An empirical study on KDIGO-defined acute kidney injury prediction in the intensive care unit.

MOTIVATION: Acute kidney injury (AKI) is a syndrome that affects a large fraction of all critically ill patients, and early diagnosis to receive adequate treatment is as imperative as it is challenging to make early. Consequently, machine learning approaches have been developed to predict AKI ahead of time. However, the prevalence of AKI is often underestimated in state-of-the-art approaches, as they rely on an AKI event annotation solely based on creatinine, ignoring urine output.We construct and evaluate early warning systems for AKI in a multi-disciplinary ICU setting, using the complete KDIGO definition of AKI. We propose several variants of gradient-boosted decision tree (GBDT)-based models, including a novel time-stacking based approach. A state-of-the-art LSTM-based model previously proposed for AKI prediction is used as a comparison, which was not specifically evaluated in ICU settings yet. RESULTS: We find that optimal performance is achieved by using GBDT with the time-based stacking technique (AUPRC = 65.7%, compared with the LSTM-based model's AUPRC = 62.6%), which is motivated by the high relevance of time since ICU admission for this task. Both models show mildly reduced performance in the limited training data setting, perform fairly across different subcohorts, and exhibit no issues in gender transfer.Following the official KDIGO definition substantially increases the number of annotated AKI events. In our study GBDTs outperform LSTM models for AKI prediction. Generally, we find that both model types are robust in a variety of challenging settings arising for ICU data. AVAILABILITY AND IMPLEMENTATION: The code to reproduce the findings of our manuscript can be found at: https://github.com/ratschlab/AKI-EWS.

Do cardiopulmonary exercise tests predict summit success and acute mountain sickness? A prospective observational field study at extreme altitude.

OBJECTIVE: During a high-altitude expedition, the association of cardiopulmonary exercise testing (CPET) parameters with the risk of developing acute mountain sickness (AMS) and the chance of reaching the summit were investigated. METHODS: Thirty-nine subjects underwent maximal CPET at lowlands and during ascent to Mount Himlung Himal (7126 m) at 4844 m, before and after 12 days of acclimatisation, and at 6022 m. Daily records of Lake-Louise-Score (LLS) determined AMS. Participants were categorised as AMS+ if moderate to severe AMS occurred. RESULTS: Maximal oxygen uptake (V̇O2max) decreased by 40.5%±13.7% at 6022 m and improved after acclimatisation (all p<0.001). Ventilation at maximal exercise (VEmax) was reduced at 6022 m, but higher VEmax was related to summit success (p=0.031). In the 23 AMS+ subjects (mean LLS 7.4±2.4), a pronounced exercise-induced oxygen desaturation (ΔSpO2exercise) was found after arrival at 4844 m (p=0.005). ΔSpO2exercise >-14.0% identified 74% of participants correctly with a sensitivity of 70% and specificity of 81% for predicting moderate to severe AMS. All 15 summiteers showed higher V̇O2max (p<0.001), and a higher risk of AMS in non-summiteers was suggested but did not reach statistical significance (OR: 3.64 (95% CI: 0.78 to 17.58), p=0.057). V̇O2max ≥49.0 mL/min/kg at lowlands and ≥35.0 mL/min/kg at 4844 m predicted summit success with a sensitivity of 46.7% and 53.3%, and specificity of 83.3% and 91.3%, respectively. CONCLUSION: Summiteers were able to sustain higher VEmax throughout the expedition. Baseline V̇O2max below 49.0 mL/min/kg was associated with a high chance of 83.3% for summit failure, when climbing without supplemental oxygen. A pronounced drop of SpO2exercise at 4844 m may identify climbers at higher risk of AMS.

Impact of Nonpharmaceutical Interventions on ICU Admissions During Lockdown for Coronavirus Disease 2019 in New Zealand-A Retrospective Cohort Study.

