many dogs in private practice undergo ovariohysterectomy (OHE) without analgesics. The purpose of this study was to determine if intraperitoneal (IP) and subcutaneous (SQ) lidocaine or bupivacaine provide analgesia following OHE. Thirty dogs presenting to the Veterinary Teaching Hospital for elective OHE were included in the study. All dogs were pre-medicated with acepromazine and butorphanol IM, induced with thiopental, and maintained with isoflurane. Dogs were randomly assigned to three groups: 10 received 8.8 mg kg−1 2% lidocaine with epinephrine IP (LID), 10 received 2.2 mg kg−1 0.75% bupivacaine IP (BUP), and 10 received 0.9% saline IP (SAL) upon completion of OHE. All IP doses were standardized to 0.88 mL kg−1 with saline. An additional 2 mL of the assigned solution was placed SC as a splash block prior to incisional closure. Dogs were scored at 0.5, 1, 2, 3, 6, 8, and 18 hours post-extubation by one observer blinded to treatment status. Dogs were evaluated using a visual analogue scale (VAS) for pain and sedation, and a scoring system that included physiologic and behavioral variables. Dogs were given supplemental analgesia with 0.22 mg kg−1 butorphanol ± acepromazine if their VAS (pain) score was >50. Parametric variables were analyzed using Student's t-test or Repeated Measures anova as appropriate. Nonparametric variables were analyzed by χ2-test. There were no significant differences in age, weight, incision length, surgery time, anesthesia time, or total thiopental dose between groups. Peak pain scores for all groups occurred at 0.5 hour and returned to baseline by 18 hours. Dogs in the BUP group had significantly lower pain scores at 0.5 hour than did dogs in the SAL group. Seven out of 10 dogs in the SAL group, 4 out of 10 dogs in the LID group, and 2 out of 10 dogs in the BUP group were given supplemental analgesia. No adverse side-effects were observed. Our findings supported the use of IP and SC bupivacaine for post-operative analgesia following OHE in the dog.

Effects of medetomidine-midazolam, acepromazine-butorphanol, and midazolam-butorphanol on induction dose of thiopental and propofol and on cardiopulmonary changes in dogs.

To evaluate dose-sparing effects of medetomidine-midazolam (MM), acepromazine-butorphanol (AB), and midazolam-butorphanol (MB) on the induction dose of thiopental and propofol and to examine cardiopulmonary changes in dogs. 23 healthy Beagles. Dogs were administered MM, AB, MB, or physiologic saline (0.9% NaCI) solution (PS) IM, and anesthesia was induced with thiopental or propofol. Cardiopulmonary measurements were obtained before and after administration of medication and 0, 5, 10, and 15 minutes after endotracheal intubation. Induction doses were reduced significantly by preanesthetic administration of MM, AB, and MB (thiopental, 20, 45, and 46% after administration of PS; propofol, 42, 58, and 74% after administration of PS, respectively). Recovery time in dogs administered MM-thiopental or MM-propofol and AB-propofol were significantly prolonged, compared with recovery time in dogs administered PS-thiopental or PS-propofol. Relatively large cardiovascular changes were induced by administration of MM, which were sustained even after the induction of anesthesia. Administration of AB and MB induced cardiovascular changes during and immediately after endotracheal intubation that were significantly decreased by induction with thiopental or propofol. However, mild hypotension developed with AB-propofol. Apnea was observed in dogs administered MM during induction of anesthesia, but most respiratory variables did not change significantly. Preanesthetic medication with MM greatly reduced the anesthesia induction dose of thiopental and propofol but caused noticeable cardiopulmonary changes. Preanesthetic medication with AB and MB moderately reduced the induction dose of thiopental and propofol and amelio rated cardiovascular changes induced by these anesthetics, although AB caused mild hypotension.

Positive experimental demonstration of the negative brain "protective" effects of anesthetics following cardiac arrest.

The cerebral metabolic effects of a massive dose of thiopental (177 mg/kg) were investigated in seven dogs. The systemic circulation was supported with an extracorporeal circuit. At an infusion rate of 2 mg/kg/min, cerebral oxygen consumption (CMR(O(2))) decreased progressively until cerebral electrical silence was produced. This occurred after a mean dose of 72 mg/kg, which caused a mean decrease in CMR(O(2)) to 58% of the control value (measured at 1.5% halothane inspired). Thereafter, despite continued at 4 mg/kg/min, CMR(O(2)) did not decrease further. The oxygen-glucose index never changed during the infusion period and, at the termination of the infusion, brain assays for ATP, phosphocreatine, lactate, and pyruvate revealed normal concentrations. It is concluded that there was no alteration in normal cerebral metabolic pathways, that cerebral metabolic effects of thiopental are secondary to functional effects, that thiopental would provide no cerebral protection during hypoxia sufficient to abolish cerebral function, and that thiopental does not uncouple oxidative phosphorylation.

