Cardiovascular effects of pregnanolone emulsion: an experimental study in artificially ventilated dogs.

The acute cardiovascular effects of pregnanolone emulsion, a new steroid preparation for intravenous anaesthesia, were investigated in artificially ventilated dogs. The anaesthetic was administered as repeated intravenous bolus injections, doubling the dosage with each injection. The plasma concentration of pregnanolone, and the haemodynamic, respiratory and metabolic variables were determined after each injection. Cardiac output and heart rate increased from the first bolus dose of the anaesthetic (0.5 mg/kg), which produced anaesthesia lasting 10 to 15 min. Both continued to increase after administration of 1.0, 2.0 and 4 mg/kg, whereas reductions of systemic arterial pressure and estimated myocardial contractility were observed only at the two highest dosages. A decrease in vascular resistance was calculated in the systemic circulation, whereas vascular resistance increased in the pulmonary circulation. A state of circulatory shock followed administration 8, 16 and 32 mg/kg of the anaesthetic.

Dopamine and dobutamine reduce myocardial d-propoxyphene content in experimentally intoxicated rats.

The effect of sympathomimetic intervention with dopamine or dobutamine on the myocardial uptake of d-propoxyphene was investigated experimentally in rats. The d-propoxyphene (19 mg kg-1 h-1) was continuously infused, intravenously, over 45 min. After 20 min of infusion the rats were given either dopamine (12.5 micrograms kg-1 min-1 or 25 micrograms kg-1 min-1), dobutamine (25 micrograms kg-1 min-1 or 45 micrograms kg-1 min-1) or normal saline (control). Each group consisted of eight rats. The myocardial d-propoxyphene content was significantly lower in the two groups given dopamine and in the group given dobutamine 45 micrograms kg-1 min-1 than in the control group (P less than 0.05). This finding indicates the benefit of early sympathomimetic intervention with either dopamine or dobutamine in d-propoxyphene intoxication.

Hypovolemic stimuli and vasopressin secretion in man.

Different non-hypotensive hypovolemic stimuli were applied to 21 healthy and 20 uremic dialysis patients. The purpose was to study the effect on plasma arginine-vasopressin concentration, using orthostasis as a reference model. Orthostasis increased the plasma AVP level in healthy subjects as well as in uremic dialysis patients. In healthy subjects plasma AVP increased both when they were normohydrated and after they had been water-depleted. Lower body negative pressure (LBNP, -40 mmHg) was applied to 11 healthy males to induce a central blood volume decrease, equal to that induced by orthostasis. The plasma AVP increased in two subjects only who became hypotensive during the investigations. Ten hemodialysis patients were volume-depleted by isolated ultrafiltration. A flow directed Swan-Ganz catheter was used to measure the central intravascular pressures. Pulmonary capillary wedge pressure was reduced to normal or subnormal values during 1-2 h of ultrafiltration, without any significant changes in plasma AVP. Plasma AVP increased only in 2 patients, who became hypotensive during the investigations. Thus, of the present non-hypotensive volume stimuli only orthostasis was able to stimulate AVP secretion. Equal or even greater reductions in central blood volumes by other stimuli had no effect on AVP secretion. The results demonstrate that isolated stimulation of low-pressure volume receptors has no effect on the secretion of AVP in humans.

The psychological effects of having a contact-person from the anesthetic staff.

Seventy-four patients admitted for elective surgery completed identical questionnaires and rating scales pre- and postoperatively. The course of anxiety was compared between patients who were either routinely informed or had contact with an anesthetic nurse available for support during the 30-min anesthesia and surgery preparation. Comparing the results with our three other studies, it is concluded that emotional support given by a "contact-person" is more effective than either detailed information or a tranquillizer.

The anticonvulsive activity and toxicity of diazepam in three different formulations. An experimental study in mice.

