Analgesic and cardiopulmonary effects of premedication with tramadol in calves anesthetized with the infusion of guaifenesin and thiamylal.

This study examined the analgesic and cardiopulmonary effects of intravenous (IV) tramadol during general intravenous anesthesia in calves. Calves were premedicated with diazepam (0.2 mg/kg, IV) with tramadol (2 mg/kg, IV) (group T) or saline (group S). Anesthesia was induced by thiamylal sodium (4 mg/kg, IV) and maintained with an infusion (2 ml/kg/hr) of 5% guaifenesin containing thiamylal sodium (2 mg/ml). Additional thiamylal sodium (1-2 mg/kg, IV) was administered when interference from the calves was observed during surgery. The total counts of additional thiamylal sodium administration, analgesia score using a visual analog scale, recovery time, and cardiopulmonary function in the different groups were assessed and compared. Group T showed significantly fewer counts of additional drug administration and a significantly higher analgesia score. Tramadol may provide adequate analgesia with minimal cardiopulmonary changes in calves during general anesthesia.

Thiamylal anaesthetic therapy for febrile refractory status epilepticus in children.

PURPOSE: To evaluate barbiturate anaesthetic therapy using thiamylal for febrile refractory status epilepticus (fRSE) in children. METHODS: This was a review of a prospectively-collected database between April 2012-March 2016 for fRSE cases treated with thiamylal anaesthetic therapy in a single paediatric hospital in Japan. The sample comprised 23 children (median age, 23 months) with fRSE that underwent thiamylal anaesthetic therapy for convulsive seizures lasting longer than 60 min, sustained after intravenous administration of benzodiazepine and non-benzodiazepine anticonvulsants. The intervention comprised protocol-based thiamylal anaesthetic therapy with bolus administration. We measured the dose and time required to achieve the burst suppression pattern (BSP) on electroencephalography, seizure recurrence, death, neurological sequelae, and complications. RESULTS: All patients except one reached the BSP. The thiamylal median dose until reaching the BSP was 27.5 mg/kg, and the median time from thiamylal administration to reaching the BSP was 109.5 min. There was one case of immediate treatment failure and one of withdrawal seizure, but no breakthrough seizure. No deaths occurred during treatment, and neurological sequelae occurred in four cases (17%). Vasopressors were administered in all cases. Other complications included 11 cases of pneumonia and one of enterocolitis. CONCLUSION: We revealed the time and dose required to reach the BSP with thiamylal anaesthetic therapy using bolus administration in children. Our results suggested that reaching the BSP with bolus administration requires markedly less time than without bolus administration, rarely causes seizure recurrence in paediatric fRSE, and causes haemodynamic dysfunction and infections as often as observed without bolus administration.

Intravenous ketogenic diet therapy for treatment of the acute stage of super-refractory status epilepticus in a pediatric patient.

BACKGROUND: A ketogenic diet has been used successfully to treat intractable epilepsy. However, the role of early intravenous initiation of ketogenic diet in the acute phase of super-refractory status epilepticus is not well-described. METHODS: An intravenous ketogenic diet was administered to a boy with super-refractory status epilepticus. At 24 hours after intravenous ketogenic diet, moderate ketosis appeared, and thiamylal was successfully weaned at 70 hours after admission. RESULTS: An intravenous ketogenic regimen led to subsequent ketosis and seizure control in a child with super-refractory status epilepticus. CONCLUSION: Early induction of ketosis may be a novel strategy to effectively treat super-refractory status epilepticus. Although there are few data regarding the early use of intravenous ketogenic diet in the treatment of super-refractory status epilepticus, it may be considered an alternative option.

Procedural sedation with dexmedetomidine during ablation of atrial fibrillation: a randomized controlled trial.

AIMS: Procedural sedation by non-anaesthesiologists with GABAergic anaesthetics has the potential risk of fatal respiratory depression. Dexmedetomidine works its sedative action via α2-adrenergic receptors, and is less associated with respiratory depression. We tested the usability of dexmedetomidine as a procedural sedative during ablation of atrial fibrillation (AF). METHODS AND RESULTS: Consecutive patients were randomized to be treated with dexmedetomidine (n = 43) or thiamylal (n = 44) as sedatives during AF ablation. Apnoeic and body movement events were monitored using a novel portable respiratory monitor, the SD-101, during the procedure. Although the majority of the patients receiving dexmedetomidine required rescue sedations with thiamylal, the respiratory disturbance index (RDI) defined as the total number of sleep-disordered breathing events divided by the recording time (10.4 ± 5.1 vs. 18.2 ± 8.1 events/h; P < 0.0001) and movement index defined as the number of body movement events per hour (7.6 ± 6.1 vs. 11.0 ± 5.5 events/h; P = 0.0098) were both significantly lower in the dexmedetomidine arm than in the thiamylal arm. A multivariate linear regression analysis including potential factors revealed that dexmedetomidine vs. thiamylal was solely and independently associated with the RDI (ß = -0.62; P = 0.0031). The occurrence of hypotension [9 (21%) vs. 4 (9%); P = 0.14] and bradycardia [4 (9%) vs. 4 (9%); P = 1.0] were similar in the patients with dexmedetomidine and thiamylal. CONCLUSION: Procedural sedation with dexmedetomidine may assure safety and patient immobility during AF ablation, and therefore may be a potential alternative for that with GABAergic anaesthetics.

