Background
Patients with COVID-19 present with a variety of clinical manifestations, ranging from mild or asymptomatic disease to severe illness and death. Whilst previous studies have clarified ...these and several other aspects of COVID-19, one of the ongoing challenges regarding COVID-19 is to determine which patients are at risk of adverse outcomes of COVID-19 infection. It is hypothesized that this is the result of insufficient inhibition of the immune response, with the vagus nerve being an important neuro-immuno-modulator of inflammation. Vagus nerve activity can be non-invasively indexed by heart-rate-variability (HRV). Therefore, we aimed to assess the prognostic value of HRV, as a surrogate marker for vagus nerve activity, in predicting mortality and intensive care unit (ICU) referral, in patients hospitalized with COVID-19.
Methods
A retrospective cohort study including all consecutive patients (n = 271) diagnosed and hospitalized with COVID-19 between March 2020 and May 2020, without a history of cardiac arrhythmias (including atrial and ventricular premature contractions), pacemaker, or current bradycardia (heart rate <50 bpm) or tachycardia (heart rate >110 bpm). HRV was based on one 10s ECG recorded at admission. 3-week survival and ICU referral were examined.
Results
HRV indexed as standard deviation of normal to normal heartbeat intervals (SDNN) predicted survival (H.R. = 0.53 95%CI: 0.31–0.92). This protective role was observed only in patients aged 70 years and older, not in younger patients. HRV below median value also predicted ICU referral within the first week of hospitalization (H.R = 0.51, 95%CI: 0.29–0.90, P = 0.021).
Conclusion
Higher HRV predicts greater chances of survival, especially in patients aged 70 years and older with COVID-19, independent of major prognostic factors. Low HRV predicts ICU indication and admission in the first week after hospitalization.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Insufficient antimicrobial exposure has been associated with worse clinical outcomes. Reportedly, flucloxacillin target attainment in critically ill patients was heterogeneous considering the study ...population selection and reported target attainment percentages. Therefore, we assessed flucloxacillin population pharmacokinetics (PK) and target attainment in critically ill patients.
This prospective, multicenter, observational study was conducted from May 2017 to October 2019 and included adult, critically ill patients administered flucloxacillin intravenously. Patients with renal replacement therapy or liver cirrhosis were excluded. We developed and qualified an integrated PK model for total and unbound serum flucloxacillin concentrations. Monte Carlo dosing simulations were performed to assess target attainment. The unbound target serum concentration was four times the minimum inhibitory concentration (MIC) for ≥ 50% of the dosing interval (ƒT
≥ 50%).
We analyzed 163 blood samples from 31 patients. A one-compartment model with linear plasma protein binding was selected as most appropriate. Dosing simulations revealed 26% ƒT
≥ 50% following continuous infusion of 12 g flucloxacillin and 51% ƒT
≥ 50% for 24 g.
Based on our dosing simulations, standard flucloxacillin daily doses of up to 12 g may substantially enhance the risk of underdosing in critically ill patients. Prospective validation of these model predictions is needed.
Objective
To provide evidence that early electroencephalography (EEG) allows for reliable prediction of poor or good outcome after cardiac arrest.
Methods
In a 5‐center prospective cohort study, we ...included consecutive, comatose survivors of cardiac arrest. Continuous EEG recordings were started as soon as possible and continued up to 5 days. Five‐minute EEG epochs were assessed by 2 reviewers, independently, at 8 predefined time points from 6 hours to 5 days after cardiac arrest, blinded for patients’ actual condition, treatment, and outcome. EEG patterns were categorized as generalized suppression (<10 μV), synchronous patterns with ≥50% suppression, continuous, or other. Outcome at 6 months was categorized as good (Cerebral Performance Category CPC = 1–2) or poor (CPC = 3–5).
