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PubMed1997

Distribution of drugs in various tissues in a brain dead man.

We examined the distribution of drugs in a 49-year-old brain-dead man. Our objective was to determine the possibility of diagnosing how and at what point the patient became brain dead. The presence of mepivacaine, pentazocine, lidocaine and thiamylal in various tissues, including seven regions of the brain were confirmed, using gas chromatography/mass spectrometry. Tissue-to-blood concentration ratios of mepivacaine, pentazocine and lidocaine in the brain were higher than these ratios in other tissues, while ratios of thiamylal were lower. Therefore, cerebral blood flow was likely to have ceased between the administration of the former drugs and that of the latter drug, in agreement with clinical records. Among seven regions of the brain, the ratios of the former three drugs were high in occipital and parietal lobes, and were low in the cerebellum and medulla oblongata. On the other hand, the ratios of the latter drug were high in the cerebellum and the medulla oblongata. Therefore, cerebral blood flow presumably ceased first in occipital and parietal lobes, and last in the cerebellum and the medulla oblongata. Based on these results, assessment of concentrations of drugs in human tissues, including various regions of brain is useful to determine the time and progression of brain death.

Analgesics, Opioid↗
PubMed2000

Dual effects of intravenous anesthetics on the function of norepinephrine transporters.

BACKGROUND: Norepinephrine transporters (NETs) terminate the neuronal transmission of norepinephrine, which is released from noradrenergic neurons. To investigate the interaction with NET, the authors examined the effects of short- and long-term treatment with anesthetics on the activity and mRNA level of NET. METHODS: To assay [3H]norepinephrine uptake, bovine adrenal medullary cells in culture were incubated with [3H]norepinephrine in the presence of intravenous anesthetics, including propofol, thiamylal, and diazepam. To study the direct interaction between the anesthetics and NET, the effect of propofol on the binding of [3H]desipramine to the plasma membrane was examined. To study the long-term effect of anesthetics, [3H]norepinephrine uptake by cells pretreated with propofol for 6-24 h and [3H]desipramine binding after pretreatment for 12 h were measured. Simultaneously, we examined the effect of anesthetics on the expression of NET mRNA using the reverse transcriptase-polymerase chain reaction. RESULTS: All of the intravenous anesthetics inhibited [3H]norepinephrine uptake in a concentration-dependent manner. The active concentrations of propofol (1-3 microm) and thiamylal (< or = 30 microm) were similar to those encountered clinically. The kinetic analysis revealed that all the anesthetics noncompetitively inhibited [3H]norepinephrine uptake. Propofol inhibited [3H]desipramine binding with a potency similar to that observed in [3H]norepinephrine uptake. Scatchard analysis showed that propofol competitively inhibited [3H]desipramine binding. On the other hand, long-term treatment of cells with propofol (10 microm) enhanced the NET functional activity and [3H]desipramine binding, and also increased the level of NET mRNA. CONCLUSIONS: These results suggest that intravenous anesthetics have a dual effect on NET; short-term treatment causes inhibition, whereas long-term treatment leads to up-regulation. The interaction of intravenous anesthetics with NET may modulate the neuronal transmission of norepinephrine during anesthesia.

Adrenal Medulla↗
PubMed2006

Effects of premedication medicines on the formation of the CYP3A4-dependent metabolite of ropivacaine, 2', 6'-Pipecoloxylidide, on human liver microsomes in vitro.

