Oxygenation during general anesthesia and thoracic surgery in a patient with Titusville low-oxygen affinity hemoglobin.

The purpose of this case study is to describe the physiological characteristics of a patient with the low-oxygen affinity Titusville hemoglobin variant. A 46-yr-old man with exertional dyspnea was diagnosed with a mediastinal lymphadenopathy of unknown origin and, to obtain definitive diagnosis by biopsy, underwent endobronchial ultrasound-guided transbronchial needle aspirate under sedation and video-assisted thoracoscopy under general anesthesia. High inspired fraction of oxygen ( FIO2 ) was used to guarantee adequate oxygenation even during the one-lung ventilation needed for thoracoscopy. Following radial and pulmonary arterial catheterization, continuous mixed-venous oxygen saturation ( SVO2 ), cardiac output, oxygen delivery (DO2), oxygen consumption (V̇o2), and oxygen extraction ratio (ERO2) were measured. Serial blood gas analyses were obtained at different FIO2 . Anesthesia and surgery were carried out safely. Data obtained during the clinical case were utilized to 1) construct an in vivo Titusville hemoglobin dissociation curve and 2) describe oxygen delivery and consumption of a human with Titusville mutation. Titusville hemoglobin showed relatively high P50 (i.e., 30 vs. normal of 27) and very low cooperativity (Hill coefficient of 1.45 vs. normal 2.27), which was compensated in our patient by increases in cardiac output, rather than by augmenting oxygen extraction.

Inflammation and primary graft dysfunction after lung transplantation: CT-PET findings.

BACKGROUND: The leading cause of early mortality after lung transplantation is Primary graft dysfunction (PGD). We assessed the lung inflammation, inflation status and inhomogeneities after lung transplantation. Our purpose was to investigate the possible differences between patients who did or did not develop PGD. METHODS: We designed a prospective observational study enrolling patients who underwent a CT-PET study within 1 week after lung transplantation. Twenty-four patients (10 after double- and 14 after single-lung) were enrolled. Respiratory and hemodynamic data were collected before, during and after lung transplantation. Each patient underwent computed tomography-positron emission tomography (CT-PET) scan early after surgery. Broncho-alveolar lavage (BAL) fluid collection was performed to analyze inflammatory mediators. RESULTS: The grafts showed a [18F]fluoro-2-deoxy-D-glucose ([18F]FDG) uptake rate of 26[18-33]*10-4 mLblood/mLtissue/min (reference values 11[7-15]*10-4). Three double- and six single-lung recipients developed PGD. The grafts of patients who developed PGD had similar [18F]FDG uptake than grafts of patients who did not (28[18-26]*10-4 versus 26[22-31]*10-4, P=0.79). Not-inflated tissue fraction was significantly higher (28[20-38]% versus 14[7-21]%, P=0.01) while well-inflated fraction was significantly lower (29[25-41]% versus 53[39-65]%, P<0.01). Inhomogeneity extent was higher in patients who developed PGD (23[18-26]% versus 14[10-20]%, P=0.01)The lung weight was 650[591-820]g versus 597[480-650]g (P=0.09)). BAL fluid analysis for inflammatory mediators did not detect a difference between the study groups. CONCLUSIONS: Compared to healthy lungs, all the grafts showed increased [18F]FDG uptake rate, but there were no differences between patients who developed PGD and patients who did not. Of note, the PGD patients showed a worse inflation status of lungs and a higher inhomogeneity extent.

Optimum support by high-flow nasal cannula in acute hypoxemic respiratory failure: effects of increasing flow rates.

