Differentiating and Managing Pediatric Shock

Executive Summary

• Shock can be classified into five main categories: hypovolemic, cardiogenic, distributive, neurogenic, and obstructive. In children, hypovolemic shock is most common, whereas distributive shock is most common in adults.
• Morbidity and mortality for pediatric shock are significant, with a mortality rate of as high as 23% in children with septic shock admitted to the intensive care unit. Appropriate and timely management in the emergency department (ED), however, is fundamental to good outcomes, since early shock diagnosis and reversal have substantial effects on morbidity and mortality.
• Tachycardia often is the first presenting symptom in children, and hypotension generally presents later. Hypotension should be defined using age-adjusted criteria. A simple formula to establish hypotension is a systolic blood pressure of < 70 + (age) x 2. Patients who present in hypotension with delayed capillary refill are at heightened risk for mortality and should warrant more aggressive management.
• Recognizing the evolution from sepsis to septic shock is critical to improving outcomes. For patients in septic shock, administer antibiotics within one hour of diagnosis. Although septic shock is a form of distributive shock, many children will present with “cold shock” caused by compensatory elevated systemic vascular resistance.
• Fluid resuscitation should begin promptly in 20 mL/kg increments (or smaller in children with heart disease) over five to 10 minutes, and vital signs and physical exam should be reassessed after each bolus. Shock that persists following a total of 40-60 mL/kg of fluid resuscitation is considered to be fluid-refractory and necessitates the use of vasoactive medications. Epinephrine and norepinephrine are favored as first-line vasoactive medications.
• To prevent missing cases of shock in the ED, give special attention to children with significant medical history, neurological abnormalities that might affect examination, or the presence of medical devices/hardware.

---

Early recognition and management of pediatric shock is critical for acute care providers. The authors review the subtle presentations, different approaches, and management strategies to effectively manage the different types of pediatric shock.

— Ann M. Dietrich, MD, FAAP, FACEP, Editor

Introduction

Clinicians working in the emergency department (ED) setting need to be adept at recognizing and treating pediatric shock because many of the critical points in management occur within the first hours of presentation. Recently, there has been active growth in pediatric shock research and guideline development. This article will review the latest literature on pediatric shock, discuss basic physiologic principles, and equip clinicians to practice the latest evidence-based management.

Septic shock is the most well-studied form of pediatric shock. Children admitted to the Pediatric Intensive Care Unit (PICU) for septic shock have mortality rates as high as 23%.^1-3 One-third of pediatric septic shock patients develop organ dysfunction, and nearly 20% of survivors develop new functional disability.⁴ Therefore, early recognition and treatment are critical to reducing morbidity and mortality. Within 60 minutes, unresolved shock can induce epithelial cell and organ injury, and early shock reversal is associated with 68% reduced mortality.^5,6 Given that many cases of shock first present to the ED, prudent management is essential to improving outcomes.

The approach to shock in pediatric patients varies significantly from that in adults. Whereas most adults present in distributive shock caused by sepsis, hypovolemic shock is the most common type in children.⁷ Additionally, pediatric physiology creates key differences in the diagnosis and management of shock compared to the care of adults.

Younger infants and neonates particularly depend mainly on heart rate to raise cardiac output. In addition to tachycardia, younger infants and children often maintain perfusion by increasing peripheral vascular resistance and venous tone to compensate for their relative inability to increase contractility and stroke volume. As a result, they are less likely to show hypotension at initial presentation. These differences have important implications for management and are discussed further in this article.

A note regarding neonatal care: Neonatal shock and sepsis management often encompass patients up to 60 days of age and carry unique nuances that are beyond the scope of this article. Beneficial resources include the 2021 American Academy of Pediatrics guideline on neonatal fever management in well-appearing infants as well as the Neonatal Resuscitation Program management algorithms, which are stratified by the appearance of the neonate on initial presentation.^8,9

Pathophysiology and Etiology

The pathophysiology of shock fundamentally involves a mismatch between metabolic supply and demand of vital organs, which is regulated by cardiac output and vascular blood flow dynamics. There are a number of causes, and shock is not always associated with hypotension. Shock can be characterized into five main types: hypovolemic, cardiogenic, distributive, neurogenic, and obstructive.

Hypovolemic Shock

Hypovolemic shock is caused by decreased blood volume because of either excessive losses (i.e., vomiting and diarrhea) or inadequate intake (i.e., a child unable to eat or drink). Vomiting and diarrhea because of gastrointestinal infections are the most common etiologies of hypovolemic shock worldwide.^10,11 Diarrhea alone is responsible for approximately half a million deaths in children younger than 5 years of age and is the fourth most common cause of death in this age group.^12,13 If left untreated, systemic vasoconstriction leads to tissue ischemia. Release of inflammatory cytokines from ischemic tissue further worsens capillary leakage, worsening the hemodynamic shock.

Cardiogenic Shock

Cardiogenic shock is caused by decreased cardiac contractility and cardiac output. Common examples of cardiogenic shock include myocarditis, dysrhythmia, and congenital heart disease. In a child with congenital heart disease, however, shock caused by a vascular obstruction (i.e., coarctation of the aorta) is classified as obstructive shock. In cardiogenic shock state, physiologic responses similar to hypovolemic shock are seen in an attempt to restore perfusion (i.e., increased heart rate and systemic vasoconstriction). However, unlike hypovolemic shock, in cardiogenic shock, it is important to pay careful attention to fluid administration to avoid worsening heart failure.