Ropivacaine is a relatively new amide-type local anaesthetic, mainly used for surgery and postoperative pain relief. In this study we have investigated the interaction between the CYP3A4 metabolite of ropivacaine, 2',6'-pipecoloxylidide (PPX), and premedication with, i.e., psychotropic and antianxiety agents (diazepam, midazolam), hypnotics (thiamylal), local anaesthetics (lidocaine), depolarizing muscular relaxants (vecuronium), antihypertensive (clonidine) and H(2)-receptor antagonist (cimetidine) using human liver microsomes in vitro. The effects of the interaction between PPX and premedications were examined using a human liver microsomal preparation in vitro. The concentrations of ropivacaine and PPX were determined by HPLC with UV detection. The apparent Michaelis-Menten constant (Km) and the maximal velocity of total metabolic formation (V(max)) of PPX, the main metabolite of ropivacaine in human liver microsomes, were 17.7 (microM, mean) and 711 (nmol/min./mg protein, mean), respectively. Five premedications (diazepam, lidocaine, cimetidine, vecuronium and clonidine) did not inhibit ropivacaine metabolism in human liver microsomes at concentrations within the therapeutic range. However, midazolam and thiamylal weakly inhibited ropivacaine metabolism in competitive manner (IC(50) 7.8 microM and 250 microM, respectively). The results show lack of interaction between ropivacaine and seven premedication medicines within the therapeutic range of ropivacaine using human liver microsomes in vitro.

Amides↗
PubMed1993

Chronic ocular hypertension alters local retinal responsiveness.

Electrophysiological responses of the retina and visual cortex to a series of grating stimuli (6-768 minutes of arc) were recorded in seven sessions using normal beagles, 21 sessions using beagles afflicted with inherited ocular hypertension, and 12 sessions using rhesus monkeys. A 15 degrees field centred around the animal's area centralis or fovea was used to stimulate the central retina. A 30 degrees field, centred on the same spot, was then used to stimulate the larger area. Two recording series were completed on each animal, with both field sizes presented in each recording session. The first recording took place 30 minutes after and the second 2 hours after the injection of thiamylal sodium. Only the signals from the toroidal 15 degrees of the retina of the hypertensive dogs were remarkably larger during the second recording (p = 0.001). No significant differences were found between the two recordings from the retinas of normal dogs or monkeys, nor were there any significant differences between the two recordings from above the cortex in any group. Several hypotheses are proposed to explain the basis for the interaction of thiamylal with the more peripheral retinal function in clinically glaucomatous dogs.

Animals↗
PubMed1987

[Barbiturate therapy in 16 cases with intracranial lesion with special reference to the indication and limitation].

The effects and indications of barbiturate therapy for brain protection, and prevention and reduction of the intracranial hypertension were investigated using an ultrashort acting barbiturate, thiamylal, in sixteen cases with intracranial lesions. Final outcome of the treatment revealed 8 good recoveries which were actively administered thiamylal during operation or immediately after. On the other hand, four cases, whose intracranial pressures (ICPS) of over 40 mmHg could not be controlled suffered brain death. Barbiturate therapy was not effective for brain protection of primary damaged lesions. It is concluded that barbiturate therapy may provide a satisfactory reduction of the intracranial hypertension in cases during the early postoperative stage or of under 40 mmHg initial ICP.

Adolescent↗
PubMed1999

Incidence of histamine release after the administration of midazolam-ketamine in allergic patients.

OBJECTIVE: We examined the effects of midazolam-ketamine which was used during the induction of anesthesia against histamine release, skin reactions and hemodynamic changes in patients with a history of allergy. SUBJECTS: Forty allergic patients and 40 non-allergic patients undergoing oral surgery were examined. METHODS: Midazolam ketamine was used for the induction of anesthesia in 40 patients with a history of allergy (M-K group) and thiamylal was used for the induction of anesthesia in 40 patients without any history of allergy (BARB group). Venous blood samples were obtained before induction as a control and 0.5, 1, 3, 5 minutes after the administration of each drug in order to measure the plasma histamine level. In addition, any observed hemodynamic changes were simultaneously recorded. The plasma histamine level was measured using the HPLC (high performance liquid chromatography) post-label system. RESULTS: The incidence of histamine release, skin reactions and hemodynamic changes were 37.5%, 10.0% and 7.5%, in the M-K group, and 40.0%, 12.5% and 12.5%, in the BARB group, respectively. Although the mean basal plasma histamine level in the M-K group (0.46 +/- 0.23 ng/ml) who had a history of allergy was much higher than that in the BARB group (0.28 +/- 0.17 ng/ml) (p < 0.001), the incidence of histamine release and clinical symptoms were similar between the two groups. CONCLUSIONS: The induction of anesthesia with midazolam-ketamine was thus found to be a valuable method for allergic patients, because the incidence of histamine release, skin reactions and hemodynamic changes in allergic patients were similar to those in non-allergic patients induced by thiamylal and no significant changes were observed in the plasma histamine level after the administration of midazolam-ketamine in spite of the high level of basal plasma histamine.