[A survival case of tetanus complicated with disseminated intravascular coagulation syndrome in the elderly, rescued by mechanical ventilation and administration of thiamylal].

A 78-year-old Japanese female was admitted to our hospital because of headache. Trismus, opisthotonus and convulsion appeared in the early morning on the second hospital day. She was diagnosed as tetanus based on these symptoms and the history of trauma on her left hand 6 days ago. A piece of bamboo was extracted from her left hand. However, Clostridium tetani was not identified. Thiamylal and mechanical ventilation were initiated combined with Pancronium, Diazepam and tetanus immune globulin. Gabexate Mesilate was also added for disseminated intravascular coagulation syndrome probably associated with rhabdomyolysis. By these treatments, she was healed leaving only a disuse syndrome of her limbs.

[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.

[Quantitative analysis of plasma concentration of barbiturate for diagnosis of brain death].

Organ transplantation from brain death patients started in Japan in 1997. However it is difficult to diagnose brain death in patients treated with barbiturate therapy. In this study, the influence of long continuous administration of barbiturate on diagnosis of brain death was investigated by measuring plasma concentration of barbiturate. In 15 patients treated with barbiturate therapy, plasma concentrations of thiamylal were measured by liquid chromatographic apparatus every day until it's level decreased below 0.1 microgram/ml after cessation of continuous administration. At the same time, plasma thiamylal levels were checked on the day when burst-suppression (b-s) pattern had disappeared in 9 cases, light reflex of pupil appeared in 7 cases and spontaneous respiration had been detected by trigger lamp in 11 cases. The plasma concentrations of thiamylal on the day when b-s pattern had disappeared differed clearly among the cases in the range of 8.8 to 37.9 micrograms/ml. Those cases in which light reflex of the pupil had been recognized were also different in the range of 17.8 to 57.8 micrograms/ml. The cases in which spontaneous respiration had been detected were in the range of 4.4 to 23.0 micrograms/ml. These concentrations varied about 4, 3 and 5 times among the cases examined. The intervals between cessation of continuous administration of thiamylal and the decrease of plasma concentration to below 0.1 microgram/ml also varied from 2 to 14 days from case to case. The minimum concentration of thiamylal on the day when b-s pattern had disappeared, light reflex of the pupil had been recognized and spontaneous respiration had been detected was 8.8, 17.8 and 4.4 micrograms/ml respectively. These results suggest that diagnosis of brain death in patients treated with barbiturate therapy is able to be made when the plasma thiamylal level is below 4.4 micrograms/ml.

A huge frontal meningioma associated with intraoperative massive bleeding and severe brain swelling--case report.

A 58 year old female presented with progressive memory disturbance and personality change. Magnetic resonance (MR) imaging disclosed a huge mass lesion accompanied by prominent oedema in the right frontal lobe. Cerebral angiogram demonstrated a vascular-rich tumour and a major drainer through diploic vein. A right frontotemporal craniotomy was performed. We encountered massive bleeding from diploic vein and dura mater immediately at the craniotomy. We were also faced with severe brain swelling at the dural incision. The tumour was solid, highly vascularised, and fairly well demarcated. We performed total removal of the tumour as quickly as possible in order to reduce the intracranial hypertension and avoid the impending brain herniation. The patient had an uneventful recovery and was asymptomatic at 10 months follow-up.

Complete recovery of consciousness in a patient with decorticate rigidity following cardiac arrest after thoracic epidural injection.

A 46-yr-old man with dysaesthesia (burning sensation) following herpes zoster in the left upper chest region was treated with a single thoracic (T2/T3) epidural injection (1.0% lidocaine 3 ml + 0.125% bupivacaine 3 ml) as an outpatient. Twenty minutes after the injection, a nurse noticed the patient to be unconscious with dilated pupils, apnoea and cardiac arrest. Following immediate cardiopulmonary resuscitation, the patient was treated with an i.v. infusion of thiamylal sodium 2-4 mg kg-1 h-1 and his lungs were mechanically ventilated. When the patient developed a characteristic decorticate posture, mild hypothermia (oesophageal temperature, 33-34 degrees C) was induced. On the 17th day of this treatment, after rewarming (35.5 degrees C) and discontinuation of the barbiturate, the patient responded to command. Weaning from the ventilator was successful on the 18th day. About 4 months after the incident, the patient was discharged with no apparent mental or motor disturbances. We suggest that mild hypothermia with barbiturate therapy may have contributed to the successful outcome in this case.

Pharmacokinetics of thiamylal enantiomers in humans.

