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Arthur S Slutsky

Publications and source records attributed to Arthur S Slutsky.

65 records · Page 4Linked to original sources
PubMed2002

Normocapnia improves cerebral oxygen delivery during conventional oxygen therapy in carbon monoxide-exposed research subjects.

STUDY OBJECTIVE: We determine whether maintaining normocapnia during hyperoxic treatment of carbon monoxide-exposed research subjects improves cerebral oxygen delivery. METHODS: This experiment used a randomized, single-blinded, crossover design. We exposed 14 human research subjects to carbon monoxide until their carboxyhemoglobin levels reached 10% to 12%. We then treated each research subject with 60 minutes of hyperoxia with or without normocapnia. Research subjects returned after at least 24 hours, were reexposed to carbon monoxide, and were given the alternate treatment. Relative changes in cerebral oxygen delivery were calculated as the product of blood oxygen content and middle cerebral artery velocity (an index of cerebral blood flow) as measured by transcranial Doppler ultrasonography. RESULTS: Maintaining normocapnia during hyperoxic treatment resulted in significantly higher cerebral oxygen delivery compared with standard oxygen treatment (P <.05; 95% confidence interval at 60 minutes 2.8% to 16.7%) as a result of the prevention of hypocapnia-induced cerebral vasoconstriction and more rapid elimination of carbon monoxide due to increased minute ventilation. CONCLUSION: If severely poisoned patients respond like our research subjects, maintaining normocapnia during initial hyperoxic treatment of carbon monoxide poisoning may lead to increased oxygen delivery to the brain. Determining the effect of such a change in conventional treatment on outcome requires clinical studies.

Adult↗
PubMed2002

Levels of exhaled nitric oxide before and after surgical and transcatheter device closure of atrial septal defects in children.

OBJECTIVES: We have shown that exhaled nitric oxide levels decrease after surgical closure of congenital left-to-right cardiac shunts. It remains unclear whether the change in exhaled nitric oxide levels reflects endothelial injury caused by the use of cardiopulmonary bypass or the decrease in pulmonary blood flow attendant on shunt closure. Transcatheter atrial septal defect closure permits shunt closure without the use of cardiopulmonary bypass. Therefore we compared changes in exhaled nitric oxide levels after surgical and transcatheter device closure of atrial septal defects. METHODS: We enrolled sequentially 30 children undergoing atrial septal defect closure. Fifteen patients (age range, 0.4-16 years; median age, 6.5 years) underwent surgical atrial septal defect closure with cardiopulmonary bypass, and 15 patients (age range, 4-17 years; median age, 8.4 years) had device closure of the atrial septal defect in the catheterization laboratory. We measured nitric oxide levels in end-tidal expiratory gas with a rapid-response chemiluminescent analyzer before and after atrial septal defect closure. RESULTS: After surgical repair of the atrial septal defect, exhaled nitric oxide decreased by 21%, from 10.9 +/- 4.4 to 8.4 +/- 3.3 ppb (P <.005), whereas after transcatheter defect closure, exhaled nitric oxide increased by 23%, from 7.6 +/- 2.6 to 9.3 +/- 3.7 ppb (P <.005). Hemoglobin levels in patients undergoing surgical intervention were significantly lower (P =.0001) postoperatively. CONCLUSIONS: We confirmed that exhaled nitric oxide, despite a fall in hemoglobin, decreases after surgical closure of atrial septal defects. In contrast, exhaled nitric oxide levels increase after transcatheter closure. Exhaled nitric oxide levels may reflect bypass-induced endothelial cell injury and are independent of changes in pulmonary blood flow.

Adolescent↗
PubMed2002

Effect of ventilator-induced lung injury on the development of reperfusion injury in a rat lung transplant model.

OBJECTIVE: Although mechanical ventilation can potentially worsen preexisting lung injury, its importance in the setting of lung transplantation has not been explored. This study was undertaken to examine the effect of 2 ventilatory strategies on the development of ischemia-reperfusion injury after lung transplantation. METHODS: In a rat lung transplant model animals were randomized into 2 groups defined by the ventilatory strategy during the early reperfusion period. In conventional mechanical ventilation the transplanted lung was ventilated with a tidal volume equal to 50% of the inspiratory capacity of the left lung and a low positive end-expiratory pressure. In minimal mechanical stress ventilation the transplanted lung was ventilated with a tidal volume equal to 20% of the inspiratory capacity of the left lung, and positive end-expiratory pressure was adjusted according to the shape of the pressure-time curve to minimize pulmonary stress. RESULTS: After 3 hours of reperfusion, oxygenation from the transplanted lung was significantly higher with minimal mechanical stress ventilation than with conventional ventilation. In addition, elastance, cytokine levels, and morphologic signs of injury were significantly lower in the group with minimal mechanical stress ventilation. CONCLUSIONS: This study demonstrates that the mode of mechanical ventilation used in the early phase of reperfusion of the transplanted lung can influence ischemia-reperfusion injury, and a protective ventilatory strategy on the basis of minimizing pulmonary mechanical stress can lead to improved lung function after lung transplantation.

