Paolo Taccone

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

ObjectiveTo 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). DesignRetrospective 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. SettingTwenty-eight Italian and two Swiss intensive care units. PatientsWe studied 225 patients meeting the criteria for ALI or ARDS. InterventionsPatients 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 ResultsWe 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 ≥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 ≥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). ConclusionALI/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.

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.

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 (r2 = .97, slope = 0.92, intercept = −1.17, p < .001) and in the volunteers (r2 = .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.

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

ObjectiveWith 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. DesignClinical study. SettingUniversity laboratory. PatientsTen intubated patients recovering from acute lung injury (Pao2/Fio2 245 ± 26 torr, positive end-expiratory pressure 9 ± 3 cm H2O). InterventionsWe 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 ResultsAt 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. ConclusionsOur 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

ObjectiveTo compare the effectiveness of normal saline, dextran, hypertonic, and hypertonic-hyperoncotic solutions in hemorrhagic shock. DesignLaboratory investigation. SettingUniversity hospital, Emergency Surgery and Intensive Care staff. SubjectsThirty-two large white female pigs. InterventionsRoutine 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 (Paco2 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 ResultsMean 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;o2, &U1E0A;o2mes, &U1E0A;o2ren), and consumption (&OV0312;o2, &OV0312;o2mes, &OV0312;o2ren) 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;o2 was significantly higher after hypertonic-hyperoncotic infusion, because of reduced hemodilution. Hypertonic and hypertonic-hyperoncotic normalized &OV0312;mes, &U1E0A;o2mes, &OV0312;o2mes, &OV0312;ren, and &U1E0A;o2ren, 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;o2 until the end of observation in contrast to normal saline, dextran, and hypertonic. ConclusionsResuscitation 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

ObjectivesTo review the physiologic approach to setting mechanical ventilation in acute lung injury/acute respiratory distress syndrome. Data SourcesMEDLINE search from 1979 to the present. Data SelectionPersonal selection of some articles we believe relevant for understanding acute lung injury/acute respiratory distress syndrome physiopathology and its physiologic management. Data SummaryKnowing 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. ConclusionsThe majority of physiologic, experimental, and clinical trial data converge on one simple concept: treat the lung gently.

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.

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.

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.

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

ObjectiveTo compare the effect on respiratory function of different continuous positive airway pressure systems and periodic hyperinflations in patients with respiratory failure. DesignProspective SettingHospital intensive care unit. PatientsSixteen 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). InterventionsWe 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. ConclusionsThe 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.