Results
We included 850 patients, of whom 46% had a good outcome. Generalized suppression and synchronous patterns with ≥50% suppression predicted poor outcome without false positives at ≥6 hours after cardiac arrest. Their summed sensitivity was 0.47 (95% confidence interval CI = 0.42–0.51) at 12 hours and 0.30 (95% CI = 0.26–0.33) at 24 hours after cardiac arrest, with specificity of 1.00 (95% CI = 0.99–1.00) at both time points. At 36 hours or later, sensitivity for poor outcome was ≤0.22. Continuous EEG patterns at 12 hours predicted good outcome, with sensitivity of 0.50 (95% CI = 0.46–0.55) and specificity of 0.91 (95% CI = 0.88–0.93); at 24 hours or later, specificity for the prediction of good outcome was <0.90.
Interpretation
EEG allows for reliable prediction of poor outcome after cardiac arrest, with maximum sensitivity in the first 24 hours. Continuous EEG patterns at 12 hours after cardiac arrest are associated with good recovery. ANN NEUROL 2019;86:203–214
To assess neurological outcome after targeted temperature management (TTM) at 33 °C vs. 36 °C, stratified by the severity of encephalopathy based on EEG-patterns at 12 and 24 h.
Post hoc analysis of ...prospective cohort study.
Five Dutch Intensive Care units.
479 adult comatose post-cardiac arrest patients.
TTM at 33 °C (n = 270) or 36 °C (n = 209) and continuous EEG monitoring.
Outcome according to the cerebral performance category (CPC) score at 6 months post-cardiac arrest was similar after 33 °C and 36 °C. However, when stratified by the severity of encephalopathy based on EEG-patterns at 12 and 24 h after cardiac arrest, the proportion of good outcome (CPC 1–2) in patients with moderate encephalopathy was significantly larger after TTM at 33 °C (66% vs. 45%; Odds Ratios 2.38, 95% CI = 1.32–4.30; p = 0.004). In contrast, with mild encephalopathy, there was no statistically significant difference in the proportion of patients with good outcome between 33 °C and 36 °C (88% vs. 81%; OR 1.68, 95% CI = 0.65–4.38; p = 0.282). Ordinal regression analysis showed a shift towards higher CPC scores when treated with TTM 33 °C as compared with 36 °C in moderate encephalopathy (cOR 2.39; 95% CI = 1.40–4.08; p = 0.001), but not in mild encephalopathy (cOR 0.81 95% CI = 0.41–1.59; p = 0.537). Adjustment for initial cardiac rhythm and cause of arrest did not change this relationship.
Effects of TTM probably depend on the severity of encephalopathy in comatose patients after cardiac arrest. These results support inclusion of predefined subgroup analyses based on EEG measures of the severity of encephalopathy in future clinical trials.
Recent studies suggest that volatile anaesthetics are safe, efficient, and reliable alternatives to the use of intravenous anaesthetics for out-of-hospital cardiac arrest (OHCA) patients admitted to ...the intensive care unit (ICU). We hypothesised that volatile anaesthetics may reduce the incidence of delirium rather than intravenous sedatives. This retrospective study aimed to investigate whether sevoflurane combined with higher targeted temperature management could decrease the incidence of delirium when compared with intravenous anaesthetics with lower targeted temperature management.
Using a propensity score-matched analysis, we retrospectively compared a target temperature management (32−34 °C) method along with intravenous sedation (TTM-33/IV) and a modified target temperature management (34−36 °C) method along with sevoflurane sedation (mTTM-36/sevo). We used the confusion assessment method for the ICU to measure the incidence of delirium. We calculated the time-dependent risk on delirium using the multivariate Cox regression model.
The incidence of delirium was significantly lower (p = 0.001) in OHCA patients of the mTTM-36/sevo group (9/56, 16.1%) than in those of the TTM-33/IV group (25/67, 37.3%). Mechanical ventilation and lengths of stay in the ICU (p < 0.001) and hospital stay (p = 0.04) were shorter in the mTTM-36/sevo group. Patients in the TTM-33/IV group required more midazolam, propofol, and fentanyl. We observed no significant difference in mortality.
A multimodal sevoflurane-based sedation regimen together with targeted temperature management resulted in a lower incidence of delirium and a shorter duration for mechanical ventilation and ICU length of stay than did the treatment with intravenous sedation combined with the classical cooling protocol.
