Myer H. Rosenthal

Inhibition of Adrenal Steroidogenesis by the Anesthetic Etomidate

The use of the intravenous anesthetic etomidate for prolonged sedation has been associated with low levels of plasma cortisol and increased mortality. We measured the cortisol and aldosterone responses to ACTH stimulation in five patients receiving etomidate, and we also studied the direct effects of etomidate on enzymes in the rat steroidogenic pathway. One patient who was receiving a 20-hour infusion of etomidate (1.3 to 1.5 mg per kilogram of body weight per hour) had marked adrenocortical suppression that was still evident four days after etomidate was discontinued. Four surgical patients receiving etomidate during their operations were all found to have adrenal suppression four hours after the operation; mean (+/- S.D.) increases in cortisol and aldosterone after ACTH stimulation were only 1.8 +/- 0.5 micrograms per deciliter and 0.5 +/- 1.1 ng per deciliter, respectively. In rat adrenal cells, etomidate produced a concentration-dependent blockade of the two mitochondrial cytochrome P-450-dependent enzymes, cholesterol-side-chain cleavage enzyme, and 11 beta-hydroxylase, without evident inhibition of the microsomal enzymes in the glucocorticoid pathway. Physicians should be aware that etomidate inhibits adrenal steroidogenesis, and they should consider treating selected patients with corticosteroids if etomidate is used.

Is intensive care worth it?–an assessment of input and outcome for the critically ill

The high cost of treatment in an ICU is clearly recognized; the ultimate benefit of that care in prolonging meaningful life is not as well quantified. We evaluated 337 mixed medical-surgical ICU patients for severity of illness and intensity of therapy and assessed their survival and quality of life 16 to 20 months after discharge. Mortality was 36.9% for emergency surgical and medical patients and 13.9% for elective surgical patients. A total of 140 patients responded to follow-up; 62.2% of patients not retired or homemakers were working full-time. Quality of life was good using both subjective and objective standards. There were few significant differences between elective surgical and other patients. Survival and life quality were related inversely to severity of illness and cost of treatment. Acute health on ICU admission predicted survival well; chronic health and age were better predictors of life quality.

Measurement of Extravascular Lung Water in Dogs Using the Thermal-Green Dye Indicator Dilution Method

The measurement of extravascular lung water by a double-indicator dilution technique using cold indocyanine green dye was evaluated in dogs. Pulmonary edema was induced in 11 animals by volume overload; 12 animals served as controls. For each measurement, the two indicators (cold dye) were injected into the superior vena cava and detected in the femoral artery. The extravascular thermal volume was calculated using the mean transit times of the two indicator curves. Pretermination measurements of extravascular thermal volume correlated closely with standard gravimetric analysis of pulmonary extravascular tissue weight (EVTV - 1.15 PEW + 2.1 ml/kg, n = 21, r = 0.97, P less than 0.001; where EVTV = extravascular thermal volume and PEW = pulmonary extravascular tissue weight). Throughout the experiment, the arterial oxygen tension and alveolar-arterial oxygen tension gradient, correlated poorly with EVTV (linear correlation: r = 0.47, 0.45, respectively). The intrapulmonary shunt correlated better with EVTV (r = 0.72). Nonlinear correlation of EVTV with intravascular pressures (left ventricular filling pressures, colloid oncotic pressures, and the pulmonary artery occlusion pressure-colloid oncotic pressure gradient) were more significant than linear relationships. The critical pressures at which lung water rapidly increased in this model occurred at left ventricular filling pressures of 22-27 mmHg and at pulmonary artery occlusion pressure-colloid oncotic pressure gradients of 25-30 mmHg. The thermal dye technique appears to provide an accurate measurement of lung water changes in this pressure edema model.

Acute Hemodynamic Effects of Nitroglycerin in Pulmonary Hypertension

Therapy of pulmonary hypertension is limited by the low potency and adverse effects of current pulmonary vasodilators. The hemodynamic effects of nitroglycerin in human pulmonary hypertension are not known. We administered nitroglycerin to nine patients with chronic pulmonary hypertension. Nitroglycerin increased cardiac index 40% (p less than 0.01), increased stroke volume 40% (p less than 0.01), decreased pulmonary vascular resistance 40% (p less than 0.01), and decreased mean pulmonary artery pressure 15% (p less than 0.01). Pulmonary vascular resistance decreased more than 25% in eight of the nine patients. In four patients the effects of intravenous nitroglycerin were reproduced by topical nitroglycerin preparations; cardiac index increased 50%, stroke volume increased 48%, pulmonary vascular resistance decreased 43%, and mean pulmonary artery pressure decreased 19%. Five of six patients treated with long-acting nitrates had substantial improvement of their symptoms. We conclude that therapy with nitroglycerin can be effective in patients with severe pulmonary hypertension.

