Increased time from physiological derangement to critical care admission associates with mortality.

BACKGROUND: Rapid response systems aim to achieve a timely response to the deteriorating patient; however, the existing literature varies on whether timing of escalation directly affects patient outcomes. Prior studies have been limited to using 'decision to admit' to critical care, or arrival in the emergency department as 'time zero', rather than the onset of physiological deterioration. The aim of this study is to establish if duration of abnormal physiology prior to critical care admission ['Score to Door' (STD) time] impacts on patient outcomes. METHODS: A retrospective cross-sectional analysis of data from pooled electronic medical records from a multi-site academic hospital was performed. All unplanned adult admissions to critical care from the ward with persistent physiological derangement [defined as sustained high National Early Warning Score (NEWS) > / = 7 that did not decrease below 5] were eligible for inclusion. The primary outcome was critical care mortality. Secondary outcomes were length of critical care admission and hospital mortality. The impact of STD time was adjusted for patient factors (demographics, sickness severity, frailty, and co-morbidity) and logistic factors (timing of high NEWS, and out of hours status) utilising logistic and linear regression models. RESULTS: Six hundred and thirty-two patients were included over the 4-year study period, 16.3% died in critical care. STD time demonstrated a small but significant association with critical care mortality [adjusted odds ratio of 1.02 (95% CI 1.0-1.04, p = 0.01)]. It was also associated with hospital mortality (adjusted OR 1.02, 95% CI 1.0-1.04, p = 0.026), and critical care length of stay. Each hour from onset of physiological derangement increased critical care length of stay by 1.2%. STD time was influenced by the initial NEWS, but not by logistic factors such as out-of-hours status, or pre-existing patient factors such as co-morbidity or frailty. CONCLUSION: In a strictly defined population of high NEWS patients, the time from onset of sustained physiological derangement to critical care admission was associated with increased critical care and hospital mortality. If corroborated in further studies, this cohort definition could be utilised alongside the 'Score to Door' concept as a clinical indicator within rapid response systems.

The ROX index has greater predictive validity than NEWS2 for deterioration in Covid-19.

BACKGROUND: Patients admitted to hospital with Covid-19 are at risk of deterioration. The National Early Warning Score (NEWS2) is widely recommended, however it's validity in Covid-19 is not established and indices more specific for respiratory failure may be more appropriate. We aim to describe the physiological antecedents to deterioration, test the predictive validity of NEWS2 and compare this to the ROX index ([SpO2/FiO2]/respiratory rate). METHOD: A single centre retrospective cohort study of adult patients who were admitted to a medical ward, between 1/3/20 and 30/5/20, with positive results for SARS-CoV-2 RNA. Physiological observations and the NEWS2 were extracted and analysed. The primary outcome was a composite of cardiac arrest, unplanned critical care admission or death within 24 hours. A generalized linear model was used to assess the association of physiological values, NEWS2 and ROX with the outcome. FINDINGS: The primary outcome occurred in 186 patients (26%). In the preceding 24 hours, deterioration was most marked in respiratory parameters, specifically in escalating oxygen requirement; tachypnoea was a late sign, whilst cardiovascular observations remained stable. The area under the receiver operating curve was 0.815 (95% CI 0.804-0.826) for NEWS2 and 0.848 (95% CI 0.837-0.858) for ROX. Applying the optimal level of ROX, the majority of patients triggered four hours earlier than with NEWS2 of 5. INTERPRETATION: NEWS2 may under-perform in Covid-19 due to intrinsic limitations of the design and the unique pathophysiology of the disease. A simple index utilising respiratory parameters can outperform NEWS2 in predicting the occurrence of adverse events.

Veno-venous extracorporeal membrane oxygenation in coronavirus disease 2019: a case series.

