Edward Lowenstein

Acute Respiratory Failure in the Adult

Effect of Mechanical Ventilation and Airway Pressures on Circulation and Blood Gas Exchange The ventilatory pattern is defined by: the inspiratory and expiratory flow rates and pressures, including...

Hemodynamic responses to mechanical ventilation with PEEP: the effect of hypervolemia.

The hemodynamic effects of prolonged mechanical ventilation with positive end-expiratory pressure (PEEP), with and without blood volume augmentation, were studied in 18 beagles anesthetized with halothane (0.7 per cent end-tidal). Addition of 12 cm H2O PEEP during mechanical ventilation in normavolemic dogs was associated with reductions of transmural cardiac filling pressures, cardiac index and stroke index to 50 per cent of control values. Circulatory adaptation did not occur. Filling pressures and flow remained unchanged during the ensuing 8 hours when PEEP was maintained. They returned to control levels when PEEP was discontinued, except for the transmural right ventricular end-diastolic pressure, which remained elevated above control levels. Systemic vascular resistance was unchanged, but pulmonary vascular resistance doubled upon addition of PEEP. Following autologous whole blood transfusion (25 ml/kg) during mechanical ventilation with PEEP, cardiac index returned to, and remained at, control levels. After PEEP was discontinued, cardiac index increased acutely and remained elevated for the remainder of the study period (as long as 7 hours). Comparable transfusion during mechanical ventilation without PEEP elevated cardiac index only transiently. Right atrial, pulmonary capillary wedge, and right and left ventricular end-diastolic pressures showed marked increases relative to atmospheric with PEEP and after transfusion. Calculated transmural pressures demonstrated clear reductions with application of PEEP, followed by increases to control levels with transfusion and further increases to above control when PEEP was discontinued. Study of ventricular function curves revealed that changes in filling pressures and not to changes in ventricular contractility. Transmural pulmonary arterial diastolic pressure rose throughout the 12 hours of study, despite return of pulmonary vascular resistance to control level with removal of PEEP. Thus, acute decreases in cardiac filling pressure, cardiac index, and stroke index persist consequent to application of PEEP, and circulatory adaptation does not occur. The apparent hemodynamic deterioration may be reversed by blood volume augmentation, but when PEEP is discontinued, hypervolemia with consequent increases in filling pressures and a move along a ventricular function curve will occur. Changes in cardiac index will depend upon the overall state of right and left ventricular contractility.

Continuous Positive-Pressure Ventilation in Acute Respiratory Failure

Abstract Continuous positive-pressure ventilation was used in eight patients with severe acute respiratory failure. Cardiac output and lung function were studied during continuous positive-pressure ventilation (mean end-expiratory pressure, 13 cm of water) and a 30-minute interval of intermittent positive-pressure ventilation. Although the mean cardiac index rose from 3.6 to 4.5 liters per minute per square meter of body-surface area, the mean intrapulmonary shunt increased by 9 per cent with changeover to intermittent positive-pressure ventilation. Satisfactory oxygenation was maintained in all patients during continuous positive-pressure ventilation with 50 per cent inspired oxygen or less. With intermittent positive-pressure ventilation arterial oxygen tension promptly fell by 161 mm of mercury, 79 per cent occurring within one minute. Prevention of air-space collapse during expiration and an increase in functional residual capacity probably explain improved oxygenation with continuous positive-pressur...

Cardiovascular Response to Large Doses of Intravenous Morphine in Man

Abstract Large doses of intravenous morphine (0.5 to 3.0 mg per kilogram of body weight) were used alone or in combination with inhalation anesthetic agents for anesthesia in over 1100 patients undergoing open-heart surgery. Morphine, 1 mg per kilogram, was administered intravenously to seven subjects with aortic-valve disease and eight without major heart or lung disease. The cardiac subjects had higher control pulse rates and lower control stroke indexes than the normal subjects. In the cardiac but not in the normal subjects, significant increases in cardiac index, stroke index, central venous pressure, and pulmonary-artery pressure, and a significant decrease in systemic vascular resistance, were observed after morphine was administered, suggesting that large doses of morphine may be used with safety in patients with minimal circulatory reserve.

Kinetics of intravenous and intramuscular morphine.