The anticonvulsive activity (ED50), acute toxicity (LD50), and minimal neurotoxicity (TD50) of diazepam in an emulsion form (Diazemuls) were compared with two different water-based diazepam solutions (Valium and Stesolid). The diazepam preparations were administered intravenously to male mice. After determination of time of peak drug activity, the ED50's were established against pentetrazol-induced convulsions, at peak drug activity. The most important difference between the three diazepam preparations was a significantly higher LD50 of diazemuls (275 mg/kg) compared to valium (49 mg/kg) and stesolid (51 mg/kg). ED50 was: diazemuls 0.24 mg/kg, valium 0.14 mg/kg and stesolid 0.10 mg/kg. The therapeutic indices (LD50/ED50) were thus calculated to be 1146 for diazemuls, 350 for valium and 510 for stesolid. Time of peak drug activity and TD50 were equal for all three drugs. No signs of pain on injection or necrosis were observed following diazemuls, whereas this was common after valium and stesolid.

Effects of prenalterol on central hemodynamics and myocardial metabolism in experimental propoxyphene-induced shock.

The hemodynamic and cardiometabolic effects of prenalterol were evaluated in propoxyphene-induced circulatory shock in 10 pentobarbital-anesthetized pigs. Circulatory shock (i.e. a systolic arterial blood pressure below 60 mmHg (8 kPa) and/or a cardiac index of less than 2.0 1 X min-1 X m-2) was induced by intravenous propoxyphene chloride 15 mg X min-1. Circulatory shock occurred after 26 +/- 3 mg X kg-1 of propoxyphene. During continuous infusion of propoxyphene, consecutive doses of prenalterol 0.5, 1.0, 2.0 and 4.0 mg i.v. were injected with an interval between increments of 8 min. The maximum effect of prenalterol was seen following the 2 mg dose. Increases were observed in mean arterial blood pressure, cardiac index, stroke volume index, left ventricular stroke work index, right ventricular stroke work index, maximum rate of rise of ventricular pressure, and total body oxygen consumption. Decreases were observed in pulmonary artery occlusion pressure, mean right atrial pressure and systemic vascular resistance, whereas heart rate and pulmonary vascular resistance remained unchanged. The cardiometabolic parameters: coronary sinus flow, coronary vascular resistance, myocardial oxygen consumption and extraction, remained low. Due to profound vasodilation, normal perfusion pressures were not reestablished. In conclusion, prenalterol improved cardiac performance by a significant positive inotropic action. However, pure inotropic stimulation was not sufficient to counteract the circulatory shock state during severe propoxyphene intoxication.

Self-poisoning treated in an ICU: drug pattern, acute mortality and short-term survival.

A total of 1558 admissions to an ICU over 5 years because of severe self-poisoning with drugs provides the basis for this study. Three drugs accounted for 60% of the admissions: overdose with barbiturates in 28%, with tricyclic antidepressants in 19% and with propoxyphene in 14%. The annual incidence of poisonings with barbiturates and tricyclic antidepressants was the same during the period, whereas the incidence of propoxyphene intoxication increased by 80%. Intensive supportive care was the main principle of treatment. All patients were artificially ventilated. The mortality rate was 6.1%, salicylate, propoxyphene and strong analgesics having the highest mortalities (11%, 9% and 9%, respectively). A mortality rate of 3% was found following overdose with tricyclic antidepressants. By 36 months after the overdose, 235 patients (18%) had died. The expected number of deaths was 39 (3%). The suicide rate in the follow-up period was 10%, in the majority (75%) of whom death was caused by a new episode of self-poisoning.

The effects of cardiac pacing on central hemodynamics in experimental propoxyphene-induced cardiac failure.

Coronary sinus pacing was evaluated in 10 pigs during propoxyphene-induced cardiac failure. From baseline, propoxyphene chloride 15 mg . min-1 was infused until circulatory shock developed. Cardiac pacing was evaluated at different dose levels expressed as % of the shock dose of propoxyphene: at intoxication levels below 50% of the shock dose, cardiac pacing improved cardiac performance. At dose levels above 50% of the shock dose cardiac performance deteriorated further during pacing. The results are consistent with a severe negative inotropic effect of propoxyphene in overdose.

