Pediatric Sepsis




Pediatric sepsis is distinct from adult sepsis in its definitions, clinical presentations, and management. Recognition of pediatric sepsis is complicated by the various pediatric-specific comorbidities that contribute to its mortality and the age- and development-specific vital sign and clinical parameters that obscure its recognition. This article outlines the clinical presentation and management of sepsis in neonates, infants, and children, and highlights some key populations who require specialized care.


Key points








  • Age-specific vital signs and development-specific clinical parameters complicate the early recognition of pediatric sepsis.



  • Early goal-directed therapy in pediatric sepsis differs from adult guidelines in the selection of inotropes and the recommendation to start vasoactive medications peripherally while securing central access.



  • Intraosseous needles and umbilical catheters are pediatric-specific modalities for providing sepsis treatment.






Introduction


Pediatric sepsis is life-threatening organ dysfunction caused by a deleterious host response to infection, and it continues to be a leading cause of death for children in the United States. Neonates, infants, and children with chronic medical conditions comprise a large percentage of those with morbidity and mortality from sepsis or septic shock. Pediatric critical care medicine has led epidemiology research efforts over the past 2 decades in an attempt to understand the burden of sepsis in children. The national incidence of pediatric sepsis was 0.56 cases per 1000 (42,364 cases per year nationally) in 1995, with an in-hospital mortality of 10.3%. From 1995 to 2005, there has been an increase in incidence from 0.56 to 0.89 cases per 1000 (with a doubled prevalence of severe sepsis in newborns) and declining mortality rate from 10.3% to 8.9%. The estimated annual health care expenditures for the treatment of pediatric severe sepsis is just under $5 billion in the United States. Although there has been a lack of research looking into rates of pediatric sepsis recognized in the emergency department (ED), a more recent study estimated that close to 100,000 children present to the ED with severe sepsis every year. EDs are at the frontline of recognizing severe sepsis and septic shock and have the resources to initiate life-saving resuscitation measures. In a landmark study, Han and colleagues demonstrated that, when community hospital EDs recognize pediatric septic shock early and initiate aggressive treatment to reverse the clinical signs of shock (eg, tachycardia, delayed capillary refill, hypotension), morbidity and mortality decrease by 50%. Patients with septic shock have significantly decreased duration of hospital and intensive care unit stays when they received 60 mL/kg of IV fluids and when complete Pediatric Advanced Life Support–directed shock protocol bundles were provided within the first hour of treatment. This article discusses the recognition and management of pediatric severe sepsis and septic shock in the ED.




Introduction


Pediatric sepsis is life-threatening organ dysfunction caused by a deleterious host response to infection, and it continues to be a leading cause of death for children in the United States. Neonates, infants, and children with chronic medical conditions comprise a large percentage of those with morbidity and mortality from sepsis or septic shock. Pediatric critical care medicine has led epidemiology research efforts over the past 2 decades in an attempt to understand the burden of sepsis in children. The national incidence of pediatric sepsis was 0.56 cases per 1000 (42,364 cases per year nationally) in 1995, with an in-hospital mortality of 10.3%. From 1995 to 2005, there has been an increase in incidence from 0.56 to 0.89 cases per 1000 (with a doubled prevalence of severe sepsis in newborns) and declining mortality rate from 10.3% to 8.9%. The estimated annual health care expenditures for the treatment of pediatric severe sepsis is just under $5 billion in the United States. Although there has been a lack of research looking into rates of pediatric sepsis recognized in the emergency department (ED), a more recent study estimated that close to 100,000 children present to the ED with severe sepsis every year. EDs are at the frontline of recognizing severe sepsis and septic shock and have the resources to initiate life-saving resuscitation measures. In a landmark study, Han and colleagues demonstrated that, when community hospital EDs recognize pediatric septic shock early and initiate aggressive treatment to reverse the clinical signs of shock (eg, tachycardia, delayed capillary refill, hypotension), morbidity and mortality decrease by 50%. Patients with septic shock have significantly decreased duration of hospital and intensive care unit stays when they received 60 mL/kg of IV fluids and when complete Pediatric Advanced Life Support–directed shock protocol bundles were provided within the first hour of treatment. This article discusses the recognition and management of pediatric severe sepsis and septic shock in the ED.




Definitions


The definition of pediatric sepsis has evolved from the efforts of the Society of Critical Care Medicine and the American College of Critical Care Medicine (ACCM), who authored the first sepsis guidelines for adults. In 2002, the ACCM in collaboration with the Society of Critical Care Medicine developed the first pediatric sepsis guidelines, highlighting the differences in management of pediatric and neonatal sepsis from adult sepsis. International definitions for pediatric systemic inflammatory response syndrome (SIRS), sepsis, septic shock, and organ dysfunction were agreed on in 2002 by the members of the International Consensus Conference on Pediatric Sepsis. Revised ACCM septic shock guidelines were written in 2007 and are based on the best current literature and expert opinion for the management of neonatal and pediatric septic shock.


