Physiological predictors of survival during high-frequency oscillatory ventilation in adults with acute respiratory distress syndrome

Introduction

Data that provide clinical criteria for the identification of patients likely to respond to high-frequency oscillatory ventilation (HFOV) are scarce. Our aim was to describe physiological predictors of survival during HFOV in adults with severe acute respiratory distress syndrome (ARDS) admitted to a respiratory failure center in the United Kingdom.

Methods

Electronic records of 102 adults treated with HFOV were reviewed retrospectively. We used logistic regression and receiving-operator characteristics curve to test associations with oxygenation and mortality.

Results

Patients had severe ARDS with a mean (SD) Murray''s score of 2.98 (0.7). Partial pressure of oxygen in arterial blood to fraction of inspired oxygen (PaO₂/FiO₂) ratio and oxygenation index improved only in survivors. The earliest time point at which the two groups differed was at three hours after commencing HFOV. An improvement of >38% in PaO₂/FiO₂ occurring at any time within the first 72 hours, was the best predictor of survival at 30 days (area under the curve (AUC) of 0.83, sensitivity 93%, specificity 78% and a positive likelihood ratio (LR) of 4.3). These patients also had a 3.5 fold greater reduction in partial pressure of carbon dioxide in arterial blood (PaCO₂). Multivariate analysis showed that HFOV was more effective in younger patients, when instituted early, and in patients with milder respiratory acidosis.

Conclusions

HFOV is effective in improving oxygenation in adults with ARDS, particularly when instituted early. Changes in PaO₂/FiO₂ during the first three hours of HFOV can identify those patients more likely to survive.     

Hypercapnic acidosis in ARDS: A tolerated side effect or an important therapeutic modality?

Citation

Kregenow DA, Rubenfeld GD, Hudson LD, Swenson ER. Hypercapnic acidosis and mortality in acute lung injury. Crit Care Med 2006;34:1–7 [1].

Background

Evidence suggests that hypercapnic acidosis may be beneficial in patients with acute lung injury, though studies have not separated the effects of HA from the effects of changes in mechanical ventilation.

Methods

Objective

We tested the hypothesis that hypercapnic acidosis is associated with reduced mortality rate in patients with acute lung injury independent of changes in mechanical ventilation.

Design

Secondary analysis of randomized clinical trial data using hypothesis-driven multivariate logistic regression.

Setting

Randomized, multiple-center trial comparing 12 mL/kg to 6 mL/kg predicted body weight (PBW) tidal volumes previously published by the National Institutes of Health Acute Respiratory Distress Syndrome (ARDS) Network.

Subjects

861 acute lung injury patients enrolled in a randomized, multiple-center trial.

Intervention

None.

Measurements and main results

The adjusted odds ratio and 95% confidence intervals (CI) for 28-day mortality rate associated with hypercapnic acidosis defined as day 1 pH <7.35 and PaCO₂ >45 mm Hg were 0.14 (95% CI 0.03–0.70, p = .016) in the 12 mL/kg PBW tidal volume group and 1.18 (95% CI 0.59–2.35, p = .639) in the 6 mL/kg PBW tidal volume group. Other definitions of hypercapnic acidosis spanning a range of magnitudes suggest a dose-response association between hypercapnic acidosis and 28-day mortality in the 12 mL/kg PBW tidal volume group. None of our definitions of hypercapnic acidosis were associated with reduction in 28-day mortality in the 6 mL/kg PBW tidal volume group.

Conclusion

Hypercapnic acidosis was associated with reduced 28-day mortality in the 12 mL/kg PBW tidal volume group after controlling for co-morbidities and severity of lung injury. These results are consistent with a protective effect of hypercapnic acidosis against ventilator-associated lung injury that was not found when the further ongoing injury was reduced by 6 mL/kg PBW tidal volumes.     

Risk factors for acute respiratory distress syndrome during neutropenia recovery in patients with hematologic malignancies

Introduction

Neutropenia recovery may be associated with deterioration in oxygenation and exacerbation of pre-existing pulmonary disease. However, risk factors for acute respiratory distress syndrome (ARDS) during neutropenia recovery in patients with hematologic malignancies have not been studied.

Methods

We studied critically ill patients with hematologic malignancies with the dual objectives of describing patients with ARDS during neutropenia recovery and identifying risk factors for ARDS during neutropenia recovery. A cohort of consecutive neutropenic patients with hematologic malignancies who were admitted to the intensive care unit (ICU) was studied. During a 6-year period, 71 patients recovered from neutropenia, of whom 38 (53.5%) developed ARDS during recovery.