Animals↗
PubMed2002

Ventilation with negative airway pressure induces a cytokine response in isolated mouse lung.

UNLABELLED: We tested the hypothesis that, under relatively low tidal volume (VT) mechanical ventilation, continuing lung decruitment induced by negative end-expiratory pressure (NEEP) would increase the lung cytokine response, potentially contributing to lung injury. Mouse lungs were excised and randomly assigned to one of 3 different ventilatory strategies: 1) the zero end-expiratory pressure group served as a control, 2) the NEEP7 group received a NEEP of -7.5 cm H(2)O, and 3) the NEEP15 group received a NEEP of -15 cm H(2)O. In all 3 groups, a VT of 7 mL/kg was used. After 2 h of ventilation, lung lavage fluid was collected for measurements of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and lactate dehydrogenase. Increases in plateau pressure before and after mechanical ventilation were significantly greater in the NEEP15 group compared with the zero end-expiratory pressure group or NEEP7 group. Lung compliance was decreased in the NEEP15 compared with the other two groups. Concentrations of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and lactate dehydrogenase in lung lavage were larger in the NEEP15 group than in the other groups. Atelectatic lung during repeated collapse and reopening of lung units accentuates the lung cytokine response that may contribute to lung injury even during relatively low VT mechanical ventilation. IMPLICATIONS: Repeated closing and reopening of lung units induced by negative end-expiratory pressure resulted in lung inflammation and cell injury even under mechanical ventilation using a normal tidal volume. This finding may have clinical relevance in certain patients who are prone to atelectasis during mechanical ventilation.

Animals↗
PubMed2002

Effects of recruiting maneuvers in patients with acute respiratory distress syndrome ventilated with protective ventilatory strategy.

BACKGROUND: A lung-protective ventilatory strategy with low tidal volume (VT) has been proposed for use in acute respiratory distress syndrome (ARDS). Alveolar derecruitment may occur during the use of a lung-protective ventilatory strategy and may be prevented by recruiting maneuvers. This study examined the hypothesis that the effectiveness of a recruiting maneuver to improve oxygenation in patients with ARDS would be influenced by the elastic properties of the lung and chest wall. METHODS: Twenty-two patients with ARDS were studied during use of the ARDSNet lung-protective ventilatory strategy: VT was set at 6 ml/kg predicted body weight and positive end-expiratory pressure (PEEP) and inspiratory oxygen fraction (Fio2) were set to obtain an arterial oxygen saturation of 90-95% and/or an arterial oxygen partial pressure (Pao2) of 60- 80 mmHg (baseline). Measurements of Pao2/Fio2, static volume-pressure curve, recruited volume (vertical shift of the volume-pressure curve), and chest wall and lung elastance (EstW and EstL: esophageal pressure) were obtained on zero end-expiratory pressure, at baseline, and at 2 and 20 min after application of a recruiting maneuver (40 cm H2O of continuous positive airway pressure for 40 s). Cardiac output (transesophageal Doppler) and mean arterial pressure were measured immediately before, during, and immediately after the recruiting maneuver. Patients were classified a priori as responders and nonresponders on the basis of the occurrence or nonoccurrence of a 50% increase in Pao2/Fio2 after the recruiting maneuver. RESULTS: Recruiting maneuvers increased Pao2/Fio2 by 20 +/- 3% in nonresponders (n = 11) and by 175 +/- 23% (n = 11; mean +/- standard deviation) in responders. On zero end-expiratory pressure, EstL (28.4 +/- 2.2 vs. 24.2 +/- 2.9 cm H2O/l) and EstW (10.4 +/- 1.8 vs. 5.6 +/- 0.8 cm H2O/l) were higher in nonresponders than in responders (P < 0.01). Nonresponders had been ventilated for a longer period of time than responders (7 +/- 1 vs. 1 +/- 0.3 days; P < 0.001). Cardiac output and mean arterial pressure decreased by 31 +/- 2 and 19 +/- 3% in nonresponders and by 2 +/- 1 and 2 +/- 1% in responders (P < 0.01). CONCLUSIONS: Application of recruiting maneuvers improves oxygenation only in patients with early ARDS who do not have impairment of chest wall mechanics and with a large potential for recruitment, as indicated by low values of EstL.

Adult↗
PubMed2002

Conventional mechanical ventilation is associated with bronchoalveolar lavage-induced activation of polymorphonuclear leukocytes: a possible mechanism to explain the systemic consequences of ventilator-induced lung injury in patients with ARDS.

