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Comparative pharmacokinetics and pharmacodynamics of remifentanil, its principle metabolite (GR90291) and alfentanil in dogs.

Remifentanil is an esterase-metabolized opioid developed for use in anesthesia. The principal metabolite of remifentanil, GR90291, is considered to be less potent. This study determined the relative potency of GR90291 and alfentanil, compared with remifentanil, in anesthetized dogs. Male dogs received thiamylal sodium, and anesthesia was maintained using isoflurane and N2O in oxygen. Each dog received a 5-min infusion of 0.5 microg/kg/min remifentanil, 500 microg/kg/min GR90291 and 1.6 mg/kg/min alfentanil in random order, separated by 1 week. Serial blood samples were collected during and after the infusion. The electroencephalogram was evaluated using aperiodic analysis. The pharmacokinetics and pharmacodynamics of remifentanil, GR90291 and alfentanil were determined using nonlinear least-squares regression analysis. Remifentanil was rapidly eliminated, with a terminal half-life of 6 min, compared with 19 min for GR90291 and alfentanil. Using the estimated concentration that elicits 50% of the maximum response (EC50) for delta EEG activity and spectral edge95, remifentanil was 4213 to 4637 times more potent than GR90291 and 7.7 to 8.5 times more potent than alfentanil. The blood-brain equilibration half-life was 2.3 to 5.2 min for remifentanil, 0.39 to 0.41 min for GR90291 and 3.1 to 3.7 min for alfentanil.

Alfentanil↗

[Re-rupture of intracranial aneurysm caused by insertion of an intraventricular drainage tube].

A 42-year-old man was admitted to our hospital with subarachnoid hemorrhage, requiring the clipping of an intracranial aneurysm and removal of intracranial hematoma. Anesthesia was induced with thiamylal and maintained with oxygen-nitrous oxide-isoflurane. Trimethaphan was administered continuously and his systolic blood pressure was stably maintained between 100-110 mmHg. Seven minutes after insertion of an intraventricular drainage tube through the dura, his blood pressure increased to 146/76 mmHg. By transdural echogram, re-rupture of the aneurysm was confirmed, and after 6 minutes, a fresh intracranial hematoma was observed. The decrease of intracranial pressure following insertion of the intraventricular drainage tube or the stimulation by several intraventricular punctures seems to have caused re-rupture of the aneurysm. When hemodynamic change is observed without obvious cause in a patient with subarachnoid hemorrhage, it is important to speculate that a re-rupture of the aneurysm has occurred, and to treat the problem accordingly.

Adult↗

[Mild hypothermia anesthesia for carotid microendoarterectomy in a patient with ischemic heart disease].

A 69 year-old male with ischemic heart disease indicated for coronary artery bypass grafting was scheduled for carotid microendoarterectomy. We induced mild hypothermia technique with vasodilation and surface cooling by convecting warming device. We examined hemodynamics by pulmonary artery catheter. Anesthesia was induced with thiamylal, fentanyl, midazolam and isoflurane in nitrous oxide and oxygen. Following administration of vecuronium, trachea was intubated. Pulmonary artery catheter was inserted from the femoral vein. Dopamine, dobutamine 3-5 micrograms.kg-1.min-1 and PGE1 5-10 ng.kg-1.min-1 were continuously administered to keep peripheral blood circulation and cardiac output (CO). Systemic vascular resistance decreased from 1800 to 591 dyne.s.cm-5 and CO increased from 2.8 to 6.9 l.min-1. The occlusion of blood flow of the right carotid artery for 40 min at 34.5 degrees C of rectal temperature did not cause any neurological deficits. No other complications such as arrhythmia, myocardial ischemia and bleeding tendency were observed. Keeping peripheral blood circulation and uniform cooling and warming are important in inducing mild hypothermia safely in a patient with ischemic heart disease.

Aged↗

[Circulatory collapse during laparoscopic cholecystectomy].

