RESUMEN
Background: Septic patients who develop acute respiratory failure (ARF) requiring mechanical ventilation represent a heterogenous subgroup of critically ill patients with widely variable clinical characteristics. Identifying distinct phenotypes of these patients may reveal insights about the broader heterogeneity in the clinical course of sepsis. We aimed to derive novel phenotypes of sepsis-induced ARF using observational clinical data and investigate their generalizability across multi-ICU specialties, considering multi-organ dynamics. Methods: We performed a multi-center retrospective study of ICU patients with sepsis who required mechanical ventilation for ≥24 hours. Data from two different high-volume academic hospital systems were used as a derivation set with N=3,225 medical ICU (MICU) patients and a validation set with N=848 MICU patients. For the multi-ICU validation, we utilized retrospective data from two surgical ICUs at the same hospitals (N=1,577). Clinical data from 24 hours preceding intubation was used to derive distinct phenotypes using an explainable machine learning-based clustering model interpreted by clinical experts. Results: Four distinct ARF phenotypes were identified: A (severe multi-organ dysfunction (MOD) with a high likelihood of kidney injury and heart failure), B (severe hypoxemic respiratory failure [median P/F=123]), C (mild hypoxia [median P/F=240]), and D (severe MOD with a high likelihood of hepatic injury, coagulopathy, and lactic acidosis). Patients in each phenotype showed differences in clinical course and mortality rates despite similarities in demographics and admission co-morbidities. The phenotypes were reproduced in external validation utilizing an external MICU from second hospital and SICUs from both centers. Kaplan-Meier analysis showed significant difference in 28-day mortality across the phenotypes (p<0.01) and consistent across both centers. The phenotypes demonstrated differences in treatment effects associated with high positive end-expiratory pressure (PEEP) strategy. Conclusion: The phenotypes demonstrated unique patterns of organ injury and differences in clinical outcomes, which may help inform future research and clinical trial design for tailored management strategies.
RESUMEN
Sepsis is a major public health emergency and one of the leading causes of morbidity and mortality in critically ill patients. For each hour treatment is delayed, shock-related mortality increases, so early diagnosis and intervention is of utmost importance. However, earlier recognition of shock requires active monitoring, which may be delayed due to subclinical manifestations of the disease at the early phase of onset. Machine learning systems can increase timely detection of shock onset by exploiting complex interactions among continuous physiological waveforms. We use a dataset consisting of high-resolution physiological waveforms from intensive care unit (ICU) of a tertiary hospital system. We investigate the use of mean arterial blood pressure (MAP), pulse arrival time (PAT), heart rate variability (HRV), and heart rate (HR) for the early prediction of shock onset. Using only five minutes of the aforementioned vital signals from 239 ICU patients, our developed models can accurately predict septic shock onset 6 to 36 hours prior to clinical recognition with area under the receiver operating characteristic (AUROC) of 0.84 and 0.8 respectively. This work lays foundations for a robust, efficient, accurate and early prediction of septic shock onset which may help clinicians in their decision-making processes. This study introduces machine learning models that provide fast and accurate predictions of septic shock onset times up to 36 hours in advance. BP, PAT and HR dynamics can independently predict septic shock onset with a look-back period of only 5 mins.
