Prevalence of and risk factors for pulmonary abnormalities in HIV-infected patients treated with antiretroviral therapy.

BACKGROUND: Pulmonary abnormalities are often present in patients infected with the human immunodeficiency virus (HIV). OBJECTIVES: The aim of the study was to determine the prevalence and characteristics of, and risk factors for, pulmonary abnormalities in HIV-positive patients. METHODS: A total of 275 HIV-positive patients [mean (± standard deviation) age 48.5 ± 6.6 years] were included in the study, of whom 95.6% had been receiving highly active antiretroviral therapy (HAART) for a mean (± standard deviation) duration of 11.9 ± 5.4 years. The median (interquartile range) CD4 lymphocyte count was 541 (392-813) cells/µL, and 92% of the patients had an undetectable viral load. We determined: (1) spirometry, static lung volumes, lung diffusing capacity, pulmonary gas exchange and exercise tolerance, and (2) the amount of emphysema via a computed tomography (CT) scan. RESULTS: Chronic cough and expectoration (47%) and breathlessness during exercise (33.9%) were commonly reported. Airflow limitation (AL) was present in 17.2%, low pulmonary diffusing capacity in 52.2% and emphysema in 10.5-37.7% of patients, depending on the method used for quantification. Most of these abnormalities had not been diagnosed or treated previously. Smoking exposure and previous tuberculosis were the main risk factors for AL, whereas smoking exposure and several variables related to HIV infection appeared to contribute to the risk of emphysema and low diffusing capacity. CONCLUSIONS: Despite HAART, pulmonary structural and functional abnormalities are frequent in HIV-positive patients. They are probably attributable to both environmental (smoking and tuberculosis) and HIV-related factors. Most of these abnormalities remain unnoticed and untreated. Given the relatively young age of these patients, these results anticipate a significant health problem in the next few years as, thanks to the efficacy of HAART, patients survive longer and experience the effects of aging.

Regulation of iNOS expression and glutathione levels in rat liver by oxygen tension.

Molecular oxygen (O(2)) regulates the expression of a variety of genes. We hypothesized that O(2) tension may regulate iNOS expression in rat liver through the production of reactive oxygen species (ROS) and the reduction of intracellular glutathione (GSH) levels. To investigate this hypothesis, we determined the effects of hyperoxia upon iNOS induction (both at the protein and mRNA level) and the intracellular concentration of GSH in an isolated in vitro perfused rat liver preparation. To study the potential involvement of ROS in the intracellular signaling pathway linking changes in oxygen tension to gene expression, we repeated these determinations in the presence of the thiol antioxidant N-acetyl-L-cysteine (NAC). We found that 95% O(2) tension caused a significant induction of the iNOS protein and mRNA levels paralleled by a significant fall in intracellular GSH concentration. The addition of NAC (1 mM) to the perfusate during hyperoxia blocked the induction of iNOS and restored GSH levels. These results indicate that molecular O(2) regulates the expression of iNOS in rat liver at the transcriptional level, most likely through the production of ROS and the reduction of intracellular GSH levels.

Exhaled nitric oxide in patients with sleep apnea.

Cardiovascular diseases are frequent in patients with obstructive sleep apnea syndrome (OSAS), but the mechanisms underlying this association are largely unknown. Nitric oxide (NO) is a key regulatory element of vascular physiology. The concentration of NO in the exhaled air ([NOexh]) appears to be reduced in patients with systemic and pulmonary hypertension. This study sought to investigate whether [NOexh] is abnormal in patients with OSAS, and to explore potential relationships between [NOexh] and the severity of OSAS. We measured [NOexh] in 24 patients with OSAS (apnea-hypopnea index (AHI), 55 +/- 4 hour-1) (x +/- SEM), and in 7 healthy volunteers in whom OSAS was excluded clinically. [NOexh] was measured on line by a chemiluminescence analyzer (Dasibi Environmental Corporation, Glendale, Calif). Seven patients with OSAS (29%) had a positive history of cardiovascular disease. Mean [NOexh] was 19.7 +/- 3.2 ppb in healthy subjects, and 22.2 +/- 3.0 ppb in patients with OSAS (p = ns). [Noexh] was not significantly different in those patients with or without cardiovascular disease. [NOexh] was not significantly related to the AHI, the body mass index, or the arterial O2 saturation at night. These results show that [NOexh] is not abnormal in patients with OSAS, and that it does not relate to the presence of cardiovascular disease or to any of various common indices of disease severity.