Effect of Injectate Volume and Temperature on Thermodilution Cardiac Output Determination

Six combinations of injectate volume (10, 5, and 3 ml) and temperature (0° C and room temperature [RT]) are recommended by the manufacturers of thermodilution cardiac output catheters and computers. We prospectively studied the accuracy and variability associated with these six combinations in critically ill patients requiring intermittent mandatory ventilation. The six methods were similar in their average estimation of cardiac output but differed markedly in their reproducibility. The 10 ml 0° C and 10 ml RT combinations produced the least variability. The 5 ml 0° C and 5 ml RT combinations produced more variability. Variability was much greater with the remaining two combinations. The 3 ml RT combination resulted in an average range of 1.71 1/min within each set of three repeat measurements and an average absolute difference of 1.51 1/min from the values obtained with 10 ml 0° C (each the mean of three injections). We recommend the use of 10 ml 0° C or 10 ml RT for cardiac output determinations in critically ill patients. If it is impacceptable ortant to minimize volume administration, the use of 5 ml injectate is acceptable for an estimation of cardiac output. The use of 3 ml injectate volumes is rarely, if ever, justified because the small reduction in volume administration results in a large increase in variability.

Hemodynamic profiles of prostaglandin E1, isoproterenol, prostacyclin, and nifedipine in experimental porcine pulmonary hypertension.

Background and MethodsWe compared the hemodynamic effects of four vasodilators in experimental embolic pulmonary hypertension in a randomized controlled trial, using nine pigs weighing 16 to 23 kg. After anesthesia induction and cannulation with arterial, central venous, and thermodilution output pulmonary artery catheters, animals were repetitively embolized with glass beads (60 to 160 μ) in order to establish pulmonary hypertension (pulmonary artery pressure [PAP] doubled from baseline). Prostaglandin E1 (PGE1), isoproterenol, prostacyclin (PGI2), and nifedipine were compared at doses producing equivalent reduction in systemic BP. ResultsOnly PGE1 and PGI2 decreased both PAP and pulmonary vascular resistance (PVR). PGE1 decreased PAP from 39 ± 1 to 33 ± 1 mm Hg; prostacyclin decreased PAP from 38 ± 1 to 31 ± 1 mm Hg and produced the largest increase in cardiac output (Qt). Isoproterenol did not change PAP, markedly increased heart rate (162 ± 8 to 216 ± 11 beats/min), and resulted in significant arrhythmias. Nifedipine increased PVR from 1044 ± 113 to 1125 ± 100 dynesec·cm-5 and decreased Qt. ConclusionVasodilators demonstrate unique hemodynamic drug profiles. Isoproterenol infusion is characterized by tachycardia and arrhythmias. Both PGE1 and PGI2 effectively decrease PAP and PVR. Nifedipine depressed Qt significantly in this glass-bead embolization model of acute pulmonary hypertension. (Crit Care 1991; 19:60)

Pulmonary Effects of Crystalloid and Colloid Resuscitation From Hemorrhagic Shock in the Presence of Oleic Acid-induced Pulmonary Capillary Injury in the Dog

The effects of resuscitation with crystalloid and colloid solutions in the presence of increased pulmonary capillary permeability were studied. Twenty-four hours after oleic acid administration, dogs were anesthetized and bled to produce hemorrhagic shock. One hour later, resuscitation was performed with saline, 5% albumin, or 6% hydroxyethyl starch solution to restore and then maintain cardiac output at pre-oleic acid values for 6 h. Dogs were recovered and, 24 h later, were reanesthetized for final measurements. Oleic acid administration resulted in increases in pulmonary artery pressure, pulmonary vascular resistance, and extravascular lung water (EVLW). Resuscitation from hemorrhagic shock restored pulmonary hemodynamics to pre-hemorrhage levels and did not affect EVLW, Pao2, shunt fraction, dead-space-to-tidal-volume ratio, or pulmonary compliance. There were no differences in these parameters related to the choice of resuscitation fluid. Saline resuscitation markedly reduced plasma oncotic pressure and the plasma oncotic-pulmonary artery occlusion pressure gradient. Values for these two variables were markedly lower with saline than with colloid resuscitation. The authors conclude that the pulmonary effects of crystalloid and colloid solutions are similar in the presence of moderate increases in pulmonary capillary permeability.