The disposition of parenteral morphine was assessed in two pharmacokinetic studies. In Study 1, 10 mg of morphine sulfate was administered by intravenous (IV) infusion, intramuscular (1M) injection, or both, to 8 healthy young adult male volunteers. Plasma morphine concentrations were determined by radioimmunoassay in multiple blood samples drawn after each dose. Mean (±SE) kinetic parameters following IV morphine were: volume of distribution (Vd), 3.2 (±0.3) Llkg; elimination half‐life (t½β), 2.9 (±0.5) hr; clearance, 14.7 (±0.9) ml/min/kg; extraction ratio, 0.70 (±0.04). After IM morphine, peak plasma levels ranged from 51 to 62 ng/ml and were reached within 20 min of injection. The absorption half‐life averaged 7.7 (±1.6) min. Systemic availability was 100% complete. In study 2, 4 elderly male patients (61 to 80 yr of age) received 45 to 80 mg of morphine sulfate IV prior to operative repair of an abdominal aortic aneurysm. Morphine pharmacokinetics were determined as described above. Kinetic variables were: Vd, 4.7 (±0.2) L/kg; t½β 4.5 (±0.3) hr; clearance, 12.4 (±1.2) ml/min/kg; extraction ratio, 0.59 (±0.05). Both studies demonstrate that morphine distribution is rapid and extensive and its t½β relatively short. IM morphine is rapidly and completely absorbed.

Myocardial ischemia due to infrarenal aortic cross-clamping during aortic surgery in patients with severe coronary artery disease.

Hemodynamic measurements were performed and ECG recorded before and shortly after infrarenal aortic crossclamping during operation for abdominal aortic aneurysm in five patients without evidence of heart disease (group I) and in ten patients with severe coronary artery disease (group II). All patients sustained an increase in systemic arterial pressure. Group I demonstrated a decrease in pulmonary artery, pulmonary capillary wedge (PCW), and central venous pressures when the aorta was clamped, whereas group II demonstrated an increase. The difference in response of the groups is significant (P ⩽ 0.05). All three patients who responded to crossclamping with increases of 7 mm Hg or greater in PCW demonstrated myocardial ischemia during cross-clamping. None of the values measured prior to cross-clamping predicted with certainty the response to cross-clamping.Sodium nitroprusside reversed the elevation of left ventricular filling pressure in all three patients, and in two patients, relieved evidence of myocardial ischemia concurrently. In the third patient, ventricular irritability was abolished by lidocaine and did not recur. We conclude that infrarenal aortic cross-clamping may cause myocardial ischemia in patients with severe coronary artery disease. This ischemia may be predicted by a rise in PCW at the time of crossclamping, and vasodilator therapy is indicated in such patients.

Association of Protamine IgE and IgG Antibodies with Life-Threatening Reactions to Intravenous Protamine

Life-threatening reactions to intravenous protamine, administered to reverse heparin anticoagulation, have been reported with increasing frequency as a consequence of the escalating use of cardiac catheterization and coronary bypass surgery. Retrospective studies have shown that such reactions are more common in diabetic patients receiving daily subcutaneous injections of protamine-insulin preparations. To determine whether anti-protamine IgE or IgG antibodies might explain the increased risk for protamine reactions among patients with protamine-insulin-dependent diabetes, we conducted a case-control study of 27 patients (diabetic and nondiabetic) who had acute reactions to intravenous protamine and 43 diabetic patients who tolerated protamine without a reaction during diagnostic or surgical procedures. Cases and controls were grouped according to previous exposure to protamine-insulin preparations. In diabetic patients who had received protamine-insulin injections, the presence of serum antiprotamine IgE antibody was a significant risk factor for acute protamine reactions (relative risk, 95; P = 1.0 X 10(-5), as was antiprotamine IgG (relative risk, 38; P = 1.2 X 10(-5). No patients without previous exposure to protamine-insulin injections had serum protamine IgE antibodies. In this group, anti-protamine IgG antibody was a risk factor for protamine reactions (relative risk, 25; P = 0.0062). We conclude that in protamine-insulin-dependent diabetics, the increased risk of serious reactions when intravenous protamine was given appeared to be caused largely by antibody-mediated mechanisms. In nondiabetic subjects, the presence of protamine IgG was significantly associated with an increased risk of acute protamine reactions, although many nondiabetic subjects who had reactions had no IgG antibodies.

