Federico Polli

Lung Stress and Strain during Mechanical Ventilation for Acute Respiratory Distress Syndrome

RATIONALE Lung injury caused by a ventilator results from nonphysiologic lung stress (transpulmonary pressure) and strain (inflated volume to functional residual capacity ratio). OBJECTIVES To determine whether plateau pressure and tidal volume are adequate surrogates for stress and strain, and to quantify the stress to strain relationship in patients and control subjects. METHODS Nineteen postsurgical healthy patients (group 1), 11 patients with medical diseases (group 2), 26 patients with acute lung injury (group 3), and 24 patients with acute respiratory distress syndrome (group 4) underwent a positive end-expiratory pressure (PEEP) trial (5 and 15 cm H2O) with 6, 8, 10, and 12 ml/kg tidal volume. MEASUREMENTS AND MAIN RESULTS Plateau airway pressure, lung and chest wall elastances, and lung stress and strain significantly increased from groups 1 to 4 and with increasing PEEP and tidal volume. Within each group, a given applied airway pressure produced largely variable stress due to the variability of the lung elastance to respiratory system elastance ratio (range, 0.33-0.95). Analogously, for the same applied tidal volume, the strain variability within subgroups was remarkable, due to the functional residual capacity variability. Therefore, low or high tidal volume, such as 6 and 12 ml/kg, respectively, could produce similar stress and strain in a remarkable fraction of patients in each subgroup. In contrast, the stress to strain ratio-that is, specific lung elastance-was similar throughout the subgroups (13.4 +/- 3.4, 12.6 +/- 3.0, 14.4 +/- 3.6, and 13.5 +/- 4.1 cm H2O for groups 1 through 4, respectively; P = 0.58) and did not change with PEEP and tidal volume. CONCLUSIONS Plateau pressure and tidal volume are inadequate surrogates for lung stress and strain. Clinical trial registered with www.clinicaltrials.gov (NCT 00143468).

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.

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.

Anatomical and functional intrapulmonary shunt in acute respiratory distress syndrome

Objectives:The lung-protective strategy employs positive end-expiratory pressure to keep open otherwise collapsed lung regions (anatomical recruitment). Improvement in venous admixture with positive end-expiratory pressure indicates functional recruitment to better gas exchange, which is not necessarily related to anatomical recruitment, because of possible global/regional perfusion modifications. Therefore, we aimed to assess the value of venous admixture (functional shunt) in estimating the fraction of nonaerated lung tissue (anatomical shunt compartment) and to describe their relationship. Design:Retrospective analysis of a previously published study. Setting:Intensive care units of four university hospitals. Patients:Fifty-nine patients with acute lung injury/acute respiratory distress syndrome. Interventions:Positive end-expiratory pressure trial at 5 and 15 cm H2O positive end-expiratory pressures. Measurements and Main Results:Anatomical shunt compartment (whole-lung computed tomography scan) and functional shunt (blood gas analysis) were assessed at 5 and 15 cm H2O positive end-expiratory pressures. Apparent perfusion ratio (perfusion per gram of nonaerated tissue/perfusion per gram of total lung tissue) was defined as the ratio of functional shunt to anatomical shunt compartment. Functional shunt was poorly correlated to the anatomical shunt compartment (r2 = .174). The apparent perfusion ratio at 5 cm H2O positive end-expiratory pressure was widely distributed and averaged 1.25 ± 0.80. The apparent perfusion ratios at 5 and 15 cm H2O positive end-expiratory pressures were highly correlated, with a slope close to identity (y = 1.10·x −0.03, r2 = .759), suggesting unchanged blood flow distribution toward the nonaerated lung tissue, when increasing positive end-expiratory pressure. Conclusions:Functional shunt poorly estimates the anatomical shunt compartment, due to the large variability in apparent perfusion ratio. Changes in anatomical shunt compartment with increasing positive end-expiratory pressure, in each individual patient, may be estimated from changes in functional shunt, only if the anatomical-functional shunt relationship at 5 cm H2O positive end-expiratory pressure is known.