PURPOSE: Limited data exist on the correlation between higher flow rates of high-flow nasal cannula (HFNC) and its physiologic effects in patients with acute hypoxemic respiratory failure (AHRF). We assessed the effects of HFNC delivered at increasing flow rate on inspiratory effort, work of breathing, minute ventilation, lung volumes, dynamic compliance and oxygenation in AHRF patients. METHODS: A prospective randomized cross-over study was performed in non-intubated patients with patients AHRF and a PaO2/FiO2 (arterial partial pressure of oxygen/fraction of inspired oxygen) ratio of ≤300 mmHg. A standard non-occlusive facial mask and HFNC at different flow rates (30, 45 and 60 l/min) were randomly applied, while maintaining constant FiO2 (20 min/step). At the end of each phase, we measured arterial blood gases, inspiratory effort, based on swings in esophageal pressure (ΔPes) and on the esophageal pressure-time product (PTPPes), and lung volume, by electrical impedance tomography. RESULTS: Seventeen patients with AHRF were enrolled in the study. At increasing flow rate, HFNC reduced ΔPes (p < 0.001) and PTPPes (p < 0.001), while end-expiratory lung volume (ΔEELV), tidal volume to ΔPes ratio (V T/ΔPes, which corresponds to dynamic lung compliance) and oxygenation improved (p < 0.01 for all factors). Higher HFNC flow rate also progressively reduced minute ventilation (p < 0.05) without any change in arterial CO2 tension (p = 0.909). The decrease in ΔPes, PTPPes and minute ventilation at increasing flow rates was better described by exponential fitting, while ΔEELV, V T/ΔPes and oxygenation improved linearly. CONCLUSIONS: In this cohort of patients with AHRF, an increasing HFNC flow rate progressively decreased inspiratory effort and improved lung aeration, dynamic compliance and oxygenation. Most of the effect on inspiratory workload and CO2 clearance was already obtained at the lowest flow rate.

Effect of prone positioning during mechanical ventilation on mortality among patients with acute respiratory distress syndrome: a systematic review and meta-analysis.

BACKGROUND: Mechanical ventilation in the prone position is used to improve oxygenation and to mitigate the harmful effects of mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). We sought to determine the effect of prone positioning on mortality among patients with ARDS receiving protective lung ventilation. METHODS: We searched electronic databases and conference proceedings to identify relevant randomized controlled trials (RCTs) published through August 2013. We included RCTs that compared prone and supine positioning during mechanical ventilation in patients with ARDS. We assessed risk of bias and obtained data on all-cause mortality (determined at hospital discharge or, if unavailable, after longest follow-up period). We used random-effects models for the pooled analyses. RESULTS: We identified 11 RCTs (n=2341) that met our inclusion criteria. In the 6 trials (n=1016) that used a protective ventilation strategy with reduced tidal volumes, prone positioning significantly reduced mortality (risk ratio 0.74, 95% confidence interval 0.59-0.95; I2=29%) compared with supine positioning. The mortality benefit remained in several sensitivity analyses. The overall quality of evidence was high. The risk of bias was low in all of the trials except one, which was small. Statistical heterogeneity was low (I2<50%) for most of the clinical and physiologic outcomes. INTERPRETATION: Our analysis of high-quality evidence showed that use of the prone position during mechanical ventilation improved survival among patients with ARDS who received protective lung ventilation.

Prone position in acute respiratory distress syndrome. Rationale, indications, and limits.

In the prone position, computed tomography scan densities redistribute from dorsal to ventral as the dorsal region tends to reexpand while the ventral zone tends to collapse. Although gravitational influence is similar in both positions, dorsal recruitment usually prevails over ventral derecruitment, because of the need for the lung and its confining chest wall to conform to the same volume. The final result of proning is that the overall lung inflation is more homogeneous from dorsal to ventral than in the supine position, with more homogeneously distributed stress and strain. As the distribution of perfusion remains nearly constant in both postures, proning usually improves oxygenation. Animal experiments clearly show that prone positioning delays or prevents ventilation-induced lung injury, likely due in large part to more homogeneously distributed stress and strain. Over the last 15 years, five major trials have been conducted to compare the prone and supine positions in acute respiratory distress syndrome, regarding survival advantage. The sequence of trials enrolled patients who were progressively more hypoxemic; exposure to the prone position was extended from 8 to 17 hours/day, and lung-protective ventilation was more rigorously applied. Single-patient and meta-analyses drawing from the four major trials showed significant survival benefit in patients with PaO2/FiO2 lower than 100. The latest PROSEVA (Proning Severe ARDS Patients) trial confirmed these benefits in a formal randomized study. The bulk of data indicates that in severe acute respiratory distress syndrome, carefully performed prone positioning offers an absolute survival advantage of 10-17%, making this intervention highly recommended in this specific population subset.

Prone ventilation reduces mortality in patients with acute respiratory failure and severe hypoxemia: systematic review and meta-analysis.