OBJECTIVES: Nonpharmaceutical interventions are implemented internationally to mitigate the spread of severe acute respiratory syndrome coronavirus 2 with the aim to reduce coronavirus disease 2019-related deaths and to protect the health system, particularly intensive care facilities from being overwhelmed. The aim of this study is to describe the impact of nonpharmaceutical interventions on ICU admissions of non-coronavirus disease 2019-related patients. DESIGN: Retrospective cohort study. SETTING: Analysis of all reported adult patient admissions to New Zealand ICUs during Level 3 and Level 4 lockdown restrictions from March 23, to May 13, 2020, in comparison with equivalent periods from 5 previous years (2015-2019). SUBJECTS: Twelve-thousand one-hundred ninety-two ICU admissions during the time periods of interest were identified. MEASUREMENTS: Patient data were obtained from the Australian and New Zealand Intensive Care Society Adult Patient Database, Australian and New Zealand Intensive Care Society critical care resources registry, and Statistics New Zealand. Study variables included patient baseline characteristics and ICU resource use. MAIN RESULTS: Nonpharmaceutical interventions in New Zealand were associated with a 39.1% decrease in ICU admission rates (p < 0.0001). Both elective (-44.2%) and acute (-36.5%) ICU admissions were significantly reduced when compared with the average of the previous 5 years (both p < 0.0001). ICU occupancy decreased from a mean of 64.3% (2015-2019) to 39.8% in 2020. Case mix, ICU resource use per patient, and ICU and hospital mortality remained unchanged. CONCLUSIONS: The institution of nonpharmaceutical interventions was associated with a significant decrease in elective and acute ICU admissions and ICU resource use. These findings may help hospitals and health authorities planning for surge capacities and elective surgery management in future pandemics.

The effect of dexmedetomidine on vasopressor requirements in patients with septic shock: a subgroup analysis of the Sedation Practice in Intensive Care Evaluation [SPICE III] Trial.

BACKGROUND: Septic shock is associated with decreased vasopressor responsiveness. Experimental data suggest that central alpha2-agonists like dexmedetomidine (DEX) increase vasopressor responsiveness and reduce catecholamine requirements in septic shock. However, DEX may also cause hypotension and bradycardia. Thus, it remains unclear whether DEX is hemodynamically safe or helpful in this setting. METHODS: In this post hoc subgroup analysis of the Sedation Practice in Intensive Care Evaluation (SPICE III) trial, an international randomized trial comparing early sedation with dexmedetomidine to usual care in critically patients receiving mechanical ventilation, we studied patients with septic shock admitted to two tertiary ICUs in Australia and Switzerland. The primary outcome was vasopressor requirements in the first 48 h after randomization, expressed as noradrenaline equivalent dose (NEq [µg/kg/min] = noradrenaline + adrenaline + vasopressin/0.4). RESULTS: Between November 2013 and February 2018, 417 patients were recruited into the SPICE III trial at both sites. Eighty-three patients with septic shock were included in this subgroup analysis. Of these, 44 (53%) received DEX and 39 (47%) usual care. Vasopressor requirements in the first 48 h were similar between the two groups. Median NEq dose was 0.03 [0.01, 0.07] µg/kg/min in the DEX group and 0.04 [0.01, 0.16] µg/kg/min in the usual care group (p = 0.17). However, patients in the DEX group had a lower NEq/MAP ratio, indicating lower vasopressor requirements to maintain the target MAP. Moreover, on adjusted multivariable analysis, higher dexmedetomidine dose was associated with a lower NEq/MAP ratio. CONCLUSIONS: In critically ill patients with septic shock, patients in the DEX group received similar vasopressor doses in the first 48 h compared to the usual care group. On multivariable adjusted analysis, dexmedetomidine appeared to be associated with lower vasopressor requirements to maintain the target MAP. TRIAL REGISTRATION: The SPICE III trial was registered at ClinicalTrials.gov ( NCT01728558 ).

Hypoxia-induced changes in plasma micro-RNAs correlate with pulmonary artery pressure at high altitude.

In vitro and animal studies revealed micro-RNAs (miRs) to be involved in modulation of hypoxia-induced pulmonary hypertension (HPH). However, knowledge of circulating miRs in humans in the context of HPH is very limited. Since symptoms of HPH are nonspecific and noninvasive diagnostic parameters do not exist, a disease-specific and hypoxemia-independent biomarker indicating HPH would be of clinical value. To examine whether plasma miR levels correlate with hypoxia-induced increase in pulmonary artery pressures, plasma miRs were assessed in a model of hypoxia-related pulmonary hypertension in humans exposed to extreme altitude. Forty healthy volunteers were repetitively examined during a high-altitude expedition up to an altitude of 7,050 m. Plasma levels of miR-17, -21, and -190 were measured by real-time quantitative PCR and correlated with systolic pulmonary artery pressure (SPAP), which was assessed by echocardiography. A significant altitude-dependent increase in circulating miR expression was found (all P values < 0.0001). Compared with baseline at 500 m, miR-17 changed by 4.72 ± 0.57-fold, miR-21 changed by 1.91 ± 0.33-fold, and miR-190 changed by 3.61 ± 0.54-fold at 7,050 m (means ± SD). Even after adjusting for hypoxemia, miR-17 and miR-190 were found to be independently correlated with increased SPAP. Progressive hypobaric hypoxia significantly affects levels of circulating miR-17, -21, and -190. Independently from the extent of hypoxemia, miR-17 and -190 significantly correlate with increased SPAP. These novel findings provide evidence for an epigenetic modulation of hypoxia-induced increase in pulmonary artery pressures by miR-17 and -190 and suggest the potential value of these miRs as biomarkers for HPH.