Effect of different cycling-off criteria and positive end-expiratory pressure during pressure support ventilation in patients with chronic obstructive pulmonary disease

Objective:During pressure support ventilation, ventilator inspiration ends when inspiratory flow drops to a given percentage of the peak inspiratory flow cycling-off criteria. This study evaluated the effect of two different cycling-off criteria on breathing pattern, respiratory effort, and gas exchange in patients with chronic obstructive pulmonary disease. Design:Clinical study. Patients:Thirteen mechanically ventilated patients with acute exacerbation of chronic obstructive pulmonary disease primarily due to pneumonia (Pao2/Fio2 291 ± 114 mm Hg, Paco2 53 ± 19 mm Hg). Interventions:Two cycling-off criteria (5% and 40% of the peak inspiratory flow) at two levels of pressure support (5 and 15 cm H2O) with and without the application of an external positive end-expiratory pressure (6 and 0 cm H2O) were applied. Measurement:Patient–ventilator time delay of cycling-off was computed as the difference between the end of inspiratory flow and the lowest value of inspiratory esophageal pressure. Inspiratory effort was estimated by computing the work of breathing, the pressure time product partitioned into the total pressure time product, and the pressure time product due to the dynamic intrinsic positive end-expiratory pressure. Results:At 5 and 15 cm H2O of pressure support ventilation, the cycling-off criteria 40% significantly reduced the patient–ventilator time delay of cycling-off from 0.40 ± 0.20 secs to 0.29 ± 0.16 secs and from 0.93 ± 0.50 secs to 0.52 ± 0.25 secs, respectively; the dynamic intrinsic positive end-expiratory pressure from 3.9 ± 1.8 cm H2O to 3.1 ± 2.1 cm H2O and from 2.4 ± 2.0 cm H2O to 1.7 ± 1.4 cm H2O, respectively; and the pressure time product due to the dynamic intrinsic positive end-expiratory pressure. At 5 cm H2O of pressure support, the cycling-off criteria 40% significantly reduced the tidal volume and the inspiratory effort. The modification of cycling-off criteria did not affect the gas exchange. Conclusion:The modification of cycling-off criteria may have a beneficial effect on reducing the dynamic hyperinflation and inspiratory effort in chronic obstructive pulmonary disease patients, especially at low levels of pressure support.

Effects of thoraco-pelvic supports during prone position in patients with acute lung injury/acute respiratory distress syndrome: a physiological study

IntroductionThis study sought to assess whether the use of thoraco-pelvic supports during prone positioning in patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) improves, deteriorates or leaves unmodified gas exchange, hemodynamics and respiratory mechanics.MethodsWe studied 11 patients with ALI/ARDS, sedated and paralyzed, mechanically ventilated in volume control ventilation. Prone positioning with or without thoraco-pelvic supports was applied in a random sequence and maintained for a 1-hour period without changing the ventilation setting. In four healthy subjects the pressures between the body and the contact surface were measured with and without thoraco-pelvic supports. Oxygenation variables (arterial and central venous), physiologic dead space, end-expiratory lung volume (helium dilution technique) and respiratory mechanics (partitioned between lung and chest wall) were measured after 60 minutes in each condition.ResultsWith thoraco-pelvic supports, the contact pressures almost doubled in comparison with those measured without supports (19.1 ± 15.2 versus 10.8 ± 7.0 cmH2O, p ≤ 0.05; means ± SD). The oxygenation-related variables were not different in the prone position, with or without thoraco-pelvic supports; neither were the CO2-related variables. The lung volumes were similar in the prone position with and without thoraco-pelvic supports. The use of thoraco-pelvic supports, however, did lead to a significant decrease in chest wall compliance from 158.1 ± 77.8 to 102.5 ± 38.0 ml/cmH2O and a significantly increased pleural pressure from 4.3 ± 1.9 to 6.1 ± 1.8 cmH2O, in comparison with the prone position without supports. Moreover, when thoraco-pelvic supports were added, heart rate increased significantly from 82.1 ± 17.9 to 86.7 ± 16.7 beats/minute and stroke volume index decreased significantly from 37.8 ± 6.8 to 34.9 ± 5.4 ml/m2. The increase in pleural pressure change was associated with a significant increase in heart rate (p = 0.0003) and decrease in stroke volume index (p = 0.0241).ConclusionThe application of thoraco-pelvic supports decreases chest wall compliance, increases pleural pressure and slightly deteriorates hemodynamics without any advantage in gas exchange. Consequently, we stopped their use in clinical practice.

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.

