Effects of N-acetylcysteine on tissue oxygenation in patients with multiple organ failure and evidence of tissue hypoxia.

Covert tissue hypoxia, particularly of the splanchnic region, appears important in the pathogenesis of multiple organ failure (MOF). This investigation evaluates the effects of N-acetylcysteine (NAC) upon several measures of tissue oxygenation in 10 patients with severe MOF and evidence of splanchnic hypoxia (as suggested by a pathologically low value (< 7.32) of the pH of the gastric mucosa (pHi)). Patients were studied following a prospective, randomized, placebo-controlled, cross-over design. Measurements included pulmonary and systemic haemodynamics, cardiac output by thermodilution, arterial and mixed venous blood gas values, blood lactate concentration, whole-body oxygen uptake by analysis of the expired gases, and pHi by tonometry. A complete set of measurements was obtained before and 45 min after the infusion of NAC (150 mg.kg-1 in 250 mL of saline) and, also, before and 45 min after the infusion of an equivalent volume of saline. NAC increased the cardiac index and vasodilated the systemic circulation (p < 0.01). However, O2 delivery to the tissues did not increase because the arterial oxygen content fell after NAC (p < 0.01). Mean O2 extraction or lactate concentration did not change after NAC, and pHi fell slightly (from 7.11 +/- 0.21 to 7.07 +/- 0.21; p < 0.05). The infusion of saline did not modify any variable significantly. The O2 extraction fraction increased exponentially in those patients with reduced O2 transport to the tissues. These results argue against a beneficial effect of N-acetylcysteine upon tissue oxygenation in patients with severe multiple organ failure and evidence of splanchnic hypoxia. Furthermore, they suggest that the mechanisms controlling the extraction of oxygen by the peripheral tissues in these patients were not impaired.

Energy expenditure in patients with multiple organ failure.

We measured the level of resting energy expenditure (BEE) and its evolution in patients with multiple organ failure (MOF). We studied 30 patients requiring mechanical ventilation and sedation. REE was measured by means of a closed circuit method on days 1-5, 7, 10 and 14 after initiating the protocol. REE values between 115% and 145% of the REE calculated from the Harris-Benedict's formula were considered as moderate hypermetabolism and values above 145% as severe hypermetabolism. A predictive formula for determining caloric requirements was developed and validated in another 25 MOF patients. In the study group, 25 patients presented moderate hypermetabolism (83%) and two severe hypermetabolism(7%). Mean REE in the whole group was stable but individual patients may have had a large variability in REE. The anthropometric variables, body temperature and reason for admission predicted the REE with a coefficient of determination of 0.73, according to the model: REE= -3295 + 105.5S - 8A + 11.7 W + 7.7 H + 93.2 T + 123.1 Tr - 145.6 Su where: S = sex (male = 1, female = 0); A: age in years; W: weight in Kg; H: height in cm; T: temperature in degrees C; Tr: trauma (Tr = 1); Su: surgical (Su = 1). The reliability of the model, taken from the validation group, showed that the shrinkage was 0.8%. In conclusion, when MOF patients are sedated they present moderate hypermetabolism. Day-to-day variability of REE in the individual patients and the large variability in estimating REE with our formula preclude its clinical utility and we recommend to measure REE in MOF patients.

Diagnosis of nosocomial pneumonia in mechanically ventilated patients by the blind protected telescoping catheter.

OBJECTIVES: To demonstrate that blind insertion of the protected telescoping catheter (PTC-NB) through the orotracheal tube can provide reliable pulmonary samples for the diagnosis of nosocomial pneumonia (NP) in ventilated patients. DESIGN: We performed a random comparison between the protected telescoping catheter introduced through a bronchofiberscope (PTC-B) and the PTC-NB to diagnose NP. SETTING: A general intensive care unit of a University Hospital. PATIENTS: 40 consecutive patients on mechanical ventilation and with suspicion of NP. The diagnosis of NP was suspected by clinical and chest X-ray findings. MEASUREMENTS AND RESULTS: NP was confirmed microbiologically in 26 (65%) patients and maintained in 8 patients by clinical and radiological criteria. PTC-NB confirmed the microbiological diagnosis of PN in 21 (80%) patients. The use of antibiotics prior taking respiratory samples reduced the sensitivity of PTC-NB and PTC-B from 100-74% and from 94-70% (p = 0.001). Both techniques agreed in 24 of 33 (73%) patients but such agreement was better when PN was on the right lung. Two patients developed a self-limiting hemoptysis after the PTC-B procedure. CONCLUSIONS: PTC-NB is as sensitive as specific as PTC-B for diagnosing PN in mechanically ventilated patients, being a much easier technique to use.

[A comparative study of intravenous diltiazem and nitroglycerin in the treatment of unstable angina]. / Estudio comparativo del diltiazem y la nitroglicerina intravenosos en el tratamiento de la angina inestable.