Results

Compared with non-ARDS patients, patients who experienced ARDS during neutropenia recovery were more likely to have pneumonia, be admitted to the ICU for respiratory failure, and receive mechanical ventilator therapy. The in-ICU mortality was significantly different between the two groups (86.8% versus 51.5%, respectively, for patients who developed ARDS during neutropenia recovery versus those who did not during neutropenia recovery). In multivariate analysis, only occurrence of pneumonia during the neutropenic episode was associated with a marked increase in the risk of ARDS (odds ratio, 4.76).

Conclusions

Patients with hematologic malignancies complicated by pneumonia during neutropenia are at increased risk for ARDS during neutropenia recovery.     

Non-invasive ventilation for acute hypoxemic respiratory failure: intubation rate and risk factors

Introduction

We assessed rates and predictive factors of non-invasive ventilation (NIV) failure in patients admitted to the intensive care unit (ICU) for non-hypercapnic acute hypoxemic respiratory failure (AHRF).

Methods

This is an observational cohort study using data prospectively collected over a three-year period in a medical ICU of a university hospital.

Results

Among 113 patients receiving NIV for AHRF, 82 had acute respiratory distress syndrome (ARDS) and 31 had non-ARDS. Intubation rates significantly differed between ARDS and non-ARDS patients (61% versus 35%, P = 0.015) and according to clinical severity of ARDS: 31% in mild, 62% in moderate, and 84% in severe ARDS (P = 0.0016). In-ICU mortality rates were 13% in non-ARDS, and, respectively, 19%, 32% and 32% in mild, moderate and severe ARDS (P = 0.22). Among patients with moderate ARDS, NIV failure was lower among those having a PaO₂/FiO₂ >150 mmHg (45% vs. 74%, p = 0.04). NIV failure was associated with active cancer, shock, moderate/severe ARDS, lower Glasgow coma score and lower positive end-expiratory pressure level at NIV initiation. Among intubated patients, ICU mortality rate was 46% overall and did not differ according to the time to intubation.

Conclusions

With intubation rates below 35% in non-ARDS and mild ARDS, NIV stands as the first-line approach; NIV may be attempted in ARDS patients with a PaO₂/FiO₂ > 150. By contrast, 84% of severe ARDS required intubation and NIV did not appear beneficial in this subset of patients. However, the time to intubation had no influence on mortality.     

The clinical usefulness of extravascular lung water and pulmonary vascular permeability index to diagnose and characterize pulmonary edema: a prospective multicenter study on the quantitative differential diagnostic definition for acute lung injury/acute respiratory distress syndrome

Introduction

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria.

Methods

The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO₂/FiO₂ ratio ≤ 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ≥ 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients'' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy.

Results

Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 ± 6.8, 14.4 ± 4.0, and 8.3 ± 2.1, respectively; P < 0.01). PVPI was higher in ALI/ARDS patients than in cardiogenic edema or pleural effusion with atelectasis patients (3.2 ± 1.4, 2.0 ± 0.8, and 1.6 ± 0.5; P < 0.01). In ALI/ARDS patients, EVLWI increased with increasing pulmonary vascular permeability (r = 0.729, P < 0.01) and was weakly correlated with intrathoracic blood volume (r = 0.236, P < 0.01). EVLWI was weakly correlated with the PaO₂/FiO₂ ratio in the ALI/ARDS and cardiogenic edema patients. A PVPI value of 2.6 to 2.85 provided a definitive diagnosis of ALI/ARDS (specificity, 0.90 to 0.95), and a value < 1.7 ruled out an ALI/ARDS diagnosis (specificity, 0.95).

Conclusion

PVPI may be a useful quantitative diagnostic tool for ARDS in patients with hypoxemic respiratory failure and radiographic infiltrates.

Trial registration

UMIN-CTR ID UMIN000003627     

Automatic protective ventilation using the ARDSNet protocol with the additional monitoring of electrical impedance tomography

Introduction

Automatic ventilation for patients with respiratory failure aims at reducing mortality and can minimize the workload of clinical staff, offer standardized continuous care, and ultimately save the overall cost of therapy. We therefore developed a prototype for closed-loop ventilation using acute respiratory distress syndrome network (ARDSNet) protocol, called autoARDSNet.

Methods

A protocol-driven ventilation using goal-oriented structural programming was implemented and used for 4 hours in seven pigs with lavage-induced acute respiratory distress syndrome (ARDS). Oxygenation, plateau pressure and pH goals were controlled during the automatic ventilation therapy using autoARDSNet. Monitoring included standard respiratory, arterial blood gas analysis and electrical impedance tomography (EIT) images. After 2-hour automatic ventilation, a disconnection of the animal from the ventilator was carried out for 10 seconds, simulating a frequent clinical scenario for routine clinical care or intra-hospital transport.

