Management of Pediatric Shock
May 15, 2021
Related Articles
-
Infectious Disease Updates
-
Noninferiority of Seven vs. 14 Days of Antibiotic Therapy for Bloodstream Infections
-
Parvovirus and Increasing Danger in Pregnancy and Sickle Cell Disease
-
Oseltamivir for Adults Hospitalized with Influenza: Earlier Is Better
-
Usefulness of Pyuria to Diagnose UTI in Children
AUTHORS
Mara O’Sullivan, MD, Emergency Medicine Resident, Wright State University, Dayton, OH
Jacob Patz, MD, Emergency Medicine Resident, Wright State University, Dayton, OH
Simranjit S. Gill, DO, Assistant Professor, Director, Emergency Medicine Simulation, Wright State University, Dayton, OH
PEER REVIEWER
Aaron N. Leetch, MD, FAAEM, FACEP, FAAP, Associate Professor of Emergency Medicine and Pediatrics, Program Director, Combined Emergency Medicine and Pediatrics Residency, University of Arizona College
of Medicine, Tucson
EXECUTIVE SUMMARY
- Shock in the pediatric patient can be difficult to identify. Subtle findings include change in behavior, fussiness, and change in appetite or voiding.
- In addition to assessment of heart rate and blood pressure, evaluate the age-adjusted shock index. Normal values for the shock index (heart rate ÷ systolic blood pressure) are < 1.22 for children ages 4 to 6 years, < 1.0 for children ages 7 to 12 years, and < 0.9 for children ages 13 to 16 years.
- Initiate early and aggressive fluid management to maintain perfusion after shock recognition.
- Do not delay administration of antibiotics in patients with septic shock awaiting blood culture draws, urine collection, or performance of a lumbar puncture.
- In fluid-refractory patients, use norepinephrine infusion for patients in “warm shock” and epinephrine infusion in patients in “cold shock.”
- Consider and treat adrenal insufficiency and hypothyroidism in patients refractory to vasopressor therapy.
Being prepared for a critically ill pediatric patient is a necessary skill for all emergency medicine (EM) physicians, especially when considering that almost one-third of emergency department (ED) patients are younger than 18 years of age.1 Depending on patient age and maturity, a clear history and physical exam can be difficult to elicit, and critical instability is less obvious in this patient population compared to adults. Although rare in this population, pediatric shock carries a high morbidity and mortality, making early recognition key. Recently, pediatric critical care and resuscitation has been the focus of ED care improvement.2
The pathophysiology of children with tissue hypoxia varies significantly from adults. Knowledge of specific clinical features, a focused evaluation, and point-of-care ultrasound (POCUS) can delineate specific types of shock. This article will focus on the key components of early recognition and treatment in pediatric shock. After reading this article, physicians will be able to develop a systematic approach for goal-directed therapy, have an understanding of safe pediatric transfer, and be familiar with new technologies, including extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS).
Relevance
Pediatric emergency care can be challenging because the patients cannot vocalize their own complaints, the examination is fraught with emotion and movement, and medical care must be family based. Pediatric medication requires weight-based dosing. Invasive testing, including laboratory tests on blood and urine, can be more difficult to obtain and may require sedation and pain management. Randomized controlled trials on children are difficult to ethically obtain; therefore, there are less pediatric-specific data and guidelines about critical resuscitation.3 The goal of this paper is to minimize the anxiety about managing pediatric critical illness and update active EM providers.
