Luciana Mascia

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.

Tidal volume lower than 6 ml/kg enhances lung protection: role of extracorporeal carbon dioxide removal.

Background:Tidal hyperinflation may occur in patients with acute respiratory distress syndrome who are ventilated with a tidal volume (VT) of 6 ml/kg of predicted body weight develop a plateau pressure (PPLAT) of 28 ≤ PPLAT ≤ 30 cm H2O. The authors verified whether VT lower than 6 ml/kg may enhance lung protection and that consequent respiratory acidosis may be managed by extracorporeal carbon dioxide removal. Methods:PPLAT, lung morphology computed tomography, and pulmonary inflammatory cytokines (bronchoalveolar lavage) were assessed in 32 patients ventilated with a VT of 6 ml/kg. Data are provided as mean ± SD or median and interquartile (25th and 75th percentile) range. In patients with 28 ≤ PPLAT ≤ 30 cm H2O (n = 10), VT was reduced from 6.3 ± 0.2 to 4.2 ± 0.3 ml/kg, and PPLAT decreased from 29.1 ± 1.2 to 25.0 ± 1.2 cm H2O (P < 0.001); consequent respiratory acidosis (Paco2 from 48.4 ± 8.7 to 73.6 ± 11.1 mmHg and pH from 7.36 ± 0.03 to 7.20 ± 0.02; P < 0.001) was managed by extracorporeal carbon dioxide removal. Lung function, morphology, and pulmonary inflammatory cytokines were also assessed after 72 h. Results:Extracorporeal assist normalized Paco2 (50.4 ± 8.2 mmHg) and pH (7.32 ± 0.03) and allowed use of VT lower than 6 ml/kg for 144 (84–168) h. The improvement of morphological markers of lung protection and the reduction of pulmonary cytokines concentration (P < 0.01) were observed after 72 h of ventilation with VT lower than 6 ml/kg. No patient-related complications were observed. Conclusions:VT lower than 6 ml/Kg enhanced lung protection. Respiratory acidosis consequent to low VT ventilation was safely and efficiently managed by extracorporeal carbon dioxide removal.

Early vs late tracheotomy for prevention of pneumonia in mechanically ventilated adult ICU patients: a randomized controlled trial.

CONTEXT Tracheotomy is used to replace endotracheal intubation in patients requiring prolonged ventilation; however, there is considerable variability in the time considered optimal for performing tracheotomy. This is of clinical importance because timing is a key criterion for performing a tracheotomy and patients who receive one require a large amount of health care resources. OBJECTIVE To determine the effectiveness of early tracheotomy (after 6-8 days of laryngeal intubation) compared with late tracheotomy (after 13-15 days of laryngeal intubation) in reducing the incidence of pneumonia and increasing the number of ventilator-free and intensive care unit (ICU)-free days. DESIGN, SETTING, AND PATIENTS Randomized controlled trial performed in 12 Italian ICUs from June 2004 to June 2008 of 600 adult patients enrolled without lung infection, who had been ventilated for 24 hours, had a Simplified Acute Physiology Score II between 35 and 65, and had a sequential organ failure assessment score of 5 or greater. INTERVENTION Patients who had worsening of respiratory conditions, unchanged or worse sequential organ failure assessment score, and no pneumonia 48 hours after inclusion were randomized to early tracheotomy (n = 209; 145 received tracheotomy) or late tracheotomy (n = 210; 119 received tracheotomy). MAIN OUTCOME MEASURES The primary endpoint was incidence of ventilator-associated pneumonia; secondary endpoints during the 28 days immediately following randomization were number of ventilator-free days, number of ICU-free days, and number of patients in each group who were still alive. RESULTS Ventilator-associated pneumonia was observed in 30 patients in the early tracheotomy group (14%; 95% confidence interval [CI], 10%-19%) and in 44 patients in the late tracheotomy group (21%; 95% CI, 15%-26%) (P = .07). During the 28 days immediately following randomization, the hazard ratio of developing ventilator-associated pneumonia was 0.66 (95% CI, 0.42-1.04), remaining connected to the ventilator was 0.70 (95% CI, 0.56-0.87), remaining in the ICU was 0.73 (95% CI, 0.55-0.97), and dying was 0.80 (95% CI, 0.56-1.15). CONCLUSION Among mechanically ventilated adult ICU patients, early tracheotomy compared with late tracheotomy did not result in statistically significant improvement in incidence of ventilator-associated pneumonia. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00262431.