Distributive Shock

Distributive shock is caused by inappropriate vasodilation and pooling of blood in the peripheral vasculature. Vasodilation largely is caused by an overactive immune response to either a pathogen or toxin (sepsis) or an allergen (anaphylaxis). Septic shock is the most common form of distributive shock. Although septic shock is a form of distributive shock, most younger children in septic shock will present with elevated systemic vascular resistance (SVR) — causing “cold shock” — to compensate for their relative inability to elevate cardiac stroke volume and contractility compared to adults.^14,15 This is differentiated from “warm shock,” named because vasodilation leads to warm extremities, flash capillary refill (refill time < 1 second), and decreased SVR.

Neurogenic Shock

Neurogenic shock is most commonly caused by a traumatic spinal cord or brain injury, which disrupts sympathetic stimulation of vascular smooth muscle tone, leading to hypotension. In this case, SVR is decreased, but there is no sympathetic stimulus to oppose the vagal tone, and the body is unable to produce tachycardia in response to the hypotension. These patients will present with bradycardia, which is a distinguishing difference between neurogenic shock and other forms of shock, which usually present with tachycardia.

Obstructive Shock

Obstructive shock is caused by an obstruction of blood flow that reduces cardiac output and organ perfusion. This can be because of cardiac tamponade, tension pneumothorax, intravascular lesions (thrombus), or vascular or cardiac outflow tract abnormalities (hypoplastic left heart syndrome, aortic coarctation, etc.). In infants between 1-3 weeks of age presenting with signs of obstructive shock, it is important to consider congenital heart disease, given the typical closure of the ductus arteriosus at this time.

Clinical Features

Shock subtypes can be distinguished by reviewing vital signs and assessing perfusion, summarized in the next section and in Table 1.^10,16

Vital Signs

Vital signs are fundamental to the diagnosis of pediatric shock. In children, the heart rate often is the first vital sign to be abnormal, and hypotension is a relatively late finding.¹⁴ Hypotension should be diagnosed using age-appropriate thresholds. There are many different formulas for hypotension thresholds in children, and one simple formula using systolic blood pressure (SBP) defines hypotension as SBP < 70 + (age) × 2.¹⁷ Note that this formula will over-classify infants and younger children with hypotension and will under-classify adolescents with hypotension.

Alternatively, the Society of Critical Care Medicine has suggested SBP thresholds to define hypotension in healthcare systems without intensive care:¹⁸

• Age < 1 year: SBP < 50 mmHg
• Age 1-5 years: SBP < 60 mmHg
• Age 5+ years: SBP < 70 mmHg
• Or, the presence of cool extremities, capillary refill > 3 seconds, and weak or fast pulse¹⁹

History and Physical Examination Findings

Each subtype of shock has its own unique history and physical exam findings that can help identify the cause of shock and guide its management.

Hypovolemic Shock. This can present with a decrease in mental status, skin turgor, sunken eyes, capillary refill, and, in infants, a sunken fontanelle. The history will help distinguish hypovolemic shock from other types of shock. Hemorrhagic shock must be identified in trauma and suspected trauma patients via the trauma survey. Bedside ultrasound can provide a focused assessment with sonography in trauma (FAST) exam to identify possible intraabdominal or pericardial bleeding.

Cardiogenic Shock. Cardiogenic shock will present with findings suggestive of heart failure, which distinguish it from hypovolemic shock. The history should include assessment of chest pain, syncope, or known cardiac anomalies or medications. In addition to peripheral perfusion abnormalities, physical exam findings suggestive of cardiogenic shock include jugular venous distention in the neck, new or evolving cardiac murmur or gallop, respiratory distress, hepatomegaly, or peripheral edema. Note that, in children, hepatomegaly often is a more reliable way to assess for right heart failure, as opposed to peripheral edema, which is a key finding in adults. Using ultrasonography, pulmonary edema can be seen as a consequence of left heart failure, a distended inferior vena cava (IVC) can indicate right heart failure, and echocardiogram can reveal left and/or right ventricular dysfunction.

Distributive Shock. The history should be tailored to identify any sources of infection (fevers, malaise, presence of implanted hardware, catheters, or medical devices) or allergen exposure (food, medication, or environmental triggers). Patients who are immunocompromised because of primary disease or secondary to immunosuppressive therapy for malignancy are at particularly high risk for decompensation from infection.

In cases of anaphylaxis, physical exam findings include facial, oral, or perioral swelling, wheezing or stridor, and an urticarial rash.

In cases of septic shock, common features include abnormal pulse quality (diminished or bounding), abnormal capillary refill (prolonged or flash), abnormally warm or cool extremities, and tachypnea (in cases of pneumonia or metabolic acidosis). Skin findings associated with septic shock include erythroderma (suggestive of toxin-mediated processes) or petechiae or purpura (suggestive of disseminated intravascular coagulation).

It is important to identify sepsis early since it is a precursor to septic shock. Although adult sepsis and septic shock definitions were revised in 2016 with the “Sepsis-3” criteria, formal revisions to pediatric definitions have yet to be made, and the 2005 Pediatric Sepsis Consensus Congress (PSCC) nomenclature still is widely used. According to the 2005 PSCC, pediatric sepsis is defined as a suspected or proven infection with an abnormal leukocyte count or core temperature (> 38.5°C or < 36°C) combined with either an abnormal heart rate or respiratory rate. Severe sepsis is defined as sepsis with either cardiovascular dysfunction or acute respiratory distress syndrome — or two or more other organ dysfunctions. Therefore, septic shock is the subset of patients with severe sepsis who have cardiovascular dysfunction.²⁰

Neurogenic Shock. Cases of neurogenic shock should include a careful trauma evaluation and neurological exam to assess for risk of spinal cord or traumatic brain injury.