The effects of dopamine on central hemodynamics and myocardial metabolism in experimental propoxyphene-induced shock.

The hemodynamic and cardiometabolic effects of dopamine were evaluated in propoxyphene-induced circulatory shock in eight pentobarbital anesthetized pigs. Circulatory shock was induced by an infusion of propoxyphene chloride 15 mg . min-1 i.v. At shock, i.e. CI less than or equal to 2.0 l . min-1 . m-2 and/or MAP less than or equal to 60 mmHg, dopamine was infused at 10, 20, 40, 80 and 160 micrograms . kg-1 . min-1 with an interval between increments of 8 min. After 30 min at 160 micrograms . kg-1 . min-1, the infusion rate was reversibly decreased. The propoxyphene infusion of 15 mg . min-1 was continued throughout the study. Dopamine improved the circulation in seven animals; one animal died in refractory shock during dopamine infusion. Dopamine infusion at shock level resulted in an increase of the following variables (% of baseline value): MAP (69%), HR (109%), CI (138%) and SVI (129%). Normalisation was seen in MRAP (120%) and in MPAOP (100%). A profound decrease in systemic vascular resistance was unchanged. Increases were seen in left and right ventricular stroke work index, to 88% and 176% of baseline, respectively. Left ventricular dP/dt increased (170%). In the coronary circulation myocardial blood flow increased (133%) as did myocardial oxygen consumption (65%) concomitant with a decrease in myocardial oxygen uptake (41%), but coronary vascular resistance progressively decreased (38%). The myocardial propoxyphene extraction changed from +54% to -86% during peak dopamine infusion. In conclusion, dopamine reversed cardiac failure in propoxyphene overdose by a marked positive inotropic stimulation restoring contractility. A marked positive chronotropic stimulation maintained a sufficient cardiac index and a normal blood pressure in spite of a profound vasodilatation which was unresponsive to dopamine.

Circulatory shock following intravenous propoxyphene poisoning. An experimental study of cardiac function and metabolism in pentobarbital-anesthetized pigs.

The effects of continuously administered intravenous propoxyphene chloride (15 mg X min-1) on ECG, systemic, pulmonary and coronary circulations and myocardial oxygenation were investigated in eight pentobarbital-anesthetized pigs. Circulatory shock, defined as a systolic blood pressure below 60 mmHg (8.0 kPa) and a cardiac output of approximately 2.0 l X min-1 X m-2, occurred after 675 to 2025 mg propoxyphene chloride. At the time when shock occurred plasma concentrations of propoxyphene ranged from 9.6 to 15.3 micrograms X ml-1 which is within the range of the lethal concentration observed in man. Statistically significant decreases were observed for the following variables: maximum rate of rise of left ventricular pressure dP/dt (-90%), mean arterial pressure (-73%), heart rate (-46%), cardiac index (-58%), stroke volume index (-22%), left ventricular stroke work index (-85%), right ventricular stroke work index (-63%) and systemic vascular resistance (-50%). Mean pulmonary arteriolar occlusion pressure increased (+42%), whereas mean right atrial pressure and pulmonary vascular resistance remained unchanged. The arteriovenous oxygen difference increased (+53%) and total body oxygen consumption decreased (-35%). The following coronary variables decreased: coronary sinus blood flow (-57%), coronary vascular resistance (-65%), myocardial oxygen consumption (-68%), myocardial oxygen extraction (-26%) and myocardial lactate extraction (-28%). Prolongation of the ECG PQ and QRS intervals were recorded shortly before shock appeared, and all animals were in sinus rhythm till the last minute before death. The results indicate that intravenously administered propoxyphene besides being a powerful negative inotropic and chronotropic agent, is also a potent systemic and coronary vasodilator.

Acute propoxyphene self-poisoning in 222 consecutive patients.

