Astride B. Seifen

Tonic-clonic activity after sufentanil.

The article by Goroszeniuk et al. (1) prompts us to report a recent experience we had with narcotics and seizures. Our patient, a 69-yr-old, 75-kg man with three vessel coronary artery disease was scheduled for coronary artery bypass grafting. Medications included propranolol, 20 mg, four times per day. After premedication with 2 mg lorazepam and 6 mg morphine, the patient was brought to the operating room where ECG leads (chest lead V) were applied and intravenous and intraarterial cannulae placed. While the patient was breathing 100% oxygen by mask, pancuronium, 1 mg, was given, followed by sufentanil, 50 pg. The patient appeared sedated; heart rate was 86 beats1 minute and blood pressure 118/70 mm Hg. Shortly after administration of these drugs, tonic-clonic activity of the extremities started. The pupils were small and equal, with conjugate deviation to the right. Movements of the extremities spontaneously ceased in less than 30 sec. Pulse and blood pressure remained unchanged from baseline during the episode. Induction was completed with incremental doses of sufentanil to a total of 1000 pg and pancuronium, 10 mg. No further abnormal movements were observed intraor postoperatively. The patient was awake with spontaneous movement of all extremities several hours later and was extubated 10 hr postoperatively. No neurologic deficits were present. He had no memory of the event, and his postoperative course was unremarkable. Grand ma1 seizure activity has been reported after as little as 100 p g of fentanyl (2). Seizure-like movement with an absence of seizure activity on a simultaneous EEG recording during fentanyl administration has been reported (3). Sebel et al. investigated the effects of high-dose fentanyl on the EEG and found no evidence of seizure activity (4). However, high-dose fentanyl in rats can induce both clinical and EEG evidence of seizures (5). The effects of sufentanil on EEG activity has been investigated by Bovill et al., who found sharp wave activity of unclear significance with no clinical evidence of seizure activity following a dose of 15 pg/kg (6). No previous reports of seizure or seizure-like activity resulting from sufentanil have appeared to our knowledge. The etiology of the abnormal movement observed by us is unclear. It may represent seizures, myoclonic activity, or an atypical form of rigidity resulting from narcotic administration. Premedication with lorazapam did not prevent its occurrence.

Pharmacokinetics of intravenous procaine infusion in humans.

Pharmacokinetic data during and following the continuous intravenous infusion of procaine are lacking. We studied 12 women undergoing hysterectomy during N2O-O2 and narcotic anesthesia. A constant infusion of 2% procaine was administered at a rate of 1 mg/kg/min to six patients (group I) and at a rate of 1.5 mg/kg/min to the other six (group II). Procaine plasma levels were determined by flame ionization gas-liquid chromatography. Using a two-compartment pharmacokinetic model, disposition kinetics were studied. Steady-state plasma levels were achieved within 20 to 30 minutes after commencement of the infusion. Following termination of the infusion the drug disappeared with a distribution half-life (t½ α) of 2.49 ± 0.36 minutes and an elimination half-life (t½β) of 7.69 ± 0.99 minutes at both infusion rates. In group I, the fraction of drug in the central compartment was 65%, the volume of distribution at steady-state was 0.79 ± 0.14 L/kg, and total body clearance 0.08 ± 0.01 L/kg/min. In group II, the fraction of drug in the central compartment was 82%, the volume of distribution at steady-state 0.34 ± 0.07 L/kg, and the total body clearance 0.04 ± 0.01 L/kg/min. These data indicate that procaine is a drug of limited distribution and tissue uptake with a short duration of action.

Aging: Effects on minimum alveolar concentration (MAC) for halothane in Fischer-344 rats

It is well-established that the anesthetic requirement (MAC) of volatile agents such as halothane is reduced in elderly patients. The current project was designed to determine whether a similar alteration in anesthetic requirement occurs in Fischer-344 (F-344) rats, an animal model often utilized in physiology and pharmacology to examine aging-related changes. Animals were exposed to increasing or decreasing levels of halothane. After equilibration at each concentration, the response to tail-clamping was used for MAC testing. MAC was reduced approximately 17% in aged (25 months) versus young adult (5 months) animals. From these data, it is concluded that the F-344 rat may be an adequate model for examination of age-dependent alterations in the actions of volatile anesthetics.

