A deep dive into burn-mediated ARDS severity assessment: a retrospective study on hematological markers.

Acute Respiratory Distress Syndrome (ARDS) is a critical form of Acute Lung Injury (ALI), challenging clinical diagnosis and severity assessment. This study evaluates the potential utility of various hematological markers in burn-mediated ARDS, including Neutrophil-to-Lymphocyte Ratio (NLR), Mean Platelet Volume (MPV), MPV-to-Lymphocyte Ratio (MPVLR), Platelet count, and Platelet Distribution Width (PDW). Employing a retrospective analysis of data collected over 12 years, this study focuses on the relationship between these hematological markers and ARDS diagnosis and severity in hospitalized patients. The study establishes NLR as a reliable systemic inflammation marker associated with ARDS severity. Elevated MPV and MPVLR also emerged as significant markers correlating with adverse outcomes. These findings suggest these economical, routinely measured markers can enhance traditional clinical criteria, offering a more objective approach to ARDS diagnosis and severity assessment. Hematological markers such as NLR, MPV, MPVLR, Platelet count, and PDW could be invaluable in clinical settings for diagnosing and assessing ARDS severity. They offer a cost-effective, accessible means to improve diagnostic accuracy and patient stratification in ARDS. However, further prospective studies are necessary to confirm these findings and investigate their integration with other diagnostic tools in diverse clinical settings.

Longitudinal assessment of IFN-I activity and immune profile in critically ill COVID-19 patients with acute respiratory distress syndrome.

BACKGROUND: Since the onset of the pandemic, only few studies focused on longitudinal immune monitoring in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) whereas their hospital stay may last for several weeks. Consequently, the question of whether immune parameters may drive or associate with delayed unfavorable outcome in these critically ill patients remains unsolved. METHODS: We present a dynamic description of immuno-inflammatory derangements in 64 critically ill COVID-19 patients including plasma IFNα2 levels and IFN-stimulated genes (ISG) score measurements. RESULTS: ARDS patients presented with persistently decreased lymphocyte count and mHLA-DR expression and increased cytokine levels. Type-I IFN response was initially induced with elevation of IFNα2 levels and ISG score followed by a rapid decrease over time. Survivors and non-survivors presented with apparent common immune responses over the first 3 weeks after ICU admission mixing gradual return to normal values of cellular markers and progressive decrease of cytokines levels including IFNα2. Only plasma TNF-α presented with a slow increase over time and higher values in non-survivors compared with survivors. This paralleled with an extremely high occurrence of secondary infections in COVID-19 patients with ARDS. CONCLUSIONS: Occurrence of ARDS in response to SARS-CoV2 infection appears to be strongly associated with the intensity of immune alterations upon ICU admission of COVID-19 patients. In these critically ill patients, immune profile presents with similarities with the delayed step of immunosuppression described in bacterial sepsis.