Modalities and accuracy of diagnosis of external ventricular drainage-related infections: a prospective multicentre observational cohort study.

BACKGROUND: Device infection is a major complication of placement external ventricular drains (EVD). Diagnostic features are often masked by underlying disease or cerebrospinal fluid (CSF) contamination by blood. We aim to assess which diagnostic modalities are applied for EVD-related infection (ERI) diagnosis and evaluate their accuracy. METHODS: This observational prospective study included 187 adult patients with an EVD. Modalities of clinical diagnosis of ERI diagnosed by treating physicians on clinical grounds and blood and CSF analysis (clinically diagnosed ERI (CD-ERI)) were assessed prospectively. Additionally, the diagnostic accuracy of clinical and laboratory parameters for the diagnosis of culture proven ERI (CP-ERI) was evaluated, using data of the study patients and including a retrospective cohort of 39 patients with CP-ERI. RESULTS: Thirty-one CD-ERIs were diagnosed in the prospective cohort. Most physicians used CSF analysis to establish the diagnosis. ROC analysis revealed an AUC of 0.575 (p = 0.0047) for the number of positive SIRS criteria and AUC of 0.5420 (p = 0.11) for the number of pathological neurological signs for diagnosis of CP-ERI. Diagnostic accuracy of laboratory values was AUC 0.596 (p = 0.0006) for serum white blood cell count (WBCC), AUC 0.550 (p = 0.2489) for serum C-reactive protein, AUC 0.644 (p < 0.0001) for CSF WBCC and AUC 0.690 for CSF WBC/red blood cell count ratio (both p < 0.0001). Neither a temporal trend in potential predictors of CP-ERI nor a correlation between clinical diagnosis and proven CSF infection was found. CONCLUSIONS: Clinicians base their diagnosis of ERI mostly on CSF analysis and occurrence of fever, leading to over-diagnosis. The accuracy of the clinical diagnosis is low. Commonly used clinical and laboratory diagnostic criteria have a low sensitivity and specificity for ERI.

Impact of Simulator-Based Training in Focused Transesophageal Echocardiography: A Randomized Controlled Trial.

BACKGROUND: The aim of the study was to determine if training in transesophageal echocardiography (TEE) using a TEE simulator improves the ability of novice operators to perform and interpret a focused critical care TEE. METHODS: In this prospective, randomized, controlled study with blinded outcome assessment, 44 intensive care unit trainees were randomly assigned to a control group receiving 4 hours of lecture-based training only, or an intervention group which was additionally trained for 4 hours using a TEE simulator. After the training intervention, each participant performed 2 TEEs in intensive care unit patients which were evaluated by blinded assessors. The imaging quality of TEEs was measured using a predefined examination quality score ranging from 0 to 100 points. The correct quantification of pathologies and the interpretation of the TEEs were evaluated by blinded assessors using focused and comprehensive expert TEEs as comparators. RESULTS: A total of 114 TEEs were assessed. The mean examination quality score was 55.9 (95% confidence interval [CI], 50.3-61.5) for TEEs of the control group, 75.6 (95% CI, 70.1-81.0) for TEEs of the intervention group, and 88.5 (95% CI, 79.3-97.7) for TEEs in the expert group. The multiple comparisons revealed significant differences between all groups (19.7 [95% CI, 12.8-26.6], P < .001 for intervention versus control; 32.6 [95% CI, 23.0-42.3], P < .001 for expert versus control; 12.9 [95% CI, 3.4-22.5], P = .008 for expert versus intervention). Substantial agreement of the quantification and interpretation ratings of basic TEEs by the intervention (86.7% for quantification and 97.1% for interpretation) or expert group (93.2% for quantification and 98.4% for interpretation) with blinded assessors was detected. The control groups TEEs agreed less (75.6% for quantification and 91.8% for interpretation). CONCLUSIONS: Simulation-based TEE training improves the ability of novice operators to perform a focused critical care TEE in comparison to lecture-based education only. After 8 hours of simulator and lecture-based training, the majority of TEEs of novices are of sufficient quality for clinical use. Furthermore, a substantial skill level in correct quantification and interpretation of imaging is achieved.