The definition of pediatric SIRS differs from the adult definition in its requirement that at least 1 of the diagnostic criteria must be high or low core body temperature or a leukocyte count abnormality ( Box 1 ). Throughout pediatric development, vital signs and laboratory values change requiring, thoughtful attention to age-related norms ( Table 1 ) for accurate and early SIRS and sepsis recognition. Tachycardia and pyrexia commonly are seen together, but are often hard to isolate from other variables such as pain, anemia, fluid volume status, respiratory distress, and fear. Unfortunately, there is no established criterion to calculate an age-appropriate heart rate (HR) in the presence of fever.



Box 1





  • Core body temperature (rectal or oral) of greater than 38.5°C or less than 36°C (tympanic, toe, axillary temperature measurements are not recommended)



  • Tachycardia



  • Tachypnea



  • Abnormal high or low leukocyte count for age or bandemia (>10% immature neutrophils)



Systemic inflammatory response syndrome = 2 out of these 4 criteria with at least 1 being abnormality in temperature or leukocyte count.


Pediatric systemic inflammatory response syndrome criteria

Data from Goldstein B, Giroir B, Randolph A, et al. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatric Critical Care Medicine 2005;6(1):2–8.


Table 1

Age-specific vital signs and laboratory values





















































Age Group Tachycardia Bradycardia Respiratory Rate Leukocyte Count Hypotension (SBP)
Birth to 1 wk >180 <100 >50 >34 <59
1 wk to 1 mo >180 <100 >40 >19.5 or <5 <79
1 mo to 1 y >180 <90 >34 >17.5 or <5 <75
2–5 y >140 >22 >15.5 or <6 <74
6–12 y >130 >18 >13.5 or <4.5 <83
13 to <18 y >110 >14 >11 or <4.5 <90

Abbreviation : SBP, systolic blood pressure.

Data from Refs.


Pediatric sepsis necessitates that the patient meet the SIRS criteria in the presence of a known or suspected infection (eg, bacterial, viral). Clinical findings that suggest an existing nidus of infection are located in Box 2 . Severe sepsis in pediatrics is recognized as sepsis with the development of cardiovascular dysfunction or acute respiratory distress syndrome, or organ dysfunction in at least 2 systems (including renal, hematologic, neurologic, hepatic, or respiratory systems). Septic shock is defined as sepsis with cardiovascular dysfunction manifesting as alterations in HR (tachycardia or bradycardia) and signs of impaired perfusion ( Box 3 ). The International Pediatric Sepsis Consensus developed organ dysfunction definitions for cardiac, respiratory, hematologic, neurologic, renal, and hepatic systems ( Box 4 ) that can guide the clinician’s diagnosis and trajectory of sepsis, severe sepsis, and septic shock. At this time, adult organ system dysfunction guidelines have not been validated in children.



Box 2





  • Petechiae or purpura + hemodynamic derangement/instability



  • Purpura fulminans



  • Fever + cough + hypoxemia + pulmonary infiltrates + leukocytosis



  • Fever or hypothermia + bulging fontanelle or nuchal rigidity + irritability



  • Temperature instability + poor glucose control + irritability (in neonates and premature infants)



  • Temperature instability + seizure (in neonate)



  • Rash with rapid migration + fever + pain + leukocytosis



  • Distended tympanic abdomen + fever + leukocytosis



  • Or recognizable infectious mediated clinical syndrome (ie, toxic shock syndrome and staphylococcal scalded skin syndrome, or Rocky Mountain spotted fever) or infectious cutaneous lesion



Clinical findings suggesting infection in pediatric patients

Data from Refs.


Box 3





  • Cool extremities



  • Pale or mottled skin



  • Diminished peripheral pulses



  • Significant difference between central and peripheral pulses



  • Flash capillary refill time or prolonged capillary refill time greater than 2 seconds



  • Change in level of consciousness from baseline or irritability



  • Decreased urine output (<0.5 mL/kg/h)



Clinical signs of poor perfusion in pediatric patients

Data from Refs.