Results

This pilot study of seven pigs showed stable and robust response for oxygenation, plateau pressure and pH value using the automated system. A 10-second disconnection at the patient-ventilator interface caused impaired oxygenation and severe acidosis. However, the automated protocol-driven ventilation was able to solve these problems. Additionally, regional ventilation was monitored by EIT for the evaluation of ventilation in real-time at bedside with one prominent case of pneumothorax.

Conclusions

We implemented an automatic ventilation therapy using ARDSNet protocol with seven pigs. All positive outcomes were obtained by the closed-loop ventilation therapy, which can offer a continuous standard protocol-driven algorithm to ARDS subjects.     

Steroids in early ARDS?

Citation

Annane D, Sebille V, Bellissant E: Effect of low doses of corticosteroids in septic shock patients with or without early acute respiratory distress syndrome. Crit Care Med 2006, 34:22–30 [1].

Background

Experimental evidence suggests that corticosteroids may be beneficial in early acute respiratory distress syndrome (ARDS).

Methods

Objective

To investigate the efficacy of low doses of corticosteroids in septic shock patients with or without early ARDS by post hoc analysis of a previously completed clinical trial.

Design

Retrospective analysis of a placebo-controlled, randomized, double-blind trial of low doses of corticosteroids in septic shock.

Setting

Nineteen intensive care units in France.

Subjects

Among the 300 septic shock patients enrolled, we selected those meeting standard criteria for ARDS at inclusion.

Intervention

Seven-day treatment with 50 mg of hydrocortisone every 6 hrs and 50 μg of 9-alpha-fludrocortisone once a day.

Measurements and main results

There were 177 patients with ARDS (placebo, n = 92; corticosteroids, n = 85) including 129 (placebo, n = 67; corticosteroids, n = 62) nonresponders and 48 (placebo, n = 25; corticosteroids, n = 23) responders. In nonresponders, there were 50 deaths (75%) in the placebo group and 33 deaths (53%) in the steroid group (hazard ratio 0.57, 95% confidence interval 0.36–0.89, p = .013; relative risk 0.71, 95% confidence interval 0.54–0.94, p = .011). The number of days alive and off the ventilator was 2.6 +/- 6.6 in the placebo group and 5.7 +/- 8.6 in the steroid group (p = .006). There was no significant difference between groups in responders. There was no significant difference between groups in the two subsets of patients without ARDS. Adverse events rates were similar in the two groups.

Conclusion

This post hoc analysis shows that a 7-day treatment with low doses of corticosteroids was associated with better outcomes in septic shock-associated early ARDS nonresponders, but not in responders and not in septic shock patients without ARDS.     

Compartmentalization of lipid peroxidation in sepsis by multidrug-resistant gram-negative bacteria: experimental and clinical evidence

Introduction

Recent evidence suggests a link between excess lipid peroxidation and specific organ failures in sepsis. No study has been performed in sepsis by multidrug-resistant (MDR) Gram-negative bacteria.

Methods

Lethal sepsis was induced in rats by the intraperitoneal injection of one MDR isolate of Pseudomonas aeruginosa. Produced malondialdehyde (MDA) was measured in tissues 5 hours after bacterial challenge with the thiobarbiturate assay followed by high-performance liquid chromatography (HPLC) analysis. Results were compared with those from a cohort of patients with ventilator-associated pneumonia (VAP) and sepsis by MDR Gram-negative bacteria. More precisely, serum MDA was measured on 7 consecutive days, and it was correlated with clinical characteristics.

Results

MDA of septic rats was greater in the liver, spleen, and aortic wall, and it was lower in the right kidney compared with sham operated-on animals. Findings were confirmed by the studied cohort. Circulating MDA was greater in patients with hepatic dysfunction and acute respiratory distress syndrome (ARDS) compared with patients without any organ failures. The opposite was found for patients with acute renal dysfunction. No differences were found between patients with ARDS without or with cardiovascular (CV) failure and patients without any organ failure. Serial measurements of MDA in serum of patients indicated that levels of MDA were greater in survivors of hepatic dysfunction and ARDS and lower in survivors of acute renal dysfunction.

Conclusions

Animal findings and results of human sepsis are complementary, and they suggest a compartmentalization of lipid peroxidation in systemic infections by MDR gram-negative bacteria.     

Veno-venous extracorporeal CO2 removal for the treatment of severe respiratory acidosis: pathophysiological and technical considerations

Introduction

While non-invasive ventilation aimed at avoiding intubation has become the modality of choice to treat mild to moderate acute respiratory acidosis, many severely acidotic patients (pH <7.20) still need intubation. Extracorporeal veno-venous CO₂ removal (ECCO₂R) could prove to be an alternative. The present animal study tested in a systematic fashion technical requirements for successful ECCO₂R in terms of cannula size, blood and sweep gas flow.