Comparison of cardiac effects of enflurane, isoflurane, and halothane in the dog heart-lung preparation.

Minimum alveolar concentration (MAC) was determined in intact dogs (N = 10 for each anesthetic) to be 2.12 +/- 0.04 vol% for enflurane (ENF), 1.28 +/- 0.04 vol% for isoflurane (ISO), and 0.94 +/- 0.03 vol% for halothane (HAL). Then, the direct cardiac effects of these three anesthetics were studied at 0.36, 0.6, 1.0, and 1.2 MAC in the dog heart-lung preparation (HLP): an in situ whole heart preparation devoid of major extracardiac influences and reflex control. All three agents produced concentration-dependent decreases in heart rate (HR) that became significantly different from control at 0.6 MAC. HAL and ISO reduced +dP/dtmax by the same degree at all MAC levels, becoming statistically significant at 0.6 MAC, while a significant reduction in +dP/dtmax for ENF occurred first at 1.0 MAC. Marked increases in left atrial pressure (LAP) were observed at 1.0 MAC for all anesthetics and the first significant depression of systemic output (SO) occurred at 1.0 MAC. Each agent produced significant shifts of the left ventricular function curves (LVFC) to the right with each consecutive MAC fraction. Marked reductions in the slope of the LVFC were first observed at 1.0 MAC, and this change in slope was more pronounced with ENF. At 1.2 MAC, ENF seemed to produce a more severe cardiodepression than HAL or ISO, as suggested by a greater incidence of cardiac failure; however, this was not statistically significant. In general, the data suggest that at MAC fractions up to 0.6, ENF is less cardiodepressant than ISO or HAL, but that ENF has a tendency to be more depressant than HAL or ISO at concentrations higher than 1.0 MAC.

Reappraisal of intravenous procaine as a short-acting anesthetic adjuvant

Our data in 74 patients demonstrate that procaine hydrochloride is a safe anesthetic adjuvant in doses of 1 mg/kg/min even when total doses are 5 to 7 g. Blood pressure, heart rate, electrocardiographic variables, and blood gases were not adversely affected. Patients had no nausea or untoward postanesthesia symptoms. Emergence from anesthesia was rapid, within less than 15 minutes in all patients, and most were fully awake before leaving the operating room. In two patients in whom blood levels were studied the drug disappeared within 40 minutes. Procaine is inexpensive,

A dosage nomogram for sodium nitroprusside-induced hypotension under anesthesia.

1.16 for 10 g, and it is not a known liver or kidney toxin. Until studies on cardiovascular dynamics and analgesic effects as in whom a low plasma cholinesterase activity is present or suspected. The clinical appraisal in 56 patients indicates its usefulness in suppressing premature venticular contractions and cough reflexes during endoscopic procedures in the respiratory tract. Procaine can be used to advantage in supplementing general anesthesia in outpatient surgery because of its brief action. For these reasons, the drug merits further study.

Effects of Volatile Anesthetics on Response to Norepinephrine and Acetylcholine in Guinea Pig Atria

Sodium nitroprusside (SNP) was used to produce deliberate hypotension in 30 selected patients, 9 to 78 years of age, for total hip replacement under halothane-N2O-O2anesthesia. Hypotension was induced in the first 13 patients by infusing a 0.01% (100 μg/ml) solution of nitroprusside (NP) in 5% dextrose. Blood pressure was diminished to a level just producing a dry surgical field. Preliminary data demonstrated that the mean arterial blood pressure (MAP) achieving this condition was 65 torr (p< 0.01) and that the minute dosage of NP (μg/min) required to consistently reduce MAP to 65 torr could not be predicted on the basis of body weight.However, the age/weight ratio (yr/kg) of each patient, plotted against the known minute dosage of NP given during anesthesia, produced a highly significant dose-response curve (P<0.001, r = −0.8226).The preliminary dose-response curve was examined in a double-blind study on an additional 17 patients. The curve derived from the prospective study did not differ from that of the preliminary study. In addition, the combined data from the retrospective and prospective studies (30 patients) gave a better statistical fit than did those from the preliminary study alone (p<0.001, r = −0.8939).The nomogram provides an additional margin of safety in the use of this potent, fast-acting drug. SNP has been found predictable and effective in reducing surgical blood loss in selected patients undergoing total hip replacement.

