Biomedical subjects
Publications and source records attributed to R J Kahn.
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Dobutamine administration has been shown to increase oxygen delivery in various conditions, but there are little data to document its effects in septic shock. We investigated the effects of dobutamine infusion at a rate of 5 micrograms/kg.min in 18 patients (mean 60 +/- 16 yr) with septic shock initially characterized by hypotension, oliguria, and hyperlactatemia in the presence of a documented source of sepsis. Early resuscitation had consisted of fluid administration and vasopressors when required. When added to this standard regimen, dobutamine had no significant effect on mean arterial pressure (MAP) (from 71 +/- 12 to 73 +/- 13 mm Hg), but markedly increased cardiac index (from 3.0 +/- 0.7 to 3.9 +/- 1.0 L/min.m2, p less than .001), stroke index (from 32 +/- 8 to 37 +/- 9 ml/m2, p less than .001) and oxygen transport (from 410 +/- 105 to 530 +/- 146 ml/min.m2, p less than .001). Oxygen consumption (VO2) increased concurrently (from 137 +/- 42 to 162 +/- 66 ml/min.m2, p less than .002). MAP increased (from 68 +/- 9 to 76 +/- 11 mm Hg) in 12 patients and decreased moderately (from 76 +/- 18 to 69 +/- 17 mm Hg) in six patients. The two subgroups of patients had similar hemodynamic profiles before the dobutamine infusion, but vasopressor therapy was already used in one of the 12 patients in the first subgroup and in three of the six patients in the second subgroup (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
In order to investigate whether the changes in PaO2 reported during acid-base disturbances are due to modifications of ventilation/perfusion relationships or only to extrapulmonary factors, we studied the hemodynamics and blood gases of eight critically ill patients maintained in constant mechanical ventilation, before and after selective correction of metabolic alkalosis by infusion of 1 N hydrochloric acid (HCl). HCl infusion decreased arterial pH from 7.55 to 7.40 (p less than 0.001) and increased PaO2 from 76 to 98 mm Hg (p less than 0.05) at the end of the study. Cardiac output and oxygen consumption did not change. In patients with initial venous admixture (QS/QT) less than 20% (n = 4), QS/QT did not change, and hemoglobin saturation decreased, whereas PaO2 increased from 87 to 96 mm Hg (p less than 0.10), indicating a shift in the oxyhemoglobin dissociation curve caused by the Bohr effect. In patients with QS/QT greater than 20% (n = 4), QS/QT decreased from 27 to 22% (p less than 0.05), hemoglobin saturation increased from 93 to 96% (p less than 0.05), and PaO2 increased from 65 to 100 mm Hg (p less than 0.05), which reflects an improvement in ventilation/perfusion relationships, probably because of enhanced hypoxic pulmonary vasoconstriction. These data indicate that metabolic alkalosis deteriorates pulmonary ventilation/perfusion relationships in patients with marked respiratory failure (QS/QT greater than 20%), and that reversing this effect with HCl infusion can improve PaO2 significantly.
The present study explored the possibility of using a short-term dobutamine infusion to disclose oxygen uptake/supply dependency. The effects of a standard dose of 5 micrograms/kg/min of dobutamine on oxygen-derived variables were studied in 73 acutely ill patients with heart failure (n = 24) or sepsis (n = 49). In each group, patients were separated according to their blood lactate concentrations (either above or below 2 mEq/L). In all patient groups, dobutamine resulted in significant increases in cardiac output and oxygen transport. However, oxygen consumption increased significantly only in patients with elevated blood lactate levels (cardiac failure: from 108 +/- 26 to 131 +/- 25 ml/min/M2, n = 8, p less than 0.01; sepsis: from 139 +/- 44 to 167 +/- 68 ml/min/M2, n = 16, p less than 0.01) and not in the other patients (heart failure: from 121 +/- 29 to 115 +/- 31 ml/min/M2, n = 28, NS; sepsis: from 158 +/- 39 to 166 +/- 45 ml/min/M2, n = 21, NS). These data, therefore, indicate that dobutamine at the dose used does not increase oxygen consumption in critically ill patients unless there is coexistent tissue hypoxia reflected by increased blood lactate levels. A short-term dobutamine infusion can be used to disclose an oxygen uptake/supply dependency phenomenon.
