Ania Nieszkowska

Acute respiratory distress syndrome: lessons from computed tomography of the whole lung.

ObjectiveThis review aims to show how computed tomography of the whole lung has modified our view of acute respiratory distress syndrome, and why it impacts on the optimization of the ventilatory strategy. Data sourcesComputed tomography allows an accurate assessment of the volumes of gas and lung tissue, respectively, and lung aeration. If computed tomographic sections are contiguous from the apex to the lung base, quantitative analysis can be performed either on the whole lung or, regionally, at the lobar level. Analysis requires a manual delineation of lung parenchyma and is facilitated by software, including a color-coding system that allows direct visualization of overinflated, normally aerated, poorly aerated, and nonaerated lung regions. In addition, lung recruitment can be measured as the amount of gas that penetrates poorly aerated and nonaerated lung regions after the application of positive intrathoracic pressure. Data SummaryThe lung in acute respiratory distress syndrome is characterized by a marked increase in lung tissue and a massive loss of aeration. The former is homogeneously distributed, although with a slight predominance in the upper lobes, whereas the latter is heterogeneously distributed. The lower lobes are essentially nonaerated, whereas the upper lobes may remain normally aerated, despite a substantial increase in regional lung tissue. The overall lung volume and the cephalocaudal lung dimensions are reduced primarily at the expense of the lower lobes, which are externally compressed by the heart and abdominal content when the patient is in the supine position. Two opposite radiologic presentations, corresponding to different lung morphologies, can be observed. In patients with focal computed tomographic attenuations, frontal chest radiography generally shows bilateral opacities in the lower quadrants and may remain normal, particularly when the lower lobes are entirely atelectatic. In patients with diffuse computed tomographic attenuations, the typical radiologic presentation of “white lungs” is observed. If these patients lie supine, lung volume is preserved in the upper lobes and reduced in the lower lobes, although the loss of aeration is equally distributed between the upper and lower lobes. This observation does not support the “opening and collapse concept” described as the “sponge model.” In fact, interstitial edema, alveolar flooding, or both, not collapse, are histologically present in all regions of the lung in acute respiratory distress syndrome. Compression atelectasis is observed only in caudal parts of the lung, where external forces (such as cardiac weight, abdominal pressure, and pleural effusion) tend to squeeze the lower lobes. When a positive intrathoracic pressure is applied to patients with focal acute respiratory distress syndrome, poorly aerated and nonaerated lung regions are recruited, whereas lung regions that are normally aerated at zero end-expiratory pressure tend to be rapidly overinflated, increasing the risk of ventilator-induced lung injury. ConclusionSelection of the optimal positive end-expiratory pressure level should not only consider optimizing alveolar recruitment, it should also focus on limiting lung overinflation and counterbalancing compression of the lower lobes by maneuvers such as appropriate body positioning. Prone and semirecumbent positions facilitate the reaeration of dependent and caudal lung regions by partially relieving cardiac and abdominal compression and may improve gas exchange.

Early Percutaneous Tracheotomy Versus Prolonged Intubation of Mechanically Ventilated Patients After Cardiac Surgery: A Randomized Trial

BACKGROUND Whether early percutaneous tracheotomy in patients who require prolonged mechanical ventilation can shorten mechanical ventilation duration and lower mortality remains controversial. OBJECTIVE To compare the outcomes of severely ill patients who require prolonged mechanical ventilation randomly assigned to early percutaneous tracheotomy or prolonged intubation. DESIGN Prospective, randomized, controlled, single-center trial (ClinicalTrials.gov registration number: NCT00347321). SETTING Academic center. PATIENTS 216 adults requiring mechanical ventilation 4 or more days after cardiac surgery. INTERVENTION Immediate early percutaneous tracheotomy or prolonged intubation with tracheotomy 15 days after randomization. MEASUREMENTS The primary end point was the number of ventilator-free days during the first 60 days after randomization. Secondary outcomes included 28-, 60-, or 90-day mortality rates; durations of mechanical ventilation, intensive care unit stay, and hospitalization; sedative, analgesic, and neuroleptic use; ventilator-associated pneumonia rate; unscheduled extubations; comfort and ease of care; and long-term health-related quality of life (HRQoL) and psychosocial evaluations. RESULTS There was no difference in ventilator-free days during the first 60 days after randomization between early percutaneous tracheotomy and prolonged intubation groups (mean, 30.4 days [SD, 22.4] vs. 28.3 days [SD, 23.7], respectively; absolute difference, 2.1 days [95% CI, -4.1 to 8.3 days]) nor in 28-, 60-, or 90-day mortality rates (16% vs. 21%, 26% vs. 28%, and 30% vs. 30%, respectively). The durations of mechanical ventilation and hospitalization, as well as frequencies of ventilator-associated pneumonia and other severe infections, were also similar. However, early percutaneous tracheotomy was associated with less intravenous sedation; less time of heavy sedation; less haloperidol use for agitation, delirium, or both; fewer unscheduled extubations; better comfort and ease of care; and earlier resumption of oral nutrition. After a median follow-up of 873 days, between-group survival, psychosocial evaluations, and HRQoL were similar. LIMITATION The prolonged intubation group had more ventilator-free days during days 1 to 60 than what was hypothesized (mean, 23.0 days [SD, 17.0]). CONCLUSION Early tracheotomy provided no benefit in terms of mechanical ventilation and length of hospital stay, rates of mortality or infectious complications, and long-term HRQoL for patients who require prolonged mechanical ventilation after cardiac surgery. However, the well-tolerated procedure was associated with less sedation, better comfort, and earlier resumption of autonomy. PRIMARY FUNDING SOURCE French Ministry of Health.