Impact of intravenous lidocaine on clinical outcomes of patients with ARDS during COVID-19 pandemia (LidoCovid): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The main objective of this study is to evaluate the effect of intravenous lidocaine on gas exchange and inflammation in acute respiratory distress syndrome due or not to Covid-19 pneumonia. TRIAL DESIGN: This is a prospective monocentric, randomized, quadruple-blinded and placebo-controlled superiority trial. This phase 3 clinical study is based on two parallel groups received either intravenous lidocaine 2% or intravenous NaCl 0.9%. PARTICIPANTS: This study has been conducted at the University Hospitals of Strasbourg (medical and surgical Intensive Care Units in Hautepierre Hospital) since the 4th November 2020. The participants are 18 years-old and older, hospitalized in ICU for a moderate to severe ARDS according to the Berlin definition; they have to be intubated and sedated for mechanical protective ventilation. All participants are affiliated to the French Social security system and a dosage of beta HCG has to be negative for women of child bearing age . For the Covid-19 subgroup, the SARS-CoV2 infection is proved by RT-PCR <7 days before admission and/or another approved diagnostic technique and/or typical CT appearance pneumonia. The data are prospectively collected in e-Case Report Forms and extracted from clinical files. INTERVENTION AND COMPARATOR: The participants are randomised in two parallel groups with a 1:1 ratio. In the experimental group, patients receive intravenous lidocaine 2% (20mg/mL) (from FRESENIUS KABI France); the infusion protocol provide a bolus of 1 mg/kg (ideal weight), followed by 3 mg/kg/h for the first hour, 1.5 mg/kg/h for the second hour, 0.72 mg/kg/h for the next 22 hours and then 0.6 mg/kg/h for 14 days at most or 24 hours after extubation or ventilator-weaning. The patients in the control group receive intravenous NaCl 0.9% (9 mg/mL) (from Aguettant, France) as placebo comparator; the infusion protocol provide a bolus of 0.05 mL/kg (ideal weight), followed by 0.15 mL/kg/h for the first hour, 0.075 mL/kg/h for the second hour, 0.036 mL/kg/h for the next 22 hours, and the 0.03 mL/kg/h for up to 14 days or 24 hours after extubation or ventilator-weaning. Lidocaine level is assessed at H4, D2, D7 and D14 to prevent local anesthetics systemic toxicity. Clinical data and biological samples are collected to assess disease progression. MAIN OUTCOMES: The primary outcome is the evolution of alveolar-capillary gas exchange measured by the PaO2/FiO2 ratio after two days of treatment. The secondary endpoints of the study include the following: Evolution of PaO2/FiO2 ratio at admission and after 21 days of treatment Number of ventilator-free days Anti-inflammatory effects by dosing inflammatory markers at different timepoints (ferritin, bicarbonate, CRP, PCT, LDH, IL-6, Troponin HS, triglycerides, complete blood count, lymphocytes) Anti-thrombotic effects by dosing platelets, aPTT, fibrinogen, D-dimers, viscoelastic testing and identification of all thromboembolic events up to 4 weeks. Plasmatic concentration of lidocaine and albumin Incidence of adverse events like cardiac rhythm disorders, need of vasopressors, any modification of the QRS, QTc or PR intervals every day Ileus recovery time Consumption of hypnotics, opioids, neuromuscular blockers. Lengths of stay in the ICU, incidence of reintubation and complications due to intensive care unit care (mortality until 90 days, pneumothorax, bacterial pneumopathy, bronchospasm, cardiogenic shock, acute renal failure, need of renal dialysis, delirium, atrial fibrillation, stroke (CAM-ICU score), tetraplegia (MCR score)). Incidence of cough and sore throat at extubation or ventilator-weaning and within 24 hours. All these outcomes will be evaluated according to positivity to Sars-Cov-2. RANDOMISATION: The participants who meet the inclusion criteria and have signed written informed consent will be randomly allocated using a computer-generated random number to either intervention group or control group. The distribution ratio of the two groups will be 1:1, with a stratification according to positivity to Sars-Cov-2. BLINDING (MASKING): All participants, care providers, investigator and outcomes assessor are blinded. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We planned to randomize fifty participants in each group, 100 participants total. TRIAL STATUS: The amended protocol version 2.1 was approved by the Ethics Committee "Comité de Protection des Personnes Sud-Méditerranée II on January 8, 2021 and by the Commission Nationale de l'Informatique et des Libertés (CNIL) on November 10, 2020. The study is currently recruiting participants; the recruitment started in November 2020 and the planned recruitment period is three years. TRIAL REGISTRATION: The trial was registered on clinicaltrials.gov on October 30, 2020 and identified by number NCT04609865 . FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Utility of Plasma GDF-15 for Diagnosis and Prognosis Assessment of ICU-Acquired Weakness in Mechanically Ventilated Patients: Prospective Observational Study.

OBJECTIVE: To identify the clinical correlations between plasma growth differentiation factor-15 (GDF-15), skeletal muscle function, and acute muscle wasting in ICU patients with mechanical ventilation. In addition, to investigate its diagnostic value for ICU-acquired weakness (ICU-AW) and its predictive value for 90-day survival in mechanically ventilated patients. METHODS: 95 patients with acute respiratory failure, who required mechanical ventilation therapy, were randomly selected among hospitalized patients from June 2017 to January 2019. The plasma GDF-15 level was detected by ELISA, the rectus femoris cross-sectional area (RFcsa) was measured by ultrasound, and the patient's muscle strength was assessed using the British Medical Research Council (MRC) muscle strength score on day 1, day 4, and day 7. Patients were divided into an ICU-AW group and a non-ICU-AW group according to their MRC-score on the 7th day. The differences in plasma GDF-15 level, MRC-score, and RFcsa between the two groups were compared on the 1st, 4th, and 7th day after being admitted to the ICU. Then, the correlations between plasma GDF-15 level, RFcsa loss, and MRC-score on day 7 were investigated. The receiver operating characteristic curve (ROC) was used to analyze the plasma GDF-15 level, RFcsa loss, and % decrease in RFcsa on the 7th day to the diagnosis of ICU-AW in mechanically ventilated patients. Moreover, the predictive value of GDF-15 on the 90-day survival status of patients was assessed using patient survival curves. RESULTS: Based on whether the 7th day MRC-score was <48, 50 cases were included in the ICU-AW group and 45 cases in the non-ICU-AW group. The length of mechanical ventilation, ICU length of stay, and hospital length of stay were significantly longer in the ICU-AW group than in the non-ICU-AW group (all P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all r = -0.60), while it was significantly positively correlated with the RFcsa loss (r = -0.60), while it was significantly positively correlated with the RFcsa loss (r = -0.60), while it was significantly positively correlated with the RFcsa loss (r = -0.60), while it was significantly positively correlated with the RFcsa loss (P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all. CONCLUSION: The plasma GDF-15 concentration level was significantly associated with skeletal muscle function and muscle wasting on day 7 in ICU patients with mechanical ventilation. Therefore, it can be concluded that the plasma GDF-15 level on the 7th day has a high diagnostic yield for ICU-acquired muscle weakness, and it can predict the 90-day survival status of ICU mechanically ventilated patients.

