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BackgroundMulti-organ dysfunction in critical illness is common and frequently involves the lungs and kidneys, often requiring organ support such as invasive mechanical ventilation (IMV), renal replacement therapy (RRT) and/or extracorporeal membrane oxygenation (ECMO).MethodsA consensus conference on the spectrum of lung–kidney interactions in critical illness was held under the auspices of the Acute Disease Quality Initiative (ADQI) in Innsbruck, Austria, in June 2018. Through review and critical appraisal of the available evidence, the current state of research, and both clinical and research recommendations were described on the following topics: epidemiology, pathophysiology and strategies to mitigate pulmonary dysfunction among patients with acute kidney injury and/or kidney dysfunction among patients with acute respiratory failure/acute respiratory distress syndrome. Furthermore, emphasis was put on patients receiving organ support (RRT, IMV and/or ECMO) and its impact on lung and kidney function.ConclusionThe ADQI 21 conference found significant knowledge gaps about organ crosstalk between lung and kidney and its relevance for critically ill patients. Lung protective ventilation, conservative fluid management and early recognition and treatment of pulmonary infections were the only clinical recommendations with higher quality of evidence. Recommendations for research were formulated, targeting lung–kidney interactions to improve care processes and outcomes in critical illness.

This trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33°C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes.

Influenza was recently reported as a risk factor for invasive aspergillosis (IA). We aimed to describe prognostic factors for influenza-associated IA (IAA) and poor outcome and mortality in critically ill patients in Switzerland. All adults with confirmed influenza admitted to the ICU at two Swiss tertiary care centres during the 2017/2018 influenza season were retrospectively evaluated. IAA was defined by clinical, mycological and radiological criteria: a positive galactomannan in bronchoalveolar lavage or histopathological or cultural evidence in respiratory specimens of Aspergillus spp., any radiological infiltrate and a compatible clinical presentation. Poor outcome was defined as a composite of in-hospital mortality, ICU length of stay (LOS), invasive ventilation for > 7 days or extracorporeal membrane oxygenation. Of 81 patients with influenza in the ICU, 9 (11%) were diagnosed with IAA. All patients with IAA had poor outcome compared to 26 (36%) patients without IAA (p < 0.001). Median ICU-LOS and mortality were 17 vs. 3 days (p < 0.01) and 3/9 (33%) vs. 13/72 (18%; p = 0.37) in patients with vs. without IAA, respectively. Patients with IAA had significantly longer durations of antibiotic therapy, vasoactive support and mechanical ventilation. Aspergillus was the most common respiratory co-pathogen (9/40, 22%) followed by classical bacterial co-pathogens. IAA was not associated with classical risk factors. Aspergillus is a common superinfection in critically ill influenza patients associated with poor outcome and longer duration of organ supportive therapies. Given the absence of classical risk factors for aspergillosis, greater awareness is necessary, particularly in those requiring organ supportive therapies.

Background To optimize right ventricular–pulmonary coupling during veno-arterial (VA) ECMO weaning, inotropes, vasopressors and/or vasodilators are used to change right ventricular (RV) function (contractility) and pulmonary artery (PA) elastance (afterload). RV–PA coupling is the ratio between right ventricular contractility and pulmonary vascular elastance and as such, is a measure of optimized crosstalk between ventricle and vasculature. Little is known about the physiology of RV–PA coupling during VA ECMO. This study describes adaptive mechanisms for maintaining RV–PA coupling resulting from changing pre- and afterload conditions in VA ECMO. Methods In 13 pigs, extracorporeal flow was reduced from 4 to 1 L/min at baseline and increased afterload (pulmonary embolism and hypoxic vasoconstriction). Pressure and flow signals estimated right ventricular end-systolic elastance and pulmonary arterial elastance. Linear mixed-effect models estimated the association between conditions and elastance. Results At no extracorporeal flow, end-systolic elastance increased from 0.83 [0.66 to 1.00] mmHg/mL at baseline by 0.44 [0.29 to 0.59] mmHg/mL with pulmonary embolism and by 1.36 [1.21 to 1.51] mmHg/mL with hypoxic pulmonary vasoconstriction ( p  < 0.001). Pulmonary arterial elastance increased from 0.39 [0.30 to 0.49] mmHg/mL at baseline by 0.36 [0.27 to 0.44] mmHg/mL with pulmonary embolism and by 0.75 [0.67 to 0.84] mmHg/mL with hypoxic pulmonary vasoconstriction ( p  < 0.001). Coupling remained unchanged (2.1 [1.8 to 2.3] mmHg/mL at baseline; − 0.1 [− 0.3 to 0.1] mmHg/mL increase with pulmonary embolism; − 0.2 [− 0.4 to 0.0] mmHg/mL with hypoxic pulmonary vasoconstriction, p  > 0.05). Extracorporeal flow did not change coupling (0.0 [− 0.0 to 0.1] per change of 1 L/min, p  > 0.05). End-diastolic volume increased with decreasing extracorporeal flow (7.2 [6.6 to 7.8] ml change per 1 L/min, p  < 0.001). Conclusions The right ventricle dilates with increased preload and increases its contractility in response to afterload changes to maintain ventricular–arterial coupling during VA extracorporeal membrane oxygenation.