Is tracheostomy associated with better outcomes for patients requiring long-term mechanical ventilation?

Objective:To evaluate the effect of tracheostomy on intensive care unit (ICU) and in-hospital mortality for patients requiring prolonged (>3 days) mechanical ventilation (MV). Design, Setting, and Patients:We retrospectively reviewed the charts of all consecutive patients admitted to our 18-bed tertiary care ICU over 3 yrs (2002–2004) and who received prolonged MV. Outcomes of tracheostomized and nontracheostomized patients were evaluated using univariable and multivariable logistic-regression analyses and by constructing a case-control cohort using a propensity score for performing tracheostomy. MV duration for controls was at least equal to the time from MV onset to tracheostomy for the matched case. Measurements and Main Results:Of the 506 patients requiring prolonged MV, 166 were tracheostomized after a median of 12 days of MV. Nontracheostomized patients had higher ICU (42% vs. 33%, p = .06) and in-hospital (48% vs. 37%, p = .03) mortality rates and shorter MV durations and ICU lengths of stay. Performing a tracheostomy (odds ratio, 0.58; 95% CI, 0.37–0.90) was independently associated with a lower probability of ICU death, even after adjusting for other important prognostic factors. No significant differences were detected between the 120 cases and their matched controls regarding ICU admission and day-3 clinical characteristics. After conditional logistic-regression analysis, tracheostomy was associated with lower risk of ICU (odds ratio, 0.47; 95% CI, 0.24–0.89) and in-hospital (odds ratio, 0.48; 95% CI, 0.25–0.90) death. Conclusions:Tracheostomy performed in our ICU for long-term MV patients was associated with lower ICU and in-hospital mortality rates, even after carefully controlling for ICU admission and day-3 clinical and physiologic differences between groups. Whether these results reflect that physicians were able to adequately select for tracheostomy patients who, despite having similar physiologic and demographic variables, had the highest probabilities of survival or that the procedure itself really affected the outcomes of these patients will remain speculative.

Mechanical Ventilation Management During Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: A Retrospective International Multicenter Study*

Objective:To describe mechanical ventilation settings in adult patients treated for an acute respiratory distress syndrome with extracorporeal membrane oxygenation and assess the potential impact of mechanical ventilation settings on ICU mortality. Design:Retrospective observational study. Setting:Three international high-volume extracorporeal membrane oxygenation centers. Patients:A total of 168 patients treated with extracorporeal membrane oxygenation for severe acute respiratory distress syndrome from January 2007 to January 2013. Interventions:We analyzed the association between mechanical ventilation settings (i.e. plateau pressure, tidal volume, and positive end-expiratory pressure) on ICU mortality using multivariable logistic regression model and Cox-proportional hazards model. Measurement and Main Results:We obtained detailed demographic, clinical, daily mechanical ventilation settings and ICU outcome data. One hundred sixty-eight patients (41 ± 14 years old; PaO2/FIO2 67 ± 19 mm Hg) fulfilled our inclusion criteria. Median duration of extracorporeal membrane oxygenation and ICU stay were 10 days (6–18 d) and 28 days (16–42 d), respectively. Lower positive end-expiratory pressure levels and significantly lower plateau pressures during extracorporeal membrane oxygenation were used in the French center than in both Australian centers (23.9 ± 1.4 vs 27.6 ± 3.7 and 27.8 ± 3.6; p < 0.0001). Overall ICU mortality was 29%. Lower positive end-expiratory pressure levels (until day 7) and lower delivered tidal volume after 3 days on extracorporeal membrane oxygenation were associated with significantly higher mortality (p < 0.05). In multivariate analysis, higher positive end-expiratory pressure levels during the first 3 days of extracorporeal membrane oxygenation support were associated with lower mortality (odds ratio, 0.75; 95% CI, 0.64–0.88; p = 0.0006). Other independent predictors of ICU mortality included time between ICU admission and extracorporeal membrane oxygenation initiation, plateau pressure greater than 30 cm H2O before extracorporeal membrane oxygenation initiation, and lactate level on day 3 of extracorporeal membrane oxygenation support. Conclusions:Protective mechanical ventilation strategies were routinely used in high-volume extracorporeal membrane oxygenation centers. However, higher positive end-expiratory pressure levels during the first 3 days on extracorporeal membrane oxygenation support were independently associated with improved survival. Further prospective trials on the optimal mechanical ventilation strategy during extracorporeal membrane oxygenation support are warranted.