Valproic acid mitigates the inflammatory response and prevents acute respiratory distress syndrome in a murine model of Escherichia coli pneumonia at the expense of bacterial clearance.

BACKGROUND: Histone deacetylase inhibitors (HDACI) are members of a family of epigenetic modifying agents with broad anti-inflammatory properties. These anti-inflammatory properties may have important therapeutic implications in acute respiratory distress syndrome (ARDS). However, administration of HDACI may create an immunosuppressive environment conducive to bacterial growth. Accordingly, the aim of the current study is to investigate the effect of HDACI valproic acid (VPA) on host inflammatory response and bacterial burden in a murine model of Escherichia coli pneumonia-induced ARDS. METHODS: ARDS was induced in male C57BL6 mice (n = 24) by endotracheal instillation of 3 × 10 E. coli. VPA (250 mg/kg) was administered 30 minutes after E. coli instillation in the intervention group. Blood samples were collected at 3 and 6 hours, and animals were sacrificed at 6 hours. Bronchoalveolar lavage (BAL) was performed, and tissue specimens were harvested. Cytokine levels were measured in blood and BAL, and so was transalveolar protein transit. Cell counts and colony forming units were quantified in BAL fluid. RESULTS: VPA reduced neutrophil influx into the lungs and local tissue destruction through decreased myeloperoxidase activity. It also ameliorated the pulmonary and systemic inflammatory response. This led to greater bacterial proliferation in the pulmonary parenchyma. CONCLUSION: Administration of VPA in a clinically relevant bacterial model of murine ARDS mitigates the host inflammatory response, essentially preventing ARDS, but creates an immunosuppressive environment that favors bacterial overgrowth.

Assessment of the optimal operating parameters during extracorporeal CO2 removal with the Abylcap® system.

PURPOSE: Lung protective ventilation is recommended in patients with acute respiratory distress syndrome (ARDS) needing mechanical ventilation. This can however be associated with hypercapnia and respiratory acidosis, such that extracorporeal CO2 removal (ECCO2R) can be applied. The aim of this study was to derive optimal operating parameters for the ECCO2R Abylcap® system (Bellco, Italy). METHODS: We included 4 ARDS patients with a partial arterial oxygen tension over the fraction of inspired oxygen (PaO2/FiO2) lower than 150 mmHg, receiving lung-protective ventilation and treated with the Abylcap® via a double lumen 13.5-Fr dialysis catheter in the femoral vein. Every 24 hours during 5 consecutive days, blood was sampled at the Abylcap® inlet and outlet for different blood flows (QB:200-300-400 mL/min) with 100% O2 gas flow (QG) of 7 L/min, and for different QG (QG: 0.5-1-1.5-3-6-8 L/min) with QB400 mL/min. CO2 and O2 transfer remained constant over 5 days for a fixed QB. RESULTS: We found that, for a fixed QG of 7 L/min, CO2 transfer linearly and significantly increased with QB (i.e. from 58 ± 8 to 98 ± 16 mL/min for QB 200 to 400 mL/min). For a fixed QB of 400 mL/min, CO2 transfer non-linearly increased with QG (i.e. from 39 ± 9 to 98 ± 16 mL/min for QG 0.5 to 8 L/min) reaching a plateau at QG of 6 L/min. CONCLUSIONS: Hence, when using the Abylcap® ECCO2R in the treatment of ARDS patients the O2 flow should be at least 6 L/min while QB should be set at its maximum.

