Assessment and management of septic shock and hypovolemia

Introduction

Sepsis remains a leading cause of morbidity and mortality in the neonatal population. There is a strong inverse relationship between the incidence of sepsis, gestational age, and birth weight. The incidence and mortality in term or late preterm infants with sepsis has slowly decreased over time, but the incidence and case-fatality rate remain high in very-low-birth-weight (VLBW) infants. This chapter addresses the clinical and hemodynamic presentation and cardiovascular and antibiotic management of neonates, with sepsis caused by bacterial infection. Primarily because of scant hemodynamic data, the clinical and cardiovascular presentation of neonates with sepsis caused by viral (herpes virus, enteroviruses, etc.) or fungal infection might be somewhat different.

Currently, there is no unified consensus definition of neonatal sepsis. ^, Definitions of neonatal sepsis in the literature emphasize microbiological evidence of infection, without consideration for potential organ dysfunction, and include general clinical practice items such as treatment duration with antibiotics. The last pediatric consensus definition was presented in 2005 and incorporated the presence of evidence for a systemic inflammatory response. However, this definition is not applicable to the newborn population as many neonates with septic shock would not qualify, similar to what was found in adults. ^, The “Sepsis-3 Group” has recently defined sepsis in adults as a life-threatening organ dysfunction caused by a dysregulated host response to infection, and septic shock is defined as a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to significantly increase mortality.

It would not be unreasonable to use a similar but adapted version for septic shock in newborns, but some questions still remain. First , the host response of newborns is different from that of adults. The fetus lives in a unique environment where protection against infection is paramount. Yet, the fetus also must avoid the development of harmful, dysregulated inflammatory immune responses that could lead to preterm birth. Birth is the transition from the intra-uterine environment with low-grade presence of maternal bacteria essential for the development of, among others, the immune system to a new environment abundant in foreign antigens and pathogens requiring a balanced immunological response. Much remains to be understood about the newborn’s immune response to infection, and whether these biochemical processes can be used in the early detection of a dysregulated immune response and/or to guide treatment of neonatal infections. ^,

Second , there is no consensus on the definition of a life-threatening organ dysfunction in newborns. Newborn illness score systems with a focus on acute physiology like the SNAPPE or CRIB scores have generally placed much emphasis on risk assessment on the first postnatal day and have not been validated for use thereafter. Sepsis-specific scores like the NEOMOD have been tested and modified for performance but are infrequently used and reported in the literature. Pediatric organ dysfunction scores have shown increased mortality for the same scoring range in newborns and older infants, but newborns showed different primary organ involvement with acute illness. The neonatal sequential organ failure assessment score (nSOFA) uses parameters of respiratory support, oxygenation, cardiovascular support, and platelet count. When applied to preterm infants with late-onset sepsis, the maximum nSOFA score at 6 hours after the clinical diagnosis was established showed a strong association with mortality and thus could be proposed as an operational definition of organ dysfunction in this population. Although the nSOFA score has an excellent diagnostic accuracy for mortality due to sepsis and all-cause mortality, its validity is highly dependent on local guidelines for the use of systemic steroids and criteria for intubation. A subsequent study revealed a wide variance between centers in all-cause mortality of preterm infants with high nSOFA scores, questioning its generalizability.

Finally , the ability of translating the “Sepsis-3” definition and its tools to the newborn population also depends on data regarding sepsis mortality. However, wide ranges of mortality have been reported for sepsis in newborns. Recent epidemiological data from research networks showed that mortality from early-onset sepsis (EOS) and late-onset sepsis (LOS) in very-low-birth-weight (VLBW) infants was in the range of 12–33% and 4–16%, respectively. ^{, , ,} Risk factors for developing EOS and LOS in VLBW infants have been amply described, but limited data are available on risk factors for death due to sepsis. Decreasing gestational age, birth weight, and the presence of gram-negative organisms are associated with higher risk of mortality due to sepsis, but more data are required to better understand the risk factors involved in the progression from sepsis to septic shock. ^, The “Sepsis-3” definition defines septic shock as a circulatory and cellular/metabolic abnormality profound enough to increase mortality. In the neonatal literature and for logistical reasons septic shock is often defined as sepsis with hypotension requiring catecholamines. The rate of infants who progress from sepsis to septic shock is reported as 26% for EOS and between 9 and 22% for LOS and depends on the infective agent. ^{, ,} Most studies did not report case fatality separately for infants with septic shock. Gorantiwar et al. presented a decade’s worth of data from a single center in Australia and reported a mortality rate of 40% in preterm infants with LOS and sepsis shock, suggesting that mortality is significantly higher when shock develops. In a yet unpublished retrospective study of similar design our group found a 33% mortality rate for preterm infants with EOS. However, the rate increased to 67% in infants who progressed from sepsis to septic shock. Data on other aspects commonly associated with mortality, such as lactate levels and lactate clearance, fluid load, fluid accumulation, and multi-organ dysfunction, have been sparsely reported for the neonatal population with sepsis. ^, Phenotyping of neonatal sepsis might be possible with accurate documentation of timing of treatments, biochemical profiles, or reporting of progression from sepsis to septic shock. ^, In summary, there is a need to develop a better understanding of the clinical, phenotypic, and even genotypic factors associated with progression from sepsis to septic shock in neonates with EOS or LOS, before we can appropriately define mortality and/or describe the appropriateness and efficacy of treatment modalities and short- and long-term outcome in the affected patient population.

Hemodynamics in sepsis