Gender impact on the outcomes of critically ill patients with nosocomial infections.

Objectives:To investigate gender impact on the outcomes of severe nosocomial infections (pneumonia, bacteremia, catheter-related bloodstream infections, poststernotomy mediastinitis, urinary infections) occurring in a large cohort of patients hospitalized in a medical-surgical intensive care unit. Highly controversial data exist regarding gender-related differences in outcomes of severe nosocomial infections, reflecting potential confounders related to case-mixes or heterogeneity of populations evaluated. Design:Retrospective study of patients admitted to our intensive care unit. Multivariable logistic regression-analysis was used to control for confounders in the evaluation of gender impact on intensive care unit death post nosocomial infections. Setting:An 18-bed tertiary referral medical-surgical intensive care unit in a teaching hospital. Patients:Mixed population of patients who developed nosocomial infections in the intensive care unit. Measurements and Main Results:Among the 5081 patients admitted to our intensive care unit from 1995 to 2004, 1341 (34% women) developed nosocomial infections. Pneumonia and mediastinitis were more frequent in men (51% vs. 44%, p = .01 and 29% vs. 22%, p = .01, respectively) whereas urinary infections predominated for women (46% vs. 24%, p < .001). Durations of mechanical ventilation and intensive care unit stays and treatment intensity did not differ between genders. However, intensive care unit mortality was higher for women (37% vs. 32%, p = .06) and this excess mortality was statistically significant (odds ratio = 1.50, 95% Confidence Interval = 1.11–2.03), after controlling for other independent risk factors of intensive care unit death. Compared with those observed for men of the same subgroup, crude ICU death rates were significantly higher for women who developed pneumonia, who were <50 yrs old or had undergone heart surgery before intensive care unit admission. However, multivariable analyses retained feminine gender as significantly associated with mortality only for the last subgroup. Conclusions:Female intensive care unit patients developing nosocomial infections seem to be at increased risk of intensive care unit mortality, after carefully controlling for other prognostic factors. Further studies are needed to elucidate the pathophysiology underlying this gender-related difference, to devise tailored gender-specific therapies that might improve outcomes.

Measurement of alveolar derecruitment in patients with acute lung injury: computerized tomography versus pressure–volume curve

IntroductionPositive end-expiratory pressure (PEEP)-induced lung derecruitment can be assessed by a pressure–volume (P–V) curve method or by lung computed tomography (CT). However, only the first method can be used at the bedside. The aim of the study was to compare both methods for assessing alveolar derecruitment after the removal of PEEP in patients with acute lung injury or acute respiratory distress syndrome.MethodsP–V curves (constant-flow method) and spiral CT scans of the whole lung were performed at PEEPs of 15 and 0 cmH2O in 19 patients with acute lung injury or acute respiratory distress syndrome. Alveolar derecruitment was defined as the difference in lung volume measured at an airway pressure of 15 cmH2O on P–V curves performed at PEEPs of 15 and 0 cmH2O, and as the difference in the CT volume of gas present in poorly aerated and nonaerated lung regions at PEEPs of 15 and 0 cmH2O.ResultsAlveolar derecruitments measured by the CT and P–V curve methods were 373 ± 250 and 345 ± 208 ml (p = 0.14), respectively. Measurements by both methods were tightly correlated (R = 0.82, p < 0.0001). The derecruited volume measured by the P–V curve method had a bias of -14 ml and limits of agreement of between -158 and +130 ml in comparison with the average derecruited volume of the CT and P–V curve methods.ConclusionAlveolar derecruitment measured by the CT and P–V curve methods are tightly correlated. However, the large limits of agreement indicate that the P–V curve and the CT method are not interchangeable.

Aerosolized antibiotics to treat ventilator-associated pneumonia.

Purpose of review This review summarizes the recent data on antibiotic aerosolization to treat ventilator-associated pneumonia. Recent findings Most studies on antibiotic aerosolization have been case reports or descriptive studies. The results of a recent randomized, placebo-controlled trial indicated that adjunctive use of nebulized antibiotic with intravenous antibiotics to treat purulent tracheobronchitis was associated with a better outcome than placebo aerosolization. A randomized study, so far published only as an abstract, showed that amikacin aerosolized with a vibrating-mesh nebulizer – a new-generation device – was well distributed in the lung parenchyma and might lead to less intravenous antibiotic use. Several thorough reviews on nebulization devices, techniques and drawbacks have been published recently. Summary Despite recent promising findings, the widespread use of aerosolized antibiotics to treat ventilator-associated pneumonia cannot be recommended. It should be restricted to the treatment of multidrug-resistant Gram-negative ventilator-associated pneumonia.