Lung ultrasonography for assessment of oxygenation response to prone position ventilation in ARDS.

PURPOSE: Prone position (PP) improves oxygenation and outcome of acute respiratory distress syndrome (ARDS) patients with a PaO2/FiO2 ratio <150 mmHg. Regional changes in lung aeration can be assessed by lung ultrasound (LUS). Our aim was to predict the magnitude of oxygenation response after PP using bedside LUS. METHODS: We conducted a prospective multicenter study that included adult patients with severe and moderate ARDS. LUS data were collected at four time points: 1 h before (baseline) and 1 h after turning the patient to PP, 1 h before and 1 h after turning the patient back to the supine position. Regional lung aeration changes and ultrasound reaeration scores were assessed at each time. Overdistension was not assessed. RESULTS: Fifty-one patients were included. Oxygenation response after PP was not correlated with a specific LUS pattern. The patients with focal and non-focal ARDS showed no difference in global reaeration score. With regard to the entire PP session, the patients with non-focal ARDS had an improved aeration gain in the anterior areas. Oxygenation response was not associated with aeration changes. No difference in PaCO2 change was found according to oxygenation response or lung morphology. CONCLUSIONS: In ARDS patients with a PaO2/FiO2 ratio ≤150 mmHg, bedside LUS cannot predict oxygenation response after the first PP session. At the bedside, LUS enables monitoring of aeration changes during PP.

Assessment of acute lung injury/acute respiratory distress syndrome using B-type brain natriuretic peptide.

OBJECTIVES: To investigate the clinical value of B-type natriuretic peptide (BNP) in the assessment of severity and prognosis in acute lung injury/acute respiratory distress syndrome (ALI/ARDS). METHODS: Plasma BNP level, arterial blood gases, serum C-reactive protein level, alveolar-arterial oxygen tension difference and oxygenation index were measured in patients with and without ALI/ARDS within 24 h of admission to an intensive care unit. Patients with ALI/ARDS were divided into mild, moderate or severe groups according to the degree of hypoxaemia. Survival >28 days was recorded. RESULTS: A total of 59 patients with ALI/ARDS and 14 patients without ALI/ARDS were included in the study. Of the patients with ALI/ARDS, 18 had mild hypoxaemia, 20 had moderate hypoxaemia and 21 had severe hypoxaemia. The mean ± SD BNP level was significantly higher in all three ALI/ARDS groups (92.41 ± 28.19 pg/ml, 170.64 ± 57.34 pg/ml and 239.06 ± 59.62 pg/ml, respectively, in the mild, moderate and severe groups) than in the non-ALI/ARDS group (47.27 ± 19.63 pg/ml); the increase in BNP level with increasing severity was also statistically significant. When divided according to outcome, the BNP level in the death group (267.07 ± 45.06 pg/ml) was significantly higher than in the survival group (128.99 ± 45.42 pg/ml). CONCLUSIONS: The BNP level may be of value in evaluating severity and prognosis in patients with ALI/ARDS.

[Assessment of chronic glucose metabolism disorders coexisting with respiratory failure in non-critical ill patients hospitalized with lower respiratory tract infections]. / Wspólistnienie zaburzen metabolizmu glukozy z niewydolnoscia oddechowa u pacjentów hospitalizowanych z powodu zakazen dolnych dróg oddechowych.

Lungs are the target organ in chronic hyperglycemia, but its large reserves causes a subclinical course of these changes. Given the results of other researchers indicating reduced active surface of gas exchange and pulmonary capillary damage, it can be assumed that diabetes and other hyperglycemic states diminish these reserves and impair effectiveness of respiratory gas exchange during pneumonia. So it is plausible to observe coexistence of glucose metabolism disorders and respiratory failure in patients hospitalized with lower respiratory tract infection. An observational study was conducted on 130 patients hospitalized with bacteriologically confirmed pneumonia. 63 patients suffering from chronic glucose metabolism disorders (A) and 67 randomly selected patients in control group (B) were observed on laboratory and clinical findings. There was no significant difference in prevalence of acute respiratory failure, although in the study group a slightly greater number of patients diagnosed with acute respiratory failure was observed. There was a significantly greater number of patients with previously confirmed chronic respiratory failure using long-term oxygen theraphy in A group (p = 0.029). The B patients with average blood glucose level > 108 mg/dl had significantly lower partial pressure of oxygen (PaO2)(gIc ≤ 108: 58.6 +/- 9.8; glc > 108: 51.7 +/- 11.1; p = 0.042). There was a statistically significant negative correlation of the average blood glucose level and PaO2 in the control group (p = 0.0152) and a significant inverse association between the average blood glucose level and the partial pressure of oxygen in patients without COPD belonging to the control group (p = 0.049). Respiratory failure is frequent in patients hospitalized with pneumonia. In patients without chronic glucose metabolism disorders with blood glucose level rising the oxygen tension decreases The association is stronger in patients without COPD.