Noninvasive ventilatory support after lung resectional surgery.

STUDY OBJECTIVES: To investigate the short-term effects of noninvasive ventilatory support (NIVS) on pulmonary gas exchange, ventilatory pattern, systemic hemodynamics, and pleural air leaks in patients submitted to elective lung resection. DESIGN: Prospective, randomized, parallel, and controlled investigation. SETTING: Thoracic Surgery Unit, Hospital Universitari Son Dureta, Palma Mallorca, Spain. PATIENTS: Nineteen patients electively submitted to lung resection because of varied clinical reasons. INTERVENTIONS: Medical therapy was standardized for all patients. Ten subjects received NIVS with a nasal ventilatory support system (BiPAP) during 1 h (study group). The remaining nine individuals constituted the control group. MEASUREMENTS AND RESULTS: Arterial blood gases, ventilatory pattern, systemic hemodynamics, and pleural air leaks were measured. Before surgery, there were no significant clinical or functional differences between groups. After surgery, and compared with preoperative measures, PaO2 decreased significantly (p<0.01) and to the same extent both in the study group (85.7+/-2.8 to 68.0+/-2.7 mm Hg) and the control group (83.6+/-2.5 to 67.3+/-2.6 mm Hg). In the study group, NIVS increased PaO2 (to 76.7+/-3.0 mm Hg; p<0.05) and decreased alveolar to arterial oxygen pressure gradient (P[A-a]O2) (27.2+/-2.7 to 17.6+/-2.3 mm Hg; p<0.05). This latter effect was still present 1 h after withdrawing NIVS. By contrast, PaO2 and P(A-a)O2 remained unchanged in the control group throughout the study. PaCO2, the ventilatory pattern, and systemic hemodynamics did not change significantly throughout the study in any group. Importantly, NIVS did not increase dead space to tidal volume ratio or worsen pleural air leaks. CONCLUSIONS: Short-term NIVS with a ventilatory support system improves the efficiency of the lung as a gas exchanger without noticeable nondesired side effects in patients submitted to lung resectional surgery.

A new bronchoscopic technique for the diagnosis of bacterial pneumonia in HIV-positive patients.

The aim of the present study was to evaluate in HIV-positive patients with bacterial pneumonia, the diagnostic value of a new endoscopic technique that uses a single catheter to perform a telescopic plugged catheter (TPC) followed by a modified protected bronchoalveolar lavage (mpBAL). Fifty-eight HIV-positive patients with respiratory infection were included in the study. Samples from TPC and mpBAL were cultured quantitatively. Standard bronchoalveolar lavage was performed to rule out opportunistic infections. According to the clinical and microbiological results, patients were classified in the study group (27 with bacterial pneumonia) or the control group (31 without bacterial pneumonia). Sensitivity of TPC was 56% [95% confidence intervals (CI) 37-75%] and its specificity was 100%; these figures were 56% (CI, 37-75%) and 94% (CI, 86-100%) for mpBAL. When both techniques were assessed together, sensitivity increased to 70% (CI, 53-87%). The use of a single catheter reduced the cost of the originally described pBAL procedure by approximately 50%. The use of a single catheter to perform a TPC followed by a mpBAL can improve the diagnostic yield in HIV-positive patients with bacterial pneumonia, and reduces its cost.

Lack of effects of moderate-high altitude upon lung function in healthy middle-aged volunteers.

This study investigates the effects of moderate-high altitude on lung function and exercise performance in 46 volunteers (19 females, 27 males), with a mean age of 42.4 +/- 1.4 years (+/- SEM) and varying smoking and exercise habits, who were not previously acclimatized. Measures obtained in the base camp (1140 m) and at altitude (2630 m), in random order, included forced spirometry, maximal voluntary ventilation, maximal inspiratory and expiratory pressures, arterial oxygen saturation and capillary lactate concentration after a standardized exercise test. The smoking history, Fagerström test and degree of habitual physical activity were also recorded for each participant. The percentage of smokers was similar in males (19%) and females (21%) (P = n.s.). Mean habitual physical activity index was 8.2 +/- 0.2 (range, 5.88-11.63). At the base camp, all lung function variables were within the normal range. Lactate concentration after exercise averaged 3.7 +/- 0.3 mm l-1. No significant change was observed at altitude, except for a higher heart rate and a lower arterial oxygen saturation (SaO2) (both at rest and after inspiratory manoeuvres). The smoking history and the degree of physical activity did not influence lung function or exercise performance at altitude. The results of this study show that in middle-aged, healthy, not particularly well-trained individuals, lung function is not significantly altered by moderate-high altitude, despite the absence of any acclimatization period and independent of their smoking history and previous exercise habits.