Pediatric visits make up about 27% of the total ED visits, and the most common reason is trauma.1 Likely because of proximity, 83% of children who seek emergency care are seen in general EDs rather than pediatric-specific EDs. In the United States, 76% of these visits are in departments with an annual pediatric patient volume of < 20,000.1,2 Regardless of ED designation, a lower annual pediatric volume is associated with higher pediatric mortality, especially for infants and younger children.1 The dichotomy of fewer visits and higher mortality necessitates EM physicians to improve pediatric critical care. The American Academy of Pediatrics (AAP) acknowledges this gap in practice and has published a policy statement about the importance of pediatric readiness in every ED. Recommendations include a pediatric emergency care coordinator with demonstration and maintenance of ED healthcare staff in pediatric care competency, pediatric-specific policies and procedures, medication safety checks, and logically organized and available pediatric-sized equipment.2
Epidemiology
Trauma and sepsis share the spotlight for most common causes of death in patients younger than 18 years of age.4-6 Trauma accounts for more potential years of lives lost in children, surpassing cancer, infectious diseases, and unexplained infant death combined.7 In 2005, sepsis affected 9.7/1,000 neonates and 2.25/1,000 infants, while severe sepsis affected 0.89/1,000 children.8 Rates of sepsis have been increasing over the past several decades and, although mortality is around 10% to 20%, it has been on a steady decline since 1980. Sepsis is most lethal to neonates; 40% of septic neonates experience significant morbidity or mortality.6
Definition and Pathophysiology
Shock is the inability for the system to meet metabolic demands, either because of the decreased delivery of oxygen or nutrients. Recognition and management of pediatric shock requires the ED physician to understand the pediatric physiologic response to poor tissue perfusion before cell membranes are compromised and cell death occurs.9,10 Pediatric patients are at high risk of shock because they have an increased baseline metabolic rate, insensible water losses, and a decreased ability to concentrate urine compared to adults.10,11
They also have physiologic coping mechanisms that make shock difficult to identify. Oxygenated hemoglobin must be circulated to tissues by cardiac output, and oxygen must be appropriately dissociated for aerobic metabolism.9,11 Children rely on heart rate to maintain cardiac output and can maximize systemic vascular resistance (SVR) to maintain a normal blood pressure.10 When pediatric compensatory mechanisms become overwhelmed, cardiovascular collapse may occur rapidly, evidenced early on through tachycardia, followed by hypotension, which is an ominous sign.9,10
Shock occurs in several forms, and understanding the underlying cause can optimize ED management. Hypovolemic shock is the most common type of shock in pediatric patients, and it can be classified as either hemorrhagic or nonhemorrhagic. Causes of hemorrhagic shock include traumatic injury, surgery, or vessel rupture leading to large-volume blood loss. Nonhemorrhagic shock encompasses fluid losses, such as those associated with diabetes insipidus, diabetes mellitus, vomiting or diarrhea, burns, or nephrotic syndrome.10,11 In hypovolemic shock, increased SVR compensates for volume loss by providing increased venous return to bolster stroke volume.
Conversely, distributive shock occurs when SVR is lost due to sepsis, anaphylaxis, or a central nervous system insult.9,10 Vascular tone fails without cytokines or neurogenic feedback, and a relative hypovolemia ensues.11 Specifically in septic shock, increased microvascular permeability increases volume losses and can present as a mixed picture of both hypovolemic and distributive shock.9,11 Cardiogenic shock results from myocardial contractility defect caused by dysrhythmias, cardiomyopathies, ischemia, or congenital abnormalities diminishing cardiac output.9,10,11 Finally, obstructive shock occurs when there is an intravascular or extravascular obstruction to cardiac outflow, such as cardiac tamponade, tension pneumothorax, hypertension in either the pulmonary or systemic vasculature, or cardiac anatomical defects.11
Clinical Features and Evaluation
Clinical evaluation begins with rapid assessment of clinical stability: circulation, respiration, and overall appearance. If possible, collect a comprehensive history, including a medical history, from the child’s caregiver while simultaneously beginning stabilization.12 Preverbal and severely ill children rely on caregivers to provide details.3 Review growth and development, birth history, relevant maternal health issues, as well as medication use, vaccination status, and exposures. Infants, young children, and children with special needs may have subtle presentations of shock, such as lethargy, fussiness, or poor eating or voiding. Caregivers are best able to detect changes in the child’s overall health.3,12
Children with concerning history or physical exam findings, such as bruises along the torso, ears, neck, frenulum, angle of the jaw, cheek, or eyelid, or burns, need to be investigated thoroughly for nonaccidental trauma (NAT). Obtain a skeletal survey, an ophthalmologic exam, and a computed tomography (CT) or magnetic resonance imaging (MRI) of the head in children with neurologic symptoms or those younger than 12 months old.13
Be aware that clinical features vary widely depending on the phase and type of shock. Complete the primary survey and physical exam while addressing these components:
• level of consciousness: alert, anxious, restless, agitated, unresponsive;
• skin: temperature, color, moisture, turgor;
• mucous membranes: color, moisture;
• peripheral veins: collapsed, distended;
• central (anterior chest) capillary refill: normal (< 2 sec), or delayed;
• pulse: rate adjusted for age, regularity, quality;
• blood pressure: pulse pressure, systolic pressure adjusted for age;
• respiration: rate adjusted for age, effort, depth;
• urine: concentration, amount.
Clues of tissue hypoxia include tachycardia, tachypnea, compromised perfusion such as delayed capillary refill, peripheral pulses, altered mentation, and decreased urine output.10,11,12
Commonly, unstable younger pediatric patients become tachycardic with cool and mottled skin, agitated or listless, and experience oliguria, known as “cold shock.”9,11 Exceptions to this include normal or slow heart rate found with substance overdose, hypoxia, or spinal cord injury, or warm and flushed extremities in early distributive shock or end-stage shock.9 Adolescents in shock are more analogous to the adult presentation, with vasodilatory pathology, creating “warm shock.” Finally, it is important to realize that children can alternate between cold and warm shock, so reassessment throughout the resuscitation is critical.