Myocardial recovery from the cardiac depressant effects of enflurane and halothane.

The in vitro chronotropic and inotropic effects of norepinephrine and acetylcholine in isolated right and left guinea pig atria were examined in the absence and presence of halothane, isoflurane, and enflurane (0.6 and 1.2 MAC). All three anesthetics elicited dose-dependent reductions in contractile force and spontaneous pacemaker activity. The maximal developed tension observed in the presence of norepinephrine was not altered by the anesthetics and corresponding ED50 values increased only in the presence of 1.2 MAC halothane and 1.2 MAC isoflurane. The anesthetics did not affect (a) the maximal positive chronotropic effect of norepinephrine, (b) the ED50 values for its positive chronotropic effect, and (c) acetylcholine-induced negative inotropic and chronotropic actions and did not induce arrhythmic activity even in the presence of the maximally effective neurotransmitter concentrations. These findings indicate that in isolated guinea pig atria volatile anesthetics, in concentrations up to 1.2 MAC, do not alter the inotropic and chronotropic effects of norepinephrine or acetylcholine and do not induce arrhythmogenic action in the presence of the neurotransmitters. These data suggest that altered atrial responsiveness to adrenergic or muscarinic stimulation does not contribute to the development of anesthetic-induced cardiac arrhythmias.

Intravenous Procaine as a Supplement to General Anesthesia for Carbon Dioxide Laser Resection of Laryngeal Papillomas in Children

Recovery from the cardiac depressant effects of enflurane and halothane was examined in the dog heart-lung preparation (HLP) and in right ventricular muscle isolated from guinea pig hearts. In the HLP. recovery was studied under two conditions: (1) After a two-hour exposure to anesthetic concentrations increasing from 0.36 to 1.2 MAC, and (2) after a one-hour exposure to a single concentration that raised the left atrial pressure (LAP) to 9 to 10 mmHg. Under either condition, +dP/dtmax. was significantly less depressed with enflurane and returned to preanesthetic control levels, while recovery with halothane remained significantly below control. Following the longer exposure. recovery of the LAP and left ventricular function curves (LVFC) was significantly less with halothane; however, this difference was not observed after the shorter exposure period. In electrically paced, isometrically contracting right ventricular strips exposed for one hour to 2.25 vol% enflurane (a concentration that reduced contractility by 45%), force development returned within 60 minutes to values above preanesthetic control values. After an identical depression for one hour with halothane (0.80 vol%), force development recovered to values less than those observed following enflurane. These data indicate that the recovery from anesthetic-induced negative inotropic effects in isolated cardiac preparations is better with enflurane than halothane.

Interaction of BAY K-8644 with effects of digoxin in the dog heart-lung preparation

Procaine suppresses the cough reflex, decreases laryngeal irritability, and has general anesthetic properties. For these reasons, 14 pediatric patients undergoing CO2 laser resection of laryngeal papillomas were studied in which an intravenous infusion of procaine (1 mg/kg/min) was added to N2O-O2 halothane/enflurane general anesthesia immediately following endotracheal intubation. These patients were compared to nine patients receiving the same anesthesia without procaine.The mean age of both groups was 11 years. There was no difference between the groups in duration of anesthesia or surgery. Emergence, however, averaged 15 minutes in study patients compared to 36 minutes in the control group (p<0.01). There was no difference in anesthetic concentrations required to maintain satisfactory operative conditions in the two groups. Muscle relaxants were required intraoperatively in seven control patients but in none of the study patients. The surgeon ranked the operative conditions excellent in all study patients but poor in seven of the nine control patients. Five of the latter required postoperative treatment of laryngeal complications, including reintubation in three. Only one of the study patients had postoperative stridor. No evidence of procaine toxicity was noted in the study patients with total doses ranging from 500–3600 mg. Intravenous procaine is useful in pediatric patients having endoscopic laryngeal operations.