BACKGROUND: Protective ventilatory strategies have resulted in a decreased mortality rate in acute respiratory distress syndrome, but the underlying mechanisms remain unclear. The authors hypothesized that (1) mechanical ventilation modulates activation of polymorphonuclear leukocytes (PMNs), (2) the consequent release of proteinases is correlated with a systemic inflammatory response and with multiple organ dysfunction, and (3) these deleterious effects can be minimized by a protective ventilatory strategy. METHODS: Human PMNs were incubated with bronchoalveolar lavage fluid obtained from patients at entry or 36 h after randomization to ventilation with either a conventional (control) or a lung-protective strategy. PMN oxidant production and surface expression of adhesion molecules and granule markers, including CD18, CD63, and L-selectin, were measured by flow cytometry. Extracellular elastase activity was quantified using a fluorescent substrate. RESULTS: Bronchoalveolar lavage obtained from both groups of patients at entry showed similar effects on PMN oxidant production and expression of surface markers. At 36 h, exposure of PMNs to bronchoalveolar lavage fluid from the control group resulted in increased PMN activation as manifested by a significant increase in oxidant production, CD18, and CD63 surface expression, and shedding of L-selectin. By contrast, these variables were unchanged at 36 h in the lung-protective group. There was a significant correlation between the changes of the variables and changes in interleukin-6 level and the number of failing organs. CONCLUSIONS: Polymorphonuclear leukocytes can be activated by mechanical ventilation, and the consequent release of elastase was correlated with the degree of systemic inflammatory response and multiple organ failure. This result may possibly explain the decreased mortality in acute respiratory distress syndrome patients treated with a lung-protective strategy.

Analysis of Variance↗
PubMed2002

Injurious ventilation induces widespread pulmonary epithelial expression of tumor necrosis factor-alpha and interleukin-6 messenger RNA.

OBJECTIVE: We examined the hypothesis that injurious strategies of mechanical ventilation alter the expression and distribution within the lung of tumor necrosis factor-alpha and interleukin-6 that are both duration and ventilation strategy dependent. SUBJECTS: Male Sprague Dawley rats. INTERVENTIONS: Lungs from rats were preserved immediately after death or were randomized to ex vivo ventilation with either a) noninjurious ventilation; b) high end-inspiratory lung volume with positive end-expiratory pressure (PEEP); c) high end-inspiratory lung volume without PEEP; or d) intermediate lung distension without PEEP, for periods ranging from 30 mins to 3 hrs. MEASUREMENT AND MAIN RESULTS: Changes in cytokines were assessed by in situ hybridization, immunocytochemistry, simultaneous in situ hybridization and immunocytochemistry, Northern analysis, and enzyme-linked immunosorbent assay. Whereas minimal expression of tumor necrosis factor-alpha and interleukin-6 mRNA was found in lungs subjected to noninjurious ventilation, the three injurious strategies resulted in a diffuse increase in expression of tumor necrosis factor-alpha and interleukin-6. The principal cells involved were the bronchial, bronchiolar, and alveolar epithelium. The changes in tumor necrosis factor-alpha mRNA and protein expression were dependent on both duration of ventilation and the ventilation strategy used. CONCLUSIONS: The vast pulmonary epithelium is a major contributor to ventilation-induced changes in cytokine production and may play an important role in the pathogenesis of lung injury and systemic sequelae in ventilated subjects.

Animals↗
PubMedDate not supplied

Injurious mechanical ventilation and end-organ epithelial cell apoptosis and organ dysfunction in an experimental model of acute respiratory distress syndrome.

CONTEXT: Recent clinical trials have demonstrated a decrease in multiple organ dysfunction syndrome (MODS) and mortality in patients with acute respiratory distress syndrome (ARDS) treated with a protective ventilatory strategy. OBJECTIVE: To examine the hypothesis that an injurious ventilatory strategy may lead to end-organ epithelial cell apoptosis and organ dysfunction. DESIGN AND SETTING: In vivo animals: 24 rabbits with acid-aspiration lung injury were ventilated with injurious or noninjurious ventilatory strategies. In vitro: rabbit epithelial cells were exposed to plasma from in vivo rabbit studies. In vivo human: plasma samples from patients included in a previous randomized controlled trial examining a lung protective strategy were analyzed (lung protection group, n = 9 and controls, n = 11). MAIN OUTCOME MEASURES: In vivo animals: biochemical markers of liver and renal dysfunction; apoptosis in end organs. In vitro: induction of apoptosis in LLC-RK1 renal tubular epithelial cells. In vivo human: correlation of plasma creatinine and soluble Fas ligand. RESULTS: The injurious ventilatory strategy led to increased rates of epithelial cell apoptosis in the kidney (mean [SE]: injurious, 10.9% [0.88%]; noninjurious, 1.86% [0.17%]; P<.001) and small intestine villi (injurious, 6.7% [0.66%]; noninjurious, 0.97% [0.14%]; P<.001), and led to the elevation of biochemical markers indicating renal dysfunction in vivo. Induction of apoptosis was increased in LLC-RK1 cells incubated with plasma from rabbits ventilated with injurious ventilatory strategy at 4 hours (P =.03) and 8 hours (P =.002). The Fas:Ig, a fusion protein that blocks soluble Fas ligand, attenuated induction of apoptosis in vitro. There was a significant correlation between changes in soluble Fas ligand and changes in creatinine in patients with ARDS (R = 0.64, P =.002). CONCLUSIONS: Mechanical ventilation can lead to epithelial cell apoptosis in the kidney and small intestine, accompanied by biochemical evidence of organ dysfunction. This may partially explain the high rate of MODS observed in patients with ARDS and the decrease in morbidity and mortality in patients treated with a lung protective strategy.

Animals↗