Methods

ECCO₂R with a 0.98 m² surface oxygenator was performed in six acidotic (pH <7.20) pigs using either a 14.5 French (Fr) or a 19Fr catheter, with sweep gas flow rates of 8 and 16 L/minute, respectively. During each experiment the blood flow was incrementally increased to a maximum of 400 mL/minute (14.5Fr catheter) and 1000 mL/minute (19Fr catheter).

Results

Amelioration of severe respiratory acidosis was only feasible when blood flow rates of 750 to 1000 mL/minute (19Fr catheter) were used. Maximal CO₂-elimination was 146.1 ± 22.6 mL/minute, while pH increased from 7.13 ± 0.08 to 7.41 ± 0.07 (blood flow of 1000 mL/minute; sweep gas flow 16 L/minute). Accordingly, a sweep gas flow of 8 L/minute resulted in a maximal CO₂-elimination rate of 138.0 ± 16.9 mL/minute. The 14.5Fr catheter allowed a maximum CO₂ elimination rate of 77.9 mL/minute, which did not result in the normalization of pH.

Conclusions

Veno-venous ECCO₂R may serve as a treatment option for severe respiratory acidosis. In this porcine model, ECCO₂R was most effective when using blood flow rates ranging between 750 and 1000 mL/minute, while an increase in sweep gas flow from 8 to 16 L/minute had less impact on ECCO₂R in this setting.     

Relationship between extravascular lung water and severity categories of acute respiratory distress syndrome by the Berlin definition

Introduction

The Berlin definition divides acute respiratory distress syndrome (ARDS) into three severity categories. The relationship between these categories and pulmonary microvascular permeability as well as extravascular lung water content, which is the hallmark of lung pathophysiology, remains to be elucidated. The aim of this study was to evaluate the relationship between extravascular lung water, pulmonary vascular permeability, and the severity categories as defined by the Berlin definition, and to confirm the associated predictive validity for severity.

Methods

The extravascular lung water index (EVLWi) and pulmonary vascular permeability index (PVPI) were measured using a transpulmonary thermodilution method for three consecutive days in 195 patients with an EVLWi of ≥10 mL/kg and who fulfilled the Berlin definition of ARDS. Collectively, these patients were seen at 23 ICUs. Using the Berlin definition, patients were classified into three categories: mild, moderate, and severe.

Results

Compared to patients with mild ARDS, patients with moderate and severe ARDS had higher acute physiology and chronic health evaluation II and sequential organ failure assessment scores on the day of enrollment. Patients with severe ARDS had higher EVLWi (mild, 16.1; moderate, 17.2; severe, 19.1; P <0.05) and PVPI (2.7; 3.0; 3.2; P <0.05). When categories were defined by the minimum PaO₂/FIO₂ ratio observed during the study period, the 28-day mortality rate increased with severity categories: moderate, odds ratio: 3.125 relative to mild; and severe, odds ratio: 4.167 relative to mild. On independent evaluation of 495 measurements from 195 patients over three days, negative and moderate correlations were observed between EVLWi and the PaO₂/FIO₂ ratio (r = -0.355, P<0.001) as well as between PVPI and the PaO₂/FIO₂ ratio (r = -0.345, P <0.001). ARDS severity was associated with an increase in EVLWi with the categories (mild, 14.7; moderate, 16.2; severe, 20.0; P <0.001) in all data sets. The value of PVPI followed the same pattern (2.6; 2.7; 3.5; P <0.001).

Conclusions

Severity categories of ARDS described by the Berlin definition have good predictive validity and may be associated with increased extravascular lung water and pulmonary vascular permeability.

Trial registration

UMIN-CTR ID UMIN000003627     

Increased plasma levels of heparin-binding protein in patients with acute respiratory distress syndrome

Introduction

Heparin-binding protein (HBP) is an antimicrobial protein stored in neutrophil granules and plays a role in endothelial permeability regulation. The aim was to assess the diagnostic and prognostic value of measuring HBP in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS).

Methods

Plasma HBP was collected from 78 patients with ALI/ARDS, 28 patients with cardiogenic pulmonary edema (CPE) and 20 healthy volunteers at enrollment. Levels of HBP were measured by ELISA.

Results

Patients with ALI/ARDS had significantly higher median levels of HBP compared with patients with CPE (17.15 (11.95 to 24.07) ng/ml vs. 9.50 (7.98 to 12.18) ng/ml, P <0.001) at enrollment. There was no significant difference between CPE patients and healthy subjects in terms of HBP value (P = 0.372). The HBP levels of nonsurvivors was significantly higher than that of survivors (23.90 (14.81 to 32.45) ng/ml vs. 16.01 (10.97 to 21.06) ng/ml, P = 0.012) and multivariate logistic regression showed HBP (odds ratio =1.52, P = 0.034) was the independent predictor for 30-day mortality in patients with ALI/ARDS.

