P. O. Jarnberg

Dopamine Infusion in Man. Plasma Catecholamine Levels and Pharmacokinetics

Dopamine is widely used in the treatment of hypotensive conditions and/or impending renal failure, but the plasma levels of dopamine and other catecholamines in association with dopamine infusion are not known. Plasma catecholamines and dopamine pharmacokinetics during and after dopamine infusion were therefore studied in man. Two and 5 μg ‐ kg‐1 ‐ min‐1 of dopamine were infused for 30 min in two groups of five patients. Dose‐dependent mean steady state levels with fairly large interindividual variations were reached within 5 min. Elimination of dopamine from plasma after termination of infusion had a biphasic course with t 1/2 around 1 min and t 1/2 β about 9 min in both groups. Noradrenaline plasma levels and blood pressure increased significantly in the 5 μg group. It is suggested that the vasoconstriction with deleterious effects on tissue perfusion, seen in conjunction with high‐dose dopamine infusion, may be due to increased noradrenaline levels.

Effects of Adenosine-induced Hypotension on Myocardial Hemodynamics and Metabolism in Fentanyl Anesthetized Patients with Peripheral Vascular Disease

The effects of adenosine on central and myocardial hemodynamics and metabolism were evaluated during fentanyl anesthesia (100 μg·kg−1) in six patients with peripheral vascular disease. Adenosine was intravenously infused, at a rate of 90 ± 20 (SEM) μkg−1·min−1, to reduce mean arterial blood pressure by approximately 20% (23 ± 2% SEM, from 82 ± 3 to 63 ± 3 SEM mmHg) during a 20-min period. Systemic and pulmonary vascular resistance indices decreased by 36 ± 3 and 32 ± 6% (SEM), and cardiac index increased by 18 ± 5%. Heart rate, ventricular filling pressures, and whole body oxygen consumption were not affected by adenosine. Despite the reduced mean arterial blood pressure, coronary sinus flow increased by 128 ± 26% (SEM) in parallel with a 96 ± 11% (SEM) increase in coronary sinus oxygen content. Left and right ventricular stroke work indices, as well as myocardial oxygen consumption, were maintained. ECG (12-lead) demonstrated signs of ischemia in one subject, while myocardial lactate uptake was unchanged in all subjects. In conclusion, adenosine-induced hypotension in patients with peripheral vascular disease increased cardiac index without affecting myocardial work, whole body, and myocardial oxygen consumptions. The marked increase in coronary sinus blood flow, indicating coronary vasodilation, was not related to increased myocardial work. Further information regarding myocardial effect of adenosine in patients with ischemic heart disease is warranted.

Lipid infusion in critically ill patients: Acute effects on hemodynamics and pulmonary gas exchange

Hemodynamics, pulmonary diffusing capacity (DLco) blood gases, oxygen consumption (Vo2) and carbon dioxide excretion (Vco2) were studied in healthy volunteers and ventilator-treated, critically ill patients before and during infusion of lipid emulsion for 4 h. Triglyceride levels rose from 1.0 mmole/L to 8.5 mmole/L in the volunteers and from 1.4 mmole/L to 6.3 mmole/L hi the patients after 4 h. No adverse effects on cardiovascular performance were observed. Increases in Vo2, and Vco2 and cardiac output were found m both groups, while RQ remained constant. No changes hi DLco and blood gases occurred.

Renal Fluoride Excretion and Plasma Fluoride Levels during and after Enflurane Anesthesia Are Dependent on Urinary pH

To determine the effects of urinarypH on fluoride ion excretion and the resulting plasma fluoride concentrations during and after enflurane anesthesia, renal function, plasma inorganic fluoride levels, and fluoride excretion were studied in two groups of patients pretreated with either NH4Cl or acetazolamide to produce acidic or alkaline urine, respectively. During anesthesia, urinary flow rate, inulin clearance (CIn) and para-aminohippurate (PAH) clearance (CPAH) were 7, 61, and 43 per cent of control values in the acidic-urine group and 22, 74, and 57 per cent of control values in the alkaline-urine group, respectively. Fractional fluoride clearances (CF/CIn) during anesthesia and operation were 0.06 ± 0.05 in the acidic-urine group (urinarypH 5.08) and 0.68 ± 0.23 in the alkaline-urine group (urinary pH 8.16). Values of total fluoride excretion during the same period were 0.06 ± 0.04 mg and 0.87 ± 0.29 mg, respectively. Mean maximal plasma levels of fluoride were 26.3 ± 7.3 μM in the acidic-urine group and 13.5 ± 2.4 μM in the alkaline-urine group. The differences between groups in fluoride clearance, fluoride excretion, and plasma fluoride levels were all statistically significant. The data clearly show that renal fluoride clearance is closely related to urinarypH

Renal Fluoride Excretion During and After Enflurane Anaesthesia: Dependency on Spontaneous Urinary pH‐Variations

Renal function, fluoride formation and excretion were studied in seven patients during and after enflurane anaesthesia and surgery. The mean maximal plasma level of fluoride was 17.4 pM. It was reached 2 h after termination of anaesthesia. Pre‐operatively, fractional fluoride clearance (CF/CIn) was 0.31. During anaesthesia and surgery it decreased to 0.10 and postoperatively rose to 0.55 and 0.77 during two consecutive measurement periods. There was a highly significant correlation (P<0.001) between this increase in CF/CIn and the simultaneous rise in urinary pH between the two periods (r=0.91).

