Long-term outcomes in survivors of acute respiratory distress syndrome ventilated in supine or prone position.

PURPOSE: The aim of this study is to examine long-term pulmonary function and quality of life in survivors of acute respiratory distress syndrome (ARDS) previously enrolled in a randomized multicenter trial testing prone compared with supine positioning (PSII study) at five Italian centers. DESIGN: Observational prospective study. SUBJECTS AND MEASUREMENTS: Pulmonary function [spirometric test, gas exchange, carbon monoxide diffusion capacity (DLCO)], high-resolution computed tomography (CT) scan, and health-related quality of life [Short Form-36 (SF-36) and St. George's Respiratory Questionnaire] were evaluated at 12 months. RESULTS: Twenty-six patients (13 in each group, mean age 54.1 ± 2.8 years, body mass index 24.5 ± 1.4 kg/m(2), PaO(2)/FiO(2) 117 ± 49 mmHg) were evaluated. There were no significant differences in demographic data, illness severity, or outcome between the prone and supine groups. The overall survival rate was 40%. Pulmonary function was in the normal range without any differences between the two groups. Quantitative lung CT scan analysis showed similar amounts for not aerated (8.1 ± 3.2% versus 7.3 ± 3.4%), poorly aerated (15.3 ± 3.6% versus 17.1 ± 4.9%), and well-aerated (64.0% ± 8.4 versus 70.2 ± 8.4%) lung regions, while overaerated lung region was slightly higher in the prone compared with the supine group (12.5 ± 6.5% versus 5.3 ± 5.5%). Health-related quality of life was similar to in healthy population. However, these patients showed reduction in daily activity specifically due to pulmonary disease as measured by the St. George's Respiratory Questionnaire. CONCLUSIONS: No differences in pulmonary function or quality of life were observed in this small group of ARDS survivor patients treated in prone versus supine position.

Prone positioning improves survival in severe ARDS: a pathophysiologic review and individual patient meta-analysis.

Prone positioning has been used for over 30 years in the management of patients with acute respiratory distress syndrome (ARDS). This maneuver has consistently proven capable of improving oxygenation in patients with acute respiratory failure. Several mechanisms can explain this observation, including possible intervening net recruitment and more homogeneously distributed alveolar inflation. It is also progressively becoming clear that prone positioning may reduce the nonphysiological stress and strain associated with mechanical ventilation, thus decreasing the risk of ventilator-induced lung injury, which is known to adversely impact patient survival. The available randomized clinical trials, however, have failed to demonstrate that prone positioning improves the outcomes of patients with ARDS overall. In contrast, the individual patient meta-analysis of the four major clinical trials available clearly shows that with prone positioning, the absolute mortality of severely hypoxemic ARDS patients may be reduced by approximately 10%. On the other hand, all data suggest that long-term prone positioning may expose patients with less severe ARDS to unnecessary complications.

Kidney instant monitoring (K.IN.G): a new analyzer to monitor kidney function.

AIM: The key role of the kidney in the regulation of body fluids and acid-base status is well known. Nonetheless, urine analysis has not received great attention in critically ill patients, likely due to the common practice of only analyzing 24-hour collected specimens. We hypothesized that the kidney may react more rapidly to minimal hemodynamic and acid-base status variations than can be assessed by a 24-hour analysis. Accordingly, we developed and tested a urine analyzer, allowing quasi-continuous urinary analysis. METHODS: A novel analyzer (Kidney INstant monitorinG--K.IN.G) was developed that allows non-invasive, quasi-continuous analysis of urine pH, sodium, chloride, potassium and ammonium levels. Analytic measurement accuracy was calculated for urine samples of patients admitted to ICUs as well as medical staff, using standard techniques as references. For clinical investigation, approximately 200 patients were connected to the analyzer after ICU admission until discharge. Clinically relevant parameters were recorded. Here, three cases are presented. RESULTS: For each analytic parameter, the accuracy of measurements obtained with the K.IN.G analyzer appeared to be acceptable as compared to those of the reference techniques. In case 1, urine analysis revealed increased urinary sodium and chloride excretion strictly in parallel with mean arterial pressure, and increased ammonium excretion which was associated with moderate hypercapnia. Case 2 showed increases in urinary pH and sodium and chloride levels following awakening after sedation suspension. In case 3, urine analysis revealed an impairment of renal concentrative power, which was associated with hypovolemia. CONCLUSION: The K.IN.G analyzer, allowing quasi-continuous monitoring of urinary pH and principal electrolyte levels, may represent a novel tool for clinical and research purposes.