Thiamylal, a chiral thiobarbiturate, is marketed as the racemate. The pharmacokinetic behavior of thiamylal enantiomers was studied in patients undergoing thiamylal treatment. The percentage of R(+)-thiamylal unbound to serum protein was 1.5 times greater than that of S(-)-enantiomer (17.5 +/- 2.6% and 11.7 +/- 2.0% mean +/- SD, p < 0.001, n = 7). The pharmacokinetic parameters of enantiomers were estimated in 6 patients. S(-)-thiamylal serum concentration was higher than R(+)-enantiomer in all patients at all time points examined. Total clearance of R(+)-thiamylal (0.27 +/- 0.23 1/hr/kg) was 1.8 times greater (p < 0.05) than that of S(-)-thiamylal (0.15 +/- 0.13). The volume of distribution at steady state of R(+)-thiamylal (3.66 +/- 1.99 l/kg) was 1.4 times higher (p < 0.05) than that of S(-)-enantiomer (2.60 +/- 1.35). The differences in these parameters may be due mainly to enantioselective binding to serum protein.

The effect of ketamine or thiamylal on succinylcholine-induced myoglobinemia under halothane anesthesia in adults.

We studied the effect of intravenous (IV) thiamylal or ketamine on the increases in serum myoglobin, creatine kinase (CK), and potassium induced by succinylcholine under halothane anesthesia. Ninety patients were divided into three groups. In Group O, succinylcholine (1.0 mg/kg) was administered after an the inhaled induction of anesthesia with halothane. In Group T, thiamylal (4.0-5.0 mg/kg), and in Group K, ketamine (1.5-2.0 mg/kg) was injected prior to succinylcholine administration. Anesthesia was maintained with halothane, nitrous oxide, and oxygen. Myoglobin increased in Group O at 60 min to 855 ng/mL (median) and CK to 98.6 IU/L. These increases were significantly higher than those of Group T (110 ng/mL and 66.4 IU/L) and Group K (110 ng/mL and 57.0 IU/L). Potassium increased in Group O only. There was no significant difference between Groups T and K for any of the three values. These results indicate that IV thiamylal and ketamine both suppress the increases of myoglobin, CK, and potassium, and that in cases when succinylcholine is used, both drugs can help to avoid myoglobinemia and limit the increases of CK and potassium.

Experimental study on the indications for barbiturate therapy. Change in haemodynamics and the influence of dopamine.

The effect of barbiturates on the cerebral haemodynamics and the influence of dopamine on barbiturates were investigated using 20 cats, and clinical indication of barbiturate therapy is discussed. Cerebral blood flow, oxygen extraction fraction, and cerebro-vascular resistance as well as physiological variables were evaluated at various concentrations of barbiturates in the blood. Thiamylal caused simultaneous reduction of mean arterial blood pressure and cerebral blood flow. As the disruption of autoregulation proceeded, cerebro-vascular resistance and oxygen extraction fraction increased till the barbiturate-induced coma stage. Furthermore, cerebro-vascular resistance increased much more markedly by the combined use of dopamine. Clinically, our results indicate barbiturates would increase cerebral circulatory disturbances caused by vasospasm following subarachnoid haemorrhage because barbiturates further increase cerebro-vascular resistance. Then again, the combined use of dopamine is not preferable because of deterioration in vasospasm.

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.

[Barbiturate therapy in traumatic cerebral vascular disease: report of two cases].

We report two cases of traumatic cerebral vascular disease which were treated successfully with barbiturate. The first case sustained blunt trauma to the bilateral vertebral arteries, resulting in complete occlusion of both arteries. After ligation of the injured vertebral arteries, multiple cerebral infarction appeared. Cerebral angiography revealed dissection and stenosis of the bilateral internal carotid arteries. We treated this case with barbiturate (Thiamylal) in combination with administration of heparin. The second case sustained cerebral contusion and traumatic subarachnoidal hemorrhage as a result of a motor cycle accident. This patient deteriorated and cerebral angiography showed diffuse cerebral arterial vasospasms. When this was treated with induced hypertension, he developed recurrent subarachnoid hemorrhage. In order to protect the brain from ischemia without elevating blood pressure, we employed barbiturate therapy and the patient recovered without major neurological deficit. The condition of severe head injury with cerebral ischemia is complicated. Therefore it has been hard for neurosurgeons to cure the patient with this condition. But we treated it with barbiturate successfully. Barbiturate therapy in severe head injury with cerebral ischemia may decrease the mortality in that group of patients considered difficult to treat with the usual therapeutic modalities.

[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.

Multisystem degeneration: drugs and square wave jerks.

We studied a 55-year-old woman with macrosquare wave jerks and macrosaccadic oscillations with a vertical component. The oscillations almost completely disappeared after administration of diazepam, clonazepam, thiamylal, or phenobarbital. A disorder of GABAergic tonic inhibitory system from the substantia nigra to superior colliculus probably plays an important the pathogenesis of these abnormal ocular movements. role in the pathogenesis of these abnormal ocular movements.