Adolescent↗
PubMed1975

Evaluation of xylazine as a sedative and preanesthetic agent in horses.

Xylazine administered intramuscularly (IM) to horses at the dose level of 2 mg/kg was an effective sedative and preanesthetic for thiamylal sodium narcosis or thiamylal sodium and halothane anesthesia. Evaluation of response of cardiovascular, respiratory, and hepatic function did not indicate serious untoward effects, although cardiac and respiratory rate decreased, calculated vigor of left ventricular contraction decreased, calculated peripheral vascular resistance increased, and transient innocuous cardiac arrhythmias occurred. Effects of the anesthetics used on respiratory function (blood gases and pH), using xylazine as a preanesthetic, were comparable with those observed when promazine was used. The onset of action of xylazine given IM was at least as rapid as that occurring when promazine was given intravenously; e.g., 5 minutes for first observable effects, and 15 to 20 minutes for maximal effect. Recovery, times from anesthesia when using xylazine administered IM as a preanesthetic agent were comparable with those reported after promazine was given intravenously; moreover, horses given xylazine were more calm during recovery and seldom tried to stand before they were able.

Anesthesia, Inhalation↗
PubMed2004

[Complete neurological recovery in a patient with decerebrate rigidity following cardiac arrest from acute airway obstruction by advanced laryngeal cancer].

A 59-year-old man presented with severe dyspnea caused by advanced laryngeal cancer. As he had disregarded the dyspnea for a month, we did not have enough information about the extent of the tumor. The pulse oximeter showed 88% with oxygen inhalation. Because of severe dyspnea, he could not maintain supine position. Fiberoptic laryngoscopy showed tumor bulk obstructing airway directly. In the operating room, at first, a cricothyroid membrane puncture was attempted under local anesthesia but the procedure was abandoned when the patient became hypoxic and unconscious. Immediately tracheostomy and cardiopulmonary resuscitation were performed. Tumor bulk had displaced the trachea and surrounding structures, making a tracheostomy difficult. Nine min after loss of consciousness, a secure airway was obtained. However, he was still unconscious and developed characteristic decerebrate rigidity. Therefore the patient was treated with infusion of thiamylal and free radical scavenger and mild hypothermia therapy (bladder temperature 34 degrees C). On the fifth day of this treatment, after rewarming and discontinuation of thiamylal, the patient responded to command. He recovered with no neurological deficits. This case suggests that combined treatment with barbiturate, free radical scavenger, and mild hypothermia therapy is effective to minimize ischemic brain damage after cardiopulmonary resuscitation.

Acute Disease↗
PubMed1991

Treatment of acute systemic toxicity after the rapid intravenous injection of ropivacaine and bupivacaine in the conscious dog.