Effects of recombinant human activated protein C on the fibrinolytic system of patients undergoing conventional or tight glycemic control.

AIM: Recombinant human activated protein C (rh-APC) and tight glycemic control (TGC) have been shown to reduce mortality in septic patients. Both interventions can reduce the plasma concentration and/or activity of the most powerful suppressor of fibrinolysis, plasminogen activator inhibitor-1 (PAI-1). Our aim was to evaluate the effects on the fibrinolytic system after the administration of rh-APC in septic patients undergoing conventional or TGC. METHODS: Posthoc analysis of data was collected from 90 patients with severe sepsis/septic shock, randomized to either conventional or TGC groups. Independent of these treatments, patients with at least two organ dysfunctions simultaneously received rh-APC. Plasma levels of multiple biochemical markers for fibrinolysis, coagulation, and inflammation were determined every day for the 1st week and then on study days 9, 11, 13, 18, 23, and 28. Clinical data and sepsis-related organ failure assessment (SOFA) scores were also recorded. RESULTS: Patients who had received rh-APC exhibited significantly more impairments in fibrinolysis at baseline (PAI-1 activity 49.76 [24.61-71.82] vs 21.92 [6.47-55-83] IU/mL, P=0.03). The reductions in plasma PAI-1 activity over time associated with rh-APC treatment were different according to whether the treatment was administered to patients undergoing conventional or TGC (P=0.01). However, the most prominent reductions were in patients undergoing conventional glycemic control. Significant interactions between the two study interventions were also found for PAI-1 concentration (P<0.001), C-reactive protein (P=0.02), and interleukin-6 levels (P<0.001). CONCLUSIONS: Both rh-APC and TGC appear to improve fibrinolysis in septic patients. The reduction in the impairment of fibrinolysis associated with rh-APC treatment seems greater in patients undergoing conventional glycemic control than in those undergoing TGC.

Gastric tonometry.

Gastric tonometry was originally proposed to assess the splanchnic perfusion. Several technological improvements have been introduced over the years and, to date, the preferred way to estimate the splanchnic perfusion is to rely on the arterial-gastric PCO2 gap. In this brief review we will discuss the value of the gastric tonometry, its physiological background and the clinical results observed so far.

Respiratory acidosis: is the correction with bicarbonate worth?

Bicarbonate infusion is traditionally used to increase pH during metabolic acidosis, but it has been also suggested to increase the pH during permissive hypercapnia. In this paper we will discuss the physicochemical effect of adding (Na+ HCO3-), first in a closed system (venous blood) and then in an open system (the blood after the lung). According to Stewart model, in the closed system two independent variables are changed (CO2 and strong ion difference). As a first result changes in pH are negligible. If the CO2 is cleared by the lung and the PCO2 is maintained as before the infusion, the rise in pH is due to the SID increase caused by the (Na+) rise. The effect is independent on (HCO3-) infusion and equivalent to adding (Na+ OH-) instead of (Na+ HCO3-).

Pathophysiology of prone positioning in the healthy lung and in ALI/ARDS.