Box 4





  • Cardiovascular (despite ≥40 mL/kg fluid bolus in 1 hour)



  • Hypotension




    • or




  • Requiring inotrope support




    • or




  • Two of the following:




    • Metabolic acidosis: base deficit greater than 5.0 mEq/L



    • Increased arterial lactate greater than 2 times the upper limit of normal



    • Oliguria: UOP less than 0.5 mL/kg/h



    • Delayed capillary refill time: greater than 5 seconds



    • Difference between core and peripheral temperature greater than 3°C





  • Hematologic



  • INR greater than 2




    • or




  • Platelet count less than 80,000/mm 3 (50% decrease from highest value within 3 days for hematology/oncology patients)




  • Hepatic



  • ALT greater than or equal to the upper limit of normal for age ×2




    • or




  • Total bilirubin 4 mg/dL or greater (newborns excluded)




  • Respiratory



  • Requiring intubation and mechanical ventilation or noninvasive ventilation measures to maintain adequate oxygenation and ventilation




    • or




  • Oxygen greater than 50% Fi o 2 to maintain oxygen saturations 92% or greater




    • or




  • Pa o 2 /Fi o 2 less than 300 with no known cyanotic cardiac defect or previously established lung disease




    • or




  • Pa co 2 greater than 65 torr or 20 mm Hg over baseline Pa co 2




  • Neurologic



  • GCS of 11 or less




    • or




  • Decline in mental status + change in GCS of 3 or more points from baseline




  • Renal



  • Serum creatinine greater than or equal to the upper limit of normal for age ×2 (or baseline creatinine ×2 in patients with chronic kidney disease)



Abbreviations: ALT, alanine aminotransferase; GCS, Glasgow Coma Score; INR, international normalized ratio; UOP, urine output.


Organ dysfunction criteria

Data from Goldstein B, Giroir B, Randolph A, et al. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatric Critical Care Medicine 2005;6(1):2–8.




Similarities between pediatric and adult sepsis


Sepsis in the pediatric and neonatal populations is a serious illness associated with considerable mortality( Box 5 ). Much like in adults, foundations of care include early recognition of sepsis, aggressive fluid resuscitation, timely administration of antibiotics, and source control. Just as comorbid conditions drive the mortality of sepsis in adult patients, medical conditions such as prematurity, congenital heart disease, solid and hematopoietic cancers, and immune deficiencies significantly increase the mortality of pediatric sepsis. The early investigation of sepsis in an infant or child includes source identification (eg, cultures and antigen testing) and inflammatory and biomarker marker evaluation (eg, white blood cell count, erythrocyte sedimentation rate, C-reactive protein analysis, lactate level). Ultrasound imaging and invasive monitoring are used to evaluate resuscitation endpoints. In all populations, disseminated intravascular coagulation (DIC) impacts the likelihood of developing multisystem organ failure.



Box 5





  • Comorbid conditions contribute significantly to mortality.



  • Acute kidney injury is an independent risk factor for mortality in critically ill children and adults.



  • Disseminated intravascular coagulation impacts the likelihood of developing multisystem organ failure as a complication of sepsis.



  • Metabolic acidosis is a common and can be monitored with serum lactate.



  • Ultrasound imaging can guide central line placement, measure contractility or evaluate ventricular filling.



  • Aggressive fluid resuscitation and prompt administration of antibiotics are goals of therapy.



  • Low tidal volume strategies are recommended during ventilatory support of sepsis.



Key similarities between pediatric and adult sepsis




Differences between pediatric and adult sepsis


Sepsis in infants and children differs in its pathophysiology, etiology, diagnosis, and management from that of adults. Most of these differences become less pronounced as children get older. The comorbid conditions most often observed in infants with sepsis are congenital heart disease and chronic lung disease, whereas cancer and neuromuscular disease emerge more often in childhood sepsis. The site of infection is also age dependent; infants tend to present with primary bacteremia, whereas older children present most often with respiratory infection and secondary bacteremia.


The pathology of illness in infants and young children is affected by their proportionally higher ratio of extracellular to intracellular fluid. The larger the percentage of extracellular fluid, the more likely decreased intake or increased losses will predispose them to rapid fluid losses. Additionally, the younger the myocardium, the more likely it is functioning at a baseline high contractile state. For this reason, pediatric patients with sepsis depend on increases in HR to generate increased cardiac output (CO) during stress. This concept plays a focal role in the interpretation of vital signs and recognition of sepsis in pediatric patients. Tachycardia is an important mechanism in maintaining CO in pediatric sepsis, but the younger the child, the higher the basal HR and the more unlikely it becomes that CO can be maintained solely by further HR increases. Children with lower CO have the highest risk of mortality. This pathophysiology explains the efficacy of inotropes as first-line therapy in fluid-refractory shock. When increasing HR is no longer able to sustain adequate CO, vasoconstriction occurs in response to decreasing stroke volume and contractility. Young infants and neonates are particularly vulnerable to the effects of afterload on left ventricular function. Thus, an abrupt decrease in left ventricular function occurs owing to the increased afterload in the setting of shock and vasoconstriction. This mechanism makes cold shock more likely in the pediatric population ( Table 2 ). Pediatric patients demonstrate greater abnormalities in vasoregulation and myocardial dysfunction when compared with adults. The end result is a different role and emphasis on inotropic support in pediatric septic shock. These physiologic differences and other differences between pediatric and adult sepsis are summarized in Box 6 .


Oct 12, 2017 | Posted by in Uncategorized | Comments Off on Pediatric Sepsis

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