Hypovolemic Shock
Hypovolemic shock state is created when circulating volume is decreased, most commonly secondary to dehydration or hemorrhage.14 Dehydration can occur when a patient has decreased intake or increased fluid losses, such as gastrointestinal losses, excessive diuresis, or burns.14 Physical exam findings suggestive of hypovolemia specifically include tachycardia, increased pulse variation, mucosal dryness, decreased tearing, lethargy, weight loss, sunken eyes and fontanelle, and increased skin turgor.6
Laboratory evaluation can show anion gap metabolic acidosis, but non-anion gap metabolic acidosis can occur if significant stool output leads to bicarbonate losses. Blood urea nitrogen to creatinine ratio is elevated, as is urine specific gravity, except in cases of inappropriate diuresis, such as diabetic ketoacidosis or diabetes insipidus. Assess electrolyte balance, since potassium or sodium disruption can occur. Also check for hypoglycemia, since nearly one-third of hypovolemic shock patients can have glucose < 60 mg/dL.14
Hemorrhagic shock is another form of hypovolemic shock, most commonly caused by traumatic, operative, or spontaneous bleeding in pediatric patients.15 Children can maintain blood pressure with up to 45% of circulatory volume loss, presenting a challenge if blood loss is not evident.7 Presentation ranges from anxiety and tachycardia with < 15% blood volume loss (BVL), to tachypnea, metabolic acidosis, and lethargy in the patient with > 30% BVL. Notably, pediatric total body blood volume is only 80-90 mL/kg for a term infant and 70 mL/kg for children older than 3 months (65 mL/kg in obese children).15 A stable hematocrit does not rule out significant blood loss, and thromboelastography is not validated in pediatric patients.15
In addition to physical exam and history, shock index (SI) can suggest the severity of pediatric injury. SI (heart rate ÷ systolic blood pressure) of > 0.9 is a well-recognized marker of mortality in adult trauma and recently has been applied to pediatric patients with age adjustment.
Shock index, pediatric age adjusted (SIPA) was evaluated in a small sample of patients 4-16 years of age who were significantly injured after blunt trauma. SIPA was able to improve prediction of children who were injured more severely, would require blood transfusions, and had a higher in-hospital mortality.16 (See Table 1.) Another method of SI application was evaluated using more than 30,000 patients ages 0-16 years to determine the delta shock index: the difference in SI from the first prehospital SI and the first ED SI. A positive delta SI was associated with an increased in-hospital and 24-hour mortality while assisting with pediatric trauma triage and accounting for pediatric vital sign variation within age groups.7
Table 1. Shock Index, Pediatric Age Adjusted | |||||
|
Normal pediatric vital sign ranges based on patient age. | |||||
|
Age |
Heart Rate |
Systolic Blood Pressure |
Diastolic Blood Pressure |
Respiratory Rate |
Maximum Normal SIPA |
|
4-6 years |
65-110 |
90-110 |
60-75 |
20-25 |
1.222222222 |
|
6-12 years |
60-100 |
100-120 |
60-75 |
14-22 |
1 |
|
> 12 years |
55-90 |
100-135 |
65-85 |
12-20 |
0.9 |
|
SIPA: shock index, pediatric age adjusted; equal to maximum normal heart rate/minimum normal SBP (systolic blood pressure) Reprinted from: Journal of Pediatric Surgery, vol. 50, Acker SN, Ross JT, Partrick DA, et al. Pediatric specific shock index accurately identifies severely injured children. p.p. 331-334. Copyright 2015, with permission from Elsevier. | |||||
Cardiogenic Shock
Cardiogenic shock ensues after cardiac output is unable to supply oxygen metabolic demands. Recognize an infant with cardiogenic shock by observing for signs of poor cardiac output: weak peripheral pulses, cyanosis, tachypnea with wheezing or rales, diaphoresis, hepatomegaly, murmurs, dysrhythmias, and neck vein distention.11,17 A history of feeding problems or weight gain issues may elicit a cardiac cause for shock in infants. Older children may complain of chest pain, exercise intolerance, or shortness of breath that progresses to syncope.17
Electrocardiogram (ECG) can hint at cardiac abnormalities as a cause of or response to shock.18 Normal pediatric ECGs have a physiologic rightward axis deviation and R wave dominance in V1, both of which should resolve by 3 years of age. In the acute setting, low voltage can suggest decreased myocardial mass or pericardial effusion, broad complex tachycardia can be either ventricular tachycardia or supraventricular tachycardia with aberrancy, and high-grade atrioventricular blocks can result from structural conduction system abnormalities.18 Evaluate for enlarged chambers (P pulmonale or P mitrale), electrolyte abnormalities with peaked-T waves or U-waves, and adverse effects of medications or intoxications.11,18 A chest X-ray can demonstrate abnormal cardiac silhouette or pulmonary edema.