Viral infections in the ICU.

Purpose of reviewThe present study reviews the precise role of viruses as causes of pneumonia in mechanically ventilated patients. Recent findingsIn patients requiring mechanical ventilation, Herpesviridae, mostly herpes simplex virus and cytomegalovirus, are commonly recovered from the respiratory tract. However, viral detection does not necessarily mean viral disease, and the exact role of viruses recovered in the respiratory tract is still being debated. Are they only benign colonizers activated in proportion to the severity of the underlying illness, or are they infectious agents with true attributable morbidity or mortality or both? SummaryRespiratory viruses are responsible for 10% of community-acquired pneumonia cases but do not cause nosocomial pneumonia. Herpesviridae, mainly herpes simplex virus and cytomegalovirus, are commonly detected in the respiratory tract of nonimmunocompromised, mechanically ventilated patients. Although their detection usually reflects viral reactivation without lung parenchymal involvement, in a particular subset of patients, viral lung disease (bronchopneumonitis) occurs. This bronchopneumonitis seems to have a true impact on outcome, but only interventional studies will be able to determine its real impact. Whether other viruses, such as mimivirus, are responsible for nosocomial pneumonia in mechanically ventilated patients requires additional studies.

Impact of Extracorporeal Membrane Oxygenation and Continuous Venovenous Hemodiafiltration on the Pharmacokinetics of Oseltamivir Carboxylate in Critically Ill Patients With Pandemic (h1n1) Influenza

Purpose The neuraminidase inhibitor oseltamivir is a recommended treatment for influenza A (H1N1) infection. In rare cases, some patients develop influenza-associated multiple organ failures, requiring rescue therapies such as extracorporeal membrane oxygenation (ECMO) or continuous venovenous hemodiafiltration (CVVHDF). This study was designed to evaluate the impact of ECMO and CVVHDF on the pharmacokinetics of oseltamivir carboxylate (OC) in critically ill patients with pandemic (H1N1) influenza treated with oseltamivir. Patients and Methods Seven critically ill patients on venovenous ECMO for severe pandemic (H1N1) influenza associated with acute respiratory distress syndrome were treated with various doses of oseltamivir (75 or 150 mg twice daily). Because of acute kidney injury, 3 of them also received CVVHDF. OC, the active form of oseltamivir, was quantified in plasma, and main pharmacokinetic parameters were determined. Results OC Cmax (1029 ± 478 ng/mL) and area under the curve (9.00 ± 4.52 mcg·h/mL) for patients on ECMO with preserved renal function were comparable with those of healthy volunteers or noncritically ill patients. Patients both on ECMO and CVVHDF had 4-to 5-fold higher OC Cmax and area under the curve. Conclusions ECMO by itself did not impact on the pharmacokinetics of OC. However, the drug accumulated in the plasma of patients on ECMO who also received CVVHDF for renal failure. Based on these results, we recommend that oseltamivir dosage should be decreased and plasma levels of OC be monitored in patients receiving CVVHDF because of acute kidney injury.

Virus-induced acute respiratory distress syndrome: Epidemiology, management and outcome

Summary The acute respiratory distress syndrome (ARDS) can be induced by viral diseases, with two virus types being responsible: respiratory viruses that cause community-acquired viral pneumonia and Herpesviridae that cause nosocomial viral pneumonia. Among the respiratory viruses that can affect the lung and cause ARDS, pandemic viruses head the list, with influenza viruses H5N1 and H1N1 2009 being the most recently identified. However, other viruses can cause severe ARDS. Notably, a novel coronavirus was responsible for the severe acute respiratory syndrome outbreak in 2003. Apart from these pandemic viruses, respiratory viruses are rarely responsible for viral pneumonia and ARDS. Other than antiviral drug (mainly oseltamivir) administration and avoidance of corticosteroids, management of ARDS due to these viruses does not differ from that for ARDS caused by other diseases. Among Herpesviridae, herpes simplex virus (HSV) and cytomegalovirus (CMV) are the two viruses causing nosocomial viral pneumonia that can evolve into ARDS. HSV is frequently recovered in the respiratory tract of mechanically ventilated patients and can sometimes be responsible for HSV bronchopneumonitis. Although not evaluated for this indication, acyclovir can be a therapeutic option for patients with HSV bronchopneumonitis and ARDS. CMV pneumonia can also occur in mechanically ventilated patients, but is difficult to diagnose because virus recovery does not necessarily mean viral disease. Ganciclovir can be considered for patients with ARDS and histology- or cytology-proven CMV pneumonia.