Background ICU risk assessment tools, routinely used for predicting population outcomes, are not recommended for evaluating individual risk. The state of health of single patients is mostly subjectively assessed to inform relatives and presumably to decide on treatment decisions. However, little is known how subjective and objective survival estimates compare. Methods We performed a prospective cohort study in mechanically ventilated critically ill patients across five European centres, assessed 62 objective markers and asked the clinical staff to subjectively estimate the probability of surviving 28 days. Results Within the 961 included patients, we identified 27 single objective predictors for 28-day survival (73.8%) and pooled them into predictive groups. While patient characteristics and treatment models performed poorly, the disease and biomarker models had a moderate discriminative performance for predicting 28-day survival, which improved for predicting 1-year survival. Subjective estimates of nurses (c-statistic [95% CI] 0.74 [0.70–0.78]), junior physicians (0.78 [0.74–0.81]) and attending physicians (0.75 [0.72–0.79]) discriminated survivors from non-survivors at least as good as the combination of all objective predictors (c-statistic: 0.67–0.72). Unexpectedly, subjective estimates were insufficiently calibrated, overestimating death in high-risk patients by about 20% in absolute terms. Combining subjective and objective measures refined discrimination and reduced the overestimation of death. Conclusions Subjective survival estimates are simple, cheap and similarly discriminative as objective models; however, they overestimate death risking that live-saving therapies are withheld. Therefore, subjective survival estimates of individual patients should be compared with objective tools and interpreted with caution if not agreeing. Trial registration ISRCTN ISRCTN59376582 , retrospectively registered October 31st 2013.

Release of hemoglobin (Hb) into the circulation is a central pathophysiologic event that contributes to morbidity and mortality in chronic hemolytic anemias and severe malaria. These toxicities arise from Hb-mediated vasoactivity, possibly due to NO scavenging and localized tissue oxidative processes. Currently, there is no established treatment that targets circulating extracellular Hb. Here, we assessed the role of haptoglobin (Hp), the primary scavenger of Hb in the circulation, in limiting the toxicity of cell-free Hb infusion. Using a canine model, we found that glucocorticoid stimulation of endogenous Hp synthesis prevented Hb-induced hemodynamic responses. Furthermore, guinea pigs administered exogenous Hp displayed decreased Hb-induced hypertension and oxidative toxicity to extravascular environments, such as the proximal tubules of the kidney. The ability of Hp to both attenuate hypertensive responses during Hb exposure and prevent peroxidative toxicity in extravascular compartments was dependent on Hb-Hp complex formation, which likely acts through sequestration of Hb rather than modulation of its NO- and O2-binding characteristics. Our data therefore suggest that therapies involving supplementation of endogenous Hb scavengers may be able to treat complications of acute and chronic hemolysis, as well as counter the adverse effects associated with Hb-based oxygen therapeutics.

Abstract Rationale Quantitative data on ventilation during acclimatization at very high altitude are scant. Therefore, we monitored nocturnal ventilation and oxygen saturation in mountaineers ascending Mt. Muztagh Ata (7,546 m). Objectives To investigate whether periodic breathing persists during prolonged stay at very high altitude. Methods A total of 34 mountaineers (median age, 46 yr; 7 women) climbed from 3,750 m within 19–20 days to the summit at 7,546 m. During ascent, repeated nocturnal recordings of calibrated respiratory inductive plethysmography, pulse oximetry, and scores of acute mountain sickness were obtained. Measurements and Main Results Nocturnal oxygen saturation decreased, whereas minute ventilation and the number of periodic breathing cycles increased with increasing altitude. At the highest camp (6,850 m), median nocturnal oxygen saturation, minute ventilation, and the number of periodic breathing cycles were 64%, 11.3 L/min, and 132.3 cycles/h. Repeated recordings within 5–8 days at 4,497 m and 5,533 m, respectively, revealed increased oxygen saturation, but no decrease in periodic breathing. The number of periodic breathing cycles was positively correlated with days of acclimatization, even when controlled for altitude, oxygen saturation, and other potential confounders, whereas symptoms of acute mountain sickness had no independent effect on periodic breathing. Conclusions Our field study provides novel data on nocturnal oxygen saturation, breathing patterns, and ventilation at very high altitude. It demonstrates that periodic breathing increases during acclimatization over 2 weeks at altitudes greater than 3,730 m, despite improved oxygen saturation consistent with a progressive increase in loop gain of the respiratory control system. Clinical trial registered with www.clinicaltrials.gov (NCT00514826).