Obstructive Shock. In cases of obstructive shock, evidence of blood flow obstruction will be apparent and can help distinguish it from cardiogenic or hypovolemic shock. As in cases of cardiogenic shock, jugular venous distention may be present in the neck, and hepatomegaly can indicate venous congestion. Additional physical exam findings can suggest obstructive physiology. Although Beck’s triad of distended neck veins, hypotension, and diminished heart sounds classically has been associated with cardiac tamponade, these findings occur in the minority of cases. In cases of suspected tension pneumothorax, assess for unilateral decreased or absent breath sounds. Additionally, differences in strength or quality of upper and lower extremity pulses could indicate differential perfusion, which can be seen with an aortic arch interruption or aortic coarctation. On point-of-care ultrasound, a distended IVC can indicate venous congestion, right ventricular dilation or systolic dysfunction can be present in cases of pulmonary embolism, and pericardial effusion can be seen in cases of cardiac tamponade.

Risk Stratifying Elements of History and Physical Exam

Hypotension and Capillary Refill. In a study of community pediatric EDs, Carcillo et al showed a progressive increase in mortality with worsening hemodynamic findings on physical exam. In their study, patients with hypotension or abnormal capillary refill (more than 3 seconds capillary refill time or with mottled extremities) had a mortality rate of 4.4% and 7.6%, respectively. When patients presented with both hypotension and abnormal capillary refill, the mortality rate was 26.9%.⁶ Therefore, patients with a combination of hypotension and capillary refill should be given careful attention with a low threshold to initiate treatment quickly and aggressively titrate vasoactive medications.

Shock Index. The shock index (SI) is defined as heart rate divided by SBP. SI has been shown to be twice as accurate as hypotension alone in predicting patients with blunt trauma who needed surgery, endotracheal intubation, or blood transfusion.²¹ In cases of septic shock, SI was associated with significantly higher mortality rates in pediatric patients.²²

Suggested cutoffs for SI in children based on age-appropriate normal vital signs include:²³

• Ages 4-6 years: SI > 1.22;
• Ages 7-12 years: SI > 1.0;
• Ages 13-16 years: SI > 0.9

Missed Cases of Sepsis

As previously mentioned, sepsis is an important precursor to pediatric shock. In a recent study at a tertiary care children’s hospital, patients with missed sepsis were more likely to progress into shock and were four times as likely to require vasoactive support.²⁴ Of patients in whom sepsis was missed, 68% had a prior PICU-level stay, 53% had a significant underlying neurologic abnormality, 28% had documented limited vascular access, 23% had a central line, and 15% were tracheostomy/ventilator dependent.²⁴ Therefore, more scrutiny should be given to children with significant medical history, neurological abnormalities that might affect examination, or presence of medical devices/hardware.

Management

To begin, Davis et al constructed an algorithm to follow to manage shock in infants and children, which is available online at https://bit.ly/3Jt8Gu9.²⁵

Immediate Interventions

After diagnosis or development of heightened suspicion for shock based on the clinical features previously described (i.e., decreased mental status and perfusion), management should begin with respiratory and hemodynamic stabilization.

Airway and Breathing. Within the first five minutes of shock recognition, all patients should receive supplemental oxygen via a 100% nonrebreather mask or high-flow nasal cannula while providers stabilize the patient’s hemodynamics. In a state of hemodynamic shock, supplemental oxygenation can help enhance oxygen delivery and counter poor perfusion. If any form of positive pressure ventilation (PPV) is needed, note that it will reduce cardiac preload because of the increased intrathoracic pressure. Therefore, fluids and vasoactive medications may be needed sooner than usual with the initiation of PPV.

Circulation. Patients in shock ideally should have two large-bore peripheral intravenous (IV) lines placed. While early IV fluids are a cornerstone of management, first, check for any signs of fluid overload (i.e., pulmonary rales, hepatomegaly, or peripheral edema) that could suggest underlying cardiac dysfunction.

IV fluid boluses should be given in 20 mL/kg increments over five to 10 minutes, and the clinician should reassess vitals and physical exam after each bolus. Development of hepatomegaly or rales suggests fluid overload or developing heart failure and should prompt a reassessment prior to administering further fluid resuscitation. In children who might be experiencing heart failure or fluid overload (i.e., patient with congenital heart disease or renal failure), boluses of 5-10 mL/kg are advisable. In the first 60 minutes, fluid resuscitation can include up to a total of 60 mL/kg of fluid, after which the case is considered to be fluid-refractory.¹⁰ There is emerging evidence that the ratio of the caliber of the IVC to that of the aorta (Ao) predicts fluid responsiveness. Evidence suggests that an initial IVC:Ao ratio of less than 0.6 to 0.8 predicts a more favorable response to IV fluids.^26,27

There is ongoing debate regarding fluid choice for resuscitation in cases of hemodynamic shock. In randomized controlled trials of critically ill adults, there have been mixed results when comparing crystalloid fluids containing high concentrations of chloride (such as normal saline solutions) vs. balanced crystalloids (such as lactated Ringer’s solution). There is evidence showing that balanced crystalloids have a lower incidence of hyperchloremic metabolic acidosis, acute kidney injury, and death, but recent studies have found minimal to no differences in outcomes.^28-30 No randomized controlled trials have been done in pediatric patients, but observational studies have associated a decreased risk of mortality with using balanced solutions for resuscitation, possibly because of the decreased risk of metabolic acidosis.^31,32 While fluid choice in the ED represents a small fraction of time in a patient’s care, one can consider resuscitation with lactated Ringer’s solution if it is available.

