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Objective: To investigate the hemodynamic effects of L-canavanine (an inhibitor of inducible, but not of constitutive, nitric oxide synthase) in endotoxic shock., Design: Controlled, randomized, experimental study., Setting: Animal laboratory., Subjects: Wistar rats., Interventions: Rats were anesthetized with pentobarbital, and hemodynamically monitored. One hour after an intravenous challenge with 5 mg/kg of Escherichia coli endotoxin, the rats were randomized to receive a continuous infusion of either L-canavanine (20 mg/kg/hr; n = 8) or vehicle only (isotonic saline, n = 11). In all animals, the infusion was given over 5 hrs at a rate of 2 mL/kg/hr. These experiments were repeated in additional rats challenged with isotonic saline instead of endotoxin (sham experiments)., Measurements and Main Results: Arterial blood pressure, heart rate, thermodilution cardiac output, central venous pressure, mean systemic filling pressure, urine output, arterial blood gases, blood lactate concentration, and hematocrit were measured. In sham experiments, hemodynamic stability was maintained throughout and L-canavanine had no detectable effect. Animals challenged with endotoxin and not treated with L-canavanine developed progressive hypotension and low cardiac output. After 6 hrs of endotoxemia, both central venous pressure and mean systemic filling pressure were significantly below their baseline values, indicating relative hypovolemia as the main determinant of reduced cardiac output. In endotoxemic animals treated with L-canavanine, hypotension was less marked, while cardiac output, central venous pressure, and mean systemic filling pressure were maintained throughout the experiment. L-canavanine had no effect on the time-course of hematocrit. L-canavanine significantly increased urine output and reduced the severity of lactic acidosis., Conclusions: Six hours after an endotoxin challenge in rats, low cardiac output develops, which appears to be primarily related to relative hypovolemia. L-canavanine, a selective inhibitor of the inducible nitric oxide synthase, increases the mean systemic filling pressure, thereby improving venous return, under these conditions.

The speed of onset of an asthma attack can be highly variable. Recent studies have tried to characterize a subgroup of patients with life-threatening asthma that occurs suddenly but often regresses very rapidly under treatment. We had the opportunity to observe the evolution of two asthmatic women hospitalized with extremely severe respiratory acidosis. One of them required immediate orotracheal intubation and mechanical ventilation during 13 h. The results of her pulmonary function tests were normal 35 h after admission. The second woman's condition improved so rapidly under treatment that she did not require intubation and mechanical ventilation. These observations suggest that bronchospasm might play an important role in the pathophysiology of transient life-threatening asthma.

Among the different mechanisms involved, polymorphonuclear leukocytes (PMNs) may play a central role in the pathogenesis of adult respiratory distress syndrome (ARDS). PMNs were evaluated in 15 patients with ARDS, in 21 at risk of developing ARDS (AR), and in 36 controls (C). Spontaneous and opsonized zymosan (OZ), phorbol myristate acetate (PMA), and F-Met-Leu-Phe (F-M-L-P)-stimulated oxygen radical production was measured by luminol- and lucigenin-enhanced chemiluminescence (CL). Spontaneous CL activity of PMNs from ARDS patients was significantly greater than that from the PMN control (luminol CL, 2.8 +/- 0.6 vs. 0.8 +/- 0.1 mV, p less than 0.001; lucigenin CL, 2.0 +/- 0.6 vs. 0.30 +/- 0.04 mV, p less than 0.001), and the CL value from AR patients (luminol CL, 1.3 +/- 0.2 mV, p less than 0.001 vs. C; lucigenin CL, 0.8 +/- 0.1 mV, p less than 0.001 vs. C) was found to be between the ARDS and C patients. The peak of PMA-stimulated CL occurred earlier and it was significantly higher in ARDS patients than in AR patients (p less than 0.05) and controls (p less than 0.001). When the CL response was elicited with F-M-L-P, no difference among the three groups was found. When stimulated with OZ, the peak CL generated by PMNs from ARDS patients was significantly depressed compared with controls (luminol CL, 26.7 +/- 1.8 vs. 40.9 +/- 2.3 mV, p less than 0.01; lucigenin CL, 5.0 +/- 0.4 vs. 7.4 +/- 0.5 mV, p less than 0.005) with a similar result being obtained from AR patients (luminol CL, 32.1 +/- 2.5 mV, p less than 0.01 vs. C). Plasma from ARDS and AR patients showed a defective opsonizing capacity, suggesting in vivo complement consumption in both patient groups. No correlation between the severity of hypoxemia, the cause of ARDS, the outcome, and the different PMN functions could be established. Our results are in agreement with a determinant role of PMNs in the development of ARDS. The opposite metabolic responses may explain both the pulmonary injury and the increased susceptibility to infections observed in patients at risk of or with ARDS.