Vasodilator therapy in vasoconstrictor-induced pulmonary hypertension in sheep

A stable preparation of pulmonary hypertension in sheep was developed using a continuous infusion of the vasoconstrictor U46619, a stable endoperoxide thromboxane A2-mimetic. Using this model, the pulmonary and systemic effects of nitroglycerin, sodium nitroprusside, hydralazine, and prostaglandin E1 were compared at doses producing equivalent reductions in systemic blood pressure. Although all four drugs decreased pulmonary artery pressure and resistance, different drug hemodynamic profiles were found. Prostaglandin E1 demonstrated the greatest pulmonary specificity and resulted in the largest decrease in pulmonary artery pressure (from 33 ± 1 to 23 ± 1 mmHg). Nitroglycerin and sodium nitroprusside demonstrated intermediate pulmonary specificity and did not affect cardiac output. Hydralazine demonstrated the least pulmonary specificity and resulted in a large decrease in systemic vascular resistance, with only a moderate decrease in pulmonary artery pressure and resistance. Rational selection of pulmonary vasodilators for clinical application will vary depending on baseline heart rate and rhythm, pulmonary artery pressure, systemic artery pressure, and cardiac output.

Pulmonary Vasodilator Effects of Nitroglycerin and Sodium Nitroprusside in Canine Oleic Acid-induced Pulmonary Hypertension

The hemodynamic effects of nitroglycerin (TNG) and sodium nitroprusside (SNP) were studied in a canine model of pulmonary hypertension. Oleic acid administration resulted in pulmonary hypertension with a 133% increase in pulmonary vascular resistance (PVR), a 40% increase in mean pulmonary artery pressure (MPAP), and a 28% decrease in cardiac output (CO). In this model, subsequent TNG administration increased CO 40%, decreased PVR 43%, and decreased MPAP 12%; pulmonary hemodynamics during TNG administration were not significantly different from those prior to oleic acid administration. SNP produced systemic hypotension but did not alter either PVR or MPAP and increased CO only 14%. The efficacy of TNG in this model may relate to its ability to dilate preferentially the pulmonary vascular bed.

Vasodilator therapy in microembolic porcine pulmonary hypertension

The hemodynamic effects of prostaglandin E1, sodium nitroprusside (SNP), nitroglycerin, and hydralazine were studied in a porcine model of elevated pulmonary vascular resistance (PVR) due to glass bead microembolization (60–150-μm diameter).Each animal received all four drugs. Each drug was titrated to produce a 30% reduction in mean systemic arterial pressure. Although all four drugs decreased PVR, distinct differences in the hemodynamic profiles of the four drugs were evident. Prostaglandin E1 produced the largest reduction in mean pulmonary artery pressure (from 41 ± 1 to 32 ± 9 mm Hg, mean ± sem) and PVR (25 ± 3 to 18 ± 2 mm Hg·L−1·min−1), and did not affect the ratio of PVR to systemic vascular resistance (PVR/SVR). Sodium nitroprusside and nitroglycerin produced moderate decreases in PVR (nitroglycerin 21 ± 2 to 18 ± 2 mm Hg·L−1·min−1, SNP 22 ± 2 to 19 ± 2 mm Hg·L−1 min−1) and in mean pulmonary artey pressure (nitroglycerin 39 ± 1 to 35 ± 1; SNP 40 ± 1 to 36 ± 2 mm Hg). Both drugs significantly increased the PVR/SVR ratio. Hydralazine was the only drug that significantly increased cardiac output (1.6 ± 0.2 to 1.9 ± 0.3 L/min). Hydralazine had no significant effect on mean pulmonary artey pressure, reduced PVR to the smallest extent (11%), and resulted in the largest increase in the PVR/SVR ratio (from 0.52 ± 0.04 to 0.80 ± 0.08).In this model of increased pulmonary vasculature resistance prostaglandin E1 caused an equivalent amount of pulmonay and systemic vasodilation, as expressed by the PVR/SVR ratio. Hydralazine caused the least amount of pulmonary vasodilation for a given amount of systemic vasodilation. Nitroglycerin and SNP were intermediate in their effects between prostaglandin E1 and hydralazine.