Prone position was initially introduced in healthy anesthetized and paralyzed subjects for surgical specific reasons. Then, it was used during acute respiratory failure to improve gas exchange. The interest on prone position during ALI/ARDS progressively increased, even if the mechanisms leading to a respiratory improvement are not yet completely understood. In normal subjects, during anesthesia and paralysis, prone position determines a more homogeneous distribution of the gravitational gradient of alveolar inflation, a ventilation distributed towards the non dependent lung regions and a reverse of the gravitational distribution of regional perfusion, even if factors other than gravity are involved. Moreover, prone position causes, both in healthy subject and in obese patients, an improvement in oxygenation and in functional residual capacity without affecting respiratory system, lung and chest wall compliance. In ALI/ARDS patients, prone position lead to a reverse of the alveolar inflation and ventilation distribution, due to the reverse of hydrostatic pressure overlying lung parenchyma, the reverse of heart weight, and the changes in chest wall shape and mechanical properties. Little data are available for the modifications in regional lung perfusion. The possible mechanisms involved in oxygenation improvement during prone position in ALI/ARDS patients are: 1) increased lung volumes; 2) redistribution of lung perfusion; 3) recruitment of dorsal spaces with more homogeneous ventilation and perfusion distribution. From a clinical point of view, prone position seems to be a very promising treatment for ALI/ARDS, even if its use is not yet a standard clinical practice. We have recently finished a randomized-controlled trial in order to investigate the clinical impact of this procedure. In the preliminary phase of the study performed in 35 Italian Intensive Care Units, we studied, from 1996 to 1998, 73 patients with a PaO2/FiO2 of 123 +/- 42 and a SAPS (Simplified Acute Physiology Score) of 38 +/- 11. After the first hour of prone positioning, the PaO2/FiO2 ratio of 76% of the patients had increased by more than 20 mmHg (responder) with a mean increase of 78 +/- 53 mmHg. The proportion of responders increased to 85% after 6 hours of prone positioning. The incidence of maneuver-related complications and severe and life-threatening complications was extremely rare. The overall mortality at ICU discharge was 51% and the ICU stay was similar in survivors and non survivors (17.8 +/- 11.6 vs 17.8 +/- 11.4 days).

Sepsis: state of the art.

In recent years, we have considerably widened our knowledge of the pathophysiology of sepsis and some procedures, aiming both to relieve symptoms and control the inflammation/coagulation reaction, have proven to be effective in increasing survival. This improves when mechanical ventilation is applied with low tidal volumes, fluid replacement and the use of cardioactive drugs are titrated on the oxygen saturation of hemoglobin in the central venous system and blood glucose does not exceed certain limits. It is also evident that inflammation and coagulation are closely related to each other. The inhibition of only one pathway, such as the inhibition of inflammation with high dosage steroids or the inhibition of coagulation with antithrombin, does not produce a survival improvement. The only molecule which has proven to be notably effective in reducing mortality is Activated Protein C interacting on coagulation/fibrinolysis, as well as on inflammation processes. Multinodal modulation of several interdependent processes may be the probable reason for the proven effectiveness of this treatment.

Effects of different continuous positive airway pressure devices and periodic hyperinflations on respiratory function.