Peripheral IV sites can be used for initial vasoactive medication administration. General agreement in the latest literature is that the risks of adverse events is low, especially if the duration of infusion is less than two hours.^33-35 These adverse events include peripheral IV line infiltration and local extravasation causing tissue ischemia, with an incidence of about 3%.³³ While the median duration of vasopressor infusion studied in children is approximately four to six hours, infiltration and extravasation generally occurs within two hours of infusion.^33-35 If IV access is not possible, intraosseous access can be established for fluid and blood administration as well as infusion of vasoactive medications. Central access is necessary if the patient’s shock is fluid refractory and if advanced hemodynamic monitoring is necessary (i.e., central venous pressure). If PICU transfer is delayed, arterial line placement in the ED can help to provide continuous blood pressure monitoring.

Blood Cultures. Blood cultures are important in the ongoing management of septic shock. Obtaining blood cultures, however, should not delay administration of antibiotics.³⁶ While the turnaround time of blood culture results makes their use limited in the ED, emerging technologies may increase the speed of blood culture results to as little as 10-30 minutes.^37-39 These mass spectrometry, enzyme-linked, and polymerase chain reaction-based strategies are in various stages of development and have the potential to become increasingly relevant tools in the management of pediatric septic shock in the ED.

Antibiotic Timing. Although considerable data exist regarding antibiotic administration for pediatric septic shock, the Surviving Sepsis Campaign (SSC) has formalized many aspects of management with its inaugural evidence-based international guidelines for sepsis management released in 2020. The SSC guidelines reviewed studies on antibiotic administration in children with pediatric sepsis, severe sepsis, and septic shock, and concluded that the significance of antibiotic timing varies with illness severity. For children presenting in septic shock, there is evidence that starting antimicrobial therapy within one hour of septic shock recognition improves morbidity and mortality.^18,40 Ideally, antibiotic administration should occur within the first five minutes of diagnosis as a part of resuscitation.

Antibiotic timing for patients not yet in shock, however, is an area of current debate. While we recommend antibiotic administration within one hour of diagnosis for patients in shock, for patients with sepsis-related organ dysfunction without shock, the evidence dictating antibiotic timing in children is weak.^18,41,42 In the studies that do demonstrate significant effects, evidence suggests that antibiotic administration within three hours of diagnosis is important because of the increased mortality risk after a three-hour delay from diagnosis of severe sepsis in patients who are not in shock.^18,36,43

Antibiotic Choice. The most recent antibiotic recommendations for the management of severe sepsis and septic shock can be found in the 2020 Surviving Sepsis pediatric guidelines.¹⁸ The pertinent details are summarized in Table 2.

Vasoactives

Shock that persists following a total of 40-60 mL/kg of fluid resuscitation is considered to be fluid-refractory and necessitates the use of vasoactive medications.⁴¹ The choice of vasoactive medication depends on the stage of treatment and patient condition. For patients experiencing high levels of peripheral vasoconstriction (cold shock), such as patients in hypovolemic or late septic shock, epinephrine is a suitable first choice, given its vasodilatory effects at low doses and its positive inotropic and chronotropic properties.

For patients exhibiting significant peripheral vasodilation (warm shock), such as patients in early stages of septic shock, norepinephrine is an ideal first choice, given its predominant effect at alpha-1 receptors that cause vasoconstriction. Although epinephrine and norepinephrine are recommended over dopamine, dopamine sometimes may be more readily available and can also be used for increasing renal blood flow, cardiac contractility, and blood pressure, depending on the dose used.¹⁸

In later stages of shock, where vasoconstriction is predominant or if cardiac performance augmentation is desired, dobutamine and milrinone can be considered. Table 3 shows a summary of vasoactive medications.¹⁰

Steroid Use

The use of steroids in shock remains controversial. Given the inconsistent evidence, the 2020 SSC International Guidelines do not recommend or refute the use of IV hydrocortisone for cases of pediatric septic shock refractory to vasoactive medications.¹⁸ Intuitively, the physiologic case for glucocorticoid use in shock is strong because glucocorticoids increase blood pressure by increasing vascular resistance via norepinephrine effects on arterioles and by increasing fluid retention via mineralocorticoid effects on the kidneys.

There are important adverse effects, however, including hyperglycemia and increased risk of hospital-acquired infections.⁵⁰ In patients with known adrenal insufficiency, stress doses of hydrocortisone of 50-100 mg/m²/day often are used to support hemodynamics.^18,44 This can be simplified to giving 25 mg of hydrocortisone to children younger than 2 years of age, 50 mg to children between 2 and 10 years of age, and 100 mg to children older than 10 years of age.

