Introduction and Sepsis Review
Whether in a pediatric or adult patient, the physiologic process of sepsis remains the same. Sepsis is a systemic inflammatory host response to infection, which can progress to acute organ dysfunction and death.1 It is the endpoint of a complex series of steps on the part of a host and invading organism that results in a dysregulated inflammatory response.2 Sepsis is a spectrum of disease starting with SIRS, progressing to sepsis, septic shock, and lastly to severe sepsis with multiorgan system dysfunction (Table 1). The incidence of pediatric sepsis is 0.56 per 1,000 population per year, with a mortality ranging from 2% to 10%, resulting in nearly 4,500 deaths per year in patients under the age of 19.3 Mortality is reduced by early recognition and therapeutic intervention: thus, it is crucial that the emergency provider be well versed in pediatric sepsis.4,5
The key to pediatric sepsis in the emergency department is identification of the septic child. Many hospitals have initiated pediatric sepsis triage screening protocols to assist with early recognition of sepsis to improve outcomes.6 Age-based vital signs are the first step in assessment. Tachycardia, tachypnea, and hypotension are based on age, and should clue the provider in to a possible illness (Table 2).1 In the pediatric patient, tachypnea and tachycardia are early findings; if hypotension is present it is an ominous sign that the patient is already far down the sepsis path. Vitals are age dependent and should ideally be referenced during evaluation on a quick card or application.
Hypothermia or fever may indicate an infectious process, while delayed capillary refill, changes in mentation, cool extremities, decreased peripheral pulses and decreased urine output all indicate poor end organ perfusion. Finally, a complete physical exam to identify the underlying cause of sepsis is crucial in source control.
Initial Resuscitation — The Surviving Sepsis Campaign7
As in adults, initial management of pediatric sepsis is goal-directed and algorithmic-based. Goals of care are based on improvement of perfusion, including normal capillary refill, normal peripheral pulses, warm extremities, improved urine output to >1 mL/kg/hr, improved mentation, and resolution of tachycardia and hypotension. These measures should be continually reassessed to ensure the effectiveness of interventions and to further direct therapy. You may note that the goals of care do not address lactate. While lactate should be measured and trended, it is not an effective marker of sepsis in the pediatric patient, and furthermore, a normal lactate may give the provider a false sense of security when looking for end organ dysfunction.8
The first step in pediatric sepsis management is providing supplemental oxygen and establishing intravenous (IV) or intraosseous (IO) access. The Surviving Sepsis Campaign recommends that access and the first bolus should be initiated within the first five minutes of presentation, thus after two unsuccessful attempts at IV access a provider should go straight to the IO.
While the goals of care are targeted at patient assessment and not laboratory values, additional testing will assist in fine tuning management and targeting antibiotics. A source of infection and signs of end organ damage should be investigated in pediatric patients with SIRS criteria. Initial studies should include point of care blood glucose, complete blood count, blood culture, urinalysis, urine culture, chemistry with calcium, and a chest radiograph. Hypoglycemia should be addressed immediately, and trended as septic pediatric patients may spuriously drop their blood sugar. The pediatric myocardium is exquisitely sensitive to calcium imbalance, resulting in decreased inotropy in the setting of hypocalcaemia. Thus, during the first few minutes of resuscitation hypocalcaemia should be corrected to support adequate cardiac output. Within the first 15 minutes an isotonic saline bolus should be completed via a push method. Within the first hour up to three 20 mL/kg push boluses should be administered via manual push until perfusion is improved or the patient develops signs of fluid overload, such as hepatomegaly or rales. If the patient remains hypotensive after adequate fluid resuscitation and/or with signs of fluid overload, a second peripheral or central line should be established to initiate vasopressor therapy.
When focusing on resuscitation it is important not to neglect early administration of antibiotics. Empiric broad-spectrum antibiotics should be given within one hour of presentation.7 Antibiotic selection is based on the suspected source and your local resistance patterns. For example, a patient with a central line or neutropenia may require additional antimicrobial coverage. If there is difficulty obtaining enough venous access, an alternative is to give the first dose of antibiotics intramuscularly.
Inotropic and Vasopressor Therapy
In the adult patient, the vasoactive therapy of choice has clearly become norepinephrine to improve systemic vascular resistance and improve cardiac output.9,10 However, the physiology of pediatric sepsis has lead to the preferential use of dopamine and epinephrine over norepinephrine.4,7 In the pediatric patient, sepsis may be marked by profound hypovolemia with an inability to accommodate via increased cardiac output. In contrast to adults whose cardiac output is dynamic and affected by both stroke volume and heart rate, cardiac output in the pediatric patient is primarily determined by heart rate, as stroke volume is relatively fixed.11 Furthermore, systemic vascular resistance in the pediatric patient increases in response to hypovolemia and relatively decreased cardiac output, which decreases peripheral perfusion and increases myocardial workload. This leads to a vicious cycle resulting in cold shock. What does this mean to the emergency care provider? Initial vasoactive therapy selection should be targeted at improving cardiac output over optimizing systematic vascular resistance.