Enoximone is a new inotropic agent, which acts by the inhibition of the type III phosphodiesterase (PDE) enzyme. The present report describes a 81-year-old female patient with severe heart failure following aortic valve replacement. Her cardiac activity was paced. The addition of enoximone (two doses of 0.5 mg/kg) to an intravenous infusion of dobutamine (8 mcg/kg/min) and sodium nitroprusside significantly increased cardiac output (CO) from 3.2 to 3.9 l/min and decreased pulmonary artery occlusive pressure (PAOP) from 22 to 16 mmHg. Another dose of enoximone 12 h later had similar effects. However, another 12 h later, after dobutamine had been discontinued, two successive injections of 0.5 mg/kg of enoximone were totally ineffective (CO from 2.6 to 2.5 l/min, PAOP 23 mmHg). When the dobutamine infusion was restarted (at 8 mcg/kg/min), the positive effects of 0.5 mg/kg of enoximone were again present (CO from 3.0 to 3.6 l/min, PAOP from 19 to 14 mmHg). This observation underscores the therapeutic value of the combination of PDE inhibitors such as enoximone with adrenergic agents such as dobutamine in the management of severe heart failure.
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Hypercapnia due to respiratory failure can be more severe when accompanied by coexistent metabolic alkalosis. We therefore tested the hypothesis that hydrochloric acid (HCl) infusion could improve PaCO2 in 15 critically ill patients admitted with mixed respiratory acidosis and metabolic alkalosis, and a pH of between 7.35 and 7.45. HCl was infused at a constant rate of 25 mmol/h until the bicarbonate concentration decreased less than 26 mmol/L, or until the pH decreased less than 7.35 (initial pH greater than 7.40) or 7.30 (initial pH less than 7.40). Administration of 170 +/- 53 mmol of HCl decreased the bicarbonate concentration from 34 +/- 3 to 25 +/- 2 mmol/L (p less than .001), the pH from 7.41 +/- 0.03 to 7.33 +/- 0.02 (p less than .001), and the PaCO2 from 54 +/- 8 to 48 +/- 8 torr (p less than .001). Postinfusion PaCO2 could be predicted accurately from the initial status of the patients (r = .95, p less than .001) except in one patient with fixed hypercapnia. PaCO2 increased from 77 +/- 19 to 94 +/- 24 torr (p less than .001) and PaO2/PAO2 increased from 59 +/- 17 to 66 +/- 17% (p less than .001). The effects of HCl were still present 12 h after the end of the infusion. No complications related to the acid infusion were noted. These results indicate that, even in the absence of alkalemia, active correction of metabolic alkalosis by HCl infusion can improve CO2 and oxygen exchange in critically ill patients with mixed respiratory acidosis and metabolic alkalosis.
The last events before death were analyzed in 258 patients who died in our ICU. Deepening coma (104 patients) and acute circulatory failure (90 patients) were the most common events preceding death. Catastrophic events accounted for only 12% of deaths. In 168 (65%) of 258 patients, death was considered inevitable and CPR was not performed. Furthermore, 22 (9%) patients were allowed to die after withdrawal of intensive care support. These observations indicate that most deaths are expected in the ICU and that "do-not-resuscitate" orders can be reasonably given in the majority of fatal cases. Moreover, complete withdrawal of intensive care support should be considered as a reasonable option in hopeless patients. Since circulatory shock was identified as the most common potentially reversible problem, better prevention and management of acute circulatory failure are needed to improve survival.
Right ventricular ejection fraction (RVEF) was measured by the thermodilution technique in a series of 127 consecutive critically ill patients monitored with a modified pulmonary artery (PA) catheter equipped with a fast response thermistor. Thermodilution RVEF was significantly lower in septic shock (23.8 +/- 8.2%, 93 measurements) than in sepsis without shock (30.3 +/- 10.1%, 118 measurements) or in the absence of sepsis or cardiopulmonary impairment (32.5 +/- 7.1%, 62 measurements). Both myocardial depression and pulmonary hypertension could account for this impairment of RV function. RVEF decreased from 35.1 +/- 9.8 to 24.2 +/- 10.4% (P less than 0.01) during development of septic shock and increased from 25.0 +/- 7.6 to 29.8 +/- 8.5% (P less than 0.05) during recovery (14 patients). Initial RVEF in septic shock was 27.8 +/- 8.6% in 11 patients who survived but only 20.9 +/- 6.7% (P less than 0.02) in the 23 patients who eventually died. Thus, RV dysfunction is common during septic shock, is directly related to its severity, and can easily be recognized in patients monitored with a PA catheter.