B-type natriuretic peptide-guided risk assessment for postoperative complications in lung cancer surgery.

BACKGROUND: Since lung cancer surgery is still associated with a high complication rate, it is important to efficiently identify patients at high risk for postoperative complications following lung cancer surgery. We previously reported that elderly patients with elevated preoperative B-type natriuretic peptide (BNP) levels (>30 pg/mL) have an increased risk for postoperative atrial fibrillation and cardiopulmonary complications following lung cancer surgery. The objective of this study was to evaluate the clinical utility of BNP-guided risk classification for postoperative complications after lung cancer surgery. METHODS: A total of 675 consecutive patients who underwent curative surgery for lung cancer in two specialized thoracic centers between 2007 and 2011 were included in this retrospective study. We evaluated the association between the incidence of postoperative complications and preoperative BNP levels. RESULTS: Univariable and multivariable stepwise logistic regression analyses revealed that an elevated preoperative BNP level was the most significant predictor of postoperative complications. All patients were classified by their preoperative BNP levels into a normal group (<30 pg/mL), a mildly elevated group (30-100 pg/mL), and a severely elevated group (>100 pg/mL). The incidence of postoperative complications was significantly higher in the severely and mildly elevated groups than in the control group (85 % and 47 % vs. 11 %, P < 0.0001). Furthermore, there were more severe complications and a higher mortality rate in the severely elevated group. CONCLUSIONS: Risk assessment using preoperative BNP levels was clinically useful for the identification of patients at high risk for postoperative complications.

[Assessment of oxygen status in critical patients with systemic inflammatory reaction].

Diagnostic ability of alveolar-arterial oxygen gradient (A-aDO2 and respiratory index (RI) for acute respiratory distress syndrome was underestimated before recent time. 68 patients with severe inhomogeneous lung injure (severe concomitant trauma, pneumonia, and pancreonecrosis) were involved in the study. Patients were divided into two groups (basic group--34 patients and control group--34 patients). There were no differences in data of severity-of-disease by APACHE II and SOFA scales and J.F. Murrey lung injury score in both groups. Conventional volume controlled and pressure control respiratory techniques were used in patients of control group. Multi-level ventilation with three levels was used in patients of basic group. Blood gas containing, A-aDO2 and RI were studied. Gas status data improved both to gas exchange efficacy in patients of basic group. The data were significant different in the control group. Thus multilevel ventilation improves alveolar ventilation and arterial oxygenation, decreases pulmonary shunt and lung injury and improves respiratory lung functions.

High lactate levels are predictors of major complications after cardiac surgery.

OBJECTIVE: Although hyperlactatemia after cardiac surgery is common, the implications of raised levels remain controversial. The aim of this study was to evaluate whether high lactate levels after cardiac surgery are predictors of major complications including mortality. PATIENTS AND METHODS: This was a substudy of TRACS (Transfusion Requirements After Cardiac Surgery), which was designed as a prospective, randomized, controlled trial evaluating the effects of a transfusion strategy on morbidity and mortality. RESULTS: Of the 502 patients enrolled, 52 (10%) had at least 1 major complication. Patients with complications were older, had a higher EuroSCORE, lower left ventricular ejection fraction, lower preoperative hemoglobin, a higher prevalence of renal disease, and received more blood transfusions than the group without complications. Lactate levels were higher in the group with complications at the end of surgery (3.6 mmol/L [2.8-5.1] vs 3.3 mmol/L [2.2-4.8]; P = .018), immediately after intensive care unit (ICU) admission (0 hour) (4.4 mmol/L [3.1-8.4] vs 4 mmol/L [2.6-6.4]; P = .048); 6 hours (4 mmol/L [2.7-5.8] vs 2.6 mmol/L [2-3.6], P < .001), and 12 hours after admission (2.3 mmol/L [1.8-3.2] vs 1.7 mmol/L [1.3-2]; P < .001). In a multivariate model, higher age (odds ratio [OR], 1.048, 95% confidence interval [CI], 1.011-1.086; P = .010), left ventricular ejection fraction (LVEF) lower than 40% (OR, 3.03; 95% CI, 1.200-7.510; P = .019 compared with LVEF of 40%-59%; OR, 3.571; 95% CI, 1.503-8.196; P = .004 compared with LVEF higher than 60%), higher EuroSCORE (OR, 1.138; 95% CI; 1.007-1.285; P = .038), red blood cell transfusion (OR, 1.230; 95% CI, 1.086-1.393; P = .001), and lactate levels 6 hours after ICU admission (OR, 3.28, 95% CI; 1.61-6.69; P = .001) are predictors of major complications. CONCLUSIONS: Hyperlactatemia 6 hours after ICU admission is an independent risk factor for worse outcomes in adult patients after cardiac surgery.