Increased endothelial microparticles and oxidative stress at extreme altitude.

PURPOSE: Hypoxia and oxidative stress affect endothelial function. Endothelial microparticles (MP) are established measures of endothelial dysfunction and influence vascular reactivity. To evaluate the effects of hypoxia and antioxidant supplementation on endothelial MP profiles, a double-blind, placebo-controlled trial, during a high altitude expedition was performed. METHODS: 29 participants were randomly assigned to a treatment group (n = 14), receiving vitamin E, C, A, and N-acetylcysteine daily, and a control group (n = 15), receiving placebo. Blood samples were obtained at 490 m (baseline), 3530, 4590, and 6210 m. A sensitive tandem mass spectrometry method was used to measure 8-iso-prostaglandin F2α and hydroxyoctadecadienoic acids as markers of oxidative stress. Assessment of MP profiles including endothelial activation markers (CD62+MP and CD144+MP) and cell apoptosis markers (phosphatidylserine+MP and CD31+MP) was performed using a standardized flow cytometry-based protocol. RESULTS: 15 subjects reached all altitudes and were included in the final analysis. Oxidative stress increased significantly at altitude. No statistically significant changes were observed comparing baseline to altitude measurements of phosphatidylserine expressing MP (p = 0.1718) and CD31+MP (p = 0.1305). Compared to baseline measurements, a significant increase in CD62+MP (p = 0.0079) and of CD144+MP was detected (p = 0.0315) at high altitudes. No significant difference in any MP level or oxidative stress markers were found between the treatment and the control group. CONCLUSION: Hypobaric hypoxia is associated with increased oxidative stress and induces a significant increase in CD62+ and CD144+MP, whereas phosphatidylserine+MP and CD31+MP remain unchanged. This indicates that endothelial activation rather than an apoptosis is the primary factor of hypoxia induced endothelial dysfunction.

Indicators of external ventricular drainage-related infections--a retrospective observational study.

BACKGROUND: External ventricular drainage (EVD) is frequently used in different groups of patients in neurocritical care. Despite the frequent use of EVD, no consensus regarding the diagnosis of EVD-related infection currently exists, and diagnosis is commonly based on criteria for the diagnosis of non-EVD-related CNS infections. This study evaluates the diagnostic accuracy of clinical and laboratory parameters for the prediction of EVD-related infection in patients with proven EVD-related infection. METHODS: In two tertiary care centers, data on EVD insertions were matched with a microbiologic database of cultured microorganisms and positive Gram stains of cerebrospinal fluid (CSF) to identify patients with EVD-related infections. Available clinical data and results of blood tests and CSF analysis were retrospectively collected. Predefined potential clinical and laboratory predictors of EVD-related infection were compared between three time points: at the time EVD insertion and 48 h before and at the time of occurrence of EVD-related infection. RESULTS: Thirty-nine patients with EVD-associated infection defined by positive CSF culture or positive CSF Gram stains and concomitant clinical signs of infection were identified. At the time of infection, a significantly higher incidence of abnormal temperature, high respiratory rate, and a slightly but significantly higher incidence of decreased mental state were observed. The assessed blood and CSF parameters did not significantly differ between the different assessment time points. CONCLUSIONS: Our analysis of 39 patients with culture positive EVD-related infection showed that commonly used clinical and laboratory parameters are not reliable infection predictors.

Hemodynamic assessment of critically ill patients using a miniaturized transesophageal echocardiography probe.