IMPORTANCE: Out-of-hospital cardiac arrest survival rates have markedly risen in the last decades, but neurological outcome only improved marginally. Despite research on more than 20 neuroprotective ...strategies involving patients in comas after cardiac arrest, none have demonstrated unequivocal evidence of efficacy; however, treatment with acyl-ghrelin has shown improved functional and histological brain recovery in experimental models of cardiac arrest and was safe in a wide variety of human study populations. OBJECTIVE: To determine safety and potential efficacy of intravenous acyl-ghrelin to improve neurological outcome in patients in a coma after cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS: A phase 2, double-blind, placebo-controlled, multicenter, randomized clinical trial, Ghrelin Treatment of Comatose Patients After Cardiac Arrest: A Clinical Trial to Promote Cerebral Recovery (GRECO), was conducted between January 18, 2019, and October 17, 2022. Adult patients 18 years or older who were in a comatose state after cardiac arrest were assessed for eligibility; patients were from 3 intensive care units in the Netherlands. Expected death within 48 hours or unfeasibility of treatment initiation within 12 hours were exclusion criteria. INTERVENTIONS: Patients were randomized to receive intravenous acyl-ghrelin, 600 μg (intervention group), or placebo (control group) within 12 hours after cardiac arrest, continued for 7 days, twice daily, in addition to standard care. MAIN OUTCOMES AND MEASURES: Primary outcome was the score on the Cerebral Performance Categories (CPC) scale at 6 months. Safety outcomes included any serious adverse events. Secondary outcomes were mortality and neuron-specific enolase (NSE) levels on days 1 and 3. RESULTS: A total of 783 adult patients in a coma after cardiac arrest were assessed for eligibility, and 160 patients (median IQR age, 68 57-75 years; 120 male 75%) were enrolled. A total of 81 patients (51%) were assigned to the intervention group, and 79 (49%) were assigned to the control group. The common odds ratio (OR) for any CPC improvement in the intervention group was 1.78 (95% CI, 0.98-3.22; P = .06). This was consistent over all CPC categories. Mean (SD) NSE levels on day 1 after cardiac arrest were significantly lower in the intervention group (34 6 μg/L vs 56 13 μg/L; P = .04) and on day 3 (28 6 μg/L vs 52 14 μg/L; P = .08). Serious adverse events were comparable in incidence and type between the groups. Mortality was 37% (30 of 81) in the intervention group vs 51% (40 of 79) in the control group (absolute risk reduction, 14%; 95% CI, −2% to 29%; P = .08). CONCLUSIONS AND RELEVANCE: In patients in a coma after cardiac arrest, intravenous treatment with acyl-ghrelin was safe and potentially effective to improve neurological outcome. Phase 3 trials are needed for conclusive evidence. TRIAL REGISTRATION: Clinicaltrialsregister.eu: EUCTR2018-000005-23-NL
Rhythmic and periodic patterns (RPPs) on the electroencephalogram (EEG) in comatose patients after cardiac arrest have been associated with high case fatality rates. A good neurological outcome ...according to the Cerebral Performance Categories (CPC) has been reported in up to 10% of cases. Data on cognitive, emotional, and quality of life outcomes are lacking. We aimed to provide insight into these outcomes at one-year follow-up.
We assessed outcome of surviving comatose patients after cardiac arrest with RPPs included in the ‘treatment of electroencephalographic status epilepticus after cardiopulmonary resuscitation’ (TELSTAR) trial at one-year follow-up, including the CPC for functional neurological outcome, a cognitive assessment, the hospital anxiety and depression scale (HADS) for emotional outcomes, and the 36-item short-form health survey (SF-36) for quality of life. Cognitive impairment was defined as a score of more than 1.5 SD below the mean on ≥ 2 (sub)tests within a cognitive domain.
Fourteen patients were included (median age 58 years, 21% female), of whom 13 had a cognitive impairment. Eleven of 14 were impaired in memory, 9/14 in executive functioning, and 7/14 in attention. The median scores on the HADS and SF-36 were all worse than expected. Based on the CPC alone, 8/14 had a good outcome (CPC 1–2).
