pancuronium and Seizures

Measurements of cerebral oxygen consumption (CVO2) may improve our understanding of cerebral oxygenation, but there are few published data for sick neonates. Although cerebral maturation is associated with an increase in cerebral glucose consumption, the relationship between CVO2 and increasing gestational age has not previously been assessed in humans. The aims of this study were to evaluate a noninvasive method for the estimation of CVO2 in the neonate using near infrared spectroscopy, and to investigate the relationship between gestational age and CVO2. Twenty babies who were undergoing intensive care in the neonatal period were studied. Cerebral hemoglobin flow (CHbF) and cerebral venous oxyhemoglobin saturation (CSVO2) were measured using near infrared spectroscopy. Arterial oxyhemoglobin saturation was measure by pulse oximetry (SpO2). CVO2 was calculated from the equation: CVO2=CHbF x (SpO2 - SvO2 x 4. The median (range) CVO2 was 0.9 (0.52-1.76) mL x 100 g(-1) min(-1). There was an increase in CVO2 with advancing gestational age (n=20, p=0.55, p=0.014). We conclude that CVO2 can be estimated in sick neonates using noninvasive optical methods. The values obtained are similar to those obtained in other studies by more invasive methods, and are in agreement with values which would be expected from the known rate of cerebral glucose consumption in neonates. Mean (SD) CVO2 at 24-26 wk was 0.5 (0.18) mL x 100 g(-1) min(-1) and rose with increasing gestation to term by 0.03 mL x 100 g(-1) min(-1) per wk.

Topics: Anticonvulsants; Brain; Child; Child, Preschool; Female; Gestational Age; Humans; Infant; Male; Morphine; Oxygen Consumption; Pancuronium; Phenobarbital; Seizures

When given for a sufficient time and dose intravenously, neuromuscular blocking drugs eventually can enter the cerebrospinal fluid (CSF). To study the potential pharmacologic consequences of neuromuscular blocking drugs in the CSF, a model was developed in the rat by using an intrathecal infusion of these drugs. A cannula was stereotaxically implanted in a lateral cerebral ventricle of anesthetized male Sprague-Dawley rats (250-300 g). Several days later, the effects of an intraventricular infusion (5 microL/min) of atracurium (0.804 mumol/mL), pancuronium (0.172 mumol/mL), and vecuronium (21.978 mumol/mL) were studied in unanesthetized rats. These rats (n = 6 in each group) exhibited dose-dependent hyperexcitability, during drug infusion, with seizures occurring at threshold doses of (mean), 0.12, 0.26, and 0.065 +/- 0.010 and 3.32 mumol/kg of atracurium, pancuronium, and vecuronium, respectively. The neuromuscular ED50 (intravenous dose required to produce a 50% depression of twitch tension) in rats determined by other investigators are 0.408, 0.115, and 0.352 mumol/kg for atracurium, pancuronium, and vecuronium, respectively. Therefore, seizure threshold doses were not related to the potencies of these drugs as neuromuscular blocking drugs. Based on these data, central nervous system effects were studied over the subseizure dose range approximating 1/100, 1/10, and 1/5 of the cumulative dose causing seizures for each drug (n = 5 for each dose). At 1/100 of seizure dose, decreased locomotor activity and piloerection occurred. At 1/10 to 1/5 of seizure dose, agitation, shivering, splayed limbs, and whole body shaking resulted.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atracurium; Central Nervous System; Dose-Response Relationship, Drug; Injections, Spinal; Male; Neuromuscular Depolarizing Agents; Pancuronium; Rats; Rats, Sprague-Dawley; Seizures; Vecuronium Bromide

We investigated the effects of pancuronium bromide pretreatment on cerebral blood flow (CBF) during bicuculline-induced seizures in anesthetized piglets. Arterial blood pressure, gases, pH, cerebral electrocortical activity, and CBF (radioactive microsphere) were monitored at baseline, 10 min after administration of pancuronium (0.3 mg/kg i.v.; n = 9) or vehicle (normal saline; n = 8), and again at 5, 15, and 60 min after bicuculline (3 mg/kg i.v.). No change in CBF from baseline was observed at 10 min after either saline or pancuronium treatment, before induction of seizures. In the saline group, CBF was 36 +/- 3 mL.min-1.100 g-1 before bicuculline and increased to 166 +/- 24 and 205 +/- 35 mL.min-1.100 g-1 at 5 and 15 min, respectively, after bicuculline, returning toward baseline by 60 min. In the pancuronium group at 5 min after bicuculline, CBF increased from 45 +/- 7 to 169 +/- 26 mL.min-1.100 g-1, but fell to 88 +/- 17 mL.min-1.100 g-1 at 15 min in contrast to saline-treated piglets. Also, at 15 min of seizures, differences between groups were observed in arterial blood pressure, gases, and pH. Although these variables were in the normal range with pancuronium treatment, the saline-treated animals had increased arterial blood pressure (81 +/- 6 mm Hg) and PCO2 (6 +/- 0.4 kPa) and decreased PO2 (7 +/- 0.5 kPa) and pH (6.91 +/- 0.06). Electrocortical activity was abnormal during seizures in both groups. At 60 min, reversal to normal activity was observed in six of nine pancuronium-treated animals versus two of eight saline-treated animals. These data suggest that pancuronium limits cerebral hyperemia during prolonged seizures by attenuating increases in blood pressure as a result of elimination of skeletal muscle activity. This leads to minimal alteration of arterial PCO2, PO2, and pH during seizures.