The course of severe propoxyphene self-poisoning in 222 consecutive patients is presented. On admission, 73% of the patients had neurological symptoms, 10% had convulsions, 45% were in respiratory failure, and impaired circulation was present in 48%. A mortality rate of 8% was observed. Twelve patients arrived in asystole of whom six were resuscitated without sequelae. The overdose was accidental in 13 patients, one of whom died. Early medical intensive care was found mandatory for a good prognosis. Before discharge from the ICU we recommend an observation-period free of cardiovascular symptoms for 24 h.

Acute self-poisoning with tricyclic antidepressants in 295 consecutive patients treated in an ICU.

Clinical findings on admission to hospital and outcome in 295 consecutive patients with severe tricyclic antidepressant self-poisoning treated in an ICU are presented. Cerebral depression was observed in 92%, convulsions in 23% and respiratory failure was present in 72%. Cardiovascular function was impaired in 44% and an abnormal ECG was found in 57%. Cardiac arrest was treated in 14 patients (6%) of whom seven were resuscitated. The mortality rate was 2%. All patients were artificially ventilated. A beneficial effect of respiratory alkalosis on cardiac arrhythmias is supported.

Haemodynamic changes during sodium nitroprusside induced hypotension and halothane/nitrous oxide anaesthesia.

The haemodynamic effects of nitroprusside (SNP) were studied in six patients undergoing surgery for intracranial aneurysm under controlled hypotension in endotracheal anaesthesia with halothane-nitrous oxide during hypocapnia. Mean arterial pressure was reduced with SNP from mean 12.25 kPa to mean 8.29 kPa (32%). There were concomitant statistically significant decreases in systemic vascular resistance (-21%), cardiac index (-17%), stroke index (-23%), pulmonary arterial mean pressure (-27%) and pulmonary capillary wedge pressure (-27%). Heart rate, central venous pressure and pulmonary vascular resistance did not change significantly. After the infusion of SNP was discontinued all parameters, except cardiac index and heart rate, returned to values not significantly different from the control values. The hypotension induced by SNP resulted from reductions in cardiac index and systemic vascular resistance. The reduction in cardiac index did not reach a critical level in any of the patients.

Moderate hypotensive anaesthesia for reduction of blood loss during total hip replacement.

Thirty-two consecutive patients scheduled for total hip replacement were randomly allocated to receive either neurolept anaesthesia or halothane anaesthesia. In the halothane group, systolic blood pressure was reduced to 10.69-13.33 kPa in normotensive patients, and to 13.33-16.0 kPa in hypertensive patients by adjusting the inspired halothane concentration and using supplementary fentanyl when necessary. In the neurolept group, no attempt was made to reduce blood pressure below the level achieved with adequate anaesthetic doses of fentanyl and droperidol. The average peroperative blood loss in the halothane group was 809 ml (range 250-1700 ml); this was significantly lower than in the neurolept anaesthesia group in which an average blood loss of 1909 ml (range 600-4900 ml) occurred. Moderate hypotensive halothane anaesthesia is recommended as an anaesthetic technique for total hip replacement.

Cardiovascular effects of etomidate used for induction and in combination with fentanyl-pancuronium for maintenance of anaesthesia in patients with valvular heart disease.

The effects of induction of anaesthesia by etomidate 3 mg kg-1 followed by continuous infusion of etomidate 2 mg min-1, fentanyl 0.01 mg.kg-1 and pancuronium 0.1 mg.kg-1 were studied in ten patients with valvular heart disease. No haemodynamic changes were seen injection of etomidate, but after fentanyl was given there was a significant decline in cardiac index (10%), in mean arterial systemic pressure (20%), in systemic vascular resistance (14%), in left ventricular minute work index (27%) and in right ventricular minute work index (21%) compared to the control values. After supplementing with pancuronium, no further significant changes were seen. There was no significant change in the pulmonary vascular resistance during the whole study. In conclusion, it appears that etomidate is a safe intravenous agent, and is worth further study, in particular in patients with minimal cardiac reserve requiring high inspired oxygen tension.