The most useful tool for evaluation of cardiac function is the echocardiography with Doppler. Structural abnormalities, systolic and diastolic function, and ejection fraction can be elicited at the bedside by a skilled ultrasonographer. Laboratory assessment of electrolytes, glucose, blood gas, cardiac biomarkers, and viral titers also can be helpful with identification of cardiac disturbances.17
Obstructive Shock
Obstructive shock occurs when a blockage in the vascular system impairs cardiac output.11 Obstruction can occur for a variety of reasons, both intravascular, such as pulmonary embolism (PE) or aortic pathology, and extravascular, such as cardiac tamponade or pneumothorax.
PE is rare in children, but it carries a 10% to 20% mortality. There is no validated pediatric clinical decision tool for PE, making it an underrecognized and dangerous cause of shock. Risk factors include obesity, a history of previous thrombus, immobility and, to a lesser extent, central venous catheters, congenital heart disease, oral contraceptive use, and cancer. Consider PE if the patient has symptoms of tachycardia, chest pain, shortness of breath, or signs of deep vein thrombosis.19,20 The most common imaging for diagnosis is a radionuclide ventilation-perfusion lung scan or CT of the pulmonary arteries. D-dimer is not a validated screening test in pediatrics.20
Ductal dependent congenital heart disease also falls in the obstructive shock category due to aortic stenosis or coarctation diminishing perfusion to lower extremities. Cardiac tamponade occurs when fluid accumulates within the pericardial sac and strangulates cardiac filling ability. Similar to adult patients, evaluate for pulsus paradoxus and Beck’s triad.11
Tension pneumothorax occurs when an injured tissue acts as a one-way valve, causing air to enter the pleural space without an exit because of closure during expiration. Ultimately, the increased thoracic cavity pressure decreases venous return (preload), which, in turn, diminishes cardiac output and potentially leads to rapid deterioration and cardiopulmonary collapse.11 Tension pneumothorax can be easily missed in pediatric patients because their smaller chests transmit breath sounds on auscultation more easily. Use ultrasound or chest X-ray in addition to the exam to assist in the diagnosis for both cardiac tamponade and tension pneumothorax.11
Distributive Shock
The three main forms of distributive shock — septic, anaphylactic, and neurogenic — share a common pathophysiology: Cardiac output is maldistributed due to a low SVR, resulting in underperfusion of vital organs. Sepsis most often presents in children with a low cardiac index that may or may not include vascular tone disturbances. Some adults and up to 20% of children present with maintained cardiac output and decreased SVR (“warm shock”).11 Evidence of cardiovascular dysfunction in the form of metabolic acidosis, elevated lactate, oliguria, prolonged capillary refill, and cool extremities qualifies as pediatric septic shock; do not wait for hypotension to make the diagnosis.21 Elevated lactate is likely a late sign of pediatric hypoperfusion, so a normal lactate is not as reassuring in this population compared to adult sepsis.6
Screening for sepsis in children can be done using the pediatric systemic inflammatory response syndrome (SIRS) modified from the adult definition:
• temperature > 38.5°C or < 36°C;
• tachycardia greater than two standard deviations (SD) above normal for age group, or bradycardia;
• respiratory rate > 2 SD above normal;
• elevated or decreased leukocyte count or > 10% immature neutrophils.6
Sepsis can occur in healthy children, but those with previous medical comorbidities and children younger than 2 years old are at a specifically elevated risk. Children who have been treated recently with broad-spectrum antibiotics or who have indwelling devices (intravascular catheters, tracheostomies) have increased mortality from gram-negative enteric bacteria and opportunistic pathogens, such as Pseudomonas or Acinetobacter. Exposure to healthcare environments increases the likelihood of nosocomial infections such as methicillin-resistant Staphylococcus aureus (MRSA).