Prognostic utility of changes in N-terminal pro-brain natriuretic Peptide combined with sequential organ failure assessment scores in patients with acute lung injury/acute respiratory distress syndrome concomitant with septic shock.

We investigated the prognostic utility of changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) in combination with Sequential Organ Failure Assessment (SOFA) score in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) concomitant with septic shock. Forty-nine mechanically ventilated patients with ALI/ARDS concomitant with septic shock were studied. N-terminal pro-brain natriuretic peptide levels were measured on the first 3 days (days 0, 1, and 2) in the intensive care unit. The median NT-proBNP levels in survivors and nonsurvivors were 3,999 vs. 2,819 pg/mL on day 0 (P = 0.719); 4,495 vs. 5,397 pg/mL on day 1 (P = 0.543); and 2,325 vs. 14,173 pg/mL on day 2 (P = 0.028). N-terminal pro-brain natriuretic peptide levels increased significantly from baseline values in nonsurvivors only. We observed a monotonic increase in 28-day mortality associated with increasing quartiles of percent change in NT-proBNP on day 2 (P < 0.0001). Kaplan-Meier survival analysis revealed that mortality was significantly higher in patients with a change in NT-proBNP of 30% or more (log-rank P < 0.0001). On day 2, areas under the receiver operating characteristic curves for predicting 28-day mortality were 0.74 for SOFA alone and 0.85 (P = 0.028) for SOFA combined with percent change in NT-proBNP. In conclusion, in patients with ALI/ARDS concomitant with septic shock, a rising trend (high percent change) in NT-proBNP levels had better prognostic utility than absolute levels. The combination of percent change in NT-proBNP with SOFA may provide superior prognostic accuracy to SOFA alone.

Assessment of regional lung recruitment and derecruitment during a PEEP trial based on electrical impedance tomography.

OBJECTIVE: To investigate whether electrical impedance tomography (EIT) is capable of monitoring regional lung recruitment and lung collapse during a positive end-expiratory pressure (PEEP) trial. DESIGN: Experimental animal study of acute lung injury. SUBJECT: Six pigs with saline-lavage-induced acute lung injury. INTERVENTIONS: An incremental and decremental PEEP trial at ten pressure levels was performed. Ventilatory, gas exchange, and hemodynamic parameters were automatically recorded. EIT and computed tomography (CT) scans of the same slice were simultaneously taken at each PEEP level. MEASUREMENTS AND RESULTS: A significant correlation between EIT and CT analyses of end-expiratory gas volumes (r=0.98 up to 0.99) and tidal volumes (r=0.55 up to r=0.88) could be demonstrated. Changes in global and regional tidal volumes and arterial oxygenation (PaO2/FiO2) demonstrated recruitment/derecruitment during the trial, but at different onsets. During the decremental trial, derecruitment first occurred in dependent lung areas. This was indicated by lowered regional tidal volumes measured in this area and by a decrease of PaO2/FiO2. At the same time, the global tidal volume still continued to increase, because the increase of ventilation of the non-dependent areas was higher than the loss in the dependent areas. This indicates that opposing regional changes might cancel each other out when combined in a global parameter. CONCLUSIONS: EIT is suitable for monitoring the dynamic effects of PEEP variations on the regional change of tidal volume. It is superior to global ventilation parameters in assessing the beginning of alveolar recruitment and lung collapse.

Acute respiratory distress syndrome: underrecognition by clinicians and diagnostic accuracy of three clinical definitions.

