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

Weiss SL, et al. The Epidemiology of Hospital Death Following Pediatric Severe Sepsis: When, Why, and How Children With Sepsis Die. Pediatr Crit Care Med. 2017 Sep;18(9):823-830.

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.


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.


Relative Bradycardia in Patients With Septic Shock Requiring Vasopressor Therapy. (Betters)

Beesley SJ, Wilson EL, Lanspa MJ, et al. Relative Bradycardia in Patients With Septic Shock Requiring Vasopressor Therapy. Crit Care Med. 2017 Feb; 45(2) :225-233.

OBJECTIVES: Tachycardia is common in septic shock, but many patients with septic shock are relatively bradycardic. The prevalence, determinants, and implications of relative bradycardia (heart rate, < 80 beats/min) in septic shock are unknown. To determine mortality associated with patients who are relatively bradycardic while in septic shock.

DESIGN: Retrospective study of patients admitted for septic shock to study ICUs during 2005-2013.

SETTING: One large academic referral hospital and two community hospitals.

PATIENTS: Adult patients with septic shock requiring vasopressors.


MEASUREMENTS: Primary outcome was 28-day mortality. We used multivariate logistic regression to evaluate the association between relative bradycardia and mortality, controlling for confounding with inverse probability treatment weighting using a propensity score.

RESULTS: We identified 1,554 patients with septic shock, of whom 686 (44%) met criteria for relative bradycardia at some time. Twenty-eight-day mortality in this group was 21% compared to 34% in the never-bradycardic group (p < 0.001). Relatively bradycardic patients were older (65 vs 60 yr; p < 0.001) and had slightly lower illness severity (Sequential Organ Failure Assessment, 10 vs 11; p = 0.004; and Acute Physiology and Chronic Health Evaluation II, 27 vs 28; p = 0.008). After inverse probability treatment weighting, covariates were balanced, and the association between relative bradycardia and survival persisted (p < 0.001).

CONCLUSIONS: Relative bradycardia in patients with septic shock is associated with lower mortality, even after adjustment for confounding. Our data support expanded investigation into whether inducing relative bradycardia will benefit patients with septic shock.

Impact of Source Control in Patients With Severe Sepsis and Septic Shock. (Betters)

Martínez ML, et al. Impact of Source Control in Patients With Severe Sepsis and Septic Shock. Crit Care Med. 2017 Jan;45(1):11-19.

OBJECTIVES: Time to clearance of pathogens is probably critical to outcome in septic shock. Current guidelines recommend intervention for source control within 12 hours after diagnosis. We aimed to determine the epidemiology of source control in the management of sepsis and to analyze the impact of timing to source control on mortality.

DESIGN: Prospective observational analysis of the Antibiotic Intervention in Severe Sepsis study, a Spanish national multicenter educational intervention to improve antibiotherapy in sepsis.

SETTING: Ninety-nine medical-surgical ICUs in Spain.

PATIENTS: We enrolled 3,663 patients with severe sepsis or septic shock during three 4-month periods between 2011 and 2013.

INTERVENTIONS: Source control and hospital mortality.

MEASUREMENTS AND MAIN RESULTS: A total of 1,173 patients (32%) underwent source control, predominantly for abdominal, urinary, and soft-tissue infections. Compared with patients who did not require source control, patients who underwent source control were older, with a greater prevalence of shock, major organ dysfunction, bacteremia, inflammatory markers, and lactic acidemia. In addition, compliance with the resuscitation bundle was worse in those undergoing source control. In patients who underwent source control, crude ICU mortality was lower (21.2% vs 25.1%; p = 0.010); after adjustment for confounding factors, hospital mortality was also lower (odds ratio, 0.809 [95% CI, 0.658-0.994]; p = 0.044). In this observational database analysis, source control after 12 hours was not associated with higher mortality (27.6% vs 26.8%; p = 0.789).

CONCLUSIONS: Despite greater severity and worse compliance with resuscitation bundles, mortality was lower in septic patients who underwent source control than in those who did not. The time to source control could not be linked to survival in this observational database.

Double-Blind Randomized Clinical Trial Comparing Dopamine and Epinephrine in Pediatric Fluid-Refractory Hypotensive Septic Shock. (Carroll)

Ramaswamy KN, et al. Double-Blind Randomized Clinical Trial Comparing Dopamine and Epinephrine in Pediatric Fluid-Refractory Hypotensive Septic Shock. Pediatr Crit Care Med. 2016 Nov;17(11):e502-e512.

OBJECTIVE: We compared efficacy of dopamine and epinephrine as first-line vasoactive therapy in achieving resolution of shock in fluid-refractory hypotensive cold septic shock.

DESIGN: Double-blind, pilot, randomized controlled study.

SETTING: Pediatric emergency and ICU of a tertiary care teaching hospital.

PATIENTS: Consecutive children 3 months to 12 years old, with fluid-refractory hypotensive septic shock, were enrolled between July 2013 and December 2014.

INTERVENTION: Enrolled children were randomized to receive either dopamine (in incremental doses, 10 to 15 to 20 μg/kg/min) or epinephrine (0.1 to 0.2 to 0.3 μg/kg/min) till end points of resolution of shock were achieved. After reaching maximum doses of test drugs, open-label vasoactive was started as per discretion of treating team. Primary outcome was resolution of shock within first hour of resuscitation. The study was registered (CTRI/2014/02/004393) and was approved by institute ethics committee.

MEASUREMENTS AND MAIN RESULTS: We enrolled 29 children in epinephrine group and 31 in dopamine group. Resolution of shock within first hour was achieved in greater proportion of children receiving epinephrine (n = 12; 41%) than dopamine (n = 4; 13%) (odds ratio, 4.8; 95% CI, 1.3-17.2; p = 0.019); the trend persisted even at 6 hours (48.3% vs 29%; p = 0.184). Children in epinephrine group had lower Sequential Organ Function Assessment score on day 3 (8 vs 12; p = 0.05) and more organ failure-free days (24 vs 20 d; p = 0.022). No significant difference in adverse events (16.1% vs 13.8%; p = 0.80) and mortality (58.1% vs 48.3%; p = 0.605) was observed between the two groups.

CONCLUSION: Epinephrine is more effective than dopamine in achieving resolution of fluid-refractory hypotensive cold shock within the first hour of resuscitation and improving organ functions.