BACKGROUND: Prone position ventilation for acute hypoxemic respiratory failure (AHRF) improves oxygenation but not survival, except possibly when AHRF is severe. OBJECTIVE: To determine effects of prone versus supine ventilation in AHRF and severe hypoxemia [partial pressure of arterial oxygen (PaO(2))/inspired fraction of oxygen (FiO(2)) <100 mmHg] compared with moderate hypoxemia (100 mmHg < or = PaO(2)/FiO(2) < or = 300 mmHg). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Electronic databases (to November 2009) and conference proceedings. METHODS: Two authors independently selected and extracted data from parallel-group randomized controlled trials comparing prone with supine ventilation in mechanically ventilated adults or children with AHRF. Trialists provided subgroup data. The primary outcome was hospital mortality in patients with AHRF and PaO(2)/FiO(2) <100 mmHg. Meta-analyses used study-level random-effects models. RESULTS: Ten trials (N = 1,867 patients) met inclusion criteria; most patients had acute lung injury. Methodological quality was relatively high. Prone ventilation reduced mortality in patients with PaO(2)/FiO(2) <100 mmHg [risk ratio (RR) 0.84, 95% confidence interval (CI) 0.74-0.96; p = 0.01; seven trials, N = 555] but not in patients with PaO(2)/FiO(2) > or =100 mmHg (RR 1.07, 95% CI 0.93-1.22; p = 0.36; seven trials, N = 1,169). Risk ratios differed significantly between subgroups (interaction p = 0.012). Post hoc analysis demonstrated statistically significant improved mortality in the more hypoxemic subgroup and significant differences between subgroups using a range of PaO(2)/FiO(2) thresholds up to approximately 140 mmHg. Prone ventilation improved oxygenation by 27-39% over the first 3 days of therapy but increased the risks of pressure ulcers (RR 1.29, 95% CI 1.16-1.44), endotracheal tube obstruction (RR 1.58, 95% CI 1.24-2.01), and chest tube dislodgement (RR 3.14, 95% CI 1.02-9.69). There was no statistical between-trial heterogeneity for most clinical outcomes. CONCLUSIONS: Prone ventilation reduces mortality in patients with severe hypoxemia. Given associated risks, this approach should not be routine in all patients with AHRF, but may be considered for severely hypoxemic patients.

Prone positioning in patients with moderate and severe acute respiratory distress syndrome: a randomized controlled trial.

CONTEXT: Post hoc analysis of a previous trial has suggested that prone positioning may improve survival in patients with severe hypoxemia and with acute respiratory distress syndrome (ARDS). OBJECTIVE: To assess possible outcome benefits of prone positioning in patients with moderate and severe hypoxemia who are affected by ARDS. DESIGN, SETTING, AND PATIENTS: The Prone-Supine II Study, a multicenter, unblinded, randomized controlled trial conducted in 23 centers in Italy and 2 in Spain. Patients were 342 adults with ARDS receiving mechanical ventilation, enrolled from February 2004 through June 2008 and prospectively stratified into subgroups with moderate (n = 192) and severe (n = 150) hypoxemia. INTERVENTIONS: Patients were randomized to undergo supine (n = 174) or prone (20 hours per day; n = 168) positioning during ventilation. MAIN OUTCOME MEASURES: The primary outcome was 28-day all-cause mortality. Secondary outcomes were 6-month mortality and mortality at intensive care unit discharge, organ dysfunctions, and the complication rate related to prone positioning. RESULTS: Prone and supine patients from the entire study population had similar 28-day (31.0% vs 32.8%; relative risk [RR], 0.97; 95% confidence interval [CI], 0.84-1.13; P = .72) and 6-month (47.0% vs 52.3%; RR, 0.90; 95% CI, 0.73-1.11; P = .33) mortality rates, despite significantly higher complication rates in the prone group. Outcomes were also similar for patients with moderate hypoxemia in the prone and supine groups at 28 days (25.5% vs 22.5%; RR, 1.04; 95% CI, 0.89-1.22; P = .62) and at 6 months (42.6% vs 43.9%; RR, 0.98; 95% CI, 0.76-1.25; P = .85). The 28-day mortality of patients with severe hypoxemia was 37.8% in the prone and 46.1% in the supine group (RR, 0.87; 95% CI, 0.66-1.14; P = .31), while their 6-month mortality was 52.7% and 63.2%, respectively (RR, 0.78; 95% CI, 0.53-1.14; P = .19). CONCLUSION: Data from this study indicate that prone positioning does not provide significant survival benefit in patients with ARDS or in subgroups of patients with moderate and severe hypoxemia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00159939.