OBJECTIVE: To determine and compare the diagnostic accuracy of three clinical definitions of acute respiratory distress syndrome (ARDS): (1) the American-European consensus conference definition; (2) the lung injury score; and (3) a recently developed Delphi definition. A second objective was to determine the accuracy of clinical diagnoses of ARDS made in daily practice. DESIGN: Independent comparison of autopsy findings with the daily status of clinical definitions, constructed with data abstracted retrospectively from medical records. SETTING: Tertiary intensive care unit. PATIENTS: One hundred thirty-eight patients from the period 1995 through 2001 who were autopsied after being mechanically ventilated. INTERVENTIONS: Clinical ARDS diagnoses were determined daily without knowledge of autopsy results. Charts were reviewed for any mention of ARDS in the clinical notes. Autopsies were reviewed independently by two pathologists for the presence of diffuse alveolar damage. The sensitivity and specificity of the definitions were determined with use of diffuse alveolar damage at autopsy as the reference standard. MEASUREMENTS AND MAIN RESULTS: Diffuse alveolar damage at autopsy was documented in 42 of 138 cases (30.4%). Only 20 of these 42 patients (47.6%) had any mention of ARDS in their chart. Sensitivities and specificities (95% confidence intervals) were as follows: American-European definition, 0.83 (0.72-0.95), 0.51 (0.41-0.61); lung injury score, 0.74 (0.61-0.87), 0.77 (0.69-0.86); and Delphi definition, 0.69 (0.55-0.83), 0.82 (0.75-0.90). Specificity was significantly higher for both the lung injury score and Delphi definition than for the American-European definition (p < .001 for both), whereas comparisons of sensitivity, which was higher for the American-European definition, were not significantly different (p = .34 and p = .07, respectively). CONCLUSIONS: Acute respiratory distress syndrome appears underrecognized by clinicians in patients who die with this syndrome. In this population, the specificities of existing clinical definitions vary considerably, which may be problematic for clinical trials.

Assessment of errors when expiratory condensate PCO2 is used as a proxy for mixed expired PCO2 during mechanical ventilation.

OBJECTIVES: We designed a series of experiments to determine whether expiratory water condensate (PconCO2) can be used as a proxy for mixed expired gas collection. METHODS: In 18 adult mechanically ventilated patients with ARDS (40 samples), simultaneous collections of arterial blood, expiratory water trap condensate, mixed expired gas, and minute ventilation were used to calculate VCO2 and VD/VT. To assess the effect of temperature, a constant gas flow (PCO2 10-30 mm Hg) was bubbled through water at temperatures of 19.5-37 degrees C. Gas and water samples were collected, immediately analyzed for PCO2, and a temperature correction factor was calculated. A lung model was constructed using a 5 L anesthesia bag connected to a mechanical ventilator with a heated humidifier. Temperature at the Y-piece was set to approximately 37 degrees C and CO2 was injected into the bag to establish an end-tidal PCO2 of 20-70 mm Hg. After equilibration, condensate was collected, PCO2 was measured, and the temperature-corrected PCO2 was compared to PECO2. The capnogram at points along the expiratory limb circuit was used to evaluate gas mixing. RESULTS: There was an over-estimation of PECO2 by PconCO2 (p < 0.001) for the patient data, resulting in an underestimation of VD/VT (p < 0.001) and an overestimation of VCO2 (p < 0.001). The temperature correction factor for PCO2 in water was -0.010 (about half of the factor used for whole blood). The bias between temperature-corrected PconCO2 and PECO2 was 0.3 +/- 3.2 mm Hg in the lung model. Mixing in the expiratory limb was poor, as evaluated by the capnogram. CONCLUSIONS: Even with temperature correction, we failed to precisely predict PECO2 from PconCO2. For measurement of VD/VT and VCO2, we do not recommend methods that use PconCO2.

[Nitric oxide inhalation test in patients with ARDS: preliminary assessment of the effect on arterial oxygenation]. / Test di inalazione di ossido nitrico (NO) in pazienti con ARDS: valutazione preliminare dell'effetto sull'ossigenazione arteriosa.