To compare the efficacy of intravenous diltiazem vs nitroglycerin in patients with unstable angina, we conducted a prospective, single blinded study enrolling 45 patients, 24 of them received diltiazem and 21 nitroglycerin. We considered drug failure if the patient experienced two or more anginal episodes or if one of them was longer than 30 minutes. There was a good response in 19 of 24 patients (79%) of the diltiazem group and 17 of 21 (81%) in the nitroglycerin group. Only one of the 5 non-response patients in the diltiazem group that was crossed to nitroglycerin was controlled, in opposition to the 4 patients crossed to diltiazem that were controlled all of them (p less than 0.05). Both drugs significantly (p less than 0.01) reduced systolic and diastolic blood pressure, but there was not difference between the two groups. Heart rate and double product decreased only in the diltiazem group (p less than 0.05). We did not find notorious side effects. We concluded that diltiazem is an alternative to nitroglycerin in patients with unstable angina.

Genetic and phenotypic variability during replication of foot-and-mouth disease virus in swine.

A plaque-purified preparation of foot-and-mouth disease virus (FMDV) of serotype C1 (C-S8c1-1), grown in cell culture, was used to infect nonimmunized pigs. No variant genomes were detected in the average populations of 50 viruses isolated from infected animals by direct RNA sequencing of the carboxy-terminal half of the VP1 gene. However, a mutant with altered phenotypic properties was present in low proportion in an infected animal. The frequency of mutants resistant to neutralization by SD6 monoclonal antibody (MAb) [SD6 epitope MAb-resistant mutants (MARMs)], directly estimated in virus from lesions of infected animals (without passage in cell culture), depended on the procedure used for its determination and ranged from 2.9 x 10(-6) (when the virus was incubated with the MAb prior to plating) to 2.6 x 10(-5) (when incubation with MAb was avoided and the MAb was maintained in the agar overlay of the titration assay). Such a difference was not found for C-S8c1-1, which consistently showed frequencies of about 4 x 10(-5). In addition, the repertoire of amino acid substitutions was similar among SD6 epitope MARMs isolated directly both from vesicles of infected animals and from C-S8c1-1. Thus, in spite of the conservation of the average sequence in the region of VP1 RNA analyzed, antigenic heterogeneity has been found in viral populations of FMDV upon replication in nonimmunized swine.

Genetic and immunogenic variations among closely related isolates of foot-and-mouth disease virus.

Genetic heterogeneity among closely related isolates of foot-and-mouth disease virus (FMDV) has been measured by direct sequencing of the VP1-coding-region RNA for three new FMDVs of serotype C1 and by additional sequences of RNA from previously reported isolates, all belonging to a single episode of disease [Sobrino et al., Gene 50 (1986) 149-159]. In the ten viruses compared, eight different VP1 are represented. The changes include amino acid substitutions at a critical antigenic determinant of VP1. We document that variations present in such natural isolates result in changes of the immunogenic properties of the viruses. Vaccines prepared with two of the FMDV C1 analyzed induce complete protection against an homologous virus but only partial protection against an heterologous virus in swine, the host from which these viruses were isolated.

The early detection of the effects of surgical shock on the viscera.

One hundred and one patients, in shock after operations were reviewed to examine the visceral effects on their prognoses. The shock was caused in 65 cases by hypovolaemia and in 36 cases by sepsis. The effects were studied on the heart and cardiovascular system, liver, kidneys, gastrointestinal system, central nervous system, lungs and blood clotting system. Surgical shock affected more frequently the lung and liver (P less than 0.05 and P less than 0.01). The lungs were most frequently involved in hypovolaemia (25 patients) and sepsis (25 cases). Pathology of the lung was associated with the highest mortality rate (P less than 0.005), followed by kidney (P less than 0.01) then heart and central nervous system (P less than 0.025). Involvement of the gastrointestinal tract or clotting system alone was not associated with higher mortality rates, except in the presence of other visceral derangements. Lung affection also had a greater mortality followed by kidney and the central nervous system. Involvement of one or several organs in failure to survive septic shock is dealt with in the discussion. It is concluded that visceral involvement secondary to shock could be of importance for prognosis.

The effect of lateral positions on gas exchange in patients with unilateral lung disease during mechanical ventilation.

Positional changes have long been known to have a gravitational effect on the distribution of pulmonary blood flow. The effect of body position, supine, right and left lateral decubitus, on gas exchange were evaluated in 10 patients with predominantly unilateral lung disease. All patients were treated with mechanical ventilation and PEEP. Arterial blood gases, measured after 15 min in each of the three positions, showed that lying on the side of the "normal" lung resulted in a higher arterial pO2 (mean: 144 mmHg) than lying on that of the "damaged" lung (mean: 86 mmHg). The delta AapO2 values were 334 to 391 mmHg. Both differences were statistically significant (p less than 0.005). No significant changes mean arterial carbon dioxide tensions were noted.