Antioxidant Actions and Early Ultrastructural Findings of Thiopental and Propofol in Experimental Spinal Cord Injury

Thiopental and propofol are effective antioxidant agents. The current study was undertaken to examine the neuroprotective effects of a single intraperitoneal dose of thiopental and propofol. Effects of the drugs were evaluated by lipid peroxidation and ultrastructural findings. Fifty male Wistar rats were divided into five groups. Group 1 was the control group. Rats underwent laminectomy only, and nontraumatized spinal cord samples were obtained 1 hour after surgical intervention. All other rats sustained a 50-g/cm contusion injury by the weight drop technique. Group 2 rats underwent spinal cord injury alone, group 3 rats received 1 mL intralipid solution intraperitoneally immediately after trauma as the vehicle group, group 4 rats received a 15-mg/kg single dose of thiopental, and group 5 rats received a 40-mg/kg single dose of propofol intraperitoneally following the trauma. Samples from groups 2, 3, 4, and 5 were obtained 1 hour after injury. Lipid peroxidation was determined by measuring the concentration of malondialdehyde in the spinal cord tissue. The ultrastructure of the spinal cord was determined by electron microscopy. The contusion injury was associated with a rise in lipid peroxidation. Compared with the trauma group there was significant attenuation in lipid peroxidation of groups 4 and 5. Ultrastructural findings showed that the rats of group 4 sustained minor damage after spinal cord injury, but there was more evident damage in group 5 rats. These results indicate that thiopental decreases lipid peroxidation and improves ultrastructure, whereas propofol decreases lipid peroxidation without improving ultrastructure 1 hour after spinal cord injury in rats.

Hepatic Failure After Rectal Acetaminophen

In Response: We thank Drs. Reddy and Srinivas very much for the comment on our case report (1). The acetaminophen suppositories given contained hard fat (adeps solidus) a mixture of mono-, di-, and triglycerides of saturated fatty acids. The bioavailability of acetaminophen is 60%–70% according to the manufacturer. We agree, however, that the dose of acetaminophen given to our patient on the first day was large. As to the doses of thiopental and metronidazole, they were those recommended by the producers and approved by the Danish Medicines Agency. The recommended dose of thiopental in Denmark in children is 7–8 mg/kg body weight. Supplementary doses may be added until the ciliary reflex can no longer be elicited. Metronidazole was given IV during operation in a single dose of 25 mg/kg body weight for prophylaxis because infection with anaerobic bacteria was feared. The comment points out some interesting possible interactions among the drugs administered to our patient. In support of their theories, it may be added that the clearance of a single oral dose of metronidazole at 30 mg/kg is much lower in malnourished children than in nourished controls (2). We agree that the fasting state may have been crucial to the hepatic failure seen in our patient. However, we still think that the exact cause of the hepatotoxicity is uncertain and that sevoflurane may have been involved. We therefore suggest that similar patients be closely monitored. Ole Andersen Søren Elkjaer Lene Bruun

Effects of propofol and thiopental on the central nervous system during nociceptive stimulation in cats.

Nociceptive stimulation may increase central nervous system (CNS) activity during anesthesia. However, it is not known whether propofol and thiopental have a similar inhibitory effect on the CNS during nociceptive stimulation. Therefore, we compared the antinociceptive effects of propofol and thiopental in cats. In 12 cats, anesthesia was induced with 4% halothane in oxygen and maintained with 0.5% halothane in oxygen. The cortical electroencephalogram (EEG) and the electrical activity from the midbrain reticular neurons (R-MUA) were measured before and after sciatic nerve stimulation. The cats were then allocated to receive cumulative doses of either propofol (n = 6) or thiopental (n = 6) i.v. at 5-min intervals. Two minutes after each dose, the cortical EEG and the R-MUA were compared before and after sciatic nerve stimulation. Propofol and thiopental depressed the basal R-MUA to a similar degree at each dose. Sciatic nerve stimulation increased the R-MUA, and there were no differences in the maximum R-MUA values between propofol and thiopental. The cortical EEGs after each dose of anesthetic without stimulation showed similar patterns, and the patterns of change with stimulation were also similar for these two anesthetics. Propofol and thiopental have similar antinociceptive effects in cats.