[Comparative evaluation of 3 types of syringes routinely used for arterial gas analysis]. / Análisis comparativo de tres tipos de jeringas utilizadas habitualmente para gasometría arterial.

This prospective study evaluates the practical utility of a special plastic syringe for collecting arterial blood samples for gasometry, comparing it to a glass syringe and a conventional plastic one, in 120 patients who came to our hospital for arterial blood analysis for a variety of reasons. The patients were randomly assigned to one of three groups according to type of syringe assigned. Technicians with experience in the technique prepared the syringes and collected the arterial blood samples after providing local anesthesia. The results showed that the special plastic syringe took less time (p < 0.05) to prepare than did the glass or conventional plastic ones. The differences were quite small, however, in absolute terms, with the special syringe requiring 17 seconds less than the glass syringe and 6 seconds less than the plastic one; the practical importance is therefore slight. No other advantages of the special syringe were observed. No patient required more than one puncture to obtain a valid arterial blood sample, the extraction times (time between arterial puncture until end of process) were similar in the three groups of patients, and the presence of post-puncture hematoma was rare in all groups. There were no differences in level of pain reported (on an analog scale) and the subjective quality of the radial pulse wave was good and similar in all three groups. In conclusion, these results show that use of the special syringe offers no important practical advantages for experienced technicians that would justify the higher price. In fact, as the conventional plastic syringes are cheaper, disposable and similarly effective in expert hands, our results suggest that their routine use for collecting arterial blood gas samples can help improve the cost-benefit ratio for a common procedure in pulmonary function units.

[The results of the operation of a monitoring unit for home oxygen therapy]. / Resultados de la actuación de una unidad de control de la oxigenoterapia domiciliaria.

OBJECTIVE: This study aims to a) analyze the prevalence of domiciliary oxygen therapy (DOT) in Mallorca, b) evaluate the cost effectiveness of the DOT monitoring unit, and c) determine the survival of patients with chronic obstructive pulmonary disease who are presently receiving DOT. METHOD: When the DOT unit was created in April 1994, the situation of all patients receiving DOT in Mallorca was assessed in a transversal study. Over the next three years, these patients were reassessed regularly and all new prescriptions were evaluated (longitudinal study). RESULTS: Before the unit began work, DOT was prescribed for 71 out of 100,000 inhabitants. DOT was withdrawn from 31% of patients assessed in the transversal study. By the end of the longitudinal study, DOT was being prescribed at a rate of 56 times per 10,000 inhabitants. The activities of the DOT unit brought about annual savings of approximately 38 million pesetas. The number of patients with liquid oxygen and concentrators increased such that the latter has become the main delivery system. The survival of COPD patients with DOT in this study seems to be longer than report. CONCLUSIONS: a) The prevalence of DOT use in Mallorca before the DOT unit began operating was too high. b) The cost effectiveness of DOT monitoring is positive because DOT use has been optimized and significant savings have ensued (= 38 millions pesetas/year). c) The survival of COPD patients receiving DOT at present appears better than that reported in the literature, possibly related to the greater efficacy of modern treatment.

[Recovery of lung function after laparoscopic cholecystectomy: the role of postoperative pain]. / Recuperación de la función pulmonar tras colecistectomía laparoscópica: papel del dolor postoperatorio.

