Pediatric Sepsis and Shock

Sepsis, septic shock, and other forms of shock are common indications for admission to the pediatric intensive care unit (PICU) and contribute substantially to morbidity and mortality in children. In this section, we review the diagnosis and management of sepsis and septic shock and provide a brief overview of other forms of shock.

Sepsis

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. The 2005 International Consensus Conference on Pediatric Sepsis defined sepsis in children as systemic inflammatory response syndrome (SIRS) in the presence of suspected or confirmed infection. SIRS is defined as a widespread inflammatory response with abnormalities in any two of the following categories: temperature, heart rate, respiratory rate, and leukocyte count.

In 2016, The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) definition for sepsis in adults was published and classified organ failure as the hallmark of sepsis. Using the Sepsis-3 definition, organ failure is now identified and characterized using the Sequential Organ Failure Assessment (SOFA) score rather than the broader SIRS criteria, which can represent adaptive immune response to infection. However, the SOFA score is not suitable for children, because it is not adjusted for age.

A 2017 study assessed, adapted, and validated the use of a pediatric SOFA (pSOFA) score to classify organ dysfunction in pediatric patients using the Sepsis-3 definition, with promising results. The pSOFA score, in addition to cutoffs for oxygenation, coagulation, neurologic, renal, and hepatic status, includes age-specific blood-pressure and renal scores. Organ dysfunction in sepsis is defined as an increase in pSOFA score >2 from baseline, with scores >8 indicating higher mortality. A descriptive table of the pSOFA score can be found here.

Septic Shock

Septic shock is diagnosed in a subset of patients with sepsis who have profound alterations in circulation and cellular metabolism with inadequate tissue perfusion. Typically, this represents patients who have sepsis and require vasopressor therapy to maintain adequate perfusion. In adults, Sepsis-3 defines septic shock as persisting hypotension requiring vasopressors to maintain mean arterial pressure ≥65 mmHg and having a serum lactate level >2 mmol/L despite adequate volume resuscitation. In children, however, hypotension is often a late finding. Therefore, pediatric shock continues to be a clinical diagnosis utilizing assessment of tissue perfusion from a combination of clinical exam findings and laboratory markers.

Clinical Signs

Clinical signs of septic shock include the following:

• markers of inadequate perfusion and infection (e.g., hypo- or hyperthermia)

• altered mental status

• tachycardia

• peripheral vasodilation (warm shock) or peripheral vasoconstriction (cold shock) with delayed capillary refill (>2 seconds)

Treatment of Sepsis and Septic Shock

The major tenets of therapy for sepsis and septic shock center around early recognition and initiation of therapy. Time is critical, and treatment should be started early. In children, septic shock can and should be recognized clinically prior to development of hypotension.

Antibiotic Treatment: Early and appropriate antibiotic therapy has been shown to be associated with reduced mortality. Therefore, empiric broad-spectrum antibiotics should be given within the first hour of recognition and tailored to specific microbiologic data as they become available with consideration of hospital antibiograms.

Fluid Resuscitation: Isotonic crystalloid is the fluid of choice for resuscitation (e.g., 0.9% NaCl or lactated Ringer solution). After each initial bolus of 20 cc/kg, assessment should be made for signs of improved cardiac output, including heart rate, capillary refill, mental status, and urine output. Additionally, the patient should be reassessed for signs of fluid overload (e.g., rales or hepatomegaly). Most patients require 40-60 cc/kg of isotonic crystalloid for improvement, after which vasoactive medications should be initiated for fluid-refractory shock.

In hemodynamically unstable patients with hemoglobin <10 g/dL, red-cell transfusion can be considered as the additional fluid of choice, although evidence suggests that lower thresholds may be safe. In 2018, the Pediatric Critical Care Transfusion and Anemia Expertise Initiative (TAXI) published updated guidelines on red-cell transfusion, recommending a hemoglobin concentration threshold of <5 g/dL for transfusion in critically ill children. TAXI also recommends against transfusion in critically ill children with a hemoglobin concentration ≥7 g/dL, and use of clinical judgement in transfusion decisions in critically ill children with hemoglobin concentrations between 5 and 7 g/dL.

Maintenance fluids should be given with isotonic saline containing 5%-10% dextrose to meet the increased glucose demands in children.