When hypothermic patients appear to be dead, the decision to resuscitate may be difficult due to lack of reliable criteria of death. To discover useful prognostic indicators, we reviewed the hospital charts of nine hypothermic victims of snow avalanches (group A: median value of rectal temperature, 29.6 degrees C; range, less than 12 degrees C to 34 degrees C) and of 15 patients with hypothermia following acute drug intoxication and/or cold exposure (group B: 28.8 degrees C; range, 25.5 degrees C to 32 degrees C. In group A, plasma potassium level on admission was extremely high (14.5 mmol/L; range, 6.8 to 24.5 mmol/L) compared with that obtained in group B (3.5 mmol/L; range, 2.7 to 5.3 mmol/L). All patients in group A were in cardiorespiratory arrest. None could be successfully resuscitated despite effective rewarming by cardiopulmonary bypass or peritoneal lavage. In contrast, all of the patients in group B recovered from hypothermia, including two in cardiorespiratory arrest. Thus, extreme hyperkalemia during acute hypothermia appears to be a reliable marker of death. It might be used to select those patients in whom heroic resuscitation efforts can be useful.

This study analyzed the history, clinical characteristics, and acid-base data in relation to the speed of decompensation in 34 patients intubated and mechanically ventilated for severe asthma. Three patterns of decompensation were established according to the delay between the onset of symptoms and endotracheal intubation: Group I, rapid decompensation (less than 3 hours); Group II, gradual development of respiratory failure (9.2 +/- 7.7 days); Group III, acute exacerbation after unstable asthma (4.2 +/- 3.6 days). Patients who developed sudden asphyxia (Group I) showed features distinct from those with a gradual worsening. Sudden asphyxic asthma is more frequent in young men and is characterized by a severe mixed acidosis with extreme hypercapnia (mean PaCO2 = 112.8 +/- 43.9 mm Hg), a higher incidence of respiratory arrest, and silent chest upon admission. Recovery is more rapid, with a shorter duration of mechanical ventilation (33.7 +/- 25.3 h versus 91.4 +/- 64.1 h in Group II). Several arguments suggest that bronchospasm plays the primary role in the pathogenesis of sudden asphyxic asthma.

To investigate the relationship between alterations in lung mechanics and acute pulmonary vascular congestion, repeated measurements of the respiratory system impedance (Zrs) were performed in 11 patients with and in seven without acute left ventricular failure. Indexes of Zrs were obtained by calculating the average and slope of the resistance and reactance in low (10 to 20 Hz) and high (20 to 50 Hz) frequency intervals. Zrs indexes in patients with ventricular failure differ significantly from those in patients without failure. Pulmonary vascular congestion is regularly associated with an abnormal frequency dependence of resistance at low frequencies and with an increased resonant frequency. Discriminant analysis of Zrs indexes allows 92% correct classification of pulmonary capillary wedge pressures lower than and those equal to or higher than 18 mm Hg. Zrs differences between patients with and without left ventricular failure are consistent with the presence of a small airways obstruction even in patients with mild left ventricular failure. Furthermore, use of Zrs indexes permits moderate and severe pulmonary vascular congestion to be distinguished from one another and this is probably due to a significant narrowing of the large airways during severe left ventricular failure.

The measurement of respiratory acoustic impedance (Zrs) by forced pseudorandom noise provides a simple means of assessing respiratory mechanics in nonintubated intensive care patients. To characterize the lung mechanical alterations induced by acute vascular congestion of the lung, Zrs was measured in 14 spontaneously breathing patients hospitalized for acute left ventricular failure. The Zrs data in the cardiac patients were compared with those of 48 semirecumbent normal subjects and those of 23 sitting asthmatic patients during allergen-induced bronchospasm. In the patients with acute left ventricular failure, the Zrs abnormalities noted were an excessive frequency dependence of resistance from 10 to 20 Hz and an abnormally low reactance at all frequencies, abnormalities qualitatively similar to those observed in the asthmatic patients but of lesser magnitude. Acute lung vascular congestion modifies the acoustic impedance of the respiratory system. Reflex-induced bronchospasm might be the main mechanism altering respiratory acoustic impedance in acute left ventricular failure.