In children without known adrenal insufficiency, the evidence for hydrocortisone in cases of shock that are refractory to vasoactive medications is mixed and insufficient to evaluate its effects.^18,51-53 The only randomized controlled trial of the use of corticosteroids in children with shock refractory to vasoactive medications, the Steroids in Fluid and/or Vasoactive Infusion Dependent Pediatric Shock (STRIPES) trial, has not yet yielded peer-reviewed results.⁵⁴

Diagnostic Studies

In the diagnostic evaluation and monitoring of shock, testing should focus on evaluating specific organ system dysfunction and monitoring parameters during resuscitation. Common diagnostic studies include a complete blood count, serum electrolytes, and a lactate level. Although no lactate thresholds have been established in children, elevated levels are associated with adverse outcomes in cases of pediatric septic shock.^18,55-58

Data in adults have shown a threshold of 2 mmol/L to identify patients in septic shock, and lactate levels of more than 2 mmol/L in children requiring vasopressors are associated with 32% mortality, vs. 16.1% for lactate levels less than 2 mmol/L.^55,59 One study showed that, as a marker of progress, normalization of lactate levels within two to four hours of presentation was associated with a decreased risk of persistent organ dysfunction.⁶⁰ Additionally, lactate levels can help prevent missed cases of sepsis, which can quickly evolve into shock. At one tertiary care center, patients with sepsis that was missed initially were significantly less likely to have lactate levels drawn.⁶¹ Blood cultures also are important, as is a urinalysis and urine culture. Inflammatory markers (such as C-reactive protein, erythrocyte sedimentation rate, and procalcitonin) can be drawn to evaluate for infectious risk as well.

A rapid blood glucose test is important in a mentally altered patient and for patients in septic shock. Stress hyperglycemia has been shown to be associated with increased morbidity and mortality in patients with septic shock through a variety of proposed metabolic, immunologic, and neurologic mechanisms.^62-65 However, targeting a low-glucose target range (blood glucose < 140 mg/dL) with insulin therapy has significant risk of hypoglycemia, and randomized controlled trials in children have not shown clinical benefits.^66,67 The 2020 SSC guidelines acknowledge that many providers target levels below 180 mg/dL because of the lower risks of hypoglycemia, although no direct comparisons have been studied.¹⁸ Children with septic shock particularly are at high risk of hypocalcemia, possibly caused by hormonal disturbances, and correction should be aimed at preventing severe hypocalcemia (ionized calcium of < 1.1 mmol/L) or cardiac arrhythmia.⁶⁸ In the 2020 SSC, target calcium levels were not given, but the committee acknowledged that most providers target normal calcium levels for children with septic shock.¹⁸

For patients presenting with hemorrhagic shock, a blood type and cross-match and coagulation studies should be obtained. For patients who are suspected to have cardiogenic shock, assessment of cardiomegaly on chest radiograph can help with establishing the diagnosis. A 12-lead electrocardiogram can be obtained to evaluate for structural signs of heart failure, although its sensitivity is poor.^69,70

Alternatively, point-of-care ultrasound is particularly helpful in determining ejection fraction, wall motion abnormalities, and the presence of fluid effusions to aid in the diagnosis of cardiogenic shock or pulmonary vascular obstruction.⁷¹

If obstructive shock is suspected because of a pneumothorax, a chest X-ray should be ordered or a beside ultrasound could be performed that shows minimal lung sliding. Point-of-care ultrasound also can be helpful in identifying cardiac tamponade. If a pulmonary embolism is suspected, visualization of flattening or bowing of the interventricular septum on bedside cardiac ultrasound has been shown to be moderately specific (83%) but poorly sensitive (40%) in adults, although its use is continually being refined.^72-74 Chest computed tomography with pulmonary angiography should be obtained if ultrasound examination is not diagnostic and the patient is stable enough.⁷⁵

Standardization of Care

Because of the high morbidity and mortality rates associated with pediatric shock, intervening early is particularly important, and timely identification and intervention are an area of process improvement. There are increasing calls for medical centers to standardize pediatric shock recognition and treatment in the ED via bundled approaches. Recommended components include:¹⁸

• systematic screening for shock and severe sepsis that might progress to shock;
• standardized detection criteria using electronic health record tools;
• bundled treatments, including fluid, antibiotic, and vasoactive medication administration; and
• constant quality improvement programs to assess the effect on clinical practice, and continuous adjustment to the institutional practice environment.

These bundles have been shown to improve PICU and hospital length of stay and mortality.^76-81 Early identification using bundled approaches is particularly important, since shock can evolve rapidly.

All patients in shock should be admitted or transferred to a PICU for further treatment.

Conclusions and Future Directions

While similar in many ways to the management of shock in adults, management of children in shock requires unique strategies and remains an active area of research. The ED plays a critical role in the care of pediatric shock because interventions within the first hour can have a significant effect on patient outcomes. Care in the ED should be aimed at maintaining or restoring the patient’s airway, oxygenation, ventilation, and circulation to achieve normal heart rate, blood pressure, and mental status. Reversal of hemodynamic abnormalities in the ED has been associated with significant reduction in mortality regardless of the stage of hemodynamic abnormality at the time of presentation. Fluid resuscitation and antibiotics (if indicated) should be administered as soon as possible, and after 40-60 mL/kg of total fluid administration, vasoactive medications should be used.