Tight glycemic control may favor fibrinolysis in patients with sepsis.

OBJECTIVE: To investigate whether tight glycemic control, in patients with sepsis, may restore a normal fibrinolysis by lowering plasminogen activator inhibitor (PAI)-1 levels. DESIGN: Prospective randomized clinical trial. SETTING: Three Italian university hospital intensive care units. PATIENTS: Ninety patients with severe sepsis/septic shock. INTERVENTIONS: Patients were randomized to receive either tight glycemic control (treatment group, target glycemia, 80-110 mg/dL) or conventional glycemic control (control group, target glycemia, 180-200 mg/dL). MEASUREMENTS: Inflammation, coagulation, and fibrinolysis markers were assessed, along with Sepsis-related Organ Failure Assessment scores, >28 days. MAIN RESULTS: In the whole population, at enrolment, inflammation and coagulation were activated in >80 of 90 patients, whereas fibrinolysis, as assessed by PAI-1 activity and concentration, was impaired in only 34 patients. The extent of the inflammatory reaction or of the coagulation activation was unrelated to outcome. In contrast, 90-day mortality rate of the 34 patients in whom fibrinolysis was definitely inhibited at study entry was twice that of the 56 patients in whom fibrinolysis was intact (44% vs. 21%, p = 0.02). After randomization, during the study, daily glycemia averaged 112 +/- 23 mg/dL in the treatment group and 159 +/- 31 mg/dL in controls (p < 0.001), with total daily administered insulin 57 +/- 59 IU and 36 +/- 44 IU, respectively (p < 0.001). A small, but significant, enhancement of fibrinolysis could be observed in the treatment group, as indicated by the time course of PAI-1 activity (p < 0.001), PAI-1 concentration (p = 0.004), and plasmin-antiplasmin complexes (p < 0.001). Morbidity, rated with the Sepsis-related Organ Failure Assessment score, became significantly lower (p = 0.03) in the treatment group. CONCLUSIONS: Fibrinolysis inhibition, in severe sepsis/septic shock, seems to have a relevant pathogenetic role. In this context, tight glycemic control seems to reduce, with time, the fibrinolytic impairment and morbidity.

Intraoperative language localization in multilingual patients with gliomas.

OBJECTIVE: Intraoperative localization of speech is problematic in patients who are fluent in different languages. Previous studies have generated various results depending on the series of patients studied, the type of language, and the sensitivity of the tasks applied. It is not clear whether languages are mediated by multiple and separate cortical areas or shared by common areas. Globally considered, previous studies recommended performing a multiple intraoperative mapping for all the languages in which the patient is fluent. The aim of this work was to study the feasibility of performing an intraoperative multiple language mapping in a group of multilingual patients with a glioma undergoing awake craniotomy for tumor removal and to describe the intraoperative cortical and subcortical findings in the area of craniotomy, with the final goal to maximally preserve patients' functional language. METHODS: Seven late, highly proficient multilingual patients with a left frontal glioma were submitted preoperatively to a battery of tests to evaluate oral language production, comprehension, and repetition. Each language was tested serially starting from the first acquired language. Items that were correctly named during these tests were used to build personalized blocks to be used intraoperatively. Language mapping was undertaken during awake craniotomies by the use of an Ojemann cortical stimulator during counting and oral naming tasks. Subcortical stimulation by using the same current threshold was applied during tumor resection, in a back and forth fashion, and the same tests. RESULTS: Cortical sites essential for oral naming were found in 87.5% of patients, those for the first acquired language in one to four sites, those for the other languages in one to three sites. Sites for each language were distinct and separate. Number and location of sites were not predictable, being randomly and widely distributed in the cortex around or less frequently over the tumor area. Subcortical stimulations found tracts for the first acquired language in four patients and for the other languages in three patients. Three of these patients decreased their fluency immediately after surgery, affecting the first acquired language, which fully recovered in two patients and partially in one. The procedure was agile and well tolerated by the patients. CONCLUSION: These findings show that multiple cortical and subcortical language mapping during awake craniotomy for tumor removal is a feasible procedure. They support the concept that intraoperative mapping should be performed for all the languages in which the patient is fluent in to preserve functional integrity.