Pneumonia remains the most common cause of pediatric sepsis. Viruses, such as influenza and parainfluenza, can cause significant pneumonia in healthy children, and respiratory syncytial virus is dangerous in premature children or those with chronic lung disease, congenital abnormalities, or immune deficiencies. Uncommon causes of pediatric sepsis include fungal organisms and, depending on exposure, tickborne illnesses can occur.8
The lifetime risk of anaphylaxis is between 1.6% and 5.1%, and one-fourth of cases occur in patients younger than age 18 years. Anaphylaxis is diagnosed if, on exposure to an allergen/trigger, there is a sudden onset of illness involving the skin or mucosa with either respiratory symptoms or hypotension/evidence of end organ damage, or at least two of the following:
• sudden onset of illness involving the skin or mucosa, respiratory symptoms;
• hypotension/evidence of end organ damage;
• gastrointestinal symptoms.22
History of exposure is key because infant anaphylaxis can be subtle, with flushing, vomiting, diarrhea, with simultaneous tachycardia or low blood pressure. There is no laboratory test available from the ED that is diagnostic for anaphylaxis.23 Overall, delayed recurrence of symptoms and signs of anaphylaxis hours after initial resolution — termed a biphasic reaction — is uncommon, but children requiring repeat doses of epinephrine, those with severe cases of anaphylaxis, and cases due to drug reactions are at risk for biphasic reactions.22
Neurogenic shock occurs when loss of sympathetic tone results in hypotension without a compensatory increase in heart rate.24 Loss of sympathetic tone occurs when the spinal cord disruption is above T7, and risk increases with higher level of spinal cord injury: 90% of complete cervical cord injuries require vasoactive support.24,25 The most common cause of pediatric spinal cord injuries includes motor vehicle collision (MVC) in which a majority of patients were improperly restrained, but other causes of spinal cord pathology include transverse myelitis, birth injury, and child abuse.25 In critically injured children with suspected spinal injury, CT is the imaging of choice. Physiologically younger children have a higher risk of occipitoatlantoaxial compromise because of their relatively larger heads. Children younger than 8 years of age are at an increased risk for ligamentous injury because of a lack of ossification and increased ligamentous laxity.
Children involved in nonaccidental trauma, falls, or pedestrian vs. motor vehicle also can have SCIWORA (spinal cord injury without radiographic abnormality), and younger, hypermobile spines are at an increased risk.24 MR imaging can be both diagnostic and prognostic in such cases.
Consider spinal cord injury in the traumatically injured patient with hypoperfusion resistant to blood products and fluid expansion.24,25 Wide pulse pressure and normal heart rate or bradycardia in the setting of hypoperfusion suggests a relative hypovolemia because of increased venous capacity.24,25
Ultrasound
Ultrasound is emerging as a noninvasive and nonradiating dynamic adjunct to physical exam for diagnosis and treatment of the unstable pediatric patient in both medical and traumatic situations. POCUS application is supported by both the AAP and American College of Emergency Physicians as a method of shock differentiation and a tool for serial examination during interventions.26,27
When reaching for an ultrasound probe, have a clinical question in mind and understand that ultrasound can rule in pathology but cannot definitively rule out.26 First, pediatric thoracic ultrasound is similar to that in adult patients.28 Lung sliding and B-lines without a lung-point can assist in excluding pneumothorax faster than chest X-ray. Pleural effusions and pneumonia can be evaluated sonographically with less radiation and more accuracy than conventional radiography.28,29
Cardiac and inferior vena cava (IVC) ultrasound can guide fluid vs. pressor/inotrope resuscitation and can be more sensitive than physical exam findings alone.4 Use caution during IVC assessment, since IVC variation in the neonate is subtle and, as a child grows, IVC size changes. POCUS has been evaluated for qualitative assessment of pediatric left-ventricular function, but data for right-ventricular function are lacking.28
Although operator familiarity with ultrasound provides limitations, it is important to note that congenital abnormalities on pediatric cardiac ultrasound can be particularly difficult to recognize.28,29
During cardiopulmonary resuscitation (CPR), POCUS can be applied to evaluate for reversible causes of cardiac arrest, such as tamponade or pneumothorax. However, do not prolong the time without chest compressions to obtain a thorough evaluation. Intra-abdominal emergencies, such as pyloric stenosis, can be identified with POCUS relatively quickly in a patient with persistent vomiting causing volume loss.29
The focused assessment with sonography for trauma (FAST) exam has not been extensively studied in pediatric abdominal trauma, but, depending on resources and access to advanced imaging, it may be helpful for serial examinations.29 Finally, ultrasound can be procedurally applied. Pediatric central venous catheter placement is complicated by smaller target size, closer proximity of other structures, and anatomic variations, causing an increased rate of procedural complications, infection, and device failure as compared to adults.28 POCUS is supported for vascular access in the pediatric population and can even help during lumbar punctures.28 Although ultrasound use in the unstable pediatric patient has lagged behind the use of POCUS in adults, research is ongoing.12
Management
Management of pediatric shock is complex, and multiple resuscitative efforts should occur in tandem. This section will follow in the familiar order of airway, breathing, and circulation.