Nearly all cardiac arrest survivors with RPPs during the comatose state have cognitive impairments at one-year follow-up. The incidence of anxiety and depression symptoms seem relatively high and quality of life relatively poor, despite ‘good’ outcomes according to the CPC.
Background
To compare three computer-assisted quantitative electroencephalography (EEG) prediction models for the outcome prediction of comatose patients after cardiac arrest regarding predictive ...performance and robustness to artifacts.
Methods
A total of 871 continuous EEGs recorded up to 3 days after cardiac arrest in intensive care units of five teaching hospitals in the Netherlands were retrospectively analyzed. Outcome at 6 months was dichotomized as “good” (Cerebral Performance Category 1–2) or “poor” (Cerebral Performance Category 3–5). Three prediction models were implemented: a logistic regression model using two quantitative features, a random forest model with nine features, and a deep learning model based on a convolutional neural network. Data from two centers were used for training and fivefold cross-validation (
n
= 663), and data from three other centers were used for external validation (
n
= 208). Model output was the probability of good outcome. Predictive performances were evaluated by using receiver operating characteristic analysis and the calculation of predictive values. Robustness to artifacts was evaluated by using an artifact rejection algorithm, manually added noise, and randomly flattened channels in the EEG.
Results
The deep learning network showed the best overall predictive performance. On the external test set, poor outcome could be predicted by the deep learning network at 24 h with a sensitivity of 54% (95% confidence interval CI 44–64%) at a false positive rate (FPR) of 0% (95% CI 0–2%), significantly higher than the logistic regression (sensitivity 33%, FPR 0%) and random forest models (sensitivity 13%, FPR, 0%) (
p
< 0.05). Good outcome at 12 h could be predicted by the deep learning network with a sensitivity of 78% (95% CI 52–100%) at a FPR of 12% (95% CI 0–24%) and by the logistic regression model with a sensitivity of 83% (95% CI 83–83%) at a FPR of 3% (95% CI 3–3%), both significantly higher than the random forest model (sensitivity 1%, FPR 0%) (
p
< 0.05). The results of the deep learning network were the least affected by the presence of artifacts, added white noise, and flat EEG channels.
Conclusions
A deep learning model outperformed logistic regression and random forest models for reliable, robust, EEG-based outcome prediction of comatose patients after cardiac arrest.
There is a lack of rapid, non-invasive tools that aid early prognostication in patients with return of spontaneous circulation (ROSC) after Out-of-Hospital Cardiac Arrest (OHCA). The shock index (SI) ...and modified shock index (MSI) have shown to be useful in several medical conditions, including myocardial infarction. In this study, we assessed the prognostic value of SI and MSI at Emergency Department (ED) triage on survival to discharge of OHCA patients.
A single-center retrospective observational cohort study. All OHCA patients with a period of ROSC between 2014 and 2019 were included. Data collection was based on the Utstein criteria. The SI and MSI at ED triage were calculated by dividing heart rate by systolic blood pressure or mean arterial pressure. Survival rates were compared between patients with a high and low SI and MSI. Subsequent Cox regression analysis was performed.
A total of 403 patients were included, of which 46% survived until hospital discharge. An elevated SI and MSI was defined by SI ≥ 1.00 and MSI ≥ 1.30. Survival to discharge, 30-day- and one-year survival were significantly lower in patients with an elevated SI and MSI (p < 0.001). An elevated SI and MSI was also associated with a higher rate of recurrent loss of circulation in the ED (p < 0.001). The 30-day survival hazard ratio was 2.24 (1.56–3.22) for SI and 2.46 (1.71–3.53) for MSI; the one-year survival hazard ratio was 2.20 (1.54–3.15) for SI and 2.38 (1.66–3.40) for MSI.
Survival to discharge and 30-day survival are lower in OHCA patients with an elevated SI and MSI at ED triage. Further studies are warranted to elucidate the causational mechanisms underlying the association between elevated SI or MSI and worse outcomes.
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