OBJECTIVES: Lung function has been shown to deteriorate after laparoscopic cholecystectomy (LC). The present study evaluated 1) the rate of recovery after LC, and 2) the pathogenic role of postoperative pain in functional deterioration. DESIGN: Lung function was measured 24 hours before LC, upon hospital discharge (48-72 h after LC), and 10 days later. All patients received metamizol after LC until discharge (2 g every 6 h i.v.). Half the patients (analgesia group) received tramadol (150 mg i.m.) 30 minutes before lung function testing on the day of hospital discharge. The remaining patients constituted the control group. PATIENTS: Twenty healthy subjects (53 4 years old) undergoing LC for gall bladder removal. All signed informed consent forms. Measures and outcomes: Patient characteristics and preoperative lung function results were similar in both groups. LC duration and postoperative course were also similar in both groups. All were discharged without complications within 72 hours after LC. Lung function upon discharge (FVC, FEV1, TLC, PaO2 and AaPO2) had deteriorated in both groups (p<0.001). Deterioration was less marked in the analgesia group (p < 0.05). Ten days later, lung function had normalized for all subjects. CONCLUSIONS: These results indicate that after LC, 1) lung function is still abnormal when the patient is discharged from hospital, 2) lung function has fully recovered within 10 days, and 3) postoperative pain contributes significantly to temporary deterioration in lung function.

[Chronic eosinophilic pneumonia and difficult to control asthma]. / Neumonía eosinófila crónica y asma de difícil control.

We report a case of typical chronic eosinophilic pneumonia (CEP), in a female of 27 years-old suffering bronchial asthma light. Although the initial answer to the treatment with steroids was satisfactory, the patient develop difficult to control asthma (DCA). DCA is a clinical situation which requires careful investigation of several potential factors which can be solved. We suggest a protocol of treatment for patients affected with DCA.

[Bronchiolitis obliterans with organizing pneumonia]. / Bronquiolitis obliterante con neumonía organizativa.

We present a typical case of Obliterant Bonchilitis with Organizative Pneumonia in a 73-years-old man. The diagnosis was established through minithoracotomy. Treated with high dosage of methylprednisolone, the clinical-radiological evolution was satisfactory. It is very important to know and correctly diagnose this entity, given its excellent therapeutical response.

Hypercapnia test and weaning outcome from mechanical ventilation in COPD patients.

We evaluated the hypercapnia response test as a weaning outcome predictor from mechanical ventilation in patients with chronic obstructive pulmonary disease (COPD). We studied 44 COPD intubated patients considered ready for a weaning trial. The hypercapnia test was based on the modified method of re-inhalation of expired air Through the hypercapnic test we calculated the ratio of the change in minute volume (V(E)) to the change in PaCO2 (deltaV(E)/deltaPaCO2), the change in airway occlusion pressure at 0.1 second of inspiration (P0.1) to change in PaCO2 (deltaP0.1/deltaPACO2), the ratio of the change in P0.1 to baseline PaCO2 (deltaP0.1/PaCO2) and the ratio of the change in V(E) to baseline PaCO2 (deltaV(E)/PaCO2). Nineteen patients were successfully weaned and 25 patients failed. No differences in baseline clinical characteristics were found between the two groups. Weaning failure COPD patients had lower deltaP0.1/deltaPaCO2 (0.19 +/- 0.11 and 0.34 +/- 0.20 cm H2O/mmHg respectively, P = 0.006) and lower deltaV(E)/deltaPaCO2 (0.21 +/- 0.15 and 0.40 +/- 0.22 l/min/mmHg respectively, P = 0.002) than successfully weaned patients. The area under the receiver operating characteristic curve to discriminate weaning outcome was for the baseline PaCO2 0.81 (95% confidence interval: 0.66 to 0.91), hypercapnic PaCO2 0.76 (0.61 to 0.88), hypercapnic drive response 0.74 (0.59 to 0.86), hypercapnic ventilatory response 0.76 (0.60 to 0.87), deltaP0.1/PaCO2 0.76 (0.60 to 0.87) and for the deltaV(E)/PaCO2 0.81 (0.67 to 0.91). COPD patients with weaning failure have a significantly more blunted response to the hypercapnia response test than weaning success patients. This test could be useful to predict weaning failure patients if the combined values of the hypercapnic drive and hypercapnic ventilatory response were below the threshold values.

The measurement of exhaled carbon monoxide is influenced by airflow obstruction.

