Clinical and Physiologic Factors Associated With Mode of Death in Pediatric Severe TBI

Aims and Objectives: Severe traumatic brain injury (sTBI) is the leading cause of death in children. Our aim was to determine the mode of death for children who died with sTBI in a Pediatric Critical Care Unit (PCCU) and evaluate factors associated with mortality.Methods: We performed a retrospective cohort study of all severely injured trauma patients (Injury Severity Score ≥ 12) with sTBI (Glasgow Coma Scale [GCS] ≤ 8 and Maximum Abbreviated Injury Scale ≥ 4) admitted to a Canadian PCCU (2000–2016). We analyzed mode of death, clinical factors, interventions, lab values within 24 h of admission (early) and pre-death (48 h prior to death), and reviewed meeting notes in patients who died in the PCCU.Results: Of 195 included patients with sTBI, 55 (28%) died in the PCCU. Of these, 31 (56%) had a physiologic death (neurologic determination of death or cardiac arrest), while 24 (44%) had withdrawal of life-sustaining therapies (WLST). Median (IQR) times to death were 35.2 (11.8, 86.4) hours in the physiologic group and 79.5 (17.6, 231.3) hours in the WLST group (p = 0.08). The physiologic group had higher partial thromboplastin time (PTT) within 24 h of admission (p = 0.04) and lower albumin prior to death (p = 0.04).Conclusions: Almost half of sTBI deaths in the PCCU were by WLST. There was a trend toward a longer time to death in these patients. We found few early and late (pre-death) factors associated with mode of death, namely higher PTT and lower albumin.

Mode of Death in Patients With Heart Failure and Preserved Ejection Fraction: Insights From PARAGON-HF Trial

Background: Patients with heart failure (HF) and preserved left ventricular ejection fraction comprise a heterogeneous group including some with mildly reduced EF. We hypothesized that mode of death differs by EF in ambulatory patients with HF and preserved left ventricular ejection fraction. Methods: PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor With Angiotensin-Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction) compared clinical outcomes in 4796 patients with chronic HF and EF ≥45% randomly assigned to sacubitril/valsartan or valsartan. We examined the mode of death in relation to baseline EF in logistic regression models and the effect of randomized treatment on cause-specific death in Cox regression models. Nonlinear relationships with continuous EF were modelled using quadratic and cubic terms. Results: Of 691 deaths during the trial, 416 (60%) were ascribed to cardiovascular, 220 (32%) to noncardiovascular, and 55 (8%) to unknown causes. Of cardiovascular deaths, 154 (37%) were due to sudden death, 118 (28%) were due to HF, 35 (8%) to stroke, 27 (6%) to myocardial infarction, and 82 (20%) to other cardiovascular causes. Rates of all-cause, cardiovascular, and sudden death were higher in those with lower left ventricular ejection fraction (all P <0.001), while rates of non-cardiovascular death were greater in patients with higher EF. Sacubitril/valsartan did not reduce overall death, cardiovascular death, or sudden death compared with valsartan, irrespective of baseline EF (all P for interaction >0.30). Conclusions: Among patients with HF and preserved left ventricular ejection fraction enrolled in PARAGON-HF, the proportion of cardiovascular and sudden death were higher in those with lower left ventricular EF, and the proportion of noncardiovascular death rose with EF. Regardless of EF, sacubitril/valsartan did not reduce death from any cause compared with valsartan. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01920711.

Mode of Death after Extracorporeal Cardiopulmonary Resuscitation

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) might be a lifesaving therapy for patients with cardiac arrest and no return of spontaneous circulation during advanced life support. However, even with ECPR, mortality of these severely sick patients is high. Little is known on the exact mode of death in these patients. Methods: Retrospective registry analysis of all consecutive patients undergoing ECPR between May 2011 and May 2020 at a single center. Mode of death was judged by two researchers. Results: A total of 274 ECPR cases were included (age 60.0 years, 47.1% shockable initial rhythm, median time-to-extracorporeal membrane oxygenation (ECMO) 53.8min, hospital survival 25.9%). The 71 survivors had shorter time-to-ECMO durations (46.0 ± 27.9 vs. 56.6 ± 28.8min, p < 0.01), lower initial lactate levels (7.9 ± 4.5 vs. 11.6 ± 8.4 mg/dL, p < 0.01), higher PREDICT-6h (41.7 ± 17.0% vs. 25.3 ± 19.0%, p < 0.01), and SAVE (0.4 ± 4.8 vs. −0.8 ± 4.4, p < 0.01) scores. Most common mode of death in 203 deceased patients was therapy resistant shock in 105/203 (51.7%) and anoxic brain injury in 69/203 (34.0%). Comparing patients deceased with shock to those with cerebral damage, patients with shock were significantly older (63.2 ± 11.5 vs. 54.3 ± 16.5 years, p < 0.01), more frequently resuscitated in-hospital (64.4% vs. 29.9%, p < 0.01) and had shorter time-to-ECMO durations (52.3 ± 26.8 vs. 69.3 ± 29.1min p < 0.01). Conclusions: Most patients after ECPR decease due to refractory shock. Older patients with in-hospital cardiac arrest might be prone to development of refractory shock. Only a minority die from cerebral damage. Research should focus on preventing post-CPR shock and treating the shock in these patients.