Conclusions

Plasma HBP levels of ALI/ARDS patients were significantly higher than that of CPE patients. HBP was a strong prognostic marker for short-term mortality in ALI/ARDS.     

Albumin versus crystalloid solutions in patients with the acute respiratory distress syndrome: a systematic review and meta-analysis

Introduction

In patients with acute respiratory distress syndrome (ARDS) fluid therapy might be necessary. The aim of this systematic review and meta-analysis is to determine the effects of colloid therapy compared to crystalloids on mortality and oxygenation in adults with ARDS.

Methods

Randomized controlled trials (RCTs) were identified through a systematic literature search of MEDLINE, EMBASE, CENTRAL and LILACS. Articles published up to 15^th February 2013 were independently screened, abstracted, and assessed (Cochrane Risk of Bias Tool) to provide evidence-based therapy recommendations. RCTs were eligible if they compared colloid versus crystalloid therapy on lung function, inflammation, damage or mortality in adults with ARDS. Primary outcome parameters were respiratory mechanics, gas exchange lung inflammation and damage as well as hospital mortality. Kidney function, need for renal replacement therapy, hemodynamic stabilization and intensive care unit (ICU) length of stay served as secondary outcomes.

Results

A total of 3 RCTs out of 4130 potential trials found in the databases were selected for qualitative and quantitative analysis totaling 206 patients who received either albumin or saline. Overall risk of bias was unclear to high in the identified trials. Calculated pooled risk of death was not statistically significant (albumin 34 of 100 (34.0%) versus 40 of 104 (38.5%), relative risk (RR) = 0.89, 95% confidence interval (CI) 0.62 to 1.28, P = 0.539). Weighted mean difference (WMD) in PaO₂/FiO₂ (mmHg) improved in the first 48 hours (WMD = 62, 95% CI 47 to 77, P <0.001, I² = 0%) after therapy start and remained stable after 7 days (WMD = 20, 95% CI 4 to 36, P = 0.017, I² = 0%).

Conclusions

There is a high need for RCTs investigating the effects of colloids in ARDS patients. Based on the findings of this review, colloid therapy with albumin improved oxygenation but did not affect mortality.     

Steroids in late ARDS?

Citation

Steinberg KP, Hudson LD, Goodman RB, Hough CL, Lanken PN, Hyzy R, Thompson BT, Ancukiewicz M: Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 2006, 354:1671–1684 [1].

Background

Persistent acute respiratory distress syndrome (ARDS) is characterized by excessive fibroproliferation, ongoing inflammation, prolonged mechanical ventilation, and a substantial risk of death. Because previous reports suggested that corticosteroids may improve survival, the study authors performed a multicenter, randomized controlled trial of corticosteroids in patients with persistent ARDS.

Methods

Objective

To determine if low dose corticosteroids would improve survival among patients with persistent ARDS.

Design

Multicenter randomized controlled trial.

Setting

25 hospitals in the United States that were part of the ARDS Clinical Trials Network.

Subjects

180 mechanically ventilated patients with ARDS of at least seven days duration.

Intervention

Subjects were randomized to either intravenous methylprednisolone (steroid group) or placebo in a double-blind fashion. Those in the steroid group received 2 mg/kg loading dose followed by 0.5 mg/kg every 6 hours for 14 days, 0.5 mg/kg every 12 hours for 7 days, and then tapering of the dose over 2–4 days.

Measurements and main results

The primary end point was mortality at 60 days. Secondary end points included the number of ventilator-free days and organ-failure-free days, biochemical markers of inflammation and fibroproliferation, and infectious complications. At 60 days, the hospital mortality rate was 28.6 percent in the placebo group (95 percent confidence interval, 20.3 to 38.6 percent) and 29.2 percent in the methylprednisolone group (95 percent confidence interval, 20.8 to 39.4 percent; P = 1.0); at 180 days, the rates were 31.9 percent (95 percent confidence interval, 23.2 to 42.0 percent) and 31.5 percent (95 percent confidence interval, 22.8 to 41.7 percent; P = 1.0), respectively. Methylprednisolone was associated with significantly increased 60- and 180-day mortality rates among patients enrolled at least 14 days after the onset of ARDS. Methylprednisolone increased the number of ventilator-free and shock-free days during the first 28 days in association with an improvement in oxygenation, respiratory-system compliance, and blood pressure with fewer days of vasopressor therapy. As compared with placebo, methylprednisolone did not increase the rate of infectious complications but was associated with a higher rate of neuromuscular weakness.