Effect of a Lung Protective Strategy for Organ Donors on Eligibility and Availability of Lungs for Transplantation A Randomized Controlled Trial

CONTEXT Many potential donor lungs deteriorate between the time of brain death and evaluation for transplantation suitability, possibly because of the ventilatory strategy used after brain death. OBJECTIVE To test whether a lung protective strategy increases the number of lungs available for transplantation. DESIGN, SETTING, AND PATIENTS Multicenter randomized controlled trial of patients with beating hearts who were potential organ donors conducted at 12 European intensive care units from September 2004 to May 2009 in the Protective Ventilatory Strategy in Potential Lung Donors Study. Interventions Potential donors were randomized to the conventional ventilatory strategy (with tidal volumes of 10-12 mL/kg of predicted body weight, positive end-expiratory pressure [PEEP] of 3-5 cm H(2)O, apnea tests performed by disconnecting the ventilator, and open circuit for airway suction) or the protective ventilatory strategy (with tidal volumes of 6-8 mL/kg of predicted body weight, PEEP of 8-10 cm H(2)O, apnea tests performed by using continuous positive airway pressure, and closed circuit for airway suction). MAIN OUTCOME MEASURES The number of organ donors meeting eligibility criteria for harvesting, number of lungs harvested, and 6-month survival of lung transplant recipients. RESULTS The trial was stopped after enrolling 118 patients (59 in the conventional ventilatory strategy and 59 in the protective ventilatory strategy) because of termination of funding. The number of patients who met lung donor eligibility criteria after the 6-hour observation period was 32 (54%) in the conventional strategy vs 56 (95%) in the protective strategy (difference of 41% [95% confidence interval {CI}, 26.5% to 54.8%]; P <.001). The number of patients in whom lungs were harvested was 16 (27%) in the conventional strategy vs 32 (54%) in the protective strategy (difference of 27% [95% CI, 10.0% to 44.5%]; P = .004). Six-month survival rates did not differ between recipients who received lungs from donors ventilated with the conventional strategy compared with the protective strategy (11/16 [69%] vs 24/32 [75%], respectively; difference of 6% [95% CI, -22% to 32%]). CONCLUSION Use of a lung protective strategy in potential organ donors with brain death increased the number of eligible and harvested lungs compared with a conventional strategy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00260676.

Patient-ventilator interaction and sleep in mechanically ventilated patients: pressure support versus proportional assist ventilation.

Objectives:To understand the role of patient-ventilator asynchrony in the etiology of sleep disruption and determine whether optimizing patient-ventilator interactions by using proportional assist ventilation improves sleep. Design:Randomized crossover clinical trial. Setting:A tertiary university medical-surgical intensive care unit. Patients:Thirteen patients during weaning from mechanical ventilation. Interventions:Patients were randomized to receive pressure support ventilation or proportional assist ventilation on the first night and then crossed over to the alternative mode for the second night. Polysomnography and measurement of light, noise, esophageal pressure, airway pressure, and flow were performed from 10 pm to 8 am. Ventilator settings (pressure level during pressure support ventilation and resistive and elastic proportionality factors during proportional assist ventilation) were set to obtain a 50% reduction of the inspiratory work (pressure time product per minute) performed during a spontaneous breathing trial. Measurements and Main Results:Arousals per hour of sleep time during pressure support ventilation were 16 (range 2–74) and 9 (range 1–41) during proportional assist ventilation (p = .02). Overall sleep quality was significantly improved on proportional assist ventilation (p < .05) due to the combined effect of fewer arousals per hour, fewer awakenings per hour (3.5 [0–24] vs. 5.5 [1–24]), and greater rapid eye movement (9% [0–31] vs. 4% [0–23]), and slow wave (3% [0–16] vs. 1% [0–10]) sleep. Tidal volume and minute ventilation were lower on proportional assist ventilation, allowing for a greater increase in Paco2 during the night. Patient-ventilator asynchronies per hour were lower with proportional assist ventilation than with pressure support ventilation (24 ± 15 vs. 53 ± 59; p = .02) and correlated with the number of arousals per hour (R2 = .65, p = .0001). Conclusions:Patient ventilator discordance causes sleep disruption. Proportional assist ventilation seems more efficacious than pressure support ventilation in matching ventilatory requirements with ventilator assistance, therefore resulting in fewer patient-ventilator asynchronies and better quality of sleep.