Continuous positive airway pressure delivered with a "helmet": effects on carbon dioxide rebreathing.

OBJECTIVE: The "helmet" has been used as a novel interface to deliver noninvasive ventilation without applying direct pressure on the face. However, due to its large volume, the helmet may predispose to CO2 rebreathing. We hypothesized that breathing with the helmet is similar to breathing in a semiclosed environment, and therefore the PCO2 inside the helmet is primarily a function of the subject's CO2 production and the flow of fresh gas through the helmet. DESIGN: Human volunteer study. SETTING: Laboratory in a university teaching hospital. SUBJECTS: Eight healthy volunteers. INTERVENTIONS: We delivered continuous positive airway pressure (CPAP) with the helmet under a variety of ventilatory conditions in a lung model and in volunteers. MEASUREMENTS AND MAIN RESULTS: Gas flow and CO2 concentration at the airway were measured continuously. End-tidal PCO2, CO2 production, and ventilatory variables were subsequently computed. We found that a) when CPAP was delivered with a ventilator, the inspired CO2 of the volunteers was high (12.4 +/- 3.2 torr [1.7 +/- 0.4 kPa]); b) when CPAP was delivered with a continuous high flow system, inspired CO2 of the volunteers was low (2.5 +/- 1.2 torr [0.3 +/- 0.2 kPa]); and c) the inspired CO2 calculated mathematically for a semiclosed system model of CO2 rebreathing was highly correlated with the values measured in a lung model (r = .97, slope = 0.92, intercept = -1.17, p < .001) and in the volunteers (r = .94, slope = 0.96, intercept = 0.90, p < .001). CONCLUSIONS: a) The helmet predisposes to CO2 rebreathing and should not be used to deliver CPAP with a ventilator; b) continuous high flow minimizes CO2 rebreathing during CPAP with the helmet; and c) minute ventilation and Pco2 should be monitored during CPAP with the helmet.

An increase of abdominal pressure increases pulmonary edema in oleic acid-induced lung injury.

Increased abdominal pressure is common in intensive care unit patients. To investigate its impact on respiration and hemodynamics we applied intraabdominal pressure (aIAP) of 0 and 20 cm H(2)O (pneumoperitoneum) in seven pigs. The whole-lung computed tomography scan and a complete set of respiratory and hemodynamics variables were recorded both in healthy lung and after oleic acid (OA) injury. In healthy lung, aIAP 20 cm H(2)O significantly lowered the gas content, leaving the tissue content unchanged. In OA-injured lung at aIAP 0 cm H(2)O, the gas content significantly decreased compared with healthy lung. The excess tissue mass (edema) amounted to 30 +/- 24% of the original tissue weight (455 +/- 80 g). The edema was primarily distributed in the base regions and was not gravity dependent. Heart volume, central venous, pulmonary artery, wedge, and systemic arterial pressures significantly increased. At aIAP 20 cm H(2)O in OA-injured lung, the central venous and pulmonary artery pressures further increased. The gas content further decreased, and the excess tissue mass rose up to 103 +/- 37% (tissue weight 905 +/- 134 g), with homogeneous distribution along the cephalocaudal and sternovertebral axis. We conclude that in OA-injured lung, the increase of IAP increases the amount of edema.

Decrease in PaCO2 with prone position is predictive of improved outcome in acute respiratory distress syndrome.