PALS Update
In 2020, the American Heart Association (AHA) released updated Pediatric Advanced Life Support (PALS) guidelines. Notable updates for ED physicians include: 20-30 breaths per minute for infants and children who are either receiving CPR with an advanced airway in place, or who are receiving rescue breathing and have a pulse. For nonshockable rhythms, patients are more likely to survive with earlier epinephrine administration, ideally within five minutes after initiating compressions. A cuffed endotracheal tube decreases the need for endotracheal tube changes. Routine use of cricoid pressure does not reduce the risk of regurgitation during bag-mask ventilation and may impede intubation success. For out-of-hospital cardiac arrest, bag-mask ventilation is comparable to advanced airway interventions.
Excellent post-cardiac arrest care is critically important to achieve the best patient outcomes. For children who do not regain consciousness after return of spontaneous circulation, begin targeted temperature management and continuous electroencephalography monitoring. Prevent hypotension, hyperoxia/hypoxia, and hypercapnia/hypocapnia. Finally, naloxone can reverse respiratory arrest caused by opioid overdose, but there is no evidence that it benefits patients in cardiac arrest.30
Airway/Breathing
Pediatric respiratory effort and adequate respiration have a greater influence over their clinical status when compared to adults, with a significant portion of their oxygen consumption dedicated to their work of breathing. Pediatric cardiac arrest is most commonly a sequela of respiratory failure.3 Give special consideration to pediatric patient airways, since children can have a relatively large occiput, small jaw, high and anterior larynx, narrow cricoid cartilage, and large tongue.31 Place all patients presenting with signs of shock on supplemental oxygen (nasal cannula, non-rebreather face mask) to combat ongoing tissue hypoxia.11
The new update to the PALS algorithm in 2020 placed greater emphasis on initiating positive pressure ventilation in pediatric patients, particularly neonates.30 Passive oxygenation or noninvasive oxygenation may not be adequate to support the patient’s respiratory demands, and intubation with mechanical ventilation may be indicated. Increased intrathoracic pressure with mechanical ventilation can lead to a reduction in venous return and preload, which may worsen already present hypotension, and sympathetic tone will be lost. Whenever possible, resuscitate with goal-directed therapy before mechanical ventilation.32
After making the decision to intubate, choose the most clinically appropriate sedation available for rapid sequence intubations (RSI). The two most prominent medications for RSI in pediatric shock patients are ketamine and etomidate.
Ketamine provides bronchodilation and releases exogenous catecholamines, causing an increase in heart rate and blood pressure. Recent evaluation of ketamine has disproven early concerns that ketamine’s direct negative inotropic properties may predominate when endogenous catecholamine stores have been depleted by chronic illness or shock.33,34 In a retrospective study published in 2019, ketamine was investigated in patients presenting both with and without septic shock and showed that in both populations, ketamine demonstrated reduced incidence of hypotension, dysrhythmias, and cardiac arrest when compared to all other induction agents.35
Etomidate was used originally as a preferred induction agent for RSI; however, potential reductions in endogenous corticosteroid production, particularly in critically ill children, have raised concerns for its use.36,37 Propofol use during RSI has been discouraged because of concerns for vasodilatory and negative inotropic effects.38 Although ketamine and etomidate both are recommended for sedation agents, ketamine appears to have fewer associated adverse effects.
Fluids
Initiate early and aggressive fluid management to maintain perfusion after shock recognition. Establish intravenous (IV) access or place an intraosseous (IO) line if vascular access is delayed.39 Neonates younger than 7 days old also have availability of an umbilical vein for catheterization.40
Current guidelines for pediatric shock advocate an initial fluid bolus of 20 mL/kg, titrated to achieve adequate organ perfusion, up to 40-60 mL/kg, or until signs of fluid overload occur: hepatomegaly, rales/crackles, and pulmonary edema.6,12
A smaller gauge IV can be used for rapid infusion using a “push/pull” method. Use a three-way stopcock to rapidly pull fluid into a syringe, and then push the fluid through the patient’s IV/IO access after turning the stopcock valve to direct flow into the IV or IO catheter.41 This can deliver a 20 mL/kg bolus within five minutes during the resuscitation and is equivalent to a pressure bag system and superior to an IV pump.42
The choice of fluid for intravascular volume expansion depends on the fluid lost. Use blood in traumatic shock and crystalloid in all other causes of shock with volume loss.11 The typical crystalloids of choice are either normal saline (NS) or lactated Ringer’s solution (LR). There is a concern for NS to induce hypernatremia, hyperchloremia, and metabolic acidosis given the volume required during pediatric shock.39,43
Multiple recent clinical studies have demonstrated a higher incidence of hyperchloremic metabolic acidosis with NS, but comparisons between LR and NS did not demonstrate significant differences in mortality, morbidity, or acute kidney injury.44-46 Either NS or LR is an acceptable fluid intervention for pediatric shock. Be attentive to temperature fluctuation with fluid infusion, especially if fluids are not warmed, since pediatric patients may struggle to regulate their core temperature.