BACKGROUND: The use of veno-venous extracorporeal membrane oxygenation (VV-ECMO) in severe hypoxaemic respiratory failure from coronavirus disease 2019 (COVID-19) has been described, but reported utilisation and outcomes are variable, and detailed information on patient characteristics is lacking. We aim to report clinical characteristics, management and outcomes of COVID-19 patients requiring VV-ECMO, admitted over 2 months to a high-volume centre in the UK. METHODS: Patient information, including baseline characteristics and clinical parameters, was collected retrospectively from electronic health records for COVID-19 VV-ECMO admissions between 3 March and 2 May 2020. Clinical management is described. Data are reported for survivors and nonsurvivors. RESULTS: We describe 43 consecutive patients with COVID-19 who received VV-ECMO. Median age was 46 years (interquartile range 35.5-52.5) and 76.7% were male. Median time from symptom onset to VV-ECMO was 14 days (interquartile range 11-17.5). All patients underwent computed tomography imaging, revealing extensive pulmonary consolidation in 95.3%, and pulmonary embolus in 27.9%. Overall, 79.1% received immunomodulation with methylprednisolone for persistent maladaptive hyperinflammatory state. Vasopressors were used in 86%, and 44.2% received renal replacement therapy. Median duration on VV-ECMO was 13 days (interquartile range 8-20). 14 patients died (32.6%) and 29 survived (67.4%) to hospital discharge. Nonsurvivors had significantly higher d-dimer (38.2 versus 9.5 mg·L-1, fibrinogen equivalent units; p=0.035) and creatinine (169 versus 73 µmol·L-1; p=0.022) at commencement of VV-ECMO. CONCLUSIONS: Our data support the use of VV-ECMO in selected COVID-19 patients. The cohort was characterised by high degree of alveolar consolidation, systemic inflammation and intravascular thrombosis.

Lung Recruitability in Severe Acute Respiratory Distress Syndrome Requiring Extracorporeal Membrane Oxygenation.

OBJECTIVES: Quantification of potential for lung recruitment may guide the ventilatory strategy in acute respiratory distress syndrome. However, there are no quantitative data on recruitability in patients with severe acute respiratory distress syndrome who require extracorporeal membrane oxygenation. We sought to quantify potential for lung recruitment and its relationship with outcomes in this cohort of patients. DESIGN: A single-center, retrospective, observational cohort study. SETTING: Tertiary referral severe respiratory failure center in a university hospital in the United Kingdom. PATIENTS: Forty-seven adults with severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: In patients with severe acute respiratory distress syndrome-mainly of pulmonary origin (86%)-the potential for lung recruitment and the weight of nonaerated, poorly aerated, normally aerated, and hyperaerated lung tissue were assessed at low (5 cmH2O) and high (45 cmH2O) airway pressures. Patients were categorized as high or low potential for lung recruitment based on the median potential for lung recruitment value of the study population. The median potential for lung recruitment was 24.3% (interquartile range = 11.4-37%) ranging from -2% to 76.3% of the total lung weight. Patients with potential for lung recruitment above the median had significantly shorter extracorporeal membrane oxygenation duration (8 vs 13 d; p = 0.013) and shorter ICU stay (15 vs 22 d; p = 0.028), but mortality was not statistically different (24% vs 46%; p = 0.159). CONCLUSIONS: We observed significant variability in potential for lung recruitment in patients with severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation. Patients with high potential for lung recruitment had a shorter ICU stay and shorter extracorporeal membrane oxygenation duration.

Severe Respiratory Failure, Extracorporeal Membrane Oxygenation, and Intracranial Hemorrhage.

OBJECTIVES: For patients supported with veno-venous extracorporeal membrane oxygenation, the occurrence of intracranial hemorrhage is associated with a high mortality. It is unclear whether intracranial hemorrhage is a consequence of the extracorporeal intervention or of the underlying severe respiratory pathology. In a cohort of patients transferred to a regional severe respiratory failure center that routinely employs admission brain imaging, we sought 1) the prevalence of intracranial hemorrhage; 2) survival and neurologic outcomes; and 3) factors associated with intracranial hemorrhage. DESIGN: A single-center, retrospective, observational cohort study. SETTING: Tertiary referral severe respiratory failure center, university teaching hospital. PATIENTS: Patients admitted between December 2011 and February 2016. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Three hundred forty-two patients were identified: 250 managed with extracorporeal support and 92 managed using conventional ventilation. The prevalence of intracranial hemorrhage was 16.4% in extracorporeal membrane oxygenation patients and 7.6% in conventionally managed patients (p = 0.04). Multivariate analysis revealed factors independently associated with intracranial hemorrhage to be duration of ventilation (d) (odds ratio, 1.13 [95% CI, 1.03-1.23]; p = 0.011) and admission fibrinogen (g/L) (odds ratio, 0.73 [0.57-0.91]; p = 0.009); extracorporeal membrane oxygenation was not an independent risk factor (odds ratio, 3.29 [0.96-15.99]; p = 0.088). In patients who received veno-venous extracorporeal membrane oxygenation, there was no significant difference in 6-month survival between patients with and without intracranial hemorrhage (68.3% vs 76.0%; p = 0.350). Good neurologic function was observed in 92%. CONCLUSIONS: We report a higher prevalence of intracranial hemorrhage than has previously been described with high level of neurologically intact survival. Duration of mechanical ventilation and admission fibrinogen, but not exposure to extracorporeal support, are independently associated with intracranial hemorrhage.