Two groups of six beagle dogs received rapid intravenous (IV) injections of ropivacaine or bupivacaine on two occasions in a blinded random fashion. Initially, a dose sufficient to cause convulsions (CD) was given followed by twice the CD (2 x CD), which was administered 48 h later. The CD of bupivacaine (4.3 mg/kg) and ropivacaine (4.9 mg/kg) caused significant (P less than 0.05) increases in heart rate and mean arterial blood pressure. There was no difference between drug groups. Seizures were abolished by 10 mg/kg of intravenous thiamylal. Endotracheal intubation and controlled respiration with O2-enriched air with no other treatment resulted in rapid and complete recovery in all dogs. All dogs receiving 2 x CD of bupivacaine (8.6 mg/kg) or ropivacaine (9.8 mg/kg) were initially treated with thiamylal and mechanical ventilation. Two dogs in the bupivacaine group developed hypotension, respiratory arrest, ventricular tachycardia, and ventricular fibrillation, which were resistant to closed chest cardiac massage, treatment with epinephrine, bretylium, and atropine, and direct current cardioversion. The four remaining dogs in the infusion group were successfully resuscitated. All of the animals in the ropivacaine-treated group survived the administration of the 2 x CD dose. Mild hypotension developed in one dog and was treated with intravenous epinephrine (0.75 mg). This resulted in nodal tachycardia, which was abolished after treatment with bretylium. Another dog had two 1-s bursts of premature ventricular contractions requiring no treatment. The rapid treatment of convulsions and cardiovascular toxicity resulted in a decreased number of deaths in both groups when compared with dogs from a previously published study in which no therapy was instituted. Thus, early aggressive treatment of central nervous system and cardiovascular system toxicity is capable of reducing the incidence of mortality associated with the rapid intravenous administration of excessive doses of local anesthetics.

Amides↗
PubMed1991

[Effects of epidural clonidine added to lidocaine solution upon the requirements of sedatives during epidural anesthesia].

The authors studied 34 patients undergoing abdominal total hysterectomy in order to evaluate whether epidural clonidine added to lidocaine solution could alter the requirements of sedatives during epidural anesthesia. Patients were randomly assigned to one of four groups; 18 ml of 2% lidocaine with 1:200,000 clonidine (n = 6), 1:100,000 clonidine (n = 7), 1:200,000 epinephrine (n = 13), or neither (plain, n = 8). The requirements of sedatives (diazepam, thiamylal) and analgesic (butorphanol) prior to the second epidural injection were compared among the four groups. The dose of intravenous diazepam or thiamylal required for sedation in the patients receiving lidocaine with 1:100,000 clonidine had a tendency to be smaller as compared with those in other three groups. There was a significant difference (P less than 0.05) in the requirement of diazepam between the patients given lidocaine with 1:100,000 clonidine and those given plain lidocaine. The present results suggest that the addition of clonidine to lidocaine solution could reduce the requirements of sedatives in epidural anesthesia.

Adult↗
PubMedDate not supplied

Influence of barbiturate anesthetic induction on circulatory responses to morphine.

Circulatory responses to morphine (1 mg/kg, 10 mg/min) following a barbiturate anesthetic induction (thiamylal 4 mg/kg) were determined in 7 patients with coronary artery disease. Compared with awake measurements, the mean arterial pressure and cardiac index were decreased 16 and 42 percent, respectively (p less than 0.05) and systemic vascular resistance increased 35% (p less than 0.05) at the end of morphine infusion. The same dose of morphine, but without prior barbiturate, has been previously reported not to significantly alter these measurements. Therefore, the assumption that morphine is associated with minimal circulatory changes may be invalidated by the prior administration of thiamylal.

Adjuvants, Anesthesia↗
PubMed1986

Barbiturate anesthesia in greyhound and mixed-breed dogs: comparative cardiopulmonary effects, anesthetic effects, and recovery rates.