The concentration of carboxyhaemoglobin (COHb) is often estimated from measurements of carbon monoxide in the exhaled air (COexh). This study investigates whether the presence of airflow obstruction significantly alters the relationship between COexh and COHb. Eighty-one regular smokers were prospectively studied and divided in four groups according to the presence and severity of airflow obstruction (none, mild, moderate, severe). In each subject, the authors measured in this order: 1) arterial blood gases; 2) haemoglobin concentration and COHb (by co-oxymetry); 3) COexh; 4) lung volumes; and 5) forced spirometry. The size of the measurement error (deltaCO) was calculated from the difference between COHb and COexh. Neither the smoking history nor COexh were different in the four groups of subjects studied. In contrast, deltaCO increased in parallel to the degree of airflow obstruction. DeltaCO was >2% (a threshold value normally used in the clinic to separate smokers from nonsmokers) only in patients with severe airflow obstruction. A stepwise multivariate analysis showed that both forced expiratory volume in one second (FEV1) (percentage reference) and COHb contributed significantly (p<0.0001) to predict deltaCO. This study shows that the estimation of carboxyhaemoglobin from exhaled carbon monoxide measurements can be inaccurate in patients with severe airflow obstruction. In these patients, the direct measurement of carboxyhaemoglobin seems advisable in clinical practice.

Noninvasive ventilatory support does not facilitate recovery from acute respiratory failure in chronic obstructive pulmonary disease.

This investigation evaluates, in a prospective, randomized and controlled manner, whether noninvasive ventilatory support (NIVS) with bilevel positive airway pressure (BiPAP) facilitates recovery from acute respiratory failure (ARF) in patients with chronic obstructive pulmonary disease (COPD). Twenty four patients (mean age (+/-SEM) 68 +/- 2 yrs) with COPD (forced expiratory volume in one second (FEV1) at discharge 33 +/- 2% predicted), who attended the emergency room because of ARF (pH 7.33 +/- 0.01; arterial oxygen tension (Pa,O2) 6.0 +/- 0.2 kPa; arterial carbon dioxide tension (Pa,CO2) 7.9 +/- 0.3 kPa), were initially randomized. Four out of the 14 patients (29%) allocated to received NIVS did not tolerate it. Of the remaining 20 patients, 10 received NIVS with BiPAP in a conventional hospital ward during the first 3 days of hospitalization (two daytime sessions of 3 h duration each). All 20 subjects were treated with oxygen, bronchodilators and steroids. On the first and third hospitalization days, before and 30 min after withdrawing oxygen therapy and/or BiPAP ventilatory support, we measured peak expiratory flow, arterial blood gas values, ventilatory pattern, occlusion pressure (P0.1), and maximal inspiratory (MIP) and maximal expiratory (MEP) pressures. All patients were discharged without requiring tracheal intubation and mechanical ventilation. Hospitalization time was similar in both groups (11.3 +/- 1.3 vs 10.6 +/- 0.9 days, control vs BiPAP, respectively). Arterial oxygenation, respiratory acidosis and airflow obstruction improved significantly throughout hospitalization in both groups. By contrast, the ventilatory pattern, P0.1, MIP and MEP did not change. NIVS with BiPAP did not cause any significant difference between groups. We conclude that noninvasive ventilatory support with bilevel positive airway pressure does not facilitate recovery from acute respiratory failure in patients with chronic obstructive pulmonary disease. Furthermore, a substantial proportion of patients (29%) do not tolerate noninvasive ventilatory support under these circumstances. From these results, we cannot recommend the use of noninvasive ventilatory support with bilevel positive airway pressure in the routine management of chronic obstructive pulmonary disease patients recovering from acute respiratory failure.

Continuous positive airway pressure is effective in treating upper airway oedema.

The case of a patient with diffuse idiopathic skeletal hyperostosis (DISH) and upper airway oedema, is described. The patient presented with alveolar hypoventilation and obstructive apnoeas during sleep. Intravenous steroids (methylprednisolone, 160 mg.day-1) for 5 days did not reduce the oedema. However, it was rapidly reversed by the use of nasal continuous positive airway pressure (nCPAP). In addition, daytime pulmonary gas exchange was improved and sleep apnoea abolished. This beneficial effect made tracheostomy unnecessary. This case report suggests that CPAP can be a potentially useful therapeutic alternative to tracheostomy in the clinical management of upper airway oedema.

Oxygen therapy during exacerbations of chronic obstructive pulmonary disease.