Antimicrobials
For patients presenting in extremis and with concerns of septic shock, administer antibiotics within one hour of arrival based on recommendations by the 2020 Surviving Sepsis Campaign.47-51 Give empiric broad-spectrum parenteral agents based on the child’s age, presenting features/focus of infection, comorbidities, and local epidemiology in relation to disease prevalence and antimicrobial resistance patterns. (See Table 2.) Consider immunization status, risk factors for immune compromise, and history of drug-resistant organisms.6 Obtain blood cultures prior to administering antibiotics, but do not delay antibiotic therapy for any reason, including lumbar puncture.47
Table 2. Antibiotic Coverage in Pediatric Sepsis61-69 | |||
|
Patient Population |
Antimicrobial Coverage |
Considerations |
Dosages (All IV Route) |
|
Neonates (0-28 days) |
Ampicillin, gentamicin, or third- or fourth-generation cephalosporin ± vancomycin ± acyclovir |
Listeria coverage with ampicillin HSV coverage with acyclovir If hospitalized since birth, replace ampicillin with vancomycin |
Ampicillin 25-50 mg/kg/dose q6h Gentamicin 2.5 mg/kg/dose q8h Acyclovir 10-15 mg/kg/dose q8h Ceftazidime 30-50 mg/kg/dose q8h
Cefepime 50 mg/kg/dose q8h
Vancomycin 15 mg/kg/dose q8h |
|
Healthy children (> 28 days to 18 years) |
Vancomycin Third-generation cephalosporin |
± amoxicillin if < 3 months of age |
Vancomycin 15 mg/kg/dose q8h Ceftriaxone 50 mg/kg/dose q12-24h
|
|
• GI source |
+ piperacillin/tazobactam OR + metronidazole OR + clindamycin |
|
Piperacillin/tazobactam
Metronidazole 7.5 mg/kg/dose q6h
Clindamycin 6-8 mg/kg/dose q8h
|
|
• Toxic shock |
+ clindamycin |
Toxin production management |
Clindamycin 6-8 mg/kg/dose q8h
|
|
Immunocompromised or indwelling device |
Vancomycin Cefepime OR Piperacillin/tazobactam OR Meropenem |
Antipseudomonal coverage Consider fungal or viral infections |
Meropenem 10-20 mg/kg/dose q8h (max. 2 g/dose) Cefepime 50 mg/kg/dose q8h
Vancomycin 15 mg/kg/dose q8h Piperacillin/tazobactam 75-100 mg/kg/dose q6h (max. 16 g/day) |
|
Recent antibiotics or penicillin-allergic |
Vancomycin Meropenem |
Alternative to meropenem: aztreonam or ciprofloxacin
|
Aztreonam 30-40 mg/kg/dose q8h
Ciprofloxacin 10 mg/kg/dose q8h
Clindamycin 6-8 mg/kg/dose q8h
|
|
Doses based on normal creatinine clearance. Piperacillin/tazobactam dosing based on piperacillin. IV: intravenous; HSV: herpes simplex virus; GI: gastrointestinal | |||
Vasoactive Medications
Increasing intravascular volume through IV fluids may not lead to a sufficient response in pediatric shock patients; signs of ongoing shock require additional cardiovascular support with vasopressors. While delaying vasopressor administration in septic shock has been shown to increase length of stay in the intensive care unit (ICU), conversely, initiating vasopressors prior to properly fluid resuscitating the patient has been shown to have an increased mortality of 30%. Thus, it is imperative to follow the American College of Critical Care Medicine (ACCM) PALS guidelines to fluid resuscitation prior to initiating vasopressors.61,93
Vasopressors increase mean arterial pressure by adjusting both cardiac output and systemic vascular resistance.54,55 Table 3 demonstrates mechanisms of action of the most common vasopressors. Do not delay beginning necessary vasopressors if the patient does not have central access, but central access should be obtained as soon as possible to reduce the risk of tissue damage if extravasation occurs.21,54,56,57 Administer pressors at the lowest effective dose to decrease the risk of adverse effects and to taper as soon as possible.54
Table 3. Inotropes and Vasopressors | ||||||
|
Medication |
Alpha-1 Sympathetic Receptor Peripheral Vasoconstriction |
Beta-1 Sympathetic Receptor Chronotrope and Inotrope |
Beta-2 Sympathetic Receptor Peripheral Vasodilation |
Dopaminergic Receptor |
Effects |
Primary Use in Fluid-Refractory Shock |
|
Norepinephrine |
High |
Moderate |
Low |
|
Increases SVR and CO |
“Warm shock” |
|
Epinephrine |
Moderate to high |
High |
Moderate |
|
Lower doses: predominantly beta-1 and -2 activity Higher doses: predominantly alpha-1 activity |
“Cold shock” |
|
Dopamine |
Moderate |
Low to high |
|
High |
Lower doses: predominantly dopaminergic activity Higher doses: predominantly alpha-1 and beta-1 activity |
Second-line agent for “cold shock” |
|
SVR: systemic vascular resistance; CO: cardiac output | ||||||
There are few contraindications for vasopressors outside of hypersensitivity reactions. Beta stimulation can cause cardiac arrhythmias, and epinephrine specifically can cause pulmonary edema. Dopamine can cause hypotension and is also arrhythmogenic. Use caution with phenylephrine in isolation, since it can cause reflex bradycardia and decreased cardiac output. Lastly, vasopressin can cause bronchoconstriction, hyponatremia, and arterial constriction.54