The Direct Vasomotor Effect of Thyroid Hormones on Rat Skeletal Muscle Resistance Arteries

The present study examines the hypothesis that the hormones have direct vasodilatory effects and attempts to determine whether the effects are endothelium-dependent. Rat skeletal muscle resistance arteries of approximately 100 micro m were dissected, and vessel diameter changes were monitored using a videodetection system. After equilibration at 37[degree sign]C, each vessel was preconstricted with the thromboxane analog U46619 1 micro M, and the percentage of dilation was measured after exposure to increasing concentrations of triiodothyronine (T3) or levothyroxine (T4) (10-10 to 10-7 M). Dilation in response to T3 was also measured after endothelial denudation and pretreatment with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA) 10 micro M, the cyclooxygenase inhibitor indomethacin 10 micro M, the adenosine triphosphate-sensitive K+ channel blocker glibenclamide 1 micro M, or the beta-adrenergic antagonist propranolol 1 micro M. Both T3 and T4 demonstrated concentration-dependent dilation of the U46619-preconstricted vessels (P < 0.001 each), with T3 having a greater effect than T4 (P < 0.05) (36% +/- 9% [mean +/- SD] dilation at 10-7 M T3 vs 24% +/- 6% dilation at 10-7 M T4). In comparison, isoproterenol 10-7 M produced 56% +/- 6% dilation. T3-mediated vasodilation was attenuated but not abolished by endothelial denudation (18% +/- 3% dilation at 10-7 M T3) (P < 0.01), L-NNA (15% +/- 7% dilation at 10-7 M T3) (P < 0.01), indomethacin (20% +/- 9% dilation at 10-7 M T3) (P < 0.05), and glibenclamide (22% +/- 7% dilation at 10-7 M T3) (P < 0.01), but it was not affected by propranolol (37% +/- 20% dilation at 10-7 M T3) (P = 0.99). We conclude that thyroid hormones possess direct vasodilatory effects with both endothelium-independent and endothelium-dependent components. Implications: Thyroid hormones may have modest direct vasodilatory effects. This may partially account for the cardiovascular actions of the hormones in hyperthyroidism or when administered pharmacologically in cardiac surgery. (Anesth Analg 1997;85:734-8)

Halothane-induced Decrease in Experimental Myocardial Ischemia in the Non-failing Canine Heart

The effect of halo thane on net myocardial oxygen balance of ischemic myocardium was studied m the non-failing canine heart. Myocardial ischemia was produced by repeated reversible occlusions of a coronary artery; the severity of ischemia was estimated by summating ST-segment elevations (ΣST) obtained by epicardial ECG mapping at 15 to 18 sites. Control measurements were obtained before and after administration of halothane (0.75 percent) to six dogs with chloralose—urethane basal anesthesia. Halothane was associated with significant decreases of systemic arterial pressure (P < .001), heart rate (P < .01), and the product of systolic arterial pressure × heart rate (P < .01), an indirect index of myocardial oxygen consumption, while left atrial pressure remained unchanged at normal levels. ΣST during occlusion was less (P < .001) during halothane (26.5 ± 7.4 {SD} mv) than before (36.G ± 5.4 mv) or after (34.4 ± 8.2 mv) its administration. Thus, halo thane decreased the severity of experimentally-induced myocardial ischemia in the non-failing canine heart. The data suggest that, in the absence of ventricular failure, halothane influences the relationship between myocardial oxygen supply and demand in a favorable direction when coronary blood flow is limited.

Acute oliguria after cardiopulmonary bypass: renal functional improvement with low-dose dopamine infusion

Hemodynamic and renal function response to low-dose (100 and 200 μg/min) dopamine infusion was studied in 15 adult cardiac surgical patients who manifested combined oliguria and left ventricular dysfunction postoperatively. Patients were studied an average of 6.6 h after ICU admission, at normothermia and after 2 consecutive hourly urine output determinations of less than 0.5 ml/kg h in the presence of a left atrial or pulmonary artery occlusion pressure over 12 mm Hg. Dopamine infusion at 100 μg/min produced improvement in creatinine, osmolar and free water clearances (70 ± 10 to 115 ± 13, 37 ± 4 to 93 ± 16 and –15 ± 2 to –37 ± 10 ml/min, respectively), and urinary sodium concentration (15 ± 5 to 29 ± 10 mEq/L). Urine flow improved overall from 22 ± 2 to 54 ± 9 ml/h; however, in 9 of 15 patients, flow was less than 0.5 ml/kg h (33 ± 5 to 50 ± 6 ml/h). In each of these 9 patients, dopamine infusion at 200 μg/min further improved urine flow as well as measured renal function. Plasma renin activity measured in 9 of the 15 patients before and during the 100 μg/min dopamine infusion was decreased from 1.95 ± 0.57 to 0.73 ± 0.39 mg/ml h. The hemodynamic effect of both dopamine doses was increased cardiac output coupled with decreased systemic (SVRI) and pulmonary vascular resistance index (PVRI). In these 15 patients, low-dose dopamine infusion produced significant improvement in renal function, with resolution of oliguria in every case, and with no deleterious hemodynamic effect.