A 52 year-old female without any cardiac disease underwent laparoscopic cholecystectomy. Anesthesia was induced with thiamylal and maintained with nitrous oxide and isoflurane. Epidural anesthesia was also used during surgery. When the intraabdominal insufflation was performed in reverse-trendelenburg position 15 minutes after the start of incision, the heart rate suddenly decreased from 75 to 49 bmp with a fall in blood pressure. Her hemodynamic state recovered immediately after the release of intraabdominal pressure and the administration of ephedrine with a rapid infusion of Hespander. The circulatory collapse did not occur when the second insufflation was tried carefully. The circulatory collapse was probably due to the vagal reflex. The decrease in cardiac preload during the reverse trendelenburg position and the epidural administration of local anesthetics may have caused or worsened the circulatory collapse. In anesthetic managements of laparoscopic cholecystectomy using general anesthesia with epidural anesthesia, prophylactic hydrogenation and prevention of parasympathetic domination are important to minimize the vagal reflex.

Anesthesia, Epidural↗

[Pretreatment with magnesium sulphate enhances vecuronium-induced neuromuscular block].

The interaction between magnesium sulphate (MgSO4) and vecuronium was investigated during isoflurane-nitrous oxide-oxygen anesthesia. Neuromuscular function was evaluated by recording the single twitch of the abductor policis muscle. Anesthesia was induced with thiamylal followed by injection of vecuronium. The effects of pretreatment with MgSO4 (20 or 40 mg.kg-1) on the potency of vecuronium were compared with observations in patients without MgSO4 pretreatment (control). We also examined the serum concentration of magnesium ions after administration of MgSO4. We found that the neuromuscular effect of vecuronium was not influenced by pretreatment with MgSO4 20 mg. On the contrary, the onset time of vecuronium was decreased and the duration of action until 25% recovery was increased by pretreatment with MgSO4 40 mg. The serum concentration of magnesium ions after administration of MgSO4 40 mg was significantly higher than that after 20 mg. We conclude that pretreatment with MgSO4 40 mg but not 20 mg enhances vecuronium-induced neuromuscular block.

Adult↗

Comparison of local infiltration of tenoxicam and intravenous tenoxicam for postoperative analgesia in herniorrhaphy.

BACKGROUND: The major complaint of herniorrhaphy is postoperative pain which occurs during the first 24 h after operation. Tenoxicam has a long half-life of 60-80 h. Local infiltration of the drug concentrates the pain control effects in the local area. The local infiltration dose can be smaller than the recommended systemic dose needfully to reach the target area to be effective. Therefore we studied the effect of preoperative local infiltration of tenoxicam on postoperative pain. METHODS: Sixty patients, belonging to ASA classes I and II, undergoing unilateral herniorrhaphy, were randomly assigned to 4 groups. General anesthesia was induced with thiamylal 5 mg/kg, fentanyl 2 micrograms/kg, and atracurium 5 mg/kg. Group 1 (G1) patients were preoperatively injected with 10 mg of tenoxicam in 10 ml normal saline or distilled water, in the operative area. Group 2 (G2) and Group 3 (G3) patients were preoperatively given intravenous tenoxicam, 20 mg and 10 mg, respectively. Group 4 (G4) patients were not given preoperative local infiltration or intravenous tenoxicam to serve as control group. The pain score was assessed at 2 h, 9 h, 24 h postoperatively in all groups. We recorded the total amount of acetaminophen used and the form of administration of the analgesic drug. All patients received general anesthesia in uniform technique. RESULTS: Pain score and amount of analgesic drug required in G1 (local infiltration group) patients were significantly decreased compared with the other groups. The postoperative pain score of Visual Analog Scale (VAS) and analgesic requirement in the four groups were ranked as follows: G1 < G2 < G3 < G4. No significant difference was observed between G2, G3 and G4. Only the pain score in G2 patients significantly decreased (p < 0.05) during the late postoperative period (24 h) when compared with G4 patients. CONCLUSIONS: Preoperative local infiltration of tenoxicam can decrease postoperative pain score significantly during the most painful period (24 h) in herniorrhaphy.

Adult↗

[The inhibition of lidocaine metabolism by various barbiturates in rat hepatic microsome].