INTRODUCTION: Hemodynamic management in intensive care patients guided by blood pressure and flow measurements often do not sufficiently reveal common hemodynamic problems. Trans-esophageal echocardiography (TEE) allows for direct measurement of cardiac volumes and function. A new miniaturized probe for TEE (mTEE) potentially provides a rapid and simplified approach to monitor cardiac function. The aim of the study was to assess the feasibility of hemodynamic monitoring using mTEE in critically ill patients after a brief operator training period. METHODS: In the context of the introduction of mTEE in a large ICU, 14 ICU staff specialists with no previous TEE experience received six hours of training as mTEE operators. The feasibility of mTEE and the quality of the obtained hemodynamic information were assessed. Three standard views were acquired in hemodynamically unstable patients: 1) for assessment of left ventricular function (LV) fractional area change (FAC) was obtained from a trans-gastric mid-esophageal short axis view, 2) right ventricular (RV) size was obtained from mid-esophageal four chamber view, and 3) superior vena cava collapsibility for detection of hypovolemia was assessed from mid-esophageal ascending aortic short axis view. Off-line blinded assessment by an expert cardiologist was considered as a reference. Inter-rater agreement was assessed using Chi-square tests or correlation analysis as appropriate. RESULTS: In 55 patients, 148 mTEE examinations were performed. Acquisition of loops in sufficient quality was possible in 110 examinations for trans-gastric mid-esophageal short axis, 118 examinations for mid-esophageal four chamber and 125 examinations for mid-esophageal ascending aortic short axis view. Inter-rater agreement (Kappa) between ICU mTEE operators and the reference was 0.62 for estimates of LV function, 0.65 for RV dilatation, 0.76 for hypovolemia and 0.77 for occurrence of pericardial effusion (all P<0.0001). There was a significant correlation between the FAC measured by ICU operators and the reference (r=0.794, P (one-tailed)<0.0001). CONCLUSIONS: Echocardiographic examinations using mTEE after brief bed-side training were feasible and of sufficient quality in a majority of examined ICU patients with good inter-rater reliability between mTEE operators and an expert cardiologist. Further studies are required to assess the impact of hemodynamic monitoring by mTEE on relevant patient outcomes.

Cognitive performance in high-altitude climbers: a comparative study of saccadic eye movements and neuropsychological tests.

Impairment of cognitive performance during and after high-altitude climbing has been described in numerous studies and has mostly been attributed to cerebral hypoxia and resulting functional and structural cerebral alterations. To investigate the hypothesis that high-altitude climbing leads to cognitive impairment, we used of neuropsychological tests and measurements of eye movement (EM) performance during different stimulus conditions. The study was conducted in 32 mountaineers participating in an expedition to Muztagh Ata (7,546 m). Neuropsychological tests comprised figural fluency, line bisection, letter and number cancellation, and a modified pegboard task. Saccadic performance was evaluated under three stimulus conditions with varying degrees of cortical involvement: visually guided pro- and anti-saccades, and visuo-visual interaction. Typical saccade parameters (latency, mean sequence, post-saccadic stability, and error rate) were computed off-line. Measurements were taken at a baseline level of 440 m and at altitudes of 4,497, 5,533, 6,265, and again at 440 m. All subjects reached 5,533 m, and 28 reached 6,265 m. The neuropsychological test results did not reveal any cognitive impairment. Complete eye movement recordings for all stimulus conditions were obtained in 24 subjects at baseline and at least two altitudes and in 10 subjects at baseline and all altitudes. Measurements of saccade performances showed no dependence on any altitude-related parameter and were well within normal limits. Our data indicates that acclimatized climbers do not seem to suffer from significant cognitive deficits during or after climbs to altitudes above 7,500 m. We demonstrated that investigation of EMs is feasible during high-altitude expeditions.

A guide to sharing open healthcare data under the General Data Protection Regulation.

Sharing healthcare data is increasingly essential for developing data-driven improvements in patient care at the Intensive Care Unit (ICU). However, it is also very challenging under the strict privacy legislation of the European Union (EU). Therefore, we explored four successful open ICU healthcare databases to determine how open healthcare data can be shared appropriately in the EU. A questionnaire was constructed based on the Delphi method. Then, follow-up questions were discussed with experts from the four databases. These experts encountered similar challenges and regarded ethical and legal aspects to be the most challenging. Based on the approaches of the databases, expert opinion, and literature research, we outline four distinct approaches to openly sharing healthcare data, each with varying implications regarding data security, ease of use, sustainability, and implementability. Ultimately, we formulate seven recommendations for sharing open healthcare data to guide future initiatives in sharing open healthcare data to improve patient care and advance healthcare.