High-dose flumazenil potentiates the hypnotic activity of propofol, but not that of thiopental, in ddY mice.

Flumazenil is a specific benzodiazepine agonist, which is reported to have a partial benzodiazepine agonist-like effect at a high dose. This study investigated the effects of flumazenil and midazolam on the hypnotic dose of propofol and thiopental in ddY mice, using a behavioral model. Mice were given either propofol or thiopental intravenously to induce hypnosis, which was defined as a loss of the righting reflex. The mice were pre-treated with flumazenil (0.05, 0.1, or 0.2 mg kg(-1)) or midazolam (0.1 or 0.2 mg kg(-1)), and given propofol or thiopental after a 30-s delay. Pre-treatment with flumazenil (0.1 or 0.2 mg kg(-1)) significantly decreased the hypnotic dose of propofol compared to the control group (9.3+/-0.39 [8.5-10.0] or 9.0+/-0.28 [8.5-9.6] vs. 10.8+/-0.42 [9.9-11.6] mg kg(-1) (ED50+/-SEM and [95% confidence interval]) P<0.05), but not that of thiopental (9.1+/-0.30 [8.5-9.7] with 0.2 mg kg(-1) flumazenil vs. 9.3+/-0.42 [8.4-10.1] mg kg(-1) with saline). Midazolam reduced the hypnotic dose of both propofol and thiopental. Flumazenil antagonized the potentiating effect of midazolam (0.2 mg kg(-1)) on the hypnotic activity of propofol. These results suggest that the hypnotic activity of propofol is potentiated by the partial agonist activity of flumazenil in ddY mice.

Educational simulation of the electroencephalogram (EEG)

We describe a model for simulating a spontaneous electroencephalogram (EEG) and for simulating the effects of anesthesia on the EEG, to allow anesthesiologists and EEG technicians to learn and practice intraoperative EEG monitoring. For this purpose, we developed a linear model to manipulate the amplitude of the activity in each of the traditional EEG frequency bands. Burst suppression patterns are simulated by manipulating an overall gain. To demonstrate the model feasibility, model parameters for thiopental and isoflurane were estimated guided by published data on the EEG effects of these anesthetic drugs. Using these estimates, EEG time signals were simulated for isoflurane at various partial pressures, and for bolus intravenous doses of thiopental. Comparison with actual recorded EEG signals showed that the changes produced by isoflurane and thiopental in the simulated signals are very similar to the changes in the actual signals, which was confirmed by two clinicians with experience and routine practice in intraoperative EEG monitoring.

Haemodynamic and cerebral effects of burst suppressing doses of thiopental and propofol in severely brain-injured patients

s and Programme: European Society of Anaesthesiologists; 9th Annual Meeting with the Swedish Society of Anaesthesiology; Gothenburg, Sweden, 7-10 April 2001: Neurosciences: Monitoring Equipment and Computers

Development and Clinical Application of Electroencephalographic Bispectrum Monitoring

Development and Clinical Application of Electroencephalographic Bispectrum Monitoring Jay Johansen;Peter Sebel; Anesthesiology

The Hemodynamic and Adrenergic Effects of Perioperative Dexmedetomidine Infusion after Vascular Surgery

We tested dexmedetomidine, an alpha(2) agonist that decreases heart rate, blood pressure, and plasma norepinephrine concentration, for its ability to attenuate stress responses during emergence from anesthesia after major vascular operations. Patients scheduled for vascular surgery received either dexmedetomidine (n = 22) or placebo (n = 19) IV beginning 20 min before the induction of anesthesia and continuing until 48 h after the end of surgery. All patients received standardized anesthesia. Heart rate and arterial blood pressure were kept within predetermined limits by varying anesthetic level and using vasoactive medications. Heart rate, arterial blood pressure, and inhaled anesthetic concentration were monitored continuously; additional measurements included plasma and urine catecholamines. During emergence from anesthesia, heart rate was slower with dexmedetomidine (73 +/- 11 bpm) than placebo (83 +/- 20 bpm) (P = 0.006), and the percentage of time the heart rate was within the predetermined hemodynamic limits was more frequent with dexmedetomidine (P < 0.05). Plasma norepinephrine levels increased only in the placebo group and were significantly lower for the dexmedetomidine group during the immediate postoperative period (P = 0.0002). We conclude that dexmedetomidine attenuates increases in heart rate and plasma norepinephrine concentrations during emergence from anesthesia. The alpha(2) agonist, dexmedetomidine, attenuates increases in heart rate and plasma norepinephrine concentrations during emergence from anesthesia in vascular surgery patients.