Diagnosis of shock in children with significant medical history, neurological abnormalities that might affect examination, or a presence of medical devices/hardware can be easily missed, and these patients should be given particular attention. Given the importance of early management in the ED, research into new risk-stratification techniques using point-of-care imaging and novel biomarkers may help improve outcomes. It is hoped that future pediatric-focused randomized controlled trials will answer questions around steroid use, choice of fluid, and optimal vasoactive agents, among others. Lastly, given the importance of timely intervention, more medical centers are adopting bundled target-based approaches to patients in shock in an effort to reduce time to treatment, reduce variation in care, and ultimately improve outcomes.

References

1. Ruth A, McCracken CE, Fortenberry JD, et all. Pediatric severe sepsis: Current trends and outcomes from the Pediatric Health Information Systems database. Pediatr Crit Care Med 2014;15:828-838.
2. Schlapbach LJ, Straney L, Alexander J, et al. Mortality related to invasive infections, sepsis, and septic shock in critically ill children in Australia and New Zealand, 2002-2013: A multicentre retrospective cohort study. Lancet Infect Dis 2015;15:46-54.
3. de Souza DC, Shieh HH, Barreira ER, et al. Epidemiology of sepsis in children admitted to PICUs in South America. Pediatr Crit Care Med 2016;17:727-734.
4. Weiss SL, Fitzgerald JC, Pappachan J, et al. Global epidemiology of pediatric severe sepsis: The Sepsis Prevalence, Outcomes, and Therapies Study. Am J Respir Crit Care Med 2015;191:1147-1157.
5. Guseinov RG, Popov SV, Gorshkov AN, et al. Effects of renal warm ischemia time on the recovery of filtration function in the experiment. Urologiia 2017;6:20-29.
6. Carcillo JA, Kuch BA, Han YY, et al. Mortality and functional morbidity after use of PALS/APLS by community physicians. Pediatrics 2009;124:500-508.
7. Topjian AA, Raymond TT, Atkins D, et al. Part 4: Pediatric basic and advanced life support: 2020 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2020;142(16_suppl_2):S469-S523.
8. Pantell RH, Roberts KB, Adams WG, et al. Evaluation and management of well-appearing febrile infants 8 to 60 days old. Pediatrics 2021;1482:e2021052228.
9. Weiner MD, Zaichkin J, eds. NRP Textbook of Neonatal Resuscitation. 8th ed. American Academy of Pediatrics; 2021.
10. Shaw KN, Bachur RG, eds. Fleisher & Ludwig’s Textbook of Pediatric Emergency Medicine. 8th ed. Wolters Kluwer; 2021.
11. Hobson MJ. Pediatric hypovolemic shock. Open Pediatr Med J 2013;7:10-15.
12. Troeger C, Forouzanfar M, Rao PC, et al. Estimates of global, regional, and national morbidity, mortality, and aetiologies of diarrhoeal diseases: A systematic analysis for the Global Burden of Disease Study 2015. Lancet Infect Dis 2017;17:909-948.
13. Wang H, Naghavi M, Allen C, et al. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016;388:1459-1544.
14. Aneja R, Carcillo J. Differences between adult and pediatric septic shock. Minerva Anestesiol 2011;77:986-992.
15. Martin K, Weiss SL. Initial resuscitation and management of pediatric septic shock. Minerva Pediatr 2015;67:141-158.
16. Kliegman R, Stanton B, St. Geme JW, et al. Nelson Textbook of Pediatrics. 19th ed. Saunders; 2016.
17. [No authors listed]. Part 10: Pediatric advanced life support. Circulation 2000;102:291-342.
18. Weiss SL, Peters MJ, Alhazzani W, et al. Surviving Sepsis Campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Pediatr Crit Care Med 2020;21:e52-e106.
19. World Health Organization. Updated guideline: Paediatric emergency triage, assessment and treatment: Care of critically-ill children. https://apps.who.int/iris/handle/10665/204463
20. Goldstein B, Giroir B, Randolph A; International Consensus Conference on Pediatric Sepsis. International Pediatric Sepsis Consensus Conference: Definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005;6:2-8.
21. Acker SN, Bredbeck B, Partrick DA, et al. Shock index, pediatric age-adjusted (SIPA) is more accurate than age-adjusted hypotension for trauma team activation. Surgery 2017;161:803-807.
22. Yasaka Y, Khemani RG, Markovitz BP. Is shock index associated with outcome in children with sepsis/septic shock? Pediatr Crit Care Med 2013;14:e372-e379.
23. Acker SN, Ross JT, Partrick DA, et al. Pediatric specific shock index accurately identifies severely injured children. J Pediatr Surg 2015;50:331-334.
24. Souganidis E, Abbadessa MK, Ku B, et al. Analysis of missed sepsis patients in a pediatric emergency department with a vital sign-based electronic sepsis alert. Pediatr Emerg Care 2022;38:e1-e4.
25. Davis AL, Carcillo JA, Aneja RK, et al. American College of Critical Care Medicine Clinical Practice parameters for hemodynamic support of pediatric and neonatal septic shock. Crit Care Med 2017;45:1061-1093.
26. Babaie S, Behzad A, Mohammadpour M, Reisi M. A comparison between the bedside sonographic measurements of the inferior vena cava indices and the central venous pressure while assessing the decreased intravascular volume in children. Adv Biomed Res 2018;7:97.
