Lung function parameters are associated with acute mountain sickness and are improved at high and extreme altitude.

At altitude, factors such as decreased barometric pressure, low temperatures, and acclimatization might affect lung function. The effects of exposure and acclimatization to high-altitude on lung function were assessed in 39 subjects by repetitive spirometry up to 6022 m during a high-altitude expedition. Subjects were classified depending on the occurrence of acute mountain sickness (AMS) and summit success to evaluate whether lung function relates to successful climb and risk of developing AMS. Peak expiratory flow (PEF), forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) increased with progressive altitude (max. +20.2 %pred, +9.3 %pred, and +6.7 %pred, all p<0.05). Only PEF improved with acclimatization (BC1 vs. BC2, +7.2 %pred, p=0.044). At altitude FEV1 (p=0.008) and PEF (p<0.001) were lower in the AMS group. The risk of developing AMS was associated with lower baseline PEF (p<0.001) and longitudinal changes in PEF (p=0.008) and FEV1 (p<0.001). Lung function was not related to summit success (7126 m). Improvement in PEF after acclimatization might indicate respiratory muscle adaptation.

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.

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.

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.

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.

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.

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.

Eligibility criteria for extracorporeal cardiopulmonary resuscitation at Auckland City Hospital: A retrospective cohort study.

OBJECTIVE: Extracorporeal cardiopulmonary resuscitation (ECPR) is a promising adjunct to routine advanced cardiac life support. Growing worldwide interest in ECPR-use has seen more tertiary centres offering ECPR programmes. New Zealand's nationwide extracorporeal membranous oxygenation service is provided at Auckland City Hospital (ACH). Despite the potential benefits of ECPR, it is currently only offered on an ad hoc basis. It remains unknown whether ACH would manage sufficient numbers of patients to warrant an ECPR programme. METHODS: A 12-month retrospective cohort study of the medical records of patients who were managed for cardiac arrest in the resuscitation room of the ED was conducted. Patient characteristics and clinical outcomes were analysed descriptively and audited against a unique set of criteria for a hypothetical ECPR programme. RESULTS: Between 1 July 2018 and 30 June 2019, 286 patients died or had a cardiac arrest for which they were managed at ACH. Sixty-five of these patients had an in-hospital cardiac arrest in the ED. Seven (10.8%) of these patients were deemed eligible for hypothetical ECPR. Only one of these seven patients survived to hospital discharge with full neurological recovery. CONCLUSIONS: An ECPR programme at ACH using standardised and agreed criteria may benefit a small number of patients and improve rates of survival to hospital discharge with preservation of neurological function. An ECPR guideline would help clarify for referring services cases that are appropriate for extracorporeal membranous oxygenation consideration, rather than discussing on an ad hoc basis.

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 ).

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.

Emergence of AnnexinVpos CD31neg CD42blow/neg extracellular vesicles in plasma of humans at extreme altitude.

BACKGROUND: Hypobaric hypoxia has been reported to cause endothelial cell and platelet dysfunction implicated in the formation of microvascular lesions, and in its extremes may contribute to vascular leakage in high altitude pulmonary edema or blood brain barrier disruption leading to cerebral micro-hemorrhage (MH). Platelet function in the development of microvascular lesions remained ill defined, and is still incompletely understood. In this study platelet- and endothelial cell-derived extracellular vesicles (PEV and EEV, respectively) and cell adhesion molecules were characterized in plasma samples of members of a high altitude expedition to delineate the contribution of platelets and endothelial cells to hypobaric hypoxia-induced vascular dysfunction. METHODS AND FINDINGS: In this observational study, platelet and endothelial cell-derived extracellular vesicles were analysed by flow-cytometry in plasma samples from 39 mountaineers participating in a medical research climbing expedition to Himlung Himal, Nepal, 7,050m asl. Megakaryocyte/platelet-derived AnnexinVpos, PECAM-1 (CD31) and glycoprotein-1b (GP1b, CD42b) positive extracellular vesicles (PEV) constituted the predominant fraction of EV in plasma samples up to 6,050m asl. Exposure to an altitude of 7,050m led to a marked decline of CD31pos CD42neg EEV as well as of CD31pos CD42bpos PEV at the same time giving rise to a quantitatively prevailing CD31neg CD42blow/neg subpopulation of AnnexinVpos EV. An almost hundredfold increase in the numbers of this previously unrecognized population of CD31neg CD42blow/neg EV was observed in all participants reaching 7,050m asl. CONCLUSIONS: The emergence of CD31neg CD42blow/neg EV was observed in all participants and thus represents an early hypoxic marker at extreme altitude. Since CD31 and CD42b are required for platelet-endothelial cell interactions, these hypobaric hypoxia-dependent quantitative and phenotypic changes of AnnexinVpos EV subpopulations may serve as early and sensitive indicators of compromised vascular homeostasis.

Continual hemodynamic monitoring with a single-use transesophageal echocardiography probe in critically ill patients with shock: a randomized controlled clinical trial.