To evaluate the effects of various barbiturates on lidocaine metabolism by cytochrome P-450 (P-450), enzyme kinetics were analyzed in an in vitro study using rat hepatic microsomes. Phenobarbital, amobarbital, hexobarbital, pentobarbital, and thiamylal showed the mixed type inhibition of lidocaine metabolism with inhibition constants being 4.89, 1.08, 2.76, 0.77 and 0.65 mM, respectively. Same as lidocaine, all barbiturates used in the present study, corresponding to binding with P-450, induced the I type of spectral change of P-450. Since these did not affect cytochrome C reductase activity, it was suggested that this inhibition of lidocaine metabolism in hepatic microsomes may have been caused by the reduction of activity on P-450 by the barbiturates.

Anesthetics, Local↗

[Pulmonary edema due to acute airway obstruction immediately after tracheal extubation].

A 33-year-old male was scheduled for tonsillectomy and pharyngoplasty due to sleep apnea syndrome. The intubation was uneventful following induction with thiamylal and vecuronium. Anesthesia was maintained with O2-N2O-sevoflurane. No complications were observed during the 90 min operation. After the termination of the anesthesia, a hyperadrenergic state was observed: arterial pressure and heart rate rose to 230/135 mmHg and 135 bpm, respectively. Immediately after extubation, he developed dyspnea with tracheal tag and stridor, and became cyanotic despite the use of a simple oxygen mask and assisted ventilation. Laryngospasm was suspected. The patient was reintubated and suctioned; pink, frothy sputum was not obtained. Arterial blood gases 5 minutes after reintubation revealed a pH of 7.24, Pao2 86 mmHg (FIo2 1.0), and Paco2 54 mmHg. Chest X-ray 30 minutes after reintubation revealed bilateral diffuse alveolar infiltration. The diagnosis was interstitial pulmonary edema. The patient was ventilated mechanically by applying a positive end-expiratory pressure of 5cm H2O, and furosemide and dopamine were administered intravenously. The patient was extubated the next day, and discharged from hospital ten days later. We considered that the lung edema was induced by the severe negative pressure generated by inspirating against a closed upper airway, as well as by the hyperadrenergic state and severe hypoxemia observed during and after extubation.

Acute Disease↗

VAGAL TUNING.

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Animals↗

Practical kinetics I: Quantitation of barbiturate stability by TLC.

The purpose of this work was the application of established techniques to the quantitation of stability investigations of liquid formulations as well as in solution kinetic studies. The process consists of streaking aliquots of reaction solution on TLC plates, development, elution, and analysis of the substances in the eluate. Several barbiturates were investigated regarding their decomposition at elevated temperatures. Reasonable correlation is noted between obtained rate constants and literature data. This technique represents a utilitarian approach to stability screening of compounds in solution, aqueous or otherwise, where chromatographic separation and analytical methodology for the pure compound are available.

Amobarbital↗

Metabolic and endocrine responses to surgery during caudal analgesia in children.

Plasma concentrations of glucose, lactate, epinephrine, norepinephrine, insulin, cortisol and growth hormone were measured in 28 healthy children, three to six years of age, before, during, and after lower abdominal surgery. The children received premedication with secobarbital, 6 mg.kg-1, pentazocine, 0.5 mg.kg-1, and atropine, 0.01 mg.kg-1 im. Fourteen children received general anaesthesia with nitrous oxide and halothane, and 14 others received caudal analgesia with 1.5% mepivacaine. Plasma glucose, epinephrine and norepinephrine concentrations remained unchanged in the general anaesthesia group, but decreased during and after surgery in the caudal analgesia group (P less than 0.05). During surgery, these concentrations were different between the two groups (P less than 0.05). Plasma insulin and cortisol concentrations increased after surgery (P less than 0.05), and growth hormone concentration increased during and after surgery in the general anaesthesia group (P less than 0.05), but the concentrations of these hormones remained unchanged during and after surgery in the caudal analgesia group. Plasma lactate concentrations were unchanged in both groups. These results indicate that caudal analgesia suppresses the metabolic and endocrine responses to stress associated with lower abdominal surgery in children.

Abdomen↗