Conclusion

These results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology. In addition, starting methylprednisolone therapy more than two weeks after the onset of ARDS may increase the risk of death. (ClinicalTrials.gov number, {"type":"clinical-trial","attrs":{"text":"NCT00295269","term_id":"NCT00295269"}}NCT00295269.)     

Oxygen alert cards and controlled oxygen: preventing emergency admissions at risk of hypercapnic acidosis receiving high inspired oxygen concentrations in ambulances and A&E departments

Background

Appropriate resuscitation of hypoxic patients is fundamental in emergency admissions. To achieve this, it is standard practice of ambulance staff to administer high concentrations of oxygen to patients who may be in respiratory distress. A proportion of patients with chronic respiratory disease will become hypercapnic on this.

Objectives and methods

A scheme was agreed between the authors'' hospital and the local ambulance service, whereby patients with a history of previous hypercapnic acidosis with a Pao₂ >10.0 kPa—indicating that oxygen may have worsened the hypercapnia—are issued with “O₂ Alert” cards and a 24% Venturi mask. The patients are instructed to show these to ambulance and A&E staff who will then use the mask to avoid excessive oxygenation. The scheme was launched in 2001 and this paper present the results of an audit of the scheme in 2004.

Results

A total of 18 patients were issued with cards, and 14 were readmitted on 69 occasions. Sufficient documentation for auditing purposes was available for 52 of the 69 episodes. Of these audited admissions, 63% were managed in the ambulance, in line with card‐holder protocol. This figure rose to 94% in the accident and emergency department.

Conclusion

These data support the usability of such a scheme to prevent iatrogenic hypercapnia in emergency admissions.     

Low plasma citrulline levels are associated with acute respiratory distress syndrome in patients with severe sepsis

Introduction

The role of nitric oxide synthase (NOS) in the pathophysiology of acute respiratory distress syndrome (ARDS) is not well understood. Inducible NOS is upregulated during physiologic stress; however, if NOS substrate is insufficient then NOS can uncouple and switch from NO generation to production of damaging peroxynitrites. We hypothesized that NOS substrate levels are low in patients with severe sepsis and that low levels of the NOS substrate citrulline would be associated with end organ damage including ARDS in severe sepsis.

Methods

Plasma citrulline, arginine and ornithine levels and nitrate/nitrite were measured at baseline in 135 patients with severe sepsis. ARDS was diagnosed by consensus definitions.

Results

Plasma citrulline levels were below normal in all patients (median 9.2 uM, IQR 5.2 - 14.4) and were significantly lower in ARDS compared to the no ARDS group (6.0 (3.3 - 10.4) vs. 10.1 (6.2 - 16.6), P = 0.002). The rate of ARDS was 50% in the lowest citrulline quartile compared to 15% in the highest citrulline quartile (P = 0.002). In multivariable analyses, citrulline levels were associated with ARDS even after adjustment for covariates including severity of illness.

Conclusions

In severe sepsis, levels of the NOS substrate citrulline are low and are associated with ARDS. Low NOS substrate levels have been shown in other disease states to lead to NOS uncoupling and oxidative injury suggesting a potential mechanism for the association between low citrulline and ARDS. Further studies are needed to determine whether citrulline supplementation could prevent the development of ARDS in patients with severe sepsis and to determine its role in NOS coupling and function.     

Assessment of respiratory system compliance with electrical impedance tomography using a positive end-expiratory pressure wave maneuver during pressure support ventilation: a pilot clinical study

Introduction

Assessment of respiratory system compliance (C_rs) can be used for individual optimization of positive end-expiratory pressure (PEEP). However, in patients with spontaneous breathing activity, the conventional methods for C_rs measurement are inaccurate because of the variable muscular pressure of the patient. We hypothesized that a PEEP wave maneuver, analyzed with electrical impedance tomography (EIT), might be suitable for global and regional assessment of C_rs during assisted spontaneous breathing.

Methods

After approval of the local ethics committee, we performed a pilot clinical study in 18 mechanically ventilated patients (61 ± 16 years (mean ± standard deviation)) who were suitable for weaning with pressure support ventilation (PSV). For the PEEP wave, PEEP was elevated by 1 cmH₂O after every fifth breath during PSV. This was repeated five times, until a total PEEP increase of 5 cmH₂O was reached. Subsequently, PEEP was reduced in steps of 1 cmH₂O in the same manner until the original PEEP level was reached. C_rs was calculated using EIT from the global, ventral and dorsal lung regions of interest. For reference measurements, all patients were also examined during controlled mechanical ventilation (CMV) with a low-flow pressure-volume maneuver. Global and regional C_rs(low-flow) was calculated as the slope of the pressure-volume loop between the pressure that corresponded to the selected PEEP and PEEP +5 cmH₂O. For additional reference, C_rs during CMV (C_rs(CMV)) was calculated as expired tidal volume divided by the difference between airway plateau pressure and PEEP.