The short-term effects of dopexamine hydrochloride, a new synthetic adrenergic agent with predominant beta 2-adrenergic and dopaminergic properties, were studied in nine patients with inadequate cardiac output during the course of an episode of respiratory failure associated with lung infection. Dopexamine at doses up to 5 microgram/kg/min had no significant effect on arterial pressure or cardiac filling pressures, but increased cardiac index from 2.0 +/- 0.2 to 2.6 +/- 0.2 L/min.m2. Left ventricular stroke work increased from 17.3 +/- 15 to 22.1 +/- 2.4 g.m/m2 (p less than 0.01) and systemic vascular resistance index decreased from 3,792 +/- 1,035 to 2,194 +/- 823 dynes.s.cm5.m2 (p less than 0.01). The increase in cardiac output was in part related to an increase in heart rate from 91 +/- 6 to 102 +/- 7 beats/min. Under a mean inspiratory oxygen fraction of 0.48, the PaO2 decreased from 105 +/- 12 to 91 +/- 11 mm Hg (p less than 0.05) as venous admixture increased from 15.8 +/- 1.0 to 18.1 +/- 1.4 percent (p less than 0.05). Accordingly, the combination of inotropic, afterload-reducing and renal vasodilating effects of dopexamine can be useful acutely to increase cardiac output in critical conditions. However, its administration can be limited by a dose-related increase in heart rate. Dopexamine, like other catecholamines, alters blood oxygenation and increases venous admixture.
The hemodynamic effects of CGP 17582 B, a new cardio-selective beta-blocking agent with moderate intrinsic sympathomimetic activity and minimal effects on myocardial contractility, were studied in patients after cardiac surgery for coronary artery bypass graft. Each patient had been treated preoperatively with beta-blocking agents and had a cineangiographic left ventricular ejection fraction between 40 and 60%. Fourteen patients were randomized to receive either 10 mg of propranolol or 50 mg of CGP 17582 B orally. Both drugs resulted in a significant and a similar decrease in heart rate. However, this was associated with a significant decrease in stroke volume after propranolol but not after CGP 17582 B, so that cardiac output significantly decreased only after propranolol. Thermodilution right ventricular ejection fraction significantly decreased after propranolol but not after CGP 17582 B. Each drug was well tolerated during the 10 following days and the recovery was uneventful in each patient. These results indicate that CGP 17582 B is a promising beta-blocking agent susceptible to reduce heart rate without altering cardiovascular function after cardiac surgery.
Thirteen patients in severe cardiogenic shock, persisting despite the use of adrenergic agents, were treated with enoximone, a recently available phosphodiesterase inhibitor. Cardiogenic shock was characterized by low cardiac output (less than 2.5 liter.min-1.m-2), elevated pulmonary artery balloon-occluded pressure (greater than or equal to 15 mm Hg), decreased urine output (less than 20 ml.hour-1) and increased blood lactate (greater than or equal to 2.0 mEq.liter-1). Ten patients were mechanically ventilated. A short-term intravenous infusion of 0.5 mg.kg-1 in 20 minutes of enoximone resulted in significant increases in cardiac index (from 1.8 +/- 0.3 to 2.9 +/- 0.3 liter.min-1.m-2, p less than 0.001) and stroke index (from 17.8 +/- 3.3 to 21.9 +/- 5.1 ml.m-2, p less than 0.001) and significant decrease in pulmonary artery balloon-occluded pressure (from 21.7 +/- 5.8 to 19.8 +/- 6.0 mm Hg, p less than 0.01) without a consistent change in mean arterial pressure (from 79 +/- 8 to 76 +/- 9 mm Hg, difference not significant). Enoximone administration decreased arterial oxygen tension (from 108 +/- 42 to 94 +/- 36 mm Hg, p less than 0.01) and increased venous admixture (from 12.8 +/- 6.5 to 16.0 +/- 8.0%, p less than 0.01). In 8 patients, a second infusion of 0.5 mg.kg-1 immediately thereafter amplified these changes. All patients but one survived the episode of cardiogenic shock and 5 patients left the hospital alive. These results indicate that the addition of enoximone to adrenergic agents in the treatment of cardiogenic shock can markedly increase cardiac output and stroke volume without substantial effects on arterial pressure.
Measurements of stroke volume (SV) by echo-Doppler techniques (2D-echocardiography, continuous and pulsed Doppler) were compared to those obtained by thermodilution in 116 critically ill patients. The best correlation was obtained with pulsed Doppler positioned in the left ventricular (LV) outflow (r = 0.78, p less than 0.001). In a subgroup of 12 patients who had LV ejection fraction less than 60% and LV end-diastolic pressure greater than 15 mmHg, we also measured the peak aortic blood velocity (PABV) and acceleration (PABA) by continuous and pulsed Doppler as indexes of myocardial contractility before coronary artery bypass graft. When compared to healthy volunteers, these patients had decreased PABV and PABA, measured by continuous Doppler (91 +/- 16 vs 79 +/- 9 cm/s, p less than 0.05 and 913 +/- 202 vs 660 +/- 149 cm/s/s, p less than 0.05, respectively). These data therefore indicate that in critically ill patients pulsed Doppler placed in the LV outflow is an adequate echo-Doppler technique to measure SV, while continuous Doppler placed in the suprasternal notch can be used to assess LV performance.
