Preservation of the ischemic canine myocardium: a comparison of hypothermia, lidoflazine, and ketanserin.

The purpose of this study was to determine whether ketanserin protects the globally ischemic canine heart and whether such protection, if present, is independent of that provided by hypothermia or calcium channel blockade with lidoflazine. Forty mongrel dogs, anesthetized with halothane, were divided into eight groups of five and subjected to one hour of global myocardial ischemia during hypothermic (30 degrees C; groups 1 to 4) or normothermic (37 degrees C; groups 5 to 8) cardiopulmonary bypass (CPB). Dogs in groups 1 and 5 served as controls with respect to prebypass myocardial protective therapy, and received only placebo (a normal saline bolus) prior to CPB. Before bypass, dogs in groups 2 and 6 received lidoflazine, 1.25 mg/kg intravenously (IV); those in groups 3 and 7 received ketanserin, 5 mg IV bolus, followed by a continuous infusion at 33 microg/min during bypass. Animals in groups 4 and 8 were given both lidoflazine and ketanserin according to the dosing schedules above. No type of pharmacologic or mechanical cardiovascular support was provided after termination of CPB. Postbypass hemodynamic performance and survival of the unsupported animal were assumed to reflect the degree of myocardial protection during CPB. One minute after bypass, mean arterial pressure and cardiac output were decreased in all groups. Cardiac output was lower in groups 5 to 8 (normothermic CPB) than in groups 1 to 4 (hypothermic CPB). After CPB, left ventricular filling pressures were elevated in all groups kept normothermic and in group 3 (hypothermic CPB plus ketanserin). By 15 minutes after CPB, there were no survivors in groups 5, 7, and 8. Sixty percent of animals in group 6 (normothermic CPB plus lidoflazine) survived to the end of the study. Relative odds of survival were increased 110-fold by hypothermia and sevenfold by lidoflazine. Conversely, treatment with ketanserin was associated with an increased likelihood of nonsurvival. It is concluded that, at the doses studied, ketanserin does not protect the canine myocardium against ischemic injury and may exert a detrimental effect when combined with calcium channel blockade in this setting.

Fentanyl pretreatment modifies anaesthetic induction with etomidate.

Haemodynamic changes and side-effects of induction of anaesthesia with etomidate were evaluated in 60 ASA Class I or II patients. The objective was to find an optimal pre-induction dose of fentanyl which eliminated haemodynamic changes and side-effects during induction and intubation without introducing other problems. Patients were randomly assigned to four groups according to the pretreatment dose of fentanyl (Group I = 2 ml normal saline; Group II = 100 micrograms of fentanyl; Group III = 250 micrograms of fentanyl; Group IV = 500 micrograms of fentanyl) administered intravenously five minutes prior to induction of anaesthesia with etomidate, 0.3 mg/kg. There was an increasing incidence of apnoea (53, 87, 87 and 100% in Groups I-IV respectively) and a decreasing incidence of myoclonus (60, 33, 13 and 0% in Groups I-IV respectively) and injection pain (53, 13, 7 and 0% in Groups I-IV respectively), P less than 0.002 chi-square test for linear trends, with increasing fentanyl dosage. The incidences of postoperative nausea and vomiting were similar in the four groups. There were also significant linear regression relationships (P less than 0.01 ANOVA for linear regression) between increasing doses of fentanyl administered before etomidate and the prevention of increases in systolic blood pressure and heart rate during the induction-intubation sequence. The data demonstrate that increasing pre-induction doses of fentanyl are more effective at minimising side-effects and preventing increases in systolic arterial blood pressure and heart rate but also increase the incidence of apnoea during induction. The results suggest that 500 micrograms of fentanyl is an ideal pretreatment dose in fit patients prior to anaesthetic induction with etomidate.

Induction of anesthesia with fentanyl or fentanyl plus etomidate in high-risk patients.

Anesthetic doses of fentanyl (46 +/- 1.3 micrograms/kg) and oxygen (group I) were compared to a moderate dose of fentanyl (3 to 4.7 micrograms/kg; mean = 3.54 +/- 0.1 micrograms/kg) + etomidate (0.4 mg/kg) intravenously (IV) (group II) during the anesthetic induction-endotracheal intubation sequence to evaluate hemodynamic changes and the incidence of side effects in 23 New York Heart Association class III and IV patients. Chest wall rigidity only occurred in group I (27%), and pain on injection (8%) and myoclonus (25%) only in group II. Patients in group I experienced transient, small increases in central venous pressure (immediately after induction) and mean pulmonary artery pressure (after tracheal intubation). Patients in group II had small, transient decreases in heart rate, mean arterial blood pressure and cardiac index after induction which returned to baseline levels immediately after tracheal intubation. The data indicate that a modest dose of fentanyl with etomidate is similar to a large (anesthetic) dose of fentanyl in terms of avoiding cardiovascular depression and preventing hemodynamic stimulation during and following the induction-tracheal intubation sequence. Our findings also demonstrate that these doses of fentanyl before etomidate decrease but do not eliminate side effects of etomidate. The results suggest that a modest dose of fentanyl followed by etomidate may be an attractive alternative to high doses of fentanyl in patients with limited cardiovascular reserve, especially when prolonged postoperative respiratory depression secondary to high doses of an opioid is undesirable.

Etomidate versus thiopental for induction of anesthesia.

Hemodynamic changes and side effects of anesthesia induction with etomidate or thiopental were evaluated in 83 ASA class I or II patients. Patients were randomly assigned to one of 12 groups according to pretreatment drug (fentanyl, 100 micrograms, or normal saline intravenously), induction agent (etomidate, 0.4 mg/kg, or thiopental, 4 mg/kg), and maintenance anesthetic technique (isoflurane-oxygen, isoflurane-nitrous oxide-oxygen, or fentanyl-nitrous oxide-oxygen). The purpose of this experiment, of factorial design, was to evaluate the combined effects of two or more experimental variables used simultaneously and to observe interaction effects. There were significant increases in heart rate in all groups, especially after tracheal intubation. These increases were attenuated but not eliminated by fentanyl pretreatment. Systolic arterial blood pressure increased significantly after intubation and was not affected either by fentanyl pretreatment or by the induction agent. Patients in whom anesthesia was induced with etomidate had a greater incidence of pain on injection and myoclonus and a lesser incidence of apnea than patients in whom anesthesia was induced with thiopental. Fentanyl pretreatment significantly decreased the incidence of pain on injection and myoclonus, but it increased the incidence of apnea when anesthesia was induced with etomidate. The incidence of postoperative nausea and vomiting was similar after thiopental and etomidate and was unaffected by fentanyl pretreatment. (ABSTRACT TRUNCATED AT 250 WORDS)