Topics: Animals; Animals, Newborn; Bicuculline; Blood Pressure; Carbon Dioxide; Cerebrovascular Circulation; Female; Hydrogen-Ion Concentration; Hyperemia; Male; Muscle Contraction; Oxygen; Pancuronium; Seizures; Swine

1. Pretreatment were pancuronium prevented convulsions and hyperthermia, but had no effect on acidemia or changes in cardiovascular parameters after intravenous (i.v.) infusion of phencyclidine (PCP). 2. While dogs survived higher amounts of PCP, they failed to regain spontaneous respiratory function. 3. Mechanical ventilation alone increased the mean lethal dose/time of PCP and reduced the effects of PCP on arterial systolic pressure, cardiac output, and PCO2. 4. EKG showed ventricular arrhythmias, which progressed to death. 5. Phenytoin pretreatment plus respiratory assistance increased the lethal dose and reduced PCP effects on cardiovascular parameters, body temperature, and cardiac rhythm. 6. Blocking of convulsions prevented hyperthermia and acidemia; respiratory support reduced circulatory effects, but respired dogs then died, at higher doses, from a primary myocardial toxicity of PCP.

Topics: Animals; Dogs; Female; Heart; Infusions, Intravenous; Male; Pancuronium; Phencyclidine; Phenytoin; Respiration, Artificial; Seizures; Time Factors

The effect of phenobarbital and pancuronium on cerebral blood flow (CBF) and CBF autoregulation are studied in newborn piglets after chemically induced seizures with bicuculline. Given 3 or 15 min after the onset of seizures, phenobarbital significantly reduces CBF (59 +/- 11 and 56 +/- 17 vs. 84 +/- 24 ml/min/100 g - p less than 0.01). Moreover, during graded hypotension induced by graded haemorrhage, phenobarbital provides reestablishment of CBF autoregulation altered by seizures. In the same experimental model, pancuronium induces in control animals a rise of CBF (61 +/- 15 vs. 38 +/- 11 ml/min/100 g - p less than 0.001). During graded hypotension pancuronium is associated to a loss of CBF autoregulation (r = 0.76, p less than 0.001). Given as an adjunct treatment, in case of seizures, pancuronium has no significant effect on changes in cerebral haemodynamics. From these data, we conclude that pancuronium jeopardizes the haemodynamic adaptation to the induced hypovolemia and that phenobarbital may present a protective effect on cerebral haemodynamics and the subsequent risk for ischaemia or haemorrhage.

Topics: Animals; Animals, Newborn; Bicuculline; Blood Gas Analysis; Cardiac Output; Cerebrovascular Circulation; Pancuronium; Phenobarbital; Seizures; Swine

Among the non-depolarizing neuromuscular blocking drugs, atracurium appears to be unique in its ability to produce cerebral stimulation in lightly anaesthetized animals. This effect is attributed to the atracurium metabolite, laudanosine. The following studies were performed to determine if pretreatments with the non-depolarizing neuromuscular blockers pancuronium, atracurium or vecuronium would differ in their effects on the seizure threshold of lignocaine. Adult mongrel cats were anaesthetized with 1.0 MAC halothane in oxygen and nitrogen. Ventilation, blood-gas tensions, acid-base balance and temperature were controlled. Cats received pancuronium 0.2 mg kg 1 i.v. (n = 7), atracurium 1.0 mg kg-1 i.v. (n = 7) or vecuronium 0.2 mg kg-1 i.v. (n = 7). Ten minutes after the administration of the myoneural blocker, all cats received lignocaine 4 mg kg-1 min-1 i.v. until the onset of EEG evidence of generalized seizure activity. At seizure onset, there were no statistically significant differences among the cumulative lignocaine doses or the serum lignocaine concentrations in cats pretreated with pancuronium, atracurium or vecuronium.

Topics: Anesthesia, Inhalation; Animals; Atracurium; Cats; Electroencephalography; Halothane; Lidocaine; Pancuronium; Seizures; Sensory Thresholds; Time Factors; Vecuronium Bromide

Topics: Brain Stem; Child; Child, Preschool; Craniocerebral Trauma; Diagnosis, Differential; Female; Humans; Male; Pancuronium; Pupil; Seizures

The EEGs of 40 infants paralyzed with D-tubocurarine or pancuronium during the neonatal period were reviewed retrospectively. The 23 infants who survived were re-examined at 1-3 yr of age. Sixteen infants had normal or mildly abnormal EEGs in the neonatal period; 3 died of nonneurologic causes; the remainder were normal at follow-up. Three of 8 infants with moderately abnormal EEGs in the neonatal period died, 2 had neurologic sequelae at follow-up, and 3 were normal at follow-up. Eleven of 16 infants with markedly abnormal EEGs died, and 5 had neurologic deficits at follow-up. Seizures occurred in 16 infants. Ten (63%) of the 16 died, whereas only 7 (29%) of 24 infants without seizures died (p less than .1). Eight infants had seizures only during paralysis. The EEG was statistically the best predictor of neurologic outcome when compared with the following variables recorded before paralysis: estimated gestational age (EGA), birth weight, Apgar score at 1 and 5 min, lowest PO2 and pH and highest PCO2. This study establishes the value of the EEG in the neurologic assessment of iatrogenically paralyzed newborns in the detection of seizures, and confirms previous studies which showed the value of EEG in predicting outcome.

