Additional predictive value of optic nerve sheath diameter for neurological prognosis after cardiac arrest: a prospective cohort study.

BACKGROUND: The goal is to estimate the additional value of ultrasonographic optic nerve sheath diameter (ONSD) measurement on days 1-3, on top of electroencephalography (EEG), pupillary light reflexes (PLR), and somatosensory evoked potentials (SSEP), for neurological outcome prediction of comatose cardiac arrest patients. We performed a prospective longitudinal cohort study in adult comatose patients after cardiac arrest. ONSD was measured on days 1-3 using ultrasound. Continuous EEG, PLR, and SSEP were acquired as standard care. Poor outcome was defined as cerebral performance categories 3-5 at 3-6 months. Logistic regression models were created for outcome prediction based on the established predictors with and without ONSD. Additional predictive value was assessed by increase in sensitivity for poor (at 100% specificity) and good outcome (at 90% specificity). RESULTS: We included 100 patients, 54 with poor outcome. Mean ONSD did not differ significantly between patients with good and poor outcome. Sensitivity for predicting poor outcome increased by adding ONSD to EEG and SSEP from 25% to 41% in all patients and from 27% to 50% after exclusion of patients with non-neurological death. CONCLUSIONS: ONSD on days 1-3 after cardiac arrest holds potential to add to neurological outcome prediction. TRIAL REGISTRATION: clinicaltrials.gov, NCT04084054. Registered 10 September 2019, https://www. CLINICALTRIALS: gov/study/NCT04084054 .

Comparing Continuous with Periodic Vital Sign Scoring for Clinical Deterioration Using a Patient Data Model.

To evaluate a minute-by-minute monitoring algorithm against a periodic early warning score (EWS) in detecting clinical deterioration and workload. Periodic EWSs suffer from large measurement intervals, causing late detection of deterioration. This might be prevented by continuous vital sign monitoring with a real-time algorithm such as the Visensia Safety Index (VSI). This prospective comparative data modeling cohort study (NCT04189653) compares continuous algorithmic alerts against periodic EWS in continuous monitored medical and surgical inpatients. We evaluated sensitivity, frequency, number of warnings needed to evaluate (NNE) and time of initial alert till escalation of care (EOC): Rapid Response Team activation, unplanned ICU admission, emergency surgery, or death. Also, the percentage of VSI alerting minutes was compared between patients with or without EOC. In 1529 admissions continuous VSI warned for 55% of EOC (95% CI: 45-64%) versus 51% (95% CI: 41-61%) by periodic EWS. NNE for VSI was 152 alerts per detected EOC (95% CI: 114-190) compared to 21 (95% CI: 17-28). It generated 0.99 warnings per day per patient compared to 0.13. Time from detection score till escalation was 8.3 hours (IQR: 2.6-24.8) with VSI versus 5.2 (IQR: 2.7-12.3) hours with EWS (P=0.074). The percentage of warning VSI minutes was higher in patients with EOC than in stable patients (2.36% vs 0.81%, P<0.001). Although sensitivity of detection was not significantly improved continuous vital sign monitoring shows potential for earlier alerts for deterioration compared to periodic EWS. A higher percentage of alerting minutes may indicate risk for deterioration.

The Effect of Continuous Versus Periodic Vital Sign Monitoring on Disease Severity of Patients with an Unplanned ICU Transfer.

Continuous vital sign monitoring (CM) may detect ward patient's deterioration earlier than periodic monitoring. This could result in timely ICU transfers or in a transfer delay due to misperceived higher level of care on the ward. The primary objective of this study was to compare patient's disease severity upon unplanned ICU transfer, before and after CM implementation. We included a one-year period before and after CM implementation between August 1, 2017 - July 31, 2019. Before implementation, surgical and internal medicine patients' vital signs were periodically monitored, compared to continuous monitoring with wireless linkage to hospital systems after implementation. In both periods the same early warning score (EWS) protocol was in place. Primary outcome was disease severity scores upon ICU transfer. Secondary outcomes were ICU and hospital length of stay, incidence of mechanical ventilation and ICU mortality. In the two one-year periods 93 and 59 unplanned ICU transfer episodes were included, respectively. Median SOFA (3 (2-6) vs 4 (2-7), p = .574), APACHE II (17 (14-20) vs 16 (14-21), p = .824) and APACHE IV (59 (46-67) vs 50 (36-65), p = .187) were comparable between both periods, as were the median ICU LOS (3.0 (1.7-5.8) vs 3.1 (1.6-6.1), p.962), hospital LOS (23.6 (11.5-38.0) vs 19 (13.9-39.2), p = .880), incidence of mechanical ventilation (28 (47%) vs 22 (54%), p.490), and ICU mortality (11 (13%) vs 10 (19%), p.420). This study shows no difference in disease severity upon unplanned ICU transfer after CM implementation for patients who have deteriorated on the ward.

Detecting Patient Deterioration Early Using Continuous Heart rate and Respiratory rate Measurements in Hospitalized COVID-19 Patients.