Results

Respiratory system compliance calculated from the PEEP wave (C_rs(PEEP wave)) correlated closely with both reference measurements (r = 0.79 for C_rs(low-flow) and r = 0.71 for C_rs(CMV)). No significant difference was observed between the mean C_rs(PEEP wave) and the mean C_rs(low-flow). However, a significant bias of +17.1 ml/cmH₂O was observed between C_rs(PEEP wave) and C_rs(CMV).

Conclusion

Analyzing a PEEP wave maneuver with EIT allows calculation of global and regional C_rs during assisted spontaneous breathing. In mechanically ventilated patients with spontaneous breathing activity, this method might be used for assessment of the global and regional mechanical properties of the respiratory system.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0679-6) contains supplementary material, which is available to authorized users.     

Cardiac index and oxygen delivery during low and high tidal volume ventilation strategies in patients with acute respiratory distress syndrome: a crossover randomized clinical trial

Introduction

The beneficial effect of low tidal volume (TV) ventilation strategy on mortality in patients with acute respiratory distress syndrome (ARDS) has been attributed to the protective effect on ventilator-induced lung injury, and yet its effect on cardiovascular function might also play an important role. The aim of this study was to assess whether low TV ventilation improves cardiac output and oxygen delivery compared with high TV ventilation strategy in patients with ARDS.

Methods

In this crossover randomized clinical trial 16 ARDS patients were recruited in an intensive care unit at a university-affiliated hospital. Each patient was ventilated for 30 min with low (6 mL/kg) and 30 min with high (12 mL/kg) TV. The two experimental periods, applied in random order and with allocation concealment, were separated by 30 min of basal ventilation. Minute ventilation was constantly maintained by appropriate respiratory rate changes.

Results

Compared with high TV ventilation, low TV ventilation showed decreased pH (7.37 vs. 7.41, P = 0.001) and increased PaCO₂ (49 vs. 43 mmHg; P = 0.002). Cardiac index and oxygen delivery index were increased with low compared with high TV ventilation (3.9 vs. 3.5 L.min^-1.m^-2, P = 0.012, and 521 vs. 463 mL.min^-1.m^-2, P = 0.002, respectively), while oxygen extraction ratio decreased (0.36 vs. 0.44, P = 0.027). In four patients oxygen extraction ratio was >0.5 during high TV but not during low TV strategy. The magnitude of the change in cardiac index was positively associated with PaCO₂ variation (P = 0.004), while it was unrelated to the magnitude of changes in TV and airway pressure. The decrease of cardiac index was predicted by PaCO₂ reduction, with and area under ROC curve of 0.72.

Conclusions

Our findings suggest that a low TV ventilation strategy increases cardiac index and oxygen delivery, thus supporting the hypothesis that the beneficial effect of low TV ventilation in patients with ARDS could be partially explained by hemodynamic improvement. In other words, low tidal volume ventilation could be protective also for the cardiovascular system and not only for the lung. The slight increase of PaCO₂ during low TV ventilation seems to predict the increase of cardiac index.

Trial registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00713713","term_id":"NCT00713713"}}NCT00713713     

Preliminary study of ventilation with 4 ml/kg tidal volume in acute respiratory distress syndrome: feasibility and effects on cyclic recruitment - derecruitment and hyperinflation

Introduction

Cyclic recruitment-derecruitment and overdistension contribute to ventilator-induced lung injury. Tidal volume (Vt) may influence both, cyclic recruitment-derecruitment and overdistension. The goal of this study was to determine if decreasing Vt from 6 to 4 ml/kg reduces cyclic recruitment-derecruitment and hyperinflation, and if it is possible to avoid severe hypercapnia.

Methods

Patients with pulmonary acute respiratory distress syndrome (ARDS) were included in a crossover study with two Vt levels: 6 and 4 ml/kg. The protocol had two parts: one bedside and other at the CT room. To avoid severe hypercapnia in the 4 ml/kg arm, we replaced the heat and moisture exchange filter by a heated humidifier, and respiratory rate was increased to keep minute ventilation constant. Data on lung mechanics and gas exchange were taken at baseline and after 30 minutes at each Vt (bedside). Thereafter, a dynamic CT (4 images/sec for 8 sec) was taken at each Vt at a fixed transverse region between the middle and lower third of the lungs. Afterward, CT images were analyzed and cyclic recruitment-derecruitment was determined as non-aerated tissue variation between inspiration and expiration, and hyperinflation as maximal hyperinflated tissue at end-inspiration, expressed as % of lung tissue weight.