Vasopressors: If volume resuscitation is inadequate or not tolerated, early vasopressor initiation is warranted. Traditionally, dopamine was historically cited as the first-line agent in pediatrics given its safety in being administered through peripheral intravenous (IV) access and its widespread availability. However, the Surviving Sepsis guidelines no longer recommend dopamine as a first-line agent. Epinephrine and norepinephrine should be considered first-line therapies for treatment of septic shock. Epinephrine increases heart rate and cardiac contractility, but it also has vasodilator effects at doses of <0.1-0.3 mcg/kg/min and vasoconstrictor effects at higher doses (>0.3 mcg/kg/min). Norepinephrine has more alpha-2-adrenergic receptor effects that make it a more potent vasoconstrictor than dopamine, while also increasing heart rate and improving cardiac contractility. Dopamine may still be used if epinephrine or norepinephrine is not readily available. After initial stabilization, selection of the appropriate vasoactive agent should be driven by the clinical features of the child’s presentation with either low cardiac output and high systemic vascular resistance (“cold shock”) or high cardiac output and low systemic vascular resistance (“warm shock”). Epinephrine should be continued for cold shock, while norepinephrine is preferred for warm shock.

Initial selection of vasopressors should be guided by institutional and departmental availability to quickly improve the patient’s perfusion and hemodynamic parameters. Newer data indicate that vasoactive drugs other than dopamine can also be started safely through peripheral access while central access is being obtained. In children, hemodynamic states may change over time, and the most appropriate vasopressor may change as well. In catecholamine-resistant shock with low systemic vascular resistance, vasopressin may be added if norepinephrine and fluids are inadequate.

Other Therapies: Intubation and respiratory support should be considered with persistent or worsening shock (see Respiratory Failure and Mechanical Ventilation in this rotation guide). In patients with refractory hypotension, consider stress dose hydrocortisone, especially if risk factors for hypoadrenalism are present. Calcium should be replaced to maintain a normalized ionized calcium. In refractory shock, extracorporeal membrane oxygenation (ECMO) may be an important consideration.

Extracorporeal Membrane Oxygenation (ECMO): ECMO is a type of mechanical cardiopulmonary support similar to cardiopulmonary bypass and is used at select centers for refractory patients with septic shock and other indications. The two primary types of ECMO are venovenous (VV) and venoarterial (VA). Both types provide lung support, but only venoarterial ECMO provides circulatory support. In addition to patients with refractory shock, ECMO can also be considered in patients with severe respiratory failure, cardiac arrest, massive pulmonary embolism, and as a bridge to heart and lung transplantation. The invasive nature of ECMO makes it fraught with adverse effects, including bleeding and infection. Survival outcomes are also dependent on the indication. Additional information about indications, mechanics, and outcomes can be found on the Extracorporeal Life Support website.

Other Types of Pediatric Shock

In addition to the physiology encountered in septic shock, inadequate tissue perfusion can also be encountered in other forms of shock.

Hypovolemic shock: Volume loss due to fluid losses or hemorrhage can cause decreased tissue perfusion leading to hypovolemic shock. Diarrhea and subsequent dehydration are a common cause in the developing world. In the case of hemorrhage, volume resuscitation should be in the form of blood transfusions.

Distributive shock: In addition to septic shock, other types of distributive shock include anaphylaxis and neurogenic shock. Anaphylaxis should be considered with a history of exposure to an allergen; it should be treated with immediate intramuscular epinephrine and may require an epinephrine infusion to restore perfusion as outlined above. Neurogenic shock can occur with a history of trauma causing severe head or spinal cord injury.

Cardiogenic shock: In the setting of decreased cardiac output from reduced preload, contractility, or afterload, inadequate tissue perfusion can ensue. Common etiologies of pediatric cardiogenic shock include arrhythmias, especially prolonged and unrecognized supraventricular tachycardia, myocarditis, and cardiomyopathies including familial, infectious, infiltrative, and structurally related. Inotropic support may be necessary in the form of drugs that improve contractility, such as dobutamine and milrinone. ECMO may be necessary in refractory cases.

Obstructive shock: Tension pneumothoraces, cardiac tamponade, massive pulmonary emboli, and ductal-dependent congenital heart lesions can also cause increased afterload resulting in abrupt circulatory collapse and shock.