In 15 critically ill patients requiring adrenergic support, right ventricular ejection fraction (RVEF) and right ventricular (RV) volumes were measured by the thermodilution technique receiving 5 micrograms/kg.min of dopamine and after replacement by the same dose of dobutamine. Shift from dopamine to dobutamine resulted in significant increases in stroke index from 28.1 +/- 3.6 to 31.0 +/- 3.8 ml/m2 (p less than .01) and significant decreases in pulmonary artery balloon-occluded pressure from 15.1 +/- 1.0 to 13.9 +/- 1.2 mm Hg (p less than .05) and right atrial pressure (RAP) from 14.0 +/- 1.3 to 12.2 +/- 1.1 mm Hg (p less than .05). RVEF increased slightly but significantly from 21.5 +/- 2.7% to 23.7 +/- 2.9% (p less than .01) so that RV end-diastolic volume (RVEDVI) was unchanged (140 +/- 12 vs. 141 +/- 12 ml, nonsignificant). RVEDVI/RAP ratio increased from 11.3 +/- 1.0 to 12.9 +/- 1.1 ml/mm Hg (p = .037). These results support the view that dobutamine has more favorable effects on RV function than dopamine in critically ill patients in the absence of profound hypotension and also indicates that higher filling pressures under dopamine administration can be related to changes in ventricular pressure/volume relationship.
The type and the incidence of complications during treatment with high-frequency jet ventilation were evaluated in 10 critically ill patients with acute respiratory failure. HFJV was used for 2 to 34 days for management of bronchopleural fistulae, tracheal rupture, laryngeal trauma or voluminous lung abscesses. The most significant technical problems observed were disconnection or kinking of the jet catheter, hypothermia and CO2 retention. Insufficient humidification could induce severe complications such as viscous bronchial secretions, desiccation of the tracheobronchial mucosa or total obturation of the endotracheal tube. Psychological tolerance of high-frequency jet ventilation was generally satisfactory but the ventilator noise was sometimes hardly tolerated. Patients could develop a psychological dependence to high-frequency jet ventilation, leading to weaning problems. Solutions are suggested to decrease the incidence and severity of the technical and psychological complications.
We investigated the potential value of vasodilating therapy in critically ill patients with inappropriately low cardiac output during acute illness. In seven patients with low flow state during septic or postoperative state, sodium nitroprusside (20-100 micrograms/min) was compared with nicergoline (NIC) (0.5 to 2.5 mg/min), a new selective alpha 1-blocking agent with negative chronotropic action. Sodium nitroprusside (NP) decreased arterial pressure (from 90 +/- 5 to 68 +/- 5 mm Hg, p less than 0.01) and pulmonary artery balloon-occluded pressure from 20.3 +/- 3.1 to 15.4 +/- 2.8 mm Hg, p less than 0.01) and increased heart rate (from 110 +/- 11 to 120 +/- 13 beats/min, p less than 0.05) but failed to increase stroke volume (from 24.7 +/- 4.8 to 23.4 +/- 4.4 ml, NS). During NIC administration, a comparable decrease in systemic vascular resistance was associated with a significant increase in stroke volume (from 21.6 +/- 3.3 to 25.6 +/- 3.2 ml/m2, p less than 0.01) and cardiac output (CO) (from 2.4 +/- 0.3 to 2.7 +/- 0.3 L/min/m2, p less than 0.025), whereas the decrease in arterial pressure was less significant (from 91 +/- 8 to 84 +/- 7 mm Hg, p less than 0.05). Because NIC has no positive inotropic action, the most likely mechanism is that a baroreceptor-mediated increase in heart rate with NP was prevented by the negative chronotropic action of NIC. Both drugs adversely affected arterial blood oxygenation. By its unique property to decrease heart rate, NIC could represent a valuable vasodilating agent, especially in acute conditions.
Bacterial colonization of the airways can lead to nosocomial respiratory infections. The emergence of Gram-negative bacteria in the upper airways is usual in critical conditions. Antimicrobial therapy and especially bacterial adherence to the airways mucosa have been incriminated in the selection of Gram-negative bacteria becoming ultimately multiresistant. Transmission of bacteria by the hands of the ICU-personnel and aspiration of bacteria represent two important factors in the airway colonization. Bacterial clearance can simultaneously be impaired by debility and altered mental state. Pulmonary infections are especially common in peritonitis or after abdominal surgery. In a series of 30 patients who had a complicated course after abdominal surgery, we observed that in all patients with acute respiratory failure, sputum cultus yielded at least one microorganism also recovered from cultus of the abdominal secretions. Acute respiratory failure was most commonly due to respiratory infection and carried a worse prognosis. Aspiration of bacteria from the gastrointestinal tract appears to represent the most common source of nosocomial bronchopulmonary superinfection in the critically ill.