BackgroundCirculatory shock and multi-organ failure remain major contributors to morbidity and mortality in critically ill patients and are associated with insufficient oxygen availability in the tissue. Intrinsic mechanisms to improve tissue perfusion, such as up-regulation of functional capillary density (FCD) and red blood cell velocity (RBCv), have been identified as maneuvers to improve oxygen extraction by the tissues; however, their role in circulatory shock and potential use as resuscitation targets remains unknown. To fill this gap, we examined the baseline and maximum recruitable FCD and RBCv in response to a topical nitroglycerin stimulus (FCDNG, RBCvNG) in patients with and without circulatory shock to test whether this may be a method to identify the presence and magnitude of a microcirculatory reserve capacity important for identifying a resuscitation target.MethodsSublingual handheld vital microscopy was performed after initial resuscitation in mechanically ventilated patients consecutively admitted to a tertiary medical ICU. FCD and RBCv were quantified using an automated computer vision algorithm (MicroTools). Patients with circulatory shock were retrospectively identified via standardized hemodynamic and clinical criteria and compared to patients without circulatory shock.Results54 patients (57 ± 14y, BMI 26.3 ± 4.9 kg/m2, SAPS 56 ± 19, 65% male) were included, 13 of whom presented with circulatory shock. Both groups had similar cardiac index, mean arterial pressure, RBCv, and RBCvNG. Heart rate (p < 0.001), central venous pressure (p = 0.02), lactate (p < 0.001), capillary refill time (p < 0.01), and Mottling score (p < 0.001) were higher in circulatory shock after initial resuscitation, while FCD and FCDNG were 10% lower (16.9 ± 4.2 and 18.9 ± 3.2, p < 0.01; 19.3 ± 3.1 and 21.3 ± 2.9, p = 0.03). Nitroglycerin response was similar in both groups, and circulatory shock patients reached FCDNG similar to baseline FCD found in patients without shock.ConclusionCritically ill patients suffering from circulatory shock were found to present with a lower sublingual FCD. The preserved nitroglycerin response suggests a dysfunction of intrinsic regulation mechanisms to increase the microcirculatory oxygen extraction capacity associated with circulatory shock and identifies a potential resuscitation target. These differences in microcirculatory hemodynamic function between patients with and without circulatory shock were not reflected in blood pressure or cardiac index.

Background In 2013 the Swiss Diagnosis Related Groups ((Swiss)-DRG) was implemented in Intensive Care Units (ICU). Its impact on hospitalizations has not yet been examined. We compared the number of ICU admissions, according to clinical severity and referring institution, and screened whether implementation of Swiss-DRG affected admission policy, ICU length-of-stay (ICU-LOS) or ICU mortality. Methods Retrospective, single centre, cohort study conducted at the University Hospital Zurich, Switzerland between January 2009 and end of September 2013. Demographic and clinical data was retrieved from a quality assurance database. Results Admissions ( n  = 17,231) before the introduction of Swiss-DRG were used to model expected admissions after DRG, and then compared to the observed admissions. Forecasting matched observations in patients with a high clinical severity admitted from internal units and external hospitals (admitted / predicted: 709 / 703, [95% Confidence Interval (CI), 658–748] and 302 / 332, [95% CI, 269–365] respectively). In patients with low severity of disease, in-house admissions became more frequent than expected and external admission were less frequent (admitted / predicted: 1972 / 1910, [95% CI, 1898–1940] and 436 / 518, [95% CI, 482–554] respectively). Various mechanisms related to Swiss-DRG may have led to these changes. DRG could not be linked to significant changes in regard to ICU-LOS and ICU mortality. Conclusions DRG introduction had not affected ICU admissions policy, except for an increase of in-house patients with a low clinical severity of disease. DRG had neither affected ICU mortality nor ICU-LOS.

The original version of this article unfortunately contained a mistake. The penultimate row of Table 4 shows INR > 1.5 which is incorrect. The correct figure is INR < 1.5. The authors apologize for the mistake. The correct table is given below.