It is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure. Preplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18 years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality. Influenza infection status was categorized into four groups: patients with influenza alone (n = 95, 5.8%), patients with influenza plus pulmonary co-infection (n = 58, 3.6%), patients with non-influenza pulmonary infection (n = 820, 50.9%), and patients without pulmonary infection (n = 638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (P < 0.001). Patients with influenza plus co-infection had the highest rates of intubation and longest ICU LOS. On crude analysis, influenza infection status was associated with ICU mortality (P < 0.001) but not hospital mortality (P = 0.09). Patients with influenza plus co-infection and patients with non-influenza infection alone had similar ICU mortality (41% and 37% respectively) that was higher than patients with influenza alone or those without infection (33% and 26% respectively). A propensity score-matched analysis did not show a difference in hospital mortality attributable to influenza infection (OR = 1.01, 95%CI 0.90–1.13, P = 0.85). Age, severity scores, ARDS, and performance status were all associated with ICU, hospital, and 90-day mortality. Category of infectious etiology of respiratory failure (influenza, non-influenza, influenza plus co-infection, and non-infectious) was associated with ICU but not hospital mortality. In a propensity score-matched analysis, influenza infection was not associated with the primary outcome of hospital mortality. Overall, influenza infection alone may not be an independent risk factor for hospital mortality in immunosuppressed patients.

Therapeutic plasma exchange (TPE) is a therapeutic intervention that separates plasma from blood cells to remove pathological factors or to replenish deficient factors. The use of TPE is increasing over the last decades. However, despite a good theoretical rationale and biological plausibility for TPE as a therapy for numerous diseases or syndromes associated with critical illness, TPE in the intensive care unit (ICU) setting has not been studied extensively. A group of eighteen experts around the globe from different clinical backgrounds used a modified Delphi method to phrase key research questions related to “TPE in the critically ill patient”. These questions focused on: (1) the pathophysiological role of the removal and replacement process, (2) optimal timing of treatment, (3) dosing and treatment regimes, (4) risk–benefit assumptions and (5) novel indications in need of exploration. For all five topics, the current understanding as well as gaps in knowledge and future directions were assessed. The content should stimulate future research in the field and novel clinical applications.

Introduction: Hemorrhagic shock induced O₂deficit triggers inflammation and multiple organ failure (MOF). Endogenous H₂S has been proposed to be involved in MOF since plasma H₂S concentration appears to increase in various types of shocks and to predict mortality. We tested the hypothesis that H₂S increases during hemorrhagic shock associated with O₂deficit, and that enhancing H₂S oxidation by hydroxocobalamin could reduce inflammation, O₂deficit or mortality.Methods: We used a urethane anesthetized rat model, where 25 ml/kg of blood was withdrawn over 30 minutes. O₂deficit, lactic acid, tumor necrosis factor (TNF)-alpha and H₂S plasma concentrations (Siegel method) were measured before and after the bleeding protocol in control animals and animals that received 140 mg/kg of hydroxocobalamin. The ability to oxidize exogenous H₂S of the plasma and supernatants of the kidney and heart homogenates was determinedin vitro.Results: We found that withdrawing 25 ml/kg of blood led to an average oxygen deficit of 122 ± 23 ml/kg. This O₂deficit was correlated with an increase in the blood lactic acid concentration and mortality. However, the low level of absorbance of the plasma at 670 nm (A₆₇₀), after addingN, N-Dimethyl-p-phenylenediamine, that is, the method used for H₂S determination in previous studies, did not reflect the presence of H₂S, but was a marker of plasma turbidity. There was no difference in plasmatic A₆₇₀before and after the bleeding protocol, despite the large oxygen deficit. The plasma sampled at the end of bleeding maintained a very large ability to oxidize exogenous H₂S (high μM), as did the homogenates of hearts and kidneys harvested just after death. Hydroxocobalamin concentrations increased in the blood in the μM range in the vitamin B12 group, and enhanced the ability of plasma and kidneys to oxidize H₂S. Yet, the survival rate, O₂deficit, H₂S plasma concentration, blood lactic acid and TNF-alpha levels were not different from the control group.Conclusions: In the presence of a large O₂deficit, H₂S did not increase in the blood in a rat model of untreated hemorrhagic shock. Hydroxocobalamin, while effective against H₂Sin vitro, did not affect the hemodynamic profile or outcome in our model.