Plasma catecholamine and free fatty acid levels during infusion of lipid emulsion in critically ill patients.

The fractional elimination rate of exogenous fat, and fat-mobilizing lipolysis in relation to plasma catecholamine (CA) levels were studied in seven ventilatortreated ICU patients. Blood levels of CA, triglycerides, cholesterol and free fatty acids (FFA) were also analyzed before and during constant infusion of a soybean oil emulsion (Intralipid). Triglyceride concentrations rose significantly during the infusion. FFA levels also increased significantly within 30 min after the infusion was begun, reflecting fatty acids derived from Intralipid triglycerides. Plasma norepinephrine levels showed large interindividual variations and were inversely related to FFA concentrations. No correlation was found between plasma CA levels and the fractional removal rate of fat. These data suggest a deficiency of substrate in these critically ill patients.

Renal Function and Fluoride Formation and Excretion During Enflurane Anaesthesia

Central circulation, renal function, and fluoride formation and excretion were studied in nine patients during enflurane anaesthesia and surgery. Cardiac output and mean systemic arterial pressure remained unchanged compared with preoperative control values. During anaesthesia and surgery, urine flow rate, inulin clearance, PAH clearance and fractional sodium excretion were 60, 65, 55, and 45% of control values, respectively. Mean peak plasma levrl of fluoride was 20.0 μM. It was reached 4 hours after termination of anaesthesia. Fluoridc clearance (CF) decreased from 23.9 ml. min‐1 to 2.7 ml. min‐1 during anaesthesia. Postoperative, CF increased to 41.6 and 76.0 ml.min‐1, rrspectively, during two consecutive measurement periods. There was no correlation between plasma fluoride levels and depression of any renal function variable.

Effects of ephedrine on renal function in patients after major vascular surgery.

The haemodynamic and renal effects of ephedrine were studied in 11 mechanically ventilated patients on the first day after major vascular surgery. Ephedrine, a sympathomimetic agent with alpha–1, beta–1, and beta–2 agonistic activity, was infused into 11 patients to achieve a 20% rise in systolic blood pressure. The doses used were 2–6 μg/kg/min, and in six of these 11 patients the dose was then doubled, 4–12 μg/kg/min for another renal function test. Blood pressure, heart rate, and cardiac output increased at both dose–ranges. Systolic pulmonary arterial pressure increased by 10% at the first dose–range. Systemic vascular resistance was unchanged and plasma catecholamine levels were unaltered in the present study. Plasma renin activity diminished by 18% and 6%, respectively. Clearance of para–aminohippuric acid increased by 20% and 6%, at the two dose–ranges, while clearance of inulin and urine flow rate increased by 24% and 29%, respectively, at the first dose–range, without further increase during the second dose–range. Fractional chloride excretion, and fractional osmolar clearance were unaltered. Fractional Na+ clearance rose by 30% and 36%, respectively. Fractional free water clearance diminished by 8% at the second dose–range. When comparing the two dose–ranges, HR, systolic and mean BP rose by 8%, 13% and 11%, respectively. Fractional K+ excretion diminished by 30%. We conclude that ephedrine given as a continuous infusion seems to have beneficial effects on renal function in patients after elective major vascular surgery.

Renal excretion of fluoride during water diuresis and induced urinary ph-changes in man

Fluoride renal clearance (CF) was studied in young healthy subjects with standard clearance technique following administration of 3 mg F as a 30-min constant infusion. High urinary flow rates were induced and experiments were performed under both urinary alkaline and acidic conditions. The data showed that a high urinary flow resulted in maximum fluoride clearance. High water diuresis may therefore be an important part in the treatment of acute fluoride intoxication.

A canine model for studying laryngospasm and its prevention

Laryngospasm, if prolonged, can result in serious sequelae due to the lack of a uniformly effective treatment. Prevention, therefore, through pharmacologic intervention, is an attractive concept. In order to study the effects of various drugs in preventing laryngospasm, a reliable animal model capable of producing sequential, repetitive episodes of laryngospasm is necessary. In this study, the canine model of laryngospasm previously described by Aviv, et al. was modified to overcome technical factors which limited its use in this regard. Details of the technique and the results from eight animals will be presented. Results in two animals with the use of prophylactic topical lidocaine will also be discussed. The reliability and reproducibility of this model make it ideal for the study of laryngospasm and open the way for investigation into its prevention.