Pressure–Time Curve Predicts Minimally Injurious Ventilatory Strategy in an Isolated Rat Lung Model

BackgroundWe tested the hypothesis that the pressure–time (P-t) curve during constant flow ventilation can be used to set a noninjurious ventilatory strategy. MethodsIn an isolated, nonperfused, lavaged model of acute lung injury, tidal volume and positive end-expiratory pressure were set to obtain: (1) a straight P-t curve (constant compliance, minimal stress); (2) a downward concavity in the P-t curve (increasing compliance, low volume stress); and (3) an upward concavity in the P-t curve (decreasing compliance, high volume stress). The P-t curve was fitted to: P =a · t b +c, where b describes the shape of the curve, b = 1 describes a straight P-t curve, b < 1 describes a downward concavity, and b > 1 describes an upward concavity. After 3 h, lungs were analyzed for histologic evidence of pulmonary damage and lavage concentration of inflammatory mediators. Ventilator-induced lung injury occurred when injury score and cytokine concentrations in the ventilated lungs were higher than those in 10 isolated lavaged rats kept statically inflated for 3 h with an airway pressure of 4 cm H2O. ResultsThe threshold value for coefficient b that discriminated best between lungs with and without histologic and inflammatory evidence of ventilator-induced lung injury (receiver–operating characteristic curve) ranged between 0.90–1.10. For such threshold values, the sensitivity of coefficient b to identify noninjurious ventilatory strategy was 1.00. A significant relation (P < 0.001) between values of coefficient b and injury score, interleukin-6, and macrophage inflammatory protein–2 was found. ConclusionsThe predictive power of coefficient b to predict noninjurious ventilatory strategy in a model of acute lung injury is high.

Cardiorespiratory Effects of Positive End-expiratory Pressure during Progressive Tidal Volume Reduction (Permissive Hypercapnia) in Patients with Acute Respiratory Distress Syndrome

Background In patients with acute respiratory distress syndrome (ARDS), the ventilatory approach is based on tidal volume (VT) of 10-15 ml/kg and positive end-expiratory pressure (PEEP). To avoid further pulmonary injury, decreasing VT and allowing PaCO2 to increase (permissive hypercapnia) has been suggested. Effects of 10 cmH sub 2 O of PEEP on respiratory mechanics, hemodynamics, and gas exchange were compared during mechanical ventilation with conventional (10-15 ml/kg) and low (5-8 ml/kg) VT.

High tidal volume is associated with the development of acute lung injury after severe brain injury : An international observational study

Objective:Although a significant number of patients with severe brain injury develop acute lung injury, only intracranial risk factors have previously been studied. We investigated the role of extracranial predisposing factors, including hemodynamic and ventilatory management, as independent predictors of acute lung injury in brain-injured patients. Design:Prospective multicenter observational study. Setting:Four European intensive care units in university-affiliated hospitals. Patients:Eighty-six severely brain-injured patients enrolled in 13 months. Interventions:None. Measurements and Main Results:All patients with severe brain injury (Glasgow Coma Scale score <9) were studied for 8 days from admission. Ventilatory pattern, respiratory system compliance, blood gas analysis, and hemodynamic profile were recorded and entered in a stepwise regression model. Length of stay in the intensive care unit, ventilator-free days, and mortality were collected. Eighteen patients (22%) developed acute lung injury on day 2.8 ± 1. They were initially ventilated with significantly higher tidal volume per predicted body weight (9.5 ± 1 vs. 10.4 ± 1.1), respiratory rate, and minute ventilation and more often required vasoactive drugs (p < .05). In addition to a lower Pao2/Fio2 (odds ratio 0.98, 95% confidence interval 0.98–0.99), the use of high tidal volume (odds ratio 5.4, 95% confidence interval 1.54–19.24) and relatively high respiratory rate (odds ratio 1.8, 95% confidence interval 1.13–2.86) were independent predictors of acute lung injury (p < .01). After the onset of acute lung injury, patients remained ventilated with similar tidal volumes to maintain mild hypocapnia and had a longer length of stay in the intensive care unit and fewer ventilator-free days (p < .05). Conclusions:In addition to a lower Pao2/Fio2, the use of high tidal volume and high respiratory rate are independent predictors of acute lung injury in patients with severe brain injury. In this patient population, alternative ventilator strategies should be considered to protect the lung and guarantee a tight CO2 control.