Venturi masks (VMs) and nasal prongs (NPs) are widely used to treat acute respiratory failure (ARF) in chronic obstructive pulmonary disease (COPD). In this study, these devices were compared in terms of their potentiality to worsen respiratory acidosis and their capacity to maintain adequate (> 90%) arterial oxygenation (Sa,O2) through time (approximately 24 h). In a randomized cross-over study, 18 consecutive COPD patients who required hospitalization because of ARF were studied. After determining baseline arterial blood gas levels (on room air), patients were randomized to receive oxygen therapy through a VM or NPs at the lowest possible inspiratory oxygen fraction that resulted in an initial Sa,O2 of > or = 90%. Arterial blood gas levels were measured again 30 min later (on O2), and Sa,O2 recorded using a computer during the subsequent approximately 24 h. Patients were then crossed-over to receive O2 therapy by means of the alternative device (NPs or VM), and the same measurements obtained again in the same order. It was observed that both the VM and NPs improved arterial oxygen tension (p<0.0001) to the same extent (p=NS), without any significant effect upon arterial carbon dioxide tension or pH. However, despite this adequate initial oxygenation, Sa,O2 was < 90% for 3.7+/-3.8 h using the VM and for 5.4+/-5.9 h using NPs (p<0.05). Regression analysis showed that the degree of arterial hypoxaemia (p<0.05) and arterial hypercapnia (p<0.05) present before starting O2 therapy and, particularly, the initial Sa,O2 achieved after initiation of O2 therapy (p<0.0001) enabled the time (in h) that patients would be poorly oxygenated (Sa,O2 < 90%) on follow-up to be predicted. These findings suggest that, in order to maintain an adequate (> 90%) level of arterial oxygenation in patients with chronic obstructive pulmonary disease and moderate acute respiratory failure: 1) the initial arterial oxygen saturation on oxygen should be maximized whenever possible by increasing the inspiratory oxygen fraction; 2) this strategy seems feasible because neither the VM nor NPs worsen respiratory acidosis significantly; and 3) the Venturi mask (better than nasal prongs) should be recommended.

Serial measurements of exhaled nitric oxide during exacerbations of chronic obstructive pulmonary disease.

Excessive inflammation seems important in chronic obstructive pulmonary disease (COPD), particularly during exacerbations of the disease. Exhaled nitric oxide concentration ([NOexh]) is a sensitive marker of bronchial inflammation in asthma; it is unclear if this is also the case in COPD. This study: 1) quantifies [NOexh] in patients with COPD (during an exacerbation and while clinically stable); 2) investigates the response of [NOexh] to i.v. steroid therapy, and its potential relationship with other relevant physiological variables; and 3) assesses the relative contributions of the central and peripheral airways to [NOexh] by collecting exhaled air in two different bags connected in series. Seventeen COPD patients (forced expiratory volume in one second (FEV1) 37.6+/-3.4% of the predicted value (+/-SEM)) hospitalized because of an exacerbation of the disease (arterial oxygen tension (Pa,O2) (7.46+/-0.72 kPa 56.1+/-5.4 mmHg), arterial carbon dioxide tension (Pa,CO2) 5.63+/-0.37 kPa 42.3+/-2.8 mmHg), pH 7.41+/-0.02) and 10 healthy subjects that served as controls were studied. On admission, [NOexh] in COPD was higher than normal (41.0+/-5.1 versus 13.3+/-0.8 parts per billion (ppb), respectively, p<0.001). Despite i.v. steroid therapy, [NOexh] remained elevated throughout recovery (37.9+/-4.8 ppb, p<0.001) until discharge (40.9+/-4.3 ppb, p<0.001). In contrast, when the patients were clinically stable (several months later), [NOexh] was significantly reduced (15.8+/-3.8 ppb, p<0.001), and no longer different from control values. [NOexh] was not related to any of the physiological variables measured during recovery (pulmonary gas exchange) or at discharge (forced spirometry, lung volumes, diffusing capacity). Finally, the contribution of the central and peripheral airways to [NOexh] was not different at any point in time. These results indicate that during exacerbations of chronic obstructive pulmonary disease, the exhaled nitric oxide concentration: 1) is higher than normal; 2) is not reduced acutely by i.v. steroids but is normalized several months after discharge; 3) is unrelated to several physiological indices of disease severity; and 4) appears to be produced homogeneously in central and peripheral airways. Overall, these results are different from those reported in asthma, suggesting that different inflammatory mechanisms are operating in both diseases.

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.