27. Kusumastuti NP, Latief A, Pudjiadi AH. Inferior vena cava/abdominal aorta ratio as a guide for fluid resuscitation. J Emerg Trauma Shock 2021;14:211-215.
28. Semler MW, Self WH, Wanderer JP, et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med 2018;378:829-839.
29. Finfer S, Micallef S, Hammond N, et al. Balanced multielectrolyte solution versus saline in critically ill adults. N Engl J Med 2022;386:815-826.
30. Self WH, Semler MW, Wanderer JP, et al. Balanced crystalloids versus saline in noncritically ill adults. N Engl J Med 2018;378:819-828.
31. Emrath ET, Fortenberry JD, Travers C, et al. Resuscitation with balanced fluids is associated with improved survival in pediatric severe sepsis. Crit Care Med 2017;45:1177-1183.
32. Weiss SL, Keele L, Balamuth F, et al. Crystalloid fluid choice and clinical outcomes in pediatric sepsis: A matched retrospective cohort study. J Pediat 2017;182:304-310.e10.
33. Owen VS, Rosgen BK, Cherak SJ, et al. Adverse events associated with administration of vasopressor medications through a peripheral intravenous catheter: A systematic review and meta-analysis. Crit Care 2021;25:146.
34. Patregnani JT, Sochet AA, Klugman D. Short-term peripheral vasoactive infusions in pediatrics: Where is the harm? Pediatr Crit Care Med 2017;18:e378-e381.
35. Charbel RC, Ollier V, Julliand S, et al. Safety of early norepinephrine infusion through peripheral vascular access during transport of critically ill children. J Am Coll Emerg Physicians Open 2021;2:e12395.
36. Weiss SL, Fitzgerald JC, Balamuth F, et al. Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis. Crit Care Med 2014;42:2409-2417.
37. Kang D-K, Ali MM, Zhang K, et al. Rapid detection of single bacteria in unprocessed blood using integrated comprehensive droplet digital detection. Nat Commun 2014;5:5427.
38. She RC, Bender JM. Advances in rapid molecular blood culture diagnostics: Healthcare impact, laboratory implications, and multiplex technologies. J Appl Lab Med 2019;3:617-630.
39. Kothari A, Morgan M, Haake DA. Emerging technologies for rapid identification of bloodstream pathogens. Clin Infect Dis 2014;59:272-278.
40. Sankar J, Garg M, Ghimire JJ, et al. Delayed administration of antibiotics beyond the first hour of recognition is associated with increased mortality rates in children with sepsis/severe sepsis and septic shock. J Pediatr 2021;233:183-190.e3.
41. Schlapbach LJ, Weiss SL, Wolf J. Reducing collateral damage from mandates for time to antibiotics in pediatric sepsis — primum non nocere. JAMA Pediatr 2019;173: 409-410.
42. Klompas M, Calandra T, Singer M. Antibiotics for sepsis — finding the equilibrium. JAMA 2018;320:1433-1434.
43. Alsadoon A, Alhamwah M, Alomar B, et al. Association of antibiotics administration timing with mortality in children with sepsis in a tertiary care hospital of a developing country. Front Pediatr 2020;8:566.
44. Pediatric and neonatal Lexi-drugs online. Lexicomp Online. http://webstore.lexi.com/ONLINE
45. Congeni B, Di Pentima C. Antimicrobial therapy. In: McInerny TK, Adam HM, Campbell DE, et al, eds. American Academy of Pediatrics Textbook of Pediatric Care. American Academy of Pediatrics;2016:441-476.
46. Paul M, Dickstein Y, Schlesinger A, et al. Beta-lactam versus beta-lactam-aminoglycoside combination therapy in cancer patients with neutropenia. Cochrane Database Syst Rev 2013;2013:CD003038.
47. Lehrnbecher T, Robinson P, Fisher B, et al. Guideline for the management of fever and neutropenia in children with cancer and hematopoietic stem-cell transplantation recipients: 2017 update. J Clin Oncol 2017;35:2082-2094.
48. Bonne SL, Kadri SS. Evaluation and management of necrotizing soft tissue infections. Infect Dis Clin North Am 2017;31:497-511.
49. Andreoni F, Zürcher C, Tarnutzer A, et al. Clindamycin affects group A Streptococcus virulence factors and improves clinical outcome. J Infect Dis 2017;215:269-277.
50. Costello JM, Graham DA, Morrow DF, et al. Risk factors for central line-associated bloodstream infection in a pediatric cardiac intensive care unit. Pediatr Crit Care Med 2009;10:453-459.
51. El-Nawawy A, Khater D, Omar H, Wali Y. Evaluation of early corticosteroid therapy in management of pediatric septic shock in pediatric intensive care patients: A randomized clinical study. Pediatr Infect Dis J 2017;36:155-159.
52. Valoor HT, Singhi S, Jayashree M. Low-dose hydrocortisone in pediatric septic shock: An exploratory study in a third world setting: Pediatr Crit Care Med 2009;10:121-125.
53. Nichols B, Kubis S, Hewlett J, et al. Hydrocortisone therapy in catecholamine-resistant pediatric septic shock: A pragmatic analysis of clinician practice and association with outcomes. Pediatr Crit Care Med 2017;18:e406-e414.
54. O’Hearn K, McNally D, Choong K, et al; Canadian Critical Care Trials Group. Steroids in fluid and/or vasoactive infusion dependent pediatric shock: Study protocol for a randomized controlled trial. Trials 2016;17:238.