The prevalence of cardiac complications and their impact on outcomes in patients with non-traumatic subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a serious condition, and a myocardial injury or dysfunction could contribute to the outcome. We assessed the prevalence and prognostic impact of cardiac involvement in a cohort with SAH. This is a prospective observational multicenter study. We included 192 patients treated for non-traumatic subarachnoid hemorrhage. We performed ECG recordings, echocardiographic examinations, and blood sampling within 24 h of admission and on days 3 and 7 and at 90 days. The primary endpoint was the evidence of cardiac involvement at 90 days, and the secondary endpoint was to examine the prevalence of a myocardial injury or dysfunction. The median age was 54.5 (interquartile range [IQR] 48.0-64.0) years, 44.3% were male and the median World Federation of Neurological Surgeons (WFNS) score was 2 (IQR 1-4). At day 90, 22/125 patients (17.6%) had left ventricular ejection fractions ≤ 50%, and 2/121 patients (1.7%) had evidence of a diastolic dysfunction as defined by mitral peak E-wave velocity by peak e' velocity (E/e') > 14. There was no prognostic impact from echocardiographic evidence of cardiac complications on neurological outcomes. The overall prevalence of cardiac dysfunction was modest. We found no demographic or SAH-related factors associated with 90 days cardiac dysfunction.

Risk assessment in the first fifteen minutes: a prospective cohort study of a simple physiological scoring system in the emergency department.

INTRODUCTION: The survival of patients admitted to an emergency department is determined by the severity of acute illness and the quality of care provided. The high number and the wide spectrum of severity of illness of admitted patients make an immediate assessment of all patients unrealistic. The aim of this study is to evaluate a scoring system based on readily available physiological parameters immediately after admission to an emergency department (ED) for the purpose of identification of at-risk patients. METHODS: This prospective observational cohort study includes 4,388 consecutive adult patients admitted via the ED of a 960-bed tertiary referral hospital over a period of six months. Occurrence of each of seven potential vital sign abnormalities (threat to airway, abnormal respiratory rate, oxygen saturation, systolic blood pressure, heart rate, low Glasgow Coma Scale and seizures) was collected and added up to generate the vital sign score (VSS). VSSinitial was defined as the VSS in the first 15 minutes after admission, VSSmax as the maximum VSS throughout the stay in ED. Occurrence of single vital sign abnormalities in the first 15 minutes and VSSinitial and VSSmax were evaluated as potential predictors of hospital mortality. RESULTS: Logistic regression analysis identified all evaluated single vital sign abnormalities except seizures and abnormal respiratory rate to be independent predictors of hospital mortality. Increasing VSSinitial and VSSmax were significantly correlated to hospital mortality (odds ratio (OR) 2.80, 95% confidence interval (CI) 2.50 to 3.14, P < 0.0001 for VSSinitial; OR 2.36, 95% CI 2.15 to 2.60, P < 0.0001 for VSSmax). The predictive power of VSS was highest if collected in the first 15 minutes after ED admission (log rank Chi-square 468.1, P < 0.0001 for VSSinitial;,log rank Chi square 361.5, P < 0.0001 for VSSmax). CONCLUSIONS: Vital sign abnormalities and VSS collected in the first minutes after ED admission can identify patients at risk of an unfavourable outcome.

Nocturnal periodic breathing during acclimatization at very high altitude at Mount Muztagh Ata (7,546 m).

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).

An automated retrospective VAE-surveillance tool for future quality improvement studies.

Ventilator-associated pneumonia (VAP) is a frequent complication of mechanical ventilation and is associated with substantial morbidity and mortality. Accurate diagnosis of VAP relies in part on subjective diagnostic criteria. Surveillance according to ventilator-associated event (VAE) criteria may allow quick and objective benchmarking. Our objective was to create an automated surveillance tool for VAE tiers I and II on a large data collection, evaluate its diagnostic accuracy and retrospectively determine the yearly baseline VAE incidence. We included all consecutive intensive care unit admissions of patients with mechanical ventilation at Bern University Hospital, a tertiary referral center, from January 2008 to July 2016. Data was automatically extracted from the patient data management system and automatically processed. We created and implemented an application able to automatically analyze respiratory and relevant medication data according to the Centers for Disease Control protocol for VAE-surveillance. In a subset of patients, we compared the accuracy of automated VAE surveillance according to CDC criteria to a gold standard (a composite of automated and manual evaluation with mediation for discrepancies) and evaluated the evolution of the baseline incidence. The study included 22'442 ventilated admissions with a total of 37'221 ventilator days. 592 ventilator-associated events (tier I) occurred; of these 194 (34%) were of potentially infectious origin (tier II). In our validation sample, automated surveillance had a sensitivity of 98% and specificity of 100% in detecting VAE compared to the gold standard. The yearly VAE incidence rate ranged from 10.1-22.1 per 1000 device days and trend showed a decrease in the yearly incidence rate ratio of 0.96 (95% CI, 0.93-1.00, p = 0.03). This study demonstrated that automated VAE detection is feasible, accurate and reliable and may be applied on a large, retrospective sample and provided insight into long-term institutional VAE incidences. The surveillance tool can be extended to other centres and provides VAE incidences for performing quality control and intervention studies.