BACKGROUND: Presenting symptoms of COVID-19 patients are unusual compared with many other illnesses. Blood pressure, heart rate, and respiratory rate may stay within acceptable ranges as the disease progresses. Consequently, intermittent monitoring does not detect deterioration as it is happening. We investigated whether continuously monitoring heart rate and respiratory rate enables earlier detection of deterioration compared with intermittent monitoring, or introduces any risks. METHODS: When available, patients admitted to a COVID-19 ward received a wireless wearable sensor which continuously measured heart rate and respiratory rate. Two intensive care unit (ICU) physicians independently assessed sensor data, indicating when an intervention might be necessary (alarms). A third ICU physician independently extracted clinical events from the electronic medical record (EMR events). The primary outcome was the number of true alarms. Secondary outcomes included the time difference between true alarms and EMR events, interrater agreement for the alarms, and severity of EMR events that were not detected. RESULTS: In clinical practice, 48 (EMR) events occurred. None of the 4 ICU admissions were detected with the sensor. Of the 62 sensor events, 13 were true alarms (also EMR events). Of these, two were related to rapid response team calls. The true alarms were detected 39 min (SD = 113) before EMR events, on average. Interrater agreement was 10%. Severity of the 38 non-detected events was similar to the severity of 10 detected events. CONCLUSION: Continuously monitoring heart rate and respiratory rate does not reliably detect deterioration in COVID-19 patients when assessed by ICU physicians.

Effect of continuous wireless vital sign monitoring on unplanned ICU admissions and rapid response team calls: a before-and-after study.

BACKGROUND: Continuous vital sign monitoring may potentially be improved through the use of wearable monitors linked wirelessly to hospital electronic patient records. By improving early detection of physiological deterioration this approach may save lives. METHODS: We performed a single-centre before-and-after study including surgical and medical patients at a university hospital in The Netherlands. The study intervention was continuous vital sign monitoring using wearable monitors linked wirelessly to hospital systems. The co-primary outcomes were unplanned ICU admission and rapid response team calls. Secondary outcomes were length of hospital stay and in-patient death. RESULTS: Our baseline cohort included 2466 admissions and our intervention cohort included 2303 admissions recruited from August 2017 to July 2019. Patients in the intervention cohort experienced fewer unplanned ICU admissions (84 [3.4%] vs 54 [2.3%]; P=0.03) and fewer rapid response team calls (107 [4.3%] vs 71 [3.1%]; P=0.02). The number of rapid response team calls that did not result in ICU admission also declined (70 [2.8%] vs 45 [2.0%]; P=0.05). The number of rapid response team calls that did result in ICU admission was not significantly different (52 [2.1%] vs 36 [1.6%]; P=0.16). There were no differences in hospital stay or in-patient deaths between the two study periods. CONCLUSIONS: Continuous monitoring of patient vital signs using wearable monitoring technology linked wirelessly to hospital systems was associated with a reduction in unplanned ICU admissions and rapid response team calls. Further research is necessary to confirm the impact of this approach on patient survival.

Algorithms for Prediction of Clinical Deterioration on the General Wards: A Scoping Review.

OBJECTIVE: The primary objective of this scoping review was to identify and describe state-of-the-art models that use vital sign monitoring to predict clinical deterioration on the general ward. The secondary objective was to identify facilitators, barriers, and effects of implementing these models. DATA SOURCES: PubMed, Embase, and CINAHL databases until November 2020. STUDY SELECTION: We selected studies that compared vital signs-based automated real-time predictive algorithms to current track-and-trace protocols in regard to the outcome of clinical deterioration in a general ward population. DATA EXTRACTION: Study characteristics, predictive characteristics and barriers, facilitators, and effects. RESULTS: We identified 1741 publications, 21 of which were included in our review. Two of the these were clinical trials, 2 were prospective observational studies, and the remaining 17 were retrospective studies. All of the studies focused on hospitalized adult patients. The reported area under the receiver operating characteristic curves ranged between 0.65 and 0.95 for the outcome of clinical deterioration. Positive predictive value and sensitivity ranged between 0.223 and 0.773 and from 7.2% to 84.0%, respectively. Input variables differed widely, and predicted endpoints were inconsistently defined. We identified 57 facilitators and 48 barriers to the implementation of these models. We found 68 reported effects, 57 of which were positive. CONCLUSION: Predictive algorithms can detect clinical deterioration on the general ward earlier and more accurately than conventional protocols, which in one recent study led to lower mortality. Consensus is needed on input variables, predictive time horizons, and definitions of endpoints to better facilitate comparative research.

Safety, tolerability and pharmacokinetics/pharmacodynamics of the adrenomedullin antibody adrecizumab in a first-in-human study and during experimental human endotoxaemia in healthy subjects.

AIMS: Adrenomedullin (ADM) is an important regulator of endothelial barrier function and vascular tone, and may represent a novel treatment target in sepsis. The non-neutralizing ADM antibody adrecizumab has shown promising results in preclinical sepsis models. In the present study, we investigated the safety, tolerability and pharmacokinetics (PK)/pharmacodynamics of adrecizumab in a first-in-man study and in a second study during experimental human endotoxaemia. METHODS: Forty-eight healthy male volunteers were enrolled in two randomized, double-blind, placebo-controlled phase I studies. In both studies, subjects received placebo or one of three doses of adrecizumab (n = 6 per group). In the second study, a bolus of 1 ng kg-1 endotoxin was followed by infusion of 1 ng kg-1 h-1 endotoxin for 3 h to induce systemic inflammation, and the study medication infusion started 1 h after endotoxin bolus administration. RESULTS: Adrecizumab showed an excellent safety profile in both studies. PK analyses showed proportional increases in the maximum plasma concentration of adrecizumab with increasing doses, a small volume of distribution, a low clearance rate and a terminal half-life of ~14 days. adrecizumab elicited a pronounced increase in plasma ADM levels, whereas levels of mid-regional pro-adrenomedullin remained unchanged, indicating that de novo synthesis of ADM was not influenced. In the second study, no effects of adrecizumab on cytokine clearance were observed, whereas endotoxin-induced flu-like symptoms resolved more rapidly. CONCLUSIONS: Administration of adrecizumab is safe and well tolerated in humans, both in the absence and presence of systemic inflammation. These findings pave the way for further investigation of adrecizumab in sepsis patients.