OBJECTIVE: To determine whether gas exchange improvement in response to the prone position is associated with an improved outcome in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). DESIGN: Retrospective analysis of patients in the pronation arm of a controlled randomized trial on prone positioning and patients enrolled in a previous pilot study of the prone position. SETTING: Twenty-eight Italian and two Swiss intensive care units. PATIENTS: We studied 225 patients meeting the criteria for ALI or ARDS. INTERVENTIONS: Patients were in prone position for 10 days for 6 hrs/day if they met ALI/ARDS criteria when assessed each morning. Respiratory variables were recorded before and after 6 hrs of pronation with unchanged ventilatory settings. MEASUREMENTS AND MAIN RESULTS: We measured arterial blood gas alterations to the first pronation and the 28-day mortality rate. The independent risk factors for death in the general population were the Pao2/Fio2 ratio (odds ratio, 0.992; confidence interval, 0.986-0.998), the minute ventilation/Paco2 ratio (odds ratio, 1.003; confidence interval, 1.000-1.006), and the concentration of plasma creatinine (odds ratio, 1.385; confidence interval, 1.116-1.720). Pao2 responders (defined as the patients who increased their Pao2/Fio2 by > or =20 mm Hg, 150 patients, mean increase of 100.6 +/- 61.6 mm Hg [13.4 +/- 8.2 kPa]) had an outcome similar to the nonresponders (59 patients, mean decrease -6.3 +/- 23.7 mm Hg [-0.8 +/- 3.2 kPa]; mortality rate 44% and 46%, respectively; relative risk, 1.04; confidence interval, 0.74-1.45, p =.65). The Paco2 responders (defined as patients whose Paco2 decreased by > or =1 mm Hg, 94 patients, mean decrease -6.0 +/- 6 mm Hg [-0.8 +/- 0.8 kPa]) had an improved survival when compared with nonresponders (115 patients, mean increase 6 +/- 6 mm Hg [0.8 +/- 0.8 kPa]; mortality rate 35.1% and 52.2%, respectively; relative risk, 1.48; confidence interval, 1.07-2.05, p =.01). CONCLUSION: ALI/ARDS patients who respond to prone positioning with reduction of their Paco2 show an increased survival at 28 days. Improved efficiency of alveolar ventilation (decreased physiologic deadspace ratio) is an important marker of patients who will survive acute respiratory failure.

Effect of different inspiratory rise time and cycling off criteria during pressure support ventilation in patients recovering from acute lung injury.

OBJECTIVE: With many mechanical ventilators, it is possible to modify the time to reach the selected airway pressure and the criteria for cycling off the inflation during pressure support ventilation. This study evaluated the effect of different inspiratory rise time and cycling off criteria on breathing pattern and work of breathing. DESIGN: Clinical study. SETTING: University laboratory. PATIENTS: Ten intubated patients recovering from acute lung injury (PaO2/FiO2 245 +/- 26 torr, positive end-expiratory pressure 9 +/- 3 cm H2O). INTERVENTIONS: We studied two inspiratory rise time criteria (shortest and longest, 0% and 40% of the breath cycle time) and two cycling off criteria (lowest and highest, 5% and 40% of the peak inspiratory flow) at 5 and 15 cm H2O of pressure support. Respiratory rate, tidal volume, and inspiratory and expiratory work of breathing (WOBI and WOBE) were measured. MEASUREMENTS AND MAIN RESULTS: At both levels of pressure support ventilation, the shortest inspiratory rise time significantly reduced the WOBI from 0.77 +/- 0.32 to 0.56 +/- 0.23 J/L and from 0.24 +/- 0.28 to 0.08 +/- 0.09 J/L without affecting respiratory rate or tidal volume. At 15 cm H2O of pressure support ventilation, the lowest cycling off criteria significantly reduced respiratory rate from 24.9 +/- 12.1 to 21.5 +/- 12.7 beats/min and increased tidal volume from 0.51 +/- 0.17 to 0.60 +/- 0.26 L. At both levels of pressure support ventilation, the modification of cycling off criteria did not influence WOBI and WOBE. CONCLUSIONS: Our results suggest that in patients recovering from acute lung injury during pressure support ventilation, a) the shortest inspiratory rise time reduces the WOBI; and b) at 15 cm H2O of pressure support ventilation, the lowest cycling off criteria reduces the respiratory rate and increases the tidal volume without modifying the WOBI and WOBE. Modifications of inspiratory rise time and cycling off criteria must be carefully adjusted during pressure support ventilation.

Resuscitation from hemorrhagic shock: experimental model comparing normal saline, dextran, and hypertonic saline solutions.

