The Epidemiology of Hospital Death Following Pediatric Severe Sepsis: When, Why, and How Children With Sepsis Die

Abstract

Objective: The epidemiology of in-hospital death after pediatric sepsis has not been well characterized. We investigated the timing, cause, mode, and attribution of death in children with severe sepsis, hypothesizing that refractory shock leading to early death is rare in the current era.

Design: Retrospective observational study.

Setting: Emergency departments and ICUs at two academic children's hospitals.

Patients: Seventy-nine patients less than 18 years old treated for severe sepsis/septic shock in 2012-2013 who died prior to hospital discharge.

Interventions: None.

Measurements and main results: Time to death from sepsis recognition, cause and mode of death, and attribution of death to sepsis were determined from medical records. Organ dysfunction was assessed via daily Pediatric Logistic Organ Dysfunction-2 scores for 7 days preceding death with an increase greater than or equal to 5 defined as worsening organ dysfunction. The median time to death was 8 days (interquartile range, 1-12 d) with 25%, 35%, and 49% of cumulative deaths within 1, 3, and 7 days of sepsis recognition, respectively. The most common cause of death was refractory shock (34%), then multiple organ dysfunction syndrome after shock recovery (27%), neurologic injury (19%), single-organ respiratory failure (9%), and nonseptic comorbidity (6%). Early deaths (≤ 3 d) were mostly due to refractory shock in young, previously healthy patients while multiple organ dysfunction syndrome predominated after 3 days. Mode of death was withdrawal in 72%, unsuccessful cardiopulmonary resuscitation in 22%, and irreversible loss of neurologic function in 6%. Ninety percent of deaths were attributable to acute or chronic manifestations of sepsis. Only 23% had a rise in Pediatric Logistic Organ Dysfunction-2 that indicated worsening organ dysfunction.

Conclusions: Refractory shock remains a common cause of death in pediatric sepsis, especially for early deaths. Later deaths were mostly attributable to multiple organ dysfunction syndrome, neurologic, and respiratory failure after life-sustaining therapies were limited. A pattern of persistent, rather than worsening, organ dysfunction preceded most deaths.

Figure 1. Days from Sepsis Recognition to Death

Frequency histogram of days from sepsis recognition to death. Inset shows timing of death within first 30 days following sepsis recognition with each bin equal to one day.

Figure 2. Proportion Treated on Days Preceding Death

The proportion of patients who died more >1 day after sepsis recognition who were hospitalized and treated with invasive mechanical ventilation, renal replacement therapies, and extracorporeal membrane oxygenation in the seven days preceding death. There was no significant change in proportion treated over time with invasive mechanical ventilation (p=0.40), renal replacement therapies (p=0.62), or extracorporeal membrane oxygenation (p=0.59).

Figure 3. Mean PELOD-2 by Day Preceding Death for Patients Who Died After Seven Days from Sepsis Recognition

Mean individual PELOD-2 scores increased by a mean of 1.5 ±4.3 in the week preceding death for the 40 patients who died >7 days following sepsis recognition (ANOVA, p=0.22). Error bars represent standard deviation.

Figure 4. Mean PELOD-2 Trajectory by Timing of Death

Mean PELOD-2 scores in the three days preceding death for patients who died ≤3 and >3 days after sepsis recognition. PELOD-2 scores did not change significantly in either group (ANOVA, p=0.45 for death ≤3 days and p=0.31 for death >3 days), and there was no difference in the change in daily PELOD-2 scores over time between groups (repeated measures ANOVA, p=0.19). Error bars represent standard deviation.