Continuous positive airway pressure for treatment of respiratory complications after abdominal surgery: a systematic review and meta-analysis

Objective:We evaluated the potential benefit of continuous positive airway pressure (CPAP) to prevent postoperative pulmonary complications (PPCs), atelectasis, pneumonia, and intubation in patients undergoing major abdominal surgery. Summary Background Data:PPCs are common during the postoperative period and may be associated with a high morbidity rate. Efficacy of CPAP to prevent PPCs occurrence is controversial. Methods:Medical literature databases were searched for randomized controlled trials examining the use of CPAP versus standard therapy in patients undergoing abdominal surgery. The meta-analysis estimated the pooled risk ratio and the number needed to treat to benefit (NNTB) for PPCs, atelectasis, and pneumonia. Results:The meta-analysis was carried out over 9 randomized controlled trials. Overall, CPAP significantly reduced the risk of (1) PPCs (risk ratio, 0.66; 95% confidence interval [CI], 0.52–0.85) with a corresponding NNTB of 14.2 (95% CI, 9.9–32.4); (2) atelectasis (risk ratio, 0.75; 95% CI, 0.58–0.97; NNTB, 7.3; 95% CI, 4.4–64.5); (3) pneumonia (risk ratio, 0.33; 95% CI, 0.14–0.75; NNTB, 18.3; 95% CI, 14.4–48.8). In all cases the variation in risk ratio attributable to heterogeneity was negligible, although there was some evidence of publication bias. Conclusions:This systematic review suggests that CPAP decreases the risk of PPCs, atelectasis, and pneumonia and supports its clinical use in patients undergoing abdominal surgery.

European society of intensive care medicine study of therapeutic hypothermia (32-35°C) for intracranial pressure reduction after traumatic brain injury (the Eurotherm3235Trial)

BackgroundTraumatic brain injury is a major cause of death and severe disability worldwide with 1,000,000 hospital admissions per annum throughout the European Union.Therapeutic hypothermia to reduce intracranial hypertension may improve patient outcome but key issues are length of hypothermia treatment and speed of re-warming. A recent meta-analysis showed improved outcome when hypothermia was continued for between 48 hours and 5 days and patients were re-warmed slowly (1°C/4 hours). Previous experience with cooling also appears to be important if complications, which may outweigh the benefits of hypothermia, are to be avoided.Methods/designThis is a pragmatic, multi-centre randomised controlled trial examining the effects of hypothermia 32-35°C, titrated to reduce intracranial pressure <20 mmHg, on morbidity and mortality 6 months after traumatic brain injury. The study aims to recruit 1800 patients over 41 months. Enrolment started in April 2010.Participants are randomised to either standard care or standard care with titrated therapeutic hypothermia. Hypothermia is initiated with 20-30 ml/kg of intravenous, refrigerated 0.9% saline and maintained using each centres usual cooling technique. There is a guideline for detection and treatment of shivering in the intervention group. Hypothermia is maintained for at least 48 hours in the treatment group and continued for as long as is necessary to maintain intracranial pressure <20 mmHg. Intracranial hypertension is defined as an intracranial pressure >20 mmHg in accordance with the Brain Trauma Foundation Guidelines, 2007.DiscussionThe Eurotherm3235Trial is the most important clinical trial in critical care ever conceived by European intensive care medicine, because it was launched and funded by the European Society of Intensive Care Medicine and will be the largest non-commercial randomised controlled trial due to the substantial number of centres required to deliver the target number of patients. It represents a new and fundamental step for intensive care medicine in Europe. Recruitment will continue until January 2013 and interested clinicians from intensive care units worldwide can still join this important collaboration by contacting the Trial Coordinating Team via the trial website http://www.eurotherm3235trial.eu.Trial registrationCurrent Controlled Trials ISRCTN34555414