The cardiovascular effects, anesthetic effects, and recovery rates were evaluated in racing Greyhounds under barbiturate anesthesia. Greyhounds and mixed-breed dogs of similar body weights were given (by IV route) thiopental (15 mg/kg), thiamylal (15 mg/kg), methohexital (10 mg/kg), and pentobarbital (20 mg/kg). The anesthesia lasted longer in Greyhound than in non-Greyhound mixed-breed dogs given thiopental, thiamylal, and methohexital. The mean times from recumbency to standing were 3 to 4 times longer for Greyhounds anesthetized with thiobarbiturates than for non-Greyhound mixed-breed dogs anesthetized with the same drugs, with recovery times for some Greyhounds lasting more than 8 hours. With thiobarbiturate anesthesia, Greyhounds had long periods of respiratory depression, struggled, and relapsed into sleep, whereas in the other dogs, the recovery was quiet. Respiratory depression related to the stage of anesthesia was produced by all barbiturates, but did not result in significant changes in blood gas values. Rectal temperature decreased in all dogs, but did not result in significant hypothermia. Cardiovascular variables and acid-base estimations in Greyhounds were not significantly different from those in mixed-breed dogs before and during barbiturate anesthesia. Packed cell volumes in Greyhounds were significantly higher than those in non-Greyhound mixed-breed dogs after the thiobarbiturates and methohexital were administered. Total plasma protein concentrations were significantly lower in Greyhounds, compared with those in the other dogs before and during barbiturate anesthesia. Methohexital is a useful alternative to thiobarbiturates for short-duration barbiturate anesthesia in Greyhounds.

Anesthesia, General↗
PubMedDate not supplied

Rise in plasma free-norepinephrine during anesthetic induction with ketamine.

Mean plasma free-norepinephrine concentration rose significantly (p less than 0.001) during induction of anesthesia with intravenous ketamine (2.0 mg/kg) in 12 patients. In contrast, no change occurred during induction with thiamylal (5.0 mg/kg) in a control group of 8 patients. No significant rise in plasma free-epinephrine concentration occurred in either ketamine or thiamylal groups. These data support the suggestion that increased venous return mediated by the sympathetic nervous system may be responsible for the increased cardiac output and hypertension known to occur during ketamine anesthesia.

Anesthesia, Intravenous↗
PubMed1994

Precipitation profile of the intravenous induction agents.

To investigate the formation of precipitation between various intravenous agents, we cross-matched the anesthetic agents commonly used in the induction phase. Thiopentone and thiamylal precipitated in combination with non-depolarizing muscle relaxants, lidocaine, morphine, and meperidine. Ketamine and etomidate were naive to these agents. Crystalloidal solutions, such as lactated Ringer, normal saline, and dextrose solution did not contribute to the formation of precipitate. In conclusion, our study indicates that intravenous line must be irrigated before and after thiopentone and/or thiamylal. In order to prevent precipitate formation, mixtures of various drugs should be avoided until in vitro assay is done.

Anesthesia, Intravenous↗
PubMed1997

Effects of intravenous anesthetics on the contraction and response of rat trachea to phosphatidylinositol.

Some intravenous anaesthetics have significant effects on the tonicity of airway smooth muscle. There are evidences for a direct relationship between airway smooth muscle contraction and phosphatidylinositol (PI) response. The aims of this study were to clarify 1) the effects of anaesthetics on the cholinergically induced contraction, and 2) the relationship between the effects on the PI response and the contraction. Rat tracheal rings or slices were incubated in Krebs-Henseleit solution containing 5.5 microM carbachol (CCh) in the presence of varying doses of anaesthetics. Thiamylal, fentanyl, ketamine and midazolam all attenuated the CCh-induced contraction. On the other hand, thiamylal augmented inositol monophosphate (IP1) accumulation, whilst ketamine, midazolam and morphine did not have the effect, and fentanyl significantly attenuated IP1 accumulation. These data suggest that airway smooth muscle can be relaxed by intravenous anaesthetics, and that the relaxing effects are not always dependent on the PI system.

Analysis of Variance↗
PubMed2002

Anesthetic management for a patient with Jansky-Bielschowsky disease.