Topics: Electroencephalography; Humans; Infant, Newborn; Infant, Premature; Pancuronium; Prognosis; Retrospective Studies; Seizures; Tubocurarine

The levels of prostaglandin D2 (PGD2) and prostaglandin F2 alpha (PGF2 alpha), being the major prostaglandins formed in mouse brain in vivo were determined using a radioimmunological technique. Under basal conditions, they were less than 8.49 ng/g for PGD2 and less than 3.76 ng/g for PGF2 alpha. During seizures, induced by the centrally acting convulsant pentylenetetrazol, cerebral concentrations of both prostaglandins were markedly enhanced as compared to basal conditions. The seizure evoked increase in brain prostaglandins could be attributed to the enhanced neuronal activity. If convulsions were induced with the spinal cord convulsant strychnine no increase in brain prostaglandins was seen although the occurring hypoxia was probably very similar. Therefore, hypoxia does not seem to play a significant role in the prostaglandin increase. The effect of pentylenetetrazol on cerebral prostaglandins was independent of the mechanical convulsions induced by the drug. Muscle relaxed mice showed the same increase in cerebral prostaglandins as convulsing mice. Muscle relaxation alone had no influence on prostaglandin formation in brain. These data indicate that the increased neuronal activity induced by centrally acting convulsants is likely to be the sole cause for the rise in cerebral prostaglandins. Brain hypoxia, another known stimulus of prostaglandin synthesis, does not seem to play an important role during convulsions.

Topics: Animals; Brain Chemistry; Hypoxia, Brain; Male; Mice; Muscle Relaxation; Neurons; Pancuronium; Pentylenetetrazole; Prostaglandins; Seizures; Strychnine; Time Factors

In experimental animals neurologic damage may occur during seizure activity whether the seizure is accompanied by motor activity and hypoxemia or whether the animal is paralyzed and normoxemic. These findings suggest that it may be important to detect seizure activity in the paralyzed neonate. Nine infants who were mechanically ventilated and paralyzed with pancuronium had their condition diagnosed as seizure activity. Vital signs were continuously monitored and six infants had either oxygen saturation or transcutaneous oxygen measured during seizure activity. For the group as a whole, rhythmic fluctuations in vital signs, cardiac rhythm, and oxygenation occurred every four minutes (range one to seven minutes) and lasted two minutes (range one to four minutes). In seven patients whose seizures were not accompanied by cardiac arrhythmias the following mean increases were noted: systolic arterial blood pressure, 15 mm Hg (range 7 to 36 mm Hg); heart rate, ten beats per minute (-11 to 30/min); oxygen saturation, 12% (range 4% to 20%); and transcutaneous oxygen, 31 mm Hg (range 14 to 45 mm Hg). Seizures in the two patients with cardiac arrhythmias were accompanied by a decrease in systolic arterial blood pressure of 27 mm Hg (range 15 to 40 mm Hg) and in oxygen saturation of 24% (range 20% to 28%). The presence of rhythmic fluctuation in vital signs and oxygenation should alert the physician to the possibility of seizure activity in the paralyzed neonate.

Topics: Anesthesia, General; Blood Pressure; Electrocardiography; Electroencephalography; Humans; Infant, Newborn; Infant, Newborn, Diseases; Monitoring, Physiologic; Oxygen; Pancuronium; Seizures

Conray (meglumine iothalamate), the contrast media frequently used in shuntograms for diagnosing malfunctioning ventriculo-peritoneal shunts, will occasionally cause severe muscular spasms and seizures. In this article, the authors describe anesthetic and critical care management of a case with this complication.

Topics: Anesthesia, Inhalation; Anesthesia, Intravenous; Cerebrospinal Fluid Shunts; Child; Diazepam; Female; Humans; Hyperventilation; Iothalamate Meglumine; Muscle Spasticity; Pancuronium; Positive-Pressure Respiration; Seizures; Thiopental

Topics: Adult; Diazepam; Female; Gastric Lavage; Humans; Male; Pancuronium; Poisoning; Respiration, Artificial; Rodenticides; Seizures; Strychnine; Suicide, Attempted

Topics: Adjuvants, Anesthesia; Adolescent; Adult; Aged; Androstanes; Animals; Blood Circulation; Child; Child, Preschool; Dogs; Female; Humans; Infant; Injections, Intravenous; Intubation, Intratracheal; Male; Middle Aged; Neuromuscular Nondepolarizing Agents; Pancuronium; Seizures