INTRODUCTION:

Missing values occur in nearly all clinical studies, despite the best efforts of the investigators, and cause frequently unrecognised biases. Our aims were (1) to assess the reporting and handling of missing values in the critical care literature; (2) to describe the impact of various techniques for handling missing values on the study results; (3) to provide guidance on the management of clinical study analysis in case of missing data.

METHODS:

We reviewed 44 published manuscripts in three critical care research journals. We used the Conflicus study database to illustrate how to handle missing values.

RESULTS:

Among 44 published manuscripts, 16 (36.4 %) provided no information on whether missing data occurred, 6 (13.6 %) declared having no missing data, 20 (45.5 %) reported that missing values occurred but did not handle them and only 2 (4.5 %) used sophisticated missing data handling methods. In our example using the Conflicus study database, we evaluated correlations linking job strain intensity to the type and proportion of missing values. Overall, 8 % of data were missing; however, using only complete cases would have resulted in discarding 24 % of the questionnaires. A greater number and a higher percentage of missing values for a particular variable were significantly associated with a lower job strain score (indicating greater stress). Among respondents who fully completed the job strain questionnaire, the comparison of those whose questionnaires did and did not have missing values showed significant differences in terms of age, number of children and country of birth. We provided an algorithm to manage clinical studies analysis in case of missing data.

CONCLUSION:

Missing data are common and generate interpretation biases. They should be reported routinely and taken into account when modelling data from clinical studies.

PURPOSE:

Pulmonary vascular dysfunction is common during acute respiratory distress syndrome (ARDS), but there is controversy concerning prevalence and prognosis of cor pulmonale during protective ventilation for ARDS.

METHODS:

This was a prospective observational study in an academic medical intensive care unit in France. Two hundred and twenty-six consecutive patients with moderate to severe ARDS (Berlin definition) ventilated with plateau pressure limited at 30 cmH2O (mean PEEP of 8.8 ± 3.6 cmH2O) underwent transesophageal echocardiography (TEE) within the first 3 days after the diagnosis of ARDS. Cor pulmonale was defined as a dilated right ventricle associated with septal dyskinesia.

RESULTS:

Cor pulmonale was detected in 49 patients (prevalence of 22 %; 95 % confidence interval, 16-27 %). Multivariate logistic regression identified infectious causes of lung injury and higher driving pressures as independent factors associated with cor pulmonale. Patients with cor pulmonale exhibited a higher incidence of shock (need for vasoactive drug) at the time of TEE and were more often managed with prone positioning and/or nitric oxide as adjunctive therapy for severe hypoxemia during ARDS course. The 28-day mortality rate was significantly higher in the group with cor pulmonale (60 vs. 36 %, p < 0.01). Multivariate logistic regression identified McCabe and Jackson class, lung injury not related to pneumonia, aspiration, or sepsis, lactic acidosis, driving pressure, and cor pulmonale as independent risk factors for 28-day mortality.

CONCLUSION:

Cor pulmonale occurrence is not negligible in ARDS patients ventilated with airway pressure limitation. Cor pulmonale was associated with sepsis and higher values of driving pressure and was an independent risk factor for 28-day mortality in our series.

PURPOSE:

To determine the global metabolomic profile as measured in circulating plasma from surviving and non-surviving patients with community-acquired pneumonia (CAP) and sepsis.

METHODS:

Random, outcome-stratified case-control sample from a prospective study of 1,895 patients hospitalized with CAP and sepsis. Cases (n = 15) were adults who died before 90 days, and controls (n = 15) were adults who survived, matched on demographics, infection type, and procalcitonin. We determined the global metabolomic profile in the first emergency department blood sample using non-targeted mass-spectrometry. We derived metabolite-based prognostic models for 90-day mortality. We determined if metabolites stimulated cytokine production by differentiated Thp1 monocytes in vitro, and validated metabolite profiles in mouse liver and kidney homogenates at 8 h in cecal ligation and puncture (CLP) sepsis.

RESULTS:

We identified 423 small molecules, of which the relative levels of 70 (17 %) were different between survivors and non-survivors (p ≤ 0.05). Broad differences were present in pathways of oxidative stress, bile acid metabolism, and stress response. Metabolite-based prognostic models for 90-day survival performed modestly (AUC = 0.67, 95 % CI 0.48, 0.81). Five nucleic acid metabolites were greater in non-survivors (p ≤ 0.05). Of these, pseudouridine increased monocyte expression of TNFα and IL1β versus control (p < 0.05). Pseudouridine was also increased in liver and kidney homogenates from CLP mice versus sham (p < 0.05 for both).

CONCLUSIONS:

Although replication is required, we show the global metabolomic profile in plasma broadly differs between survivors and non-survivors of CAP and sepsis. Metabolite-based prognostic models had modest performance, though metabolites of oxidative stress may act as putative damage-associated molecular patterns.