Early prediction of circulatory failure in the intensive care unit using machine learning.

Intensive-care clinicians are presented with large quantities of measurements from multiple monitoring systems. The limited ability of humans to process complex information hinders early recognition of patient deterioration, and high numbers of monitoring alarms lead to alarm fatigue. We used machine learning to develop an early-warning system that integrates measurements from multiple organ systems using a high-resolution database with 240 patient-years of data. It predicts 90% of circulatory-failure events in the test set, with 82% identified more than 2 h in advance, resulting in an area under the receiver operating characteristic curve of 0.94 and an area under the precision-recall curve of 0.63. On average, the system raises 0.05 alarms per patient and hour. The model was externally validated in an independent patient cohort. Our model provides early identification of patients at risk for circulatory failure with a much lower false-alarm rate than conventional threshold-based systems.

New insights into ocular blood flow at very high altitudes.

Little is known about the ocular and cerebral blood flow during exposure to increasingly hypoxic conditions at high altitudes. There is evidence that an increase in cerebral blood flow resulting from altered autoregulation constitutes a risk factor for acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) by leading to capillary overperfusion and vasogenic cerebral edema. The retina represents the only part of the central nervous system where capillary blood flow is visible and can be measured by noninvasive means. In this study we aimed to gain insights into retinal and choroidal autoregulatory properties during hypoxia and to correlate circulatory changes to symptoms of AMS and clinical signs of HACE. This observational study was performed within the scope of a high-altitude medical research expedition to Mount Muztagh Ata (7,546 m). Twenty seven participants underwent general and ophthalmic examinations up to a maximal height of 6,800 m. Examinations included fundus photography and measurements of retinal and choroidal blood flow, as well as measurement of arterial oxygen saturation and hematocrit. The initial increase in retinal blood velocity was followed by a decrease despite further ascent, whereas choroidal flow increase occurred later, at even higher altitudes. The sum of all adaptational mechanisms resulted in a stable oxygen delivery to the retina and the choroid. Parameters reflecting the retinal circulation and optic disc swelling correlated well with the occurrence of AMS-related symptoms. We demonstrate that sojourns at high altitudes trigger distinct behavior of retinal and choroidal blood flow. Increase in retinal but not in choroidal blood flow correlated with the occurrence of AMS-related symptoms.

Patterns in the longitudinal oropharyngeal microbiome evolution related to ventilator-associated pneumonia.

Background: The aim of the study was to evaluate the composition and the temporal evolution of the oropharyngeal microbiome in antibiotic-naïve patients requiring mechanical ventilation and to gain new insights into the pathogenesis of ventilator-associated pneumonia (VAP). Methods: Prospective, observational single-center nested case-control study. Patients with acute critical illness and anticipated duration of mechanical ventilation > 4 days were eligible. We took oropharyngeal swabs (and if available, tracheal secretions) daily, starting at the day of intubation. The microbiota was characterized by 16S rRNA high-throughput sequencing and compared between patients developing VAP versus controls. Results: Five patients developed VAP. In three patient the causative pathogens were Enterobacteriaceae and in two Haemophilus influenzae. Locally weighted polynomial regression suggested that the within diversity (=alpha) was lower in Enterobacteriaceae VAP patients between days two to five of mechanical ventilation when compared to controls. Detection of Enterobacteriaceae in the oropharynx occurred on day two of follow-up and consisted of a single operational taxonomic unit in 2/3 patients with enterobacterial VAP. Conclusions: In acutely-ill patients who developed enterobacterial VAP the causative pathogen gained access to the oropharynx early after starting mechanical ventilation and outgrew the commensal members of the microbiome. Whether a specific pattern of the oropharyngeal microbiome between days three to five of mechanical ventilation may predict VAP enterobacterial VAP has to be evaluated in further studies.