OBJECTIVE: To compare the effect on respiratory function of different continuous positive airway pressure systems and periodic hyperinflations in patients with respiratory failure. DESIGN: Prospective SETTING: Hospital intensive care unit. PATIENTS: Sixteen intubated patients (eight men and eight women, age 54 +/- 18 yrs, PaO2/FiO2 277 +/- 58 torr, positive end-expiratory pressure 6.2 +/- 2.0 cm H2O). INTERVENTIONS: We evaluated continuous flow positive airway pressure systems with high or low flow plus a reservoir bag equipped with spring-loaded mechanical or underwater seal positive end-expiratory pressure valve and a continuous positive airway pressure by a Servo 300 C ventilator with or without periodic hyperinflations (three assisted breaths per minute with constant inspiratory pressure of 30 cm H2O over positive end-expiratory pressure). MEASUREMENTS AND MAIN RESULTS: We measured the respiratory pattern, work of breathing, dyspnea sensation, end-expiratory lung volume, and gas exchange. We found the following: a) Work of breathing and gas exchange were comparable between continuous flow systems; b) the ventilator continuous positive airway pressure was not different compared with continuous flow systems; and c) continuous positive airway pressure with periodic hyperinflations reduced work of breathing (10.7 +/- 9.5 vs. 6.3 +/- 5.7 J/min, p <.05) and dyspnea sensation (1.6 +/- 1.2 vs. 1.1 +/- 0.8 cm, p <.05) increased end-expiratory lung volume (1.6 +/- 0.8 vs. 2.0 +/- 0.9 L, p <.05) and PaO2 (100 +/- 21 vs. 120 +/- 25 torr, p <.05) compared with ventilator continuous positive airway pressure. CONCLUSIONS: The continuous flow positive airway pressure systems tested are equally efficient; a ventilator can provide satisfactory continuous positive airway pressure; and the use of periodic hyperinflations during continuous positive airway pressure can improve respiratory function and reduce the work of breathing.

Mesenteric and renal oxygen transport during hemorrhage and reperfusion: evaluation of optimal goals for resuscitation.

BACKGROUND: Changes in flow to the gut and the kidney during hemorrhage and resuscitation contribute to organ dysfunction and outcome. We evaluated regional and splanchnic oxygen (O2) flow distribution and calculated oxygen supply distribution during hemorrhage and reperfusion and compared them with global measures. METHODS: Seven anesthetized pigs were instrumented to evaluate global hemodynamics, visceral blood flow, and oxygen transport. Tonometric pH probes were positioned in the stomach and jejunum. Animals were bled to 45 mm Hg for 1 hour. Crystalloids and blood were infused during the following 2 hours to normalize blood pressure, heart rate, urine output, and hemo- globin. RESULTS: During hemorrhage, mesenteric flow and O2 consumption were significantly decreased, whereas systemic consumption remained normal. Renal flow was reduced, but renal O2 consumption remained normal. After resuscitation, despite normal hemodynamics, neither systemic, mesenteric, nor renal O2 delivery returned to baseline. Lactate remained significantly increased. Arterial pH, base excess, and gastric and jejunal pH were all decreased. CONCLUSION: During hemorrhage, the gut is more prone than other regions to O2 consumption supply dependency. After resuscitation, standard clinical parameters do not detect residual O2 debt. Lactate, arterial pH, base excess, and intramucosal gut pH are all markers of residual tissue hypoperfusion.

Effect of prone positioning on the survival of patients with acute respiratory failure.

BACKGROUND: Although placing patients with acute respiratory failure in a prone (face down) position improves their oxygenation 60 to 70 percent of the time, the effect on survival is not known. METHODS: In a multicenter, randomized trial, we compared conventional treatment (in the supine position) of patients with acute lung injury or the acute respiratory distress syndrome with a predefined strategy of placing patients in a prone position for six or more hours daily for 10 days. We enrolled 304 patients, 152 in each group. RESULTS: The mortality rate was 23.0 percent during the 10-day study period, 49.3 percent at the time of discharge from the intensive care unit, and 60.5 percent at 6 months. The relative risk of death in the prone group as compared with the supine group was 0.84 at the end of the study period (95 percent confidence interval, 0.56 to 1.27), 1.05 at the time of discharge from the intensive care unit (95 percent confidence interval, 0.84 to 1.32), and 1.06 at six months (95 percent confidence interval, 0.88 to 1.28). During the study period the mean (+/-SD) increase in the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen, measured each morning while patients were supine, was greater in the prone than the supine group (63.0+/-66.8 vs. 44.6+/-68.2, P=0.02). The incidence of complications related to positioning (such as pressure sores and accidental extubation) was similar in the two groups. CONCLUSIONS: Although placing patients with acute respiratory failure in a prone position improves their oxygenation, it does not improve survival.