Intravascular versus surface cooling for targeted temperature management after out-of-hospital cardiac arrest - an analysis of the TTM trial data.

BACKGROUND: Targeted temperature management is recommended after out-of-hospital cardiac arrest and may be achieved using a variety of cooling devices. This study was conducted to explore the performance and outcomes for intravascular versus surface devices for targeted temperature management after out-of-hospital cardiac arrest. METHOD: A retrospective analysis of data from the Targeted Temperature Management trial. N = 934. A total of 240 patients (26%) managed with intravascular versus 694 (74%) with surface devices. Devices were assessed for speed and precision during the induction, maintenance and rewarming phases in addition to adverse events. All-cause mortality, as well as a composite of poor neurological function or death, as evaluated by the Cerebral Performance Category and modified Rankin scale were analysed. RESULTS: For patients managed at 33 °C there was no difference between intravascular and surface groups in the median time taken to achieve target temperature (210 [interquartile range (IQR) 180] minutes vs. 240 [IQR 180] minutes, p = 0.58), maximum rate of cooling (1.0 [0.7] vs. 1.0 [0.9] °C/hr, p = 0.44), the number of patients who reached target temperature (within 4 hours (65% vs. 60%, p = 0.30); or ever (100% vs. 97%, p = 0.47), or episodes of overcooling (8% vs. 34%, p = 0.15). In the maintenance phase, cumulative temperature deviation (median 3.2 [IQR 5.0] °C hr vs. 9.3 [IQR 8.0] °C hr, p = <0.001), number of patients ever out of range (57.0% vs. 91.5%, p = 0.006) and median time out of range (1 [IQR 4.0] hours vs. 8.0 [IQR 9.0] hours, p = <0.001) were all significantly greater in the surface group although there was no difference in the occurrence of pyrexia. Adverse events were not different between intravascular and surface groups. There was no statistically significant difference in mortality (intravascular 46.3% vs. surface 50.0%; p = 0.32), Cerebral Performance Category scale 3-5 (49.0% vs. 54.3%; p = 0.18) or modified Rankin scale 4-6 (49.0% vs. 53.0%; p = 0.48). CONCLUSIONS: Intravascular and surface cooling was equally effective during induction of mild hypothermia. However, surface cooling was associated with less precision during the maintenance phase. There was no difference in adverse events, mortality or poor neurological outcomes between patients treated with intravascular and surface cooling devices. TRIAL REGISTRATION: TTM trial ClinicalTrials.gov number https://clinicaltrials.gov/ct2/show/NCT01020916 NCT01020916; 25 November 2009.

Scoring systems for the characterization of sepsis and associated outcomes.

Sepsis is responsible for the utilisation of a significant proportion of healthcare resources and has high mortality rates. Early diagnosis and prompt interventions are associated with better outcomes but is impeded by a lack of diagnostic tools and the heterogeneous and enigmatic nature of sepsis. The recently updated definitions of sepsis have moved away from the centrality of inflammation and the systemic inflammatory response syndrome (SIRS) criteria which have been shown to be non-specific. Sepsis is now defined as a "life-threatening organ dysfunction caused by a dysregulated host response to infection". The Quick (q) Sequential (Sepsis-related) Organ Failure Assessment (SOFA) score is proposed as a surrogate for organ dysfunction and may act as a risk predictor for patients with known or suspected infection, as well as being a prompt for clinicians to consider the diagnosis of sepsis. Early warning scores (EWS) are track and trigger physiological monitoring systems that have become integrated within many healthcare systems for the detection of acutely deteriorating patients. The recent study by Churpek and colleagues sought to compare qSOFA to more established alerting criteria in a population of patients with presumed infection, and compared the ability to predict death or unplanned intensive care unit (ICU) admission. This perspective paper discusses recent advances in the diagnostic criteria for sepsis and how qSOFA may fit into the pre-existing models of acute care and sepsis quality improvement.