PURPOSE: To describe the anesthetic management of a patient with Jansky-Bielschowsky disease (JBD), the late infantile form of neuronal ceroid lipofuscinosis, characterized by dementia, severe and drug resistant grand mal, myoclonic seizures, and blindness. CLINICAL FEATURES: A 14-yr-old girl with JBD was scheduled for resection of a gingival tumour and an infected sinus in the sacral area. Her preanesthetic examination revealed extreme muscle atrophy and dementia. Grand mal, myoclonic seizures, and upper airway obstruction were frequent. Following iv induction with thiamylal, anesthesia was maintained with sevoflurane, N(2)O and O(2). Her trachea was intubated without using muscle relaxants. Muscle relaxants were not used during the operation. Apart from an intractable hypothermia, the intraoperative course was uneventful. The emergence of anesthesia was smooth, except for persisting seizures. CONCLUSION: General anesthesia using thiamylal and sevoflurane provided satisfactory conditions during operation in a patient with JBD. Intraoperative hypothermia required particular attention.

Adolescent↗
PubMed2004

Premedication medicines do not cause drug metabolic interaction with propofol using human liver microsomes in vitro.

OBJECTIVE: Propofol (2,6-diisopropylphenol) is widely used for anesthetic induction as well as for chronic sedation in intensive care units. In this study, we investigated the interaction between propofol and premedications, i.e., psychotropic and antianxiety agents (diazepam, midazolam), hypnotics (thiamylal), local anesthetics (lidocaine), depolarizing muscular relaxants (vecuronium), an antihypertensive (clonidine) and an H2-receptor antagonist (cimetidine) using human liver microsomes in vitro. METHODS: The interaction effects between propofol and premedications were examined using human liver microsomal preparation in vitro. The concentration of propofol was determined by HPLC with UV detection. RESULTS: The apparent Michaelis-Menten constant (Km) and the maximal velocity of total metabolic formation (Vmax) of propofol in human liver microsomes were 123 microM and 26.1 micromol/min per milligram of mg protein, respectively. Seven premedications (diazepam, midazolam, thiamylal, lidocaine, cimetidine, vecuronium, and clonidine) did not inhibit propofol metabolism in human liver microsomes at concentrations within the therapeutic range. CONCLUSIONS: These results showed no interactions between propofol and seven premedication drugs within the therapeutic range of propofol using human liver microsomes in vitro.

Anesthetics, Intravenous↗
PubMed2003

Hemodynamic and bispectral index responses to tracheal intubation during isoflurane or sevoflurane anesthesia.

PURPOSE: The effects of volatile anesthetics on change in the bispectral index (BIS) due to tracheal intubation are unclear. We investigated hemodynamic and BIS responses to intubation during isoflurane or sevoflurane anesthesia. METHODS: After obtaining Institutional Review Board approval and informed consent, we randomly allocated 40 patients of American Society of Anesthesiologists (ASA) physical status I to receive either isoflurane (ISO group; n = 20) or sevoflurane (SEV group; n = 20). The patients were anesthetized with thiamylal and were ventilated with 100% oxygen, using a mask. The inspired concentrations of isoflurane and sevoflurane were gradually increased and maintained at end-tidal anesthetic concentrations of 2 minimum alveolar concentration (MAC) during the study period. Tracheal intubation was performed 15 min after the end-tidal anesthetic concentrations had reached 2 MAC. Mean arterial pressure (MAP), heart rate (HR), and BIS were recorded before induction, at the loss of consciousness, before laryngoscopy, and at 1, 3, and 5 min after intubation. RESULTS: Anesthesia with 2 MAC volatile anesthetics increased HR in the ISO group, and decreased MAP in the SEV group. The BIS value decreased from 95 +/- 3 and 96 +/- 2 before thiamylal to 39 +/- 9 and 38 +/- 10 before intubation in the ISO and SEV groups, respectively. MAP and HR were significantly increased in both groups 1 and 3 min after intubation, but BIS remained unchanged. CONCLUSION: Anesthesia with 2 MAC of isoflurane and sevoflurane was effective to suppress the change in BIS due to intubation but was not sufficient to prevent changes in hemodynamic responses.

Adult↗