The effect of different volumes and temperatures of saline on the bladder pressure measurement in critically ill patients

IntroductionIntra-abdominal hypertension is common in critically ill patients and is associated with increased severity of organ failure and mortality. The techniques most commonly used to estimate intra-abdominal pressure are measurements of bladder and gastric pressures. The bladder technique requires that the bladder be infused with a certain amount of saline, to ensure that there is a conductive fluid column between the bladder and the transducer. The aim of this study was to evaluate the effect of different volumes and temperatures of infused saline on bladder pressure measurements in comparison with gastric pressure.MethodsThirteen mechanically ventilated critically ill patients (11 male; body mass index 25.5 ± 4.6 kg/m2; arterial oxygen tension/fractional inspired oxygen ratio 225 ± 48 mmHg) were enrolled. Bladder pressure was measured using volumes of saline from 50 to 200 ml at body temperature (35 to 37°C) and room temperature (18 to 20°C).ResultsBladder pressure was no different between 50 ml and 100 ml saline (9.5 ± 3.7 mmHg and 13.7 ± 5.6 mmHg), but it significantly increased with 150 and 200 ml (21.1 ± 10.4 mmHg and 27.1 ± 15.5 mmHg). Infusion of saline at room temperature caused a significantly greater bladder pressure compared with saline at body temperature. The lowest difference between bladder and gastric pressure was obtained with a volume of 50 ml.ConclusionThe bladder acts as a passive structure, transmitting intra-abdominal pressure only with saline volumes between 50 ml and 100 ml. Infusion of a saline at room temperature caused a higher bladder pressure, probably because of contraction of the detrusor bladder muscle.

Dilutional acidosis: where do the protons come from?

PurposeTo investigate the mechanism of acidosis developing after saline infusion (dilutional acidosis or hyperchloremic acidosis).MethodsWe simulated normal extracellular fluid dilution by infusing distilled water, normal saline and lactated Ringer’s solution. Simulations were performed either in a closed system or in a system open to alveolar gases using software based on the standard laws of mass action and mass conservation. In vitro experiments diluting human plasma were performed to validate the model.ResultsIn our computerized model with constant pKs, diluting extracellular fluid modeled as a closed system with distilled water, normal saline or lactated Ringer’s solution is not associated with any pH modification, since all its determinants (strong ion difference, CO2 content and weak acid concentration) decrease at the same degree, maintaining their relative proportions unchanged. Experimental data confirmed the simulation results for normal saline and lactated Ringer’s solution, whereas distilled water dilution caused pH to increase. This is due to the increase of carbonic pK induced by the dramatic decrease of ionic strength. Acidosis developed only when the system was open to gases due to the increased CO2 content, both in its dissociated (bicarbonate) and undissociated form (dissolved CO2).ConclusionsThe increase in proton concentration observed after dilution of the extracellular system derives from the reaction of CO2 hydration, which occurs only when the system is open to the gases. Both Stewart’s approach and the traditional approach may account for these results.

Balancing volume resuscitation and ascites management in cirrhosis

Purpose of review Patients with cirrhosis have total extracellular fluid overload but central effective circulating hypovolaemia. The resulting neurohumoral compensatory response favours the accumulation of fluids into the peritoneal cavity (ascites) and may hinder renal perfusion (hepatorenal syndrome). Their deranged systemic haemodynamics (hyperdynamic circulatory syndrome) is characterized by elevated cardiac output with decreased systemic vascular resistance and low blood pressure. Recent findings Molecular and biological mechanisms determining cirrhosis-induced haemodynamic alterations are progressively being elucidated. The need for a goal-directed assessment of volume resuscitation (especially with volumetric techniques) in patients with cirrhosis is becoming more and more evident. The role of fluid expansion with albumin and the use of splanchnic vasopressors in a variety of cirrhosis-related conditions has recently been investigated. Summary The response to fluid loading in patients with advanced cirrhosis is abnormal, primarily resulting in expansion of their noncentral blood volume compartment. Colloid solutions, in particular albumin, are best used in these patients. Albumin may be effective in preventing the haemodynamic derangements associated with large-volume paracentesis (paracentesis-induced circulatory dysfunction), in preventing renal failure during spontaneous bacterial peritonitis and, in association with splanchnic vasopressors, in caring for patients with the hepatorenal syndrome.