Timing and mode of in-hospital death in a contemporary population with acute myocardial infarction

Funding Acknowledgements Type of funding sources: None. Background Although presenting features and early complications of acute myocardial infarction (AMI) are clear to the medical community, little is known about the timing and mode of in-hospital death. The purpose of this study is to characterize the timing and mode of in-hospital death following AMI. Methods We analysed in-hospital deaths among 4800 patients with AMI admitted in a single tertiary centre between 2006 and 2019. Baseline demographic and clinical characteristics, the type of AMI, treatments, the timing and mode of death data were collected. The mode of death, analysed by two independent clinicians in case of doubt, was classified as cardiovascular, which included cardiac and non-cardiac causes, or non-cardiovascular death. Results A total of 194 (4%) patients (pts) aged 76 [68-81] years and 61% males died during the hospital stay in the study period of 10 years. ST segment elevation AMI (STEMI) was the most frequent (70%), mostly of the anterior wall (2/3 of STEMI). Most (48%) of the 194 patients presented in Killip Kimball class IV (48%), and 16% presented in cardiorespiratory arrest. The majority (69%) had undergone myocardial revascularization during hospitalization. Most deaths occurred earlier (median 48 [5-240] hours). Overall, 40% patients died within 24 hours after admission, 12% died during the second day, 19% during days 3–7, 19% during days 8–30, and 10% after day 30 (Figure 1). Cardiovascular (82%) was the most common mode of death, mainly due to cardiac causes (76%) (Figure 2). Re-infarction and bleeding accounted for 3% and 5% of deaths, respectively. The median time delay to death is different according to mode of death (1,4 [0,1-4,9] days for CV death and 19 [7,8- 47,7] days for non-CV death, p = 0,001), whereas the timing and mode of death were similar in STEMI and non-STEMI. Conclusion In this contemporary single-centre population with AMI, the majority of in-hospital deaths occurred early after admission. The largest proportion of modes of death was pump failure. Early diagnosis and treatment may be critical to improve survival after AMI. Abstract Figure. Timing and mode of early death after ACS

The Relationship of LVEF and Myocardial Scar to Long-Term Mortality Risk and Mode of Death in Patients with Non-Ischemic Cardiomyopathy

Background: Non-ischemic cardiomyopathy (NICM) is a leading cause of reduced left ventricular ejection fraction (LVEF) and is associated with high mortality risk from progressive heart failure and arrhythmias. Myocardial scar on cardiovascular magnetic resonance imaging (CMR) is increasingly recognized as risk marker for adverse outcomes, however LV dysfunction remains the basis for determining a patient's eligibility for primary prophylaxis implantable cardioverter-defibrillator (ICD). We wanted to investigate the relationship of LVEF and scar to long term mortality and mode of death in a large cohort of patients with NICM. Methods: This study is a prospective, longitudinal outcomes registry of 1020 consecutive patients with NICM who underwent clinical CMR for the assessment of LVEF and scar at three centers. Results: During a median follow-up of 5.2 (IQR 3.8, 6.6) years 277 (27%) patients died. On survival analysis LVEF≤35% and scar were strongly associated with all-cause (log-rank test p=0.002 and p<0.001, respectively) and cardiac death (p=0.001 and p<0.001, respectively). While scar was strongly related to sudden cardiac death (SCD) (p=0.001), there was no significant association between LVEF≤35% and SCD-risk (p=0.57). On multivariable analysis including established clinical factors, LVEF and scar are independent risk-markers of all-cause and cardiac death. The addition of LVEF provided incremental prognostic value albeit insignificant discrimination improvement by C-statistic for all-cause and cardiac death, however no incremental prognostic value for SCD. Conversely, scar extent demonstrated significant incremental prognostic value and discrimination improvement for all three endpoints. On net reclassification analysis, the addition of LVEF resulted in no significant improvement for all-cause death 11.0% (95% CI -6.2-25.9%), cardiac death 9.8% (95% CI -5.7-29.3%), and SCD 7.5% (95% CI -41.2-42.9%). Conversely, the addition of scar extent resulted in significant reclassification improvement of 25.5% (95% CI 11.7-41.0%) for all-cause death, 27.0% (95% CI 11.6-45.2%) for cardiac death, and 40.6% (95% CI 10.5-71.8%) for SCD. Conclusions: Myocardial scar and LVEF are both risk markers for all-cause and cardiac death in patients with NICM. However, while myocardial scar has strong and incremental prognostic value for SCD risk stratification, LVEF has no incremental prognostic value over clinical parameters. Scar assessment should be incorporated into patient selection criteria for primary prevention ICD placement.