OBJECTIVE: Inhaled NO can improve arterial oxygenation in ARDS. We evaluated the incidence and the magnitude of this effect during a short test of NO inhalation. This was performed in 24 consecutive mechanically ventilated patients with ARDS in order to assess the interest of NO for the therapy of hypoxemia in each case. DESIGN: Retro-spective study. SETTING: ICU in a University Hospital. PATIENTS: 24 hypoxemic patients with ARDS (lung injury score, LIS, 2.9 +/- 0.52), treated with conventional mechanical ventilation. INTERVENTIONS: Tests were performed using a mean inhalatory NO dose of 14 +/- 6 ppm. A pair of PaO2 data was obtained for each patient from two blood gas analysis, performed one just before and one 15 min after the start of NO inhalation. RESULTS: The mean baseline PaO2 was 76 +/- 21 mmHg and significantly increased with NO inhalation to 97 +/- 34 mmHg (p = 0.0001). Considering the individual response to NO, patients were arbitrarily classified as responders when the increase of PaO2 from baseline was > or = 10%. Sixteen patients were identified as responders, showing a mean increase of PaO2 from baseline by 40 +/- 26%, while the remaining 8 patients resulted non responders (mean change 1 +/- 5.7%). In no case a clinically significant decrease of PaO2 was observed during NO inhalation. The response to NO did not correlate with the LIS (r = 0.019) and with baseline PaO2 (r = 0.31). CONCLUSIONS: Inhaled NO doses of 14 +/- 6 ppm increased on the average the PaO2 in a group of ARDS patients, the individual response being however variable. A deterioration of arterial oxygenation was never observed. Even if the criteria for predicting the response to NO still remain to be defined, a short test seems to reliably provide a first estimate of the magnitude of the response.

Effect of maximizing oxygen delivery on morbidity and mortality rates in critically ill patients: a prospective, randomized, controlled study.

OBJECTIVE: To determine the effects of optimizing oxygen delivery (DO2) to "supranormal" levels on morbidity and mortality in patients with sepsis, septic shock, and adult respiratory distress syndrome. DESIGN: A prospective, randomized, controlled trial. SETTING: A 16-bed surgical intensive care unit (ICU) and 14-bed mixed medical/surgical ICU in two separate hospitals in the University of Hawaii Surgical and Internal Medicine Residency programs. PATIENTS: During a 1-yr period, 67 patients who had pulmonary artery catheters and who met the criteria for sepsis or septic shock, adult respiratory distress syndrome, or hypovolemic shock were enrolled in the study. Patients admitted to the ICU who were < 18 yrs old, or with a do-not-resuscitate order, or those patients who faced imminent death (< 24 hrs), such as those patients with uncontrollable hemorrhage or brain death, were excluded from the study. INTERVENTIONS: Patients were randomized into treatment and control groups. The treatment group was assigned a therapeutic DO2 indexed (DO2I) goal of > 600 mL/min/m2. Interventions to attain this goal included fluid boluses, administration of blood products, and the use of inotropes. The control group was not assigned to a specific therapeutic goal other than "normal" values of DO2I of 450 to 550 mL/min/m2. Every attempt was made to reach the therapeutic goals within the first 24 hrs after entry into the study. Hemodynamic measurements were obtained on study patients every 4 hrs until the end of the study. The severity of illness was evaluated using the Therapeutic Intervention Scoring System, and the Acute Physiology and Chronic Health Evaluation II scoring system. MEASUREMENTS AND MAIN RESULTS: There were 32 patients in the control group and 35 patients in the treatment group. The groups were similar in age, sex, number of organ dysfunctions, Acute Physiology and Chronic Health Evaluation II and Therapeutic Intervention scores. There were no statistical differences between the two groups in mortality, development of organ failure, ICU days, and hospital days. Upon analysis, it became apparent that the patients comprised clinically distinct subgroups, including: a) a treatment group who achieved supranormal DO2I; b) a control group with normal DO2I; c) a treatment group who failed to reach target DO2I; d) a control group who self-generated to high DO2I values; and e) a small number of patients who could not even reach a normal DO2I of 450 mL/min/m2. These subgroups were found to be similar and matched. The mortality rate was significantly lower for patients in groups who reached supranormal values of DO2I whether treated or self-generated as compared with patients who reached normal DO2I values (14% vs. 56%, p = .01). CONCLUSIONS: Although there was no statistically significant difference in the control vs. treatment groups, subgroup analysis demonstrated a strong, significant difference between patients with supranormal values of oxygen transport vs. patients with normal levels of DO2. Supranormal values of DO2I, whether self-generated or as a result of treatment, resulted in a statistically significant decrease in mortality rate. This study adds to the weight of evidence that current standard of care of treating critically ill patients to normal DO2I should be reconsidered, and that maximizing to high DO2I might be a more appropriate therapeutic end-point.

Acute lung injury. Assessment of tissue oxygenation.

The physiologic factors governing oxygen delivery to the peripheral tissues are briefly reviewed to show how tissue PO2 is defended when acute lung injury causes arterial hypoxemia. A loss of recruitable capillary reserve in the tissues may be another serious consequence of the same events that cause lung injury in the adult respiratory distress syndrome, and may cause a defect in tissue oxygen extraction.