PURPOSE: Mortality in circulatory shock is high. Enhanced resolution of shock may improve outcomes. We aim to determine whether adding hemodynamic monitoring with continual transesophageal echocardiography (hTEE) to usual care accelerates resolution of hemodynamic instability. METHODS: 550 patients with circulatory shock were randomly assigned to four groups stratified using hTEE (hTEE vs usual care) and assessment frequency (minimum every 4 h vs 8 h). Primary outcome was time to resolution of hemodynamic instability, analyzed as intention-to-treat (ITT) analysis at day 6 and in a predefined secondary analysis at days 3 and 28. RESULTS: Of 550 randomized patients, 271 with hTEE and 274 patients with usual care were eligible and included in the ITT analysis. Time to resolution of hemodynamic instability did not differ within the first 6 days [hTEE vs usual care adjusted sub-hazard ratio (SHR) 1.20, 95% confidence interval (CI) 0.98-1.46, p = 0.067]. Time to resolution of hemodynamic instability during the 72 h of hTEE monitoring was shorter in patients with TEE (hTEE vs usual care SHR 1.26, 95% CI 1.02-1.55, p = 0.034). Assessment frequency had no influence. Time to resolution of clinical signs of hypoperfusion, duration of organ support, length of stay and mortality in the intensive care unit and hospital, and mortality at 28 days did not differ between groups. CONCLUSIONS: In critically ill patients with shock, hTEE monitoring or hemodynamic assessment frequency did not influence resolution of hemodynamic instability or mortality within the first 6 days. TRIAL REGISTRATION AND STATISTICAL ANALYSIS PLAN: ClinicalTrials.gov Identifier: NCT02048566.

Correction to: Continual hemodynamic monitoring with a single-use transesophageal echocardiography probe in critically ill patients with shock: a randomized controlled clinical trial.

The original version of this article unfortunately contained a mistake.

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.

Recruitment of non-perfused sublingual capillaries increases microcirculatory oxygen extraction capacity throughout ascent to 7126 m.

KEY POINTS: A physiological response to increase microcirculatory oxygen extraction capacity at high altitude is to recruit capillaries. In the present study, we report that high altitude-induced sublingual capillary recruitment is an intrinsic mechanism of the sublingual microcirculation that is independent of changes in cardiac output, arterial blood pressure or systemic vascular hindrance. Using a topical nitroglycerin challenge to the sublingual microcirculation, we show that high altitude-related capillary recruitment is a functional response of the sublingual microcirculation as opposed to an anatomical response associated with angiogenesis. The concurrent presence of a low capillary density and high microvascular reactivity to topical nitroglycerin at sea level was found to be associated with a failure to reach the summit, whereas the presence of a high baseline capillary density with the ability to further increase maximum recruitable capillary density upon ascent to an extreme altitude was associated with summit success. ABSTRACT: A high altitude (HA) stay is associated with an increase in sublingual capillary total vessel density (TVD), suggesting microvascular recruitment. We hypothesized that microvascular recruitment occurs independent of cardiac output changes, that it relies on haemodynamic changes within the microcirculation as opposed to structural changes and that microcirculatory function is related to individual performance at HA. In 41 healthy subjects, sublingual handheld vital microscopy and echocardiography were performed at sea level (SL), as well as at 6022 m (C2) and 7042 m (C3), during ascent to 7126 m within 21 days. Sublingual topical nitroglycerin was applied to measure microvascular reactivity and maximum recruitable TVD (TVDNG ). HA exposure decreased resting cardiac output, whereas TVD (mean ± SD) increased from 18.81 ± 3.92 to 20.92 ± 3.66 and 21.25 ± 2.27 mm mm-2 (P < 0.01). The difference between TVD and TVDNG was 2.28 ± 4.59 mm mm-2 at SL (P < 0.01) but remained undetectable at HA. Maximal TVDNG was observed at C3. Those who reached the summit (n = 15) demonstrated higher TVD at SL (P < 0.01), comparable to TVDNG in non-summiters (n = 21) at SL and in both groups at C2. Recruitment of sublingual capillary TVD to increase microcirculatory oxygen extraction capacity at HA was found to be an intrinsic mechanism of the microcirculation independent of cardiac output changes. Microvascular reactivity to topical nitroglycerin demonstrated that HA-related capillary recruitment is a functional response as opposed to a structural change. The performance of the vascular microcirculation needed to reach the summit was found to be associated with a higher TVD at SL and the ability to further increase TVDNG upon ascent to extreme altitude.

Correction to: Effects of hemodynamic monitoring using a single-use transesophageal echocardiography probe in critically ill patients - study protocol for a randomized controlled trial.

Following publication of the original article [1], the authors reported an error in the sample size calculation.

Short-term recovery pattern of plasma fibrinogen after cardiac surgery: A prospective observational study.

Low plasma fibrinogen level is common after cardiopulmonary bypass (CPB). Current substitution practice with fibrinogen concentrate generally follows a single measurement and cut-off values from the literature, whereas early postoperative endogenous fibrinogen kinetics is incompletely described and widely disregarded. The aim of this study was to determine the short-term recovery pattern of plasma fibrinogen after CPB weaning. Our hypothesis was that in the absence of surgical bleeding, CPB-induced hypofibrinogenemia would resolve spontaneously and predictably within a few hours. In a prospective, observational study of 26 patients undergoing conventional CPB (cCPB) or minimally invasive extracorporeal circulation (MiECC), Clauss fibrinogen level (C-FIB) was determined at 10 closely spaced time points after protamine administration. Primary endpoint was the time to recovery of post-CPB fibrinogen levels to ≥1.5 g/L. C-FIB reached its nadir after protamine administration corresponding to 62 ± 5% (mean ± SD) of the baseline level after cCPB and 68 ± 7% after MiECC (p = 0.027 vs. cCPB). C-FIB recovered spontaneously at a nearly constant rate of approximately 0.08 g/L per hour. In all patients, C-FIB was ≥1.5 g/L at 4 hours and ≥2.0 g/L at 13 hours after CPB weaning. Following cardiac surgery with CPB and in the absence of surgical bleeding, spontaneous recovery of normal endogenous fibrinogen levels can be expected at a rate of 0.08 g/L per hour. Administration of fibrinogen concentrate triggered solely by a single-point measurement of low plasma fibrinogen some time after CPB is not justified.

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.