Timing of Multiorgan Dysfunction among Hospitalized Infants with Fatal Fulminant Sepsis

Abstract

Objective Identify the progression of specific signs of multiorgan dysfunction among infants with fatal sepsis.

Study Design Cohort study of 679 infants who died within 3 days of the start of a late-onset sepsis (LOS) episode in neonatal intensive care units from 1997 to 2012. We extracted clinical and laboratory data on the day of death (day 0) and the preceding 5 days (days −5 to −1).

Results Median (25th percentile–75th percentile) gestational age was 25 (24–28) weeks. Compared with day −1, day 0 was characterized by an increased requirement for mechanical ventilation and higher mean fraction of inspired oxygen. Measures of cardiorespiratory support and the proportion of infants with neutropenia began to rise on day −2.

Conclusion Hospitalized infants with fatal LOS manifest respiratory, cardiovascular, renal, immune, and hematologic dysfunction. Knowledge of these factors and their timing may be important for the development and testing of novel therapeutics to reduce sepsis mortality.

Keywords

sepsis - infant - neonate - multiorgan dysfunction - death

• References

• 1 Brocklehurst P, Farrell B, King A , et al; INIS Collaborative Group. Treatment of neonatal sepsis with intravenous immune globulin. N Engl J Med 2011; 365 (13) 1201-1211
• 2 Hornik CP, Fort P, Clark RH , et al. Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units. Early Hum Dev 2012; 88 (Suppl. 02) S69-S74
• 3 Mitha A, Foix-L'Hélias L, Arnaud C , et al; EPIPAGE Study Group. Neonatal infection and 5-year neurodevelopmental outcome of very preterm infants. Pediatrics 2013; 132 (2) e372-e380
• 4 Person MK, Esposito DH, Holman RC, Mehal JM, Stoll BJ. Risk factors for infectious disease death among infants in the United States. Pediatr Infect Dis J 2014; 33 (11) e280-e285
• 5 Stoll BJ, Hansen NI, Bell EF , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 2010; 126 (3) 443-456
• 6 Stoll BJ, Hansen N, Fanaroff AA , et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 2002; 110 (2 Pt 1): 285-291
• 7 Wynn J, Cornell TT, Wong HR, Shanley TP, Wheeler DS. The host response to sepsis and developmental impact. Pediatrics 2010; 125 (5) 1031-1041
• 8 Wynn JL, Wong HR. Pathophysiology and treatment of septic shock in neonates. Clin Perinatol 2010; 37 (2) 439-479
• 9 Hornik CP, Benjamin DK, Becker KC , et al. Use of the complete blood cell count in early-onset neonatal sepsis. Pediatr Infect Dis J 2012; 31 (8) 799-802
• 10 Olsen IE, Groveman SA, Lawson ML, Clark RH, Zemel BS. New intrauterine growth curves based on United States data. Pediatrics 2010; 125 (2) e214-e224
• 11 Maheshwari A. Neutropenia in the newborn. Curr Opin Hematol 2014; 21 (1) 43-49
• 12 Wiedmeier SE, Henry E, Sola-Visner MC, Christensen RD. Platelet reference ranges for neonates, defined using data from over 47,000 patients in a multihospital healthcare system. J Perinatol 2009; 29 (2) 130-136
• 13 Bateman DA, Thomas W, Parravicini E, Polesana E, Locatelli C, Lorenz JM. Serum creatinine concentration in very-low-birth-weight infants from birth to 34-36.  wk postmenstrual age. Pediatr Res 2015; 77 (5) 696-702
• 14 Levit O, Bhandari V, Li FY, Shabanova V, Gallagher PG, Bizzarro MJ. Clinical and laboratory factors that predict death in very low birth weight infants presenting with late-onset sepsis. Pediatr Infect Dis J 2014; 33 (2) 143-146
• 15 Hofer N, Zacharias E, Müller W, Resch B. Performance of the definitions of the systemic inflammatory response syndrome and sepsis in neonates. J Perinat Med 2012; 40 (5) 587-590
• 16 Wynn JL, Wong HR, Shanley TP, Bizzarro MJ, Saiman L, Polin RA. Time for a neonatal-specific consensus definition for sepsis. Pediatr Crit Care Med 2014; 15 (6) 523-528
• 17 Wynn JL, Neu J, Moldawer LL, Levy O. Potential of immunomodulatory agents for prevention and treatment of neonatal sepsis. J Perinatol 2009; 29 (2) 79-88
• 18 Qian L, Liu C, Zhuang W , et al; Chinese Collaborative Study Group for Neonatal Respiratory Diseases. Neonatal respiratory failure: a 12-month clinical epidemiologic study from 2004 to 2005 in China. Pediatrics 2008; 121 (5) e1115-e1124
• 19 Tan K, Lai NM, Sharma A. Surfactant for bacterial pneumonia in late preterm and term infants. Cochrane Database Syst Rev 2012; 2 (2) CD008155
• 20 Alkan S, Ozer EA, Ilhan O, Sutcuoglu S, Tatli M. Surfactant treatment for neonatal respiratory disorders other than respiratory distress syndrome. J Matern Fetal Neonatal Med 2015; 28 (2) 131-133
• 21 Bissinger R, Carlson C, Michel Y, Dooley C, Hulsey T, Jenkins D. Secondary surfactant administration in neonates with respiratory decompensation. J Perinatol 2008; 28 (3) 192-198