Thiopental intensifies the euthyroid sick syndrome after cardiopulmonary resuscitation.

The study protocol was approved by the Human Studies Committee of the School of Medicine, Keio University. Informed consent was obtained from the patients’ families. Five subjects who received continuous intravenous thiopental following successful cardiopulmonary resuscitation at the General Intensive Care Unit of Keio University Hospital were studied (Table 1). After they had been successfully resuscitated and cardiovascular stability had been achieved, the patients received a 5mg·kg21 intravenous dose of thiopental followed by a continuous infusion at the rate of 3mg·kg21·h21 over 48 to 72h. The duration of thiopental administration was determined by clinical status, such as convulsions. Blood samples were obtained from each patient before thiopental administration (time 1), after 24h of intravenous thiopental (time 2), at the end of thiopental administration (time 3), and 24h after the termination of thiopental (time 4). Serum samples were separated and stored at 220°C until assayed. They were analyzed for total thyroxine (T4), total triiodothyronine (T3), free triiodothyronine (fT3), reverse triiodothyronine (rT3), and thynoid-stimulating hormone (TSH) by radioimmunoassay (RIA). Corticotropin (ACTH) was also measured to assess pituitary function in three cases (patients 2, 3, and 4). Routine hematologic and chemical analyses were done daily, and the data were recorded. Medications such as adrenocortical steroids and dopamine, which may influence thyroid function, were administered at the physician’s discretion and also recorded.

Midazolam premedication and thiopental induction of anaesthesia: interactions at multiple end-points

We have studied the effects of midazolam premedication on multiple anaesthetic end-points (hypnotic, loss of verbal contact (LVC); motor, dropping an infusion flex or bag (DF); analgesic, loss of reaction to painful stimulation (LRP); and EEG, attainment of burst suppression (BUR)) during induction by slow thiopental infusion at a rate of 55 mg kg-1 h-1. Patients received midazolam 0.05 mg kg-1 i.v. (group TM, n = 12) or no midazolam (group T0, n = 13). ED50 and ED95 values and group medians for times and doses at the end-points were measured. Midazolam premedication reduced significantly thiopental ED50 and ED95 values at all end-points (exception for ED95 for BUR). Potentiation was greatest for the motor end-point (dropping the infusion bag (DF)) (ED95 +52%, ED50 +23%, median +39%), and smallest for painful stimulation (LRP) (median +18%; ED50 +13%). For LRP and DF, premedication was associated with significant, non-parallel increases in the slope of the thiopental dose-response curves, resulting in marked potency ratio changes from ED50 to ED95 (LRP +31%, DF +29%). There were no such increases for LVC or BUR. The interaction between midazolam and thiopental varied with the anaesthetic end-point and may also depend on the dose of thiopental. Our data suggest that the mechanism of interaction between midazolam premedication and thiopental was different for motor effects or analgesia (DF, LRP) compared with hypnotic effects or cortical depression (LVC, BUR), in agreement with the different central nervous system substrates underlying these distinct anaesthetic end-points.

Retention of nociceptor responses during deep barbiturate anesthesia in frogs

Bullfrogs ( Rana catesbeiana) anesthetized with a large dose of thiopental (42.8 mg/kg) retained movement responses to nociceptor stimuli despite an average plasma drug level of 51 mg/l, of which 63% was bound to plasma proteins. This concentration, when corrected to include only unbound and uncharged drug, was 2-fold greater than those reported to abolish nociceptor response (NR) during surgical anesthesia in man. The median anesthetic dose (AD 50) for loss of the righting reflex was 11.2 mg/kg by s.c. injection into the abdominal lymph sac; however, at 54.0 mg/kg, all frogs retained NRs, although otherwise deeply anesthetized. The ratio of NR-blocking dose to light AD was thus >4.8, as compared to <2 in mammalian studies. Whole body levels of thiopental determined at 3 h after intralymphatic injection showed that about half the injected drug had been eliminated by this time and that termination of anesthesia was chiefly due to drug elimination. Even though the pharmacokinetics of thiopental appears to differ markedly in frogs and men, the poor analgesia seen in the present study frequently has been reported during clinical barbiturate anesthesia. Since this deficiency is much more pronounced in the bullfrog than in man, its neurophysiological basis might profitably be studied using the bullfrog as a model; however, the high mortality associated with deep thiopental anesthesia in the frog should preclude its use as a practical anesthetic in amphibia.