Several recent studies have analyzed epinephrine, norepinephrine, and dopamine and their utility during pediatric shock resuscitations. In neonatal shock, dopamine has demonstrated notable efficacy and is regarded as a vasopressor of choice in this population, following the ACCM 2017 guidelines.43
Beyond the neonatal population, however, dopamine’s superiority over epinephrine has been questioned. In a randomized controlled trial in 2015, Ventura et al observed that patients started on dopamine had a significant increase in mortality and hospital-acquired infections compared to epinephrine.58 Dopamine and epinephrine were compared again in a double-blind study by Ramaswamy et al. Pediatric patients in fluid-refractory shock demonstrated quicker shock resolution in the epinephrine group than the dopamine group, although no difference in mortality was observed.59 A review in 2020 compared the efficacy of dopamine and epinephrine in pediatric shock and showed an overall similar efficacy and safety, and highlighted the need for additional investigation and further evaluation.60
The ACCM 2017 guidelines recommend epinephrine as the first-line treatment for “cold” fluid-refractory shock, and dopamine as the second-line treatment if epinephrine is unavailable. The guidelines also are in favor of norepinephrine administration in situations of “warm” shock because of its vasoconstrictive action without a significant increase in heart rate.43
Endpoints of Resuscitation
There is little prospectively validated data about endpoints of resuscitation in pediatric shock. Lingering hypoperfusion with compensated shock may lead to continued organ dysfunction, even with normalized vital signs.48 No single type of monitoring can dictate when pediatric shock has resolved.11 Multiple factors, including vitals and physical exam findings, guide clinical endpoints of shock reversal, including normalization of vital signs, return to baseline mentation, capillary refill less than three seconds, urine output of > 1 mL/kg/hour, and palpable distal pulses.
Monitor for signs of heart failure or fluid overload in patients receiving a high volume of fluids. Central venous pressure (CVP) goals are not specified in pediatric literature, but < 5 mmHg may suggest more IV fluid is needed. If central access is available and the catheter is placed at the junction of the superior vena cava (SVC) and right atrium, mixed venous oxygen (SvO2) can guide septic shock management. A normal SvO2 is approximately 75%; < 70% indicates a deficiency of oxygen delivery or increased oxygen extraction.21 Target an SvO2 of ≥ 70%.70
Lactate does not have a clear role in the diagnosis or management of pediatric septic shock, but it is considered best practice and is weakly recommended by the Surviving Sepsis Campaign to follow lactate until normalization.47
Finally, systolic blood pressure thresholds vary across different pediatric critical care governing bodies for defining hypotension. A study by Roberts et al in 2020 collected data from more than 85,000 children in an ED or acute care/intensive care setting at a tertiary care pediatric hospital and determined that mean arterial pressure (MAP) may be more sensitive for identifying hypotension than systolic blood pressure.71 The Surviving Sepsis Campaign 2020 update recommends a MAP of between the fifth and 50th percentile, or greater than 50th percentile for age, according to expert consensus without supporting clinical trial data.48
Steroids
Suspect adrenal insufficiency in pediatric patients with shock unresponsive to intervention, especially in patients with head or abdominal trauma, steroid use, sepsis, and use of etomidate.11 If patients are presenting with signs of shock and there is concern for adrenal insufficiency (known pituitary or adrenal pathologies, or recent steroid use in the past six months), administer a stress dose hydrocortisone in addition to other resuscitation cares.
For patients without a known or suspected adrenal insufficiency, steroid intervention during resuscitation is more controversial. In 2019, Yang et al conducted a meta-analysis of published studies. Through their analysis, they found that corticosteroids are likely not beneficial and that there was not a consistent pattern of an increase or decrease in mortality or morbidity.72 This is consistent with previous research that similarly suggested against routine corticosteroid administration in pediatric septic shock.6,73,74
Anaphylactic Shock
Treatment for anaphylaxis includes epinephrine as first-line therapy, with glucocorticoids and antihistamines as second-line therapy.22 Initiate intramuscular (IM) epinephrine even