55. Schlapbach LJ, MacLaren G, Festa M, et al; Australian & New Zealand Intensive Care Society (ANZICS) Centre for Outcomes & Resource Evaluation (CORE) and Australian & New Zealand Intensive Care Society (ANZICS) Paediatric Study Group. Prediction of pediatric sepsis mortality within 1 h of intensive care admission. Intensive Care Med 2017;43:1085-1096.
56. Bai Z, Zhu X, Li M, et al. Effectiveness of predicting in-hospital mortality in critically ill children by assessing blood lactate levels at admission. BMC Pediatr 2014;14:83.
57. Chen M, Lu X, Hu L, et al. Development and validation of a mortality risk model for pediatric sepsis. Medicine (Baltimore) 2017;96:e6923.
58. Scott HF, Brou L, Deakyne SJ, et al. Association between early lactate levels and 30-day mortality in clinically suspected sepsis in children. JAMA Pediatr 2017;171:249-255.
59. Shankar-Hari M, Phillips GS, Levy ML, et al. Developing a new definition and assessing new clinical criteria for septic shock: For the third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 2016;315:775-787.
60. Scott HF, Brou L, Deakyne SJ, et al. Lactate clearance and normalization and prolonged organ dysfunction in pediatric sepsis. J Pediatr 2016;170:149-155.e1-e4.
61. Scott HF, Greenwald EE, Bajaj L, et al. The sensitivity of clinician diagnosis of sepsis in tertiary and community-based emergency settings. J Pediatr 2018;195:220-227.e1.
62. Faustino EV, Apkon M. Persistent hyperglycemia in critically ill children. J Pediatr 2005;146:30-34.
63. Wintergerst KA, Buckingham B, Gandrud L, et al. Association of hypoglycemia, hyperglycemia, and glucose variability with morbidity and death in the pediatric intensive care unit. Pediatrics 2006;118:173-179.
64. Yung M, Wilkins B, Norton L, et al. Glucose control, organ failure, and mortality in pediatric intensive care. Pediatr Crit Care Med 2008;9:147-152.
65. Srinivasan V, Spinella PC, Drott HR, et al. Association of timing, duration, and intensity of hyperglycemia with intensive care unit mortality in critically ill children. Pediatr Crit Care Med 2004;5:329-336.
66. Agus MSD, Steil GM, Wypij D, et al. Tight glycemic control versus standard care after pediatric cardiac surgery. N Engl J Med 2012;367:1208-1219.
67. Macrae D, Grieve R, Allen E, et al. A randomized trial of hyperglycemic control in pediatric intensive care. N Engl J Med 2014;370:107-118.
68. Cardenas-Rivero N, Chernow B, Stoiko MA, et al. Hypocalcemia in critically ill children. J Pediatr 1989;114:946-951.
69. Fonseca C, Mota T, Morais H, et al. The value of the electrocardiogram and chest X-ray for confirming or refuting a suspected diagnosis of heart failure in the community. Eur J Heart Fail 2004;6:807-812.
70. Rivenes SM, Colan SD, Easley KA, et al. Usefulness of the pediatric electrocardiogram in detecting left ventricular hypertrophy: Results from the Prospective Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P2C2 HIV) multicenter study. Am Heart J 2003;145:716-723.
71. Miller AF, Arichai P, Gravel CA, et al. Use of cardiac point-of-care ultrasound in the pediatric emergency department. Pediatr Emerg Care 2022;38:e300-e305.
72. Lieveld A, Heldeweg MLA, Smit JM, et al. Multi-organ point-of-care ultrasound for detection of pulmonary embolism in critically ill COVID-19 patients — A diagnostic accuracy study. J Crit Care 2022;69:153992.
73. Zhu R, Ma XC. Clinical value of ultrasonography in diagnosis of pulmonary embolism in critically ill patients. J Transl Intern Med 2017;5:200-204.
74. Alerhand S, Sundaram T, Gottlieb M. What are the echocardiographic findings of acute right ventricular strain that suggest pulmonary embolism? Anaesth Crit Care Pain Med 2021;40:100852.
75. Moore AJE, Wachsmann J, Chamarthy MR, et al. Imaging of acute pulmonary embolism: An update. Cardiovasc Diagn Ther 2018;8:225-243.
76. Akcan Arikan A, Williams EA, Graf JM, et al. Resuscitation bundle in pediatric shock decreases acute kidney injury and improves outcomes. J Pediatr 2015;167:1301-1305.e1.
77. Rodrigues-Santos G, de Magalhães-Barbosa MC, Raymundo CE, et al. Improvement of 1st-hour bundle compliance and sepsis mortality in pediatrics after the implementation of the surviving sepsis campaign guidelines. J Pediatr (Rio J) 2021;97:459-467.
78. Evans IVR, Phillips GS, Alpern ER, et al. Association between the New York sepsis care mandate and in-hospital mortality for pediatric sepsis. JAMA 2018;320:358-367.
79. Lane RD, Funai T, Reeder R, Larsen GY. High reliability pediatric septic shock quality improvement initiative and decreasing mortality. Pediatrics 2016;138:e20154153.
80. Balamuth F, Weiss SL, Fitzgerald JC, et al. Protocolized treatment is associated with decreased organ dysfunction in pediatric severe sepsis. Pediatr Crit Care Med 2016;17:817-822.
81. Cruz AT, Perry AM, Williams EA, et al. Implementation of goal-directed therapy for children with suspected sepsis in the emergency department. Pediatrics 2011;127:e758-e766.