Historically, vasoactive therapy in the pediatric patient was targeted at either cold shock or warm shock depending on presentation. As most pediatric patients have increased systemic vascular resistance and decreased cardiac output, resulting in cold shock, the initial preferred agents are dopamine or epinephrine. Despite emerging literature that indicates epinephrine may be preferable to dopamine, in current practice either is considered appropriate as a first-line vasopressor for fluid-refractory shock in the pediatric patient.11,12 For the rare pediatric patient with warm shock, indicated by normal capillary refill and warm extremities with persistent hypotension, norepinephrine should be considered as a second-line vasopressor.11
Additional Management Principles
When a patient fails to improve in spite of appropriate and aggressive therapy, consider additional etiologies of shock including pneumothorax, pericardial tamponade, adrenal insufficiency, and profound anemia.7 In fluid- and vasopressor-refractory shock, consider empiric hydrocortisone to treat a potential relative adrenal insufficiency. Further, involvement of the pediatric intensive care unit team early may facilitate initiation of additional therapies in the critically ill patient, such as additional vasoactive agents like milrinone and extracorporeal membrane oxygenation (ECMO).11,13,14
Table 1. Definitions within the Spectrum of Sepsis1
SIRS — Systemic Inflammatory Response Syndrome
Temp >38.5 °C or <36 °C PLUS one of the following:
Age specific leukocytosis or leukopenia or >10% bands
Tachycardia >2 SD above age normal OR Bradycardia <10th percentile for age (<1 years old)
Tachypnea >2 SD above age normal
Sepsis — SIRS plus suspected infection (viral, bacterial, fungal, parasitic)
Septic Shock — Sepsis plus cardiovascular dysfunction:
Hypotension <5th percentile for age, SBP <2 SD below age normal
Need for vasoactive drugs to maintain normal BP
Two of the following:
Unexplained metabolic acidosis: base deficit >5 mEq/L
Increased arterial lactate >2 times upper limit
Oliguria: urine output <0.5 mL/kg/hr
Prolonged capillary refill: >5 sec
Core to peripheral temperature gap >3 °C
Severe Sepsis — Sepsis plus acute respiratory distress syndrome (ARDS) OR Cardiovascular Dysfunction OR ‰¥2 organ dysfunctions:
Respiratory ”“ hypoxemia, hypercapnea
Neurologic ”“ altered mental status
Renal ”“ increase in creatinine
Hepatic ”“ elevated ALT or bilirubin
Hematologic ”“ thrombocytopenia, elevated INR
Table 2. Modified Normal Systolic Blood Pressure by Age1
Normal Systolic Blood Pressure by Age
>60 mmHg for term neonate
>70 mmHg in infants <1 year
>70 mmHg + (age x 2) in children <10 years
>90 mmHg in children >10 years
Summary and Key Points
- Early recognition of pediatric sepsis is crucial in reducing morbidity and mortality. Hypotension is a late finding of hemodynamic instability in pediatrics.
- Initial goals of therapy in the first hour are to establish vascular access, provide oxygen supplementation, push isotonic crystalloid fluid boluses, correct hypoglycemia and hypocalcaemia, provide broad-spectrum antibiotics, and initiate inotropic therapy as indicated.
- Consider additional etiologies of shock ”“ adrenal insufficiency, pneumothorax, pericardial tamponade, or anemia.
- Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics*. Pediatric Critical Care Medicine. 2005; 6: 2”“8.
- Bateman SL, Seed PC. Procession to Pediatric Bacteremia and Sepsis: Covert Operations and Failures in Diplomacy. Pediatrics. 2010; 126: 137”“150.
- Watson RS, Carcillo JA, Linde-Zwirble WT, Clermont G, Lidicker J, Angus DC. The epidemiology of severe sepsis in children in the United States. Am J Respir Crit Care Med. 2003; 167: 695”“701.
- Arnal LE, Stein F. Pediatric septic shock: Why has mortality decreased?-the utility of goal-directed therapy. Seminars in Pediatric Infectious Diseases. 2003; 14: 165”“172.
- Han YY, Carcillo JA, Dragotta MA, et al. Early Reversal of Pediatric-Neonatal Septic Shock by Community Physicians is Associated With Improved Outcome. Pediatrics. 2003; 112: 793”“799.
- Cruz AT, Perry AM, Williams EA, Graf JM, Wuestner ER, Patel B. Implementation of Goal-Directed Therapy for Children With Suspected Sepsis in the Emergency Department. Pediatrics. 2011; 127: e758”“e766.
- The Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup*, Dellinger RP, Levy MM, et al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012. Intensive Care Med. 2013; 39: 165”“228.
- de Oliveira CF, de Oliveira DSF, Gottschald AFC, et al. ACCM/PALS haemodynamic support guidelines for paediatric septic shock: an outcomes comparison with and without monitoring central venous oxygen saturation. Intensive Care Med. 2008; 34: 1065”“1075.
- Vasu TS, Cavallazzi R, Hirani A, Kaplan G, Leiby B, Marik PE. Norepinephrine or Dopamine for Septic Shock: Systematic Review of Randomized Clinical Trials. Journal of Intensive Care Medicine. 2012; 27: 172”“178.
- De Backer D, Biston P, Devriendt J, et al. Comparison of Dopamine and Norepinephrine in the Treatment of Shock. N Engl J Med. 2010; 362: 779”“789.
- Brierley J, Carcillo JA, Choong K, et al. Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine*. Critical Care Medicine. 2009; 37: 666”“688.
- Ventura A, GÃ³es P, Fernandes IC, Hsin SH. Randomized Double-Blind Trial of Dopamine or Epinephrine As First-Line Vasoactive Drugs in Fluid Refractory Pediatric Septic Shock. Pediatric Critical Care Medicine Supplement. 2014; 15: 5.
- MacLaren G, Butt W, Best D, Donath S. Extracorporeal membrane oxygenation for refractory septic shock in children: One institution”™s experience*. Pediatric Critical Care Medicine. 2007; 8: 447-451.
- MacLaren G, Butt W. Central extracorporeal membrane oxygenation for refractory pediatric septic shock. Pediatric Critical Care Medicine. 2011; 12: 133-136.