Results

We analyzed 10 patients. Decreasing Vt from 6 to 4 ml/kg consistently decreased cyclic recruitment-derecruitment from 3.6 (2.5 to 5.7) % to 2.9 (0.9 to 4.7) % (P <0.01) and end-inspiratory hyperinflation from 0.7 (0.3 to 2.2) to 0.6 (0.2 to 1.7) % (P = 0.01). No patient developed severe respiratory acidosis or severe hypercapnia when decreasing Vt to 4 ml/kg (pH 7.29 (7.21 to 7.46); PaCO2 48 (26 to 51) mmHg).

Conclusions

Decreasing Vt from 6 to 4 ml/kg reduces cyclic recruitment-derecruitment and hyperinflation. Severe respiratory acidosis may be effectively prevented by decreasing instrumental dead space and by increasing respiratory rate.     

Biomarkers of lung epithelial injury and inflammation distinguish severe sepsis patients with acute respiratory distress syndrome

Introduction

Despite recent modifications, the clinical definition of the acute respiratory distress syndrome (ARDS) remains non-specific, leading to under-diagnosis and under-treatment. This study was designed to test the hypothesis that a biomarker panel would be useful for biologic confirmation of the clinical diagnosis of ARDS in patients at risk of developing ARDS due to severe sepsis.

Methods

This was a retrospective case control study of 100 patients with severe sepsis and no evidence of ARDS compared to 100 patients with severe sepsis and evidence of ARDS on at least two of their first four ICU days. A panel that included 11 biomarkers of inflammation, fibroblast activation, proteolytic injury, endothelial injury, and lung epithelial injury was measured in plasma from the morning of ICU day two. A backward elimination model building strategy on 1,000 bootstrapped data was used to select the best performing biomarkers for further consideration in a logistic regression model for diagnosis of ARDS.

Results

Using the five best-performing biomarkers (surfactant protein-D (SP-D), receptor for advanced glycation end-products (RAGE), interleukin-8 (IL-8), club cell secretory protein (CC-16), and interleukin-6 (IL-6)) the area under the receiver operator characteristic curve (AUC) was 0.75 (95% CI: 0.7 to 0.84) for the diagnosis of ARDS. The AUC improved to 0.82 (95% CI: 0.77 to 0.90) for diagnosis of severe ARDS, defined as ARDS present on all four of the first four ICU days.

Conclusions

Abnormal levels of five plasma biomarkers including three biomarkers generated by lung epithelium (SP-D, RAGE, CC-16) provided excellent discrimination for diagnosis of ARDS in patients with severe sepsis. Altered levels of plasma biomarkers may be useful biologic confirmation of the diagnosis of ARDS in patients with sepsis, and also potentially for selecting patients for clinical trials that are designed to reduce lung epithelial injury.     

Diffuse myocardial fibrosis in hypertrophic cardiomyopathy can be identified by cardiovascular magnetic resonance,and is associated with left ventricular diastolic dysfunction

Background

The presence of myocardial fibrosis is associated with worse clinical outcomes in hypertrophic cardiomyopathy (HCM). Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) sequences can detect regional, but not diffuse myocardial fibrosis. Post-contrast T₁ mapping is an emerging CMR technique that may enable the non-invasive evaluation of diffuse myocardial fibrosis in HCM. The purpose of this study was to non-invasively detect and quantify diffuse myocardial fibrosis in HCM with CMR and examine its relationship to diastolic performance.

Methods

We performed CMR on 76 patients - 51 with asymmetric septal hypertrophy due to HCM and 25 healthy controls. Left ventricular (LV) morphology, function and distribution of regional myocardial fibrosis were evaluated with cine imaging and LGE. A CMR T₁ mapping sequence determined the post-contrast myocardial T₁ time as an index of diffuse myocardial fibrosis. Diastolic function was assessed by transthoracic echocardiography.

Results

Regional myocardial fibrosis was observed in 84% of the HCM group. Post-contrast myocardial T₁ time was significantly shorter in patients with HCM compared to controls, consistent with diffuse myocardial fibrosis (498 ± 80 ms vs. 561 ± 47 ms, p < 0.001). In HCM patients, post-contrast myocardial T₁ time correlated with mean E/e’ (r = −0.48, p < 0.001).

Conclusions

Patients with HCM have shorter post-contrast myocardial T₁ times, consistent with diffuse myocardial fibrosis, which correlate with estimated LV filling pressure, suggesting a mechanistic link between diffuse myocardial fibrosis and abnormal diastolic function in HCM.