OBJECTIVE: To compare the effectiveness of normal saline, dextran, hypertonic, and hypertonic-hyperoncotic solutions in hemorrhagic shock. DESIGN: Laboratory investigation. SETTING: University hospital, Emergency Surgery and Intensive Care staff. SUBJECTS: Thirty-two large white female pigs. INTERVENTIONS: Routine care included: anesthesia and sedation (ketamine 10 mg/kg, droperidol 0.25 mg/kg, diazepam 0.7 mg/kg, fentanyl 0.006 mg/kg, 2% enflurane, 20% nitrous oxide, pancuronium bromide 0.13 mg/kg); volume-controlled ventilation (Paco(2) 35-40 torr; 4.7-5.4 kPa); cannulation of right carotid artery and pulmonary artery. Three flow probes (subdiaphragmatic aorta, superior mesenteric artery, right renal artery) and regional venous catheters (superior mesenteric vein, right renal vein) were positioned. Animals were bled to 45 mm Hg for 1 hr and resuscitated with four different fluids and blood to normal aortic blood flow and hemoglobin. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure and blood flow through abdominal aorta ([OV0312](aor)), mesenteric artery ([OV0312](mes)), and renal artery ([OV0312](ren)) were continuously monitored. Cardiac output, systemic and regional oxygen delivery ([U1E0A]o(2), [U1E0A]o(2mes), [U1E0A]o(2ren)), and consumption ([OV0312]o(2), [OV0312]o(2mes), [OV0312]o(2ren)) were recorded every 30 mins. Baseline [OV0312](aor) was restored with different amounts of fluids in the four groups: normal saline (91.35 +/- 22.18 mL/kg); dextran (16.24 +/- 4.42 mL/kg); hypertonic (13.70 +/- 1.44 mL/kg); and hypertonic-hyperoncotic (9.11 +/- 1.20 mL/kg). The amount of sodium load was less using dextran and hypertonic-hyperoncotic and sodium levels were only transiently increased after hypertonic infusion. Mean arterial pressure and cardiac output were normalized in all groups. Animals resuscitated with normal saline and dextran showed increased pulmonary artery pressures. [U1E0A]o(2) was significantly higher after hypertonic-hyperoncotic infusion, because of reduced hemodilution. Hypertonic and hypertonic-hyperoncotic normalized [OV0312](mes), [U1E0A]o(2mes), [OV0312]o(2mes), [OV0312](ren), and [U1E0A]o(2ren), whereas normal saline and dextran did not achieve this result. At the end of the experiment, hypertonic-hyperoncotic maintained mean arterial pressure, cardiac output, and [U1E0A]o(2) until the end of observation in contrast to normal saline, dextran, and hypertonic. CONCLUSIONS: Resuscitation with a small volume of hypertonic-hyperoncotic solution allows systemic and splanchnic hemodynamic and oxygen transport recovery, without an increase in pulmonary artery pressure. It only transiently increased sodium concentration.

Physiologic rationale for ventilator setting in acute lung injury/acute respiratory distress syndrome patients.

OBJECTIVES: To review the physiologic approach to setting mechanical ventilation in acute lung injury/acute respiratory distress syndrome. DATA SOURCES: MEDLINE search from 1979 to the present. DATA SELECTION: Personal selection of some articles we believe relevant for understanding acute lung injury/acute respiratory distress syndrome physiopathology and its physiologic management. DATA SUMMARY: Knowing the underlying pathology is key to estimating the potential for recruitment. The potential for recruitment is rather low when the consolidation of pulmonary units exceeds collapse, as in diffuse pneumonia. In contrast, when pulmonary unit collapse exceeds consolidation, as in acute lung injury/acute respiratory distress syndrome from extrapulmonary origin, the potential for recruitment may be high. To exploit the potential for recruitment, a transpulmonary pressure greater than the opening pressure must be applied to the lung. To do so, chest wall elastance must be measured or estimated. To avoid collapse after recruitment, a positive end-expiratory pressure greater than the compressive forces operating on the lung and an alveolar ventilation sufficient to prevent absorption atelectasis must be provided. Indeed, avoidance of stretch (low airway plateau pressure) and prevention of cyclic collapse and reopening (adequate positive end-expiratory pressure and alveolar ventilation) are the physiologic cornerstones of mechanical ventilation in acute lung injury/acute respiratory distress syndrome. When considering all the randomized clinical trials reported so far, it is tempting to speculate that transpulmonary pressure and stresses, rather than tidal volume per se, are the key factors that may have an impact on mortality. CONCLUSIONS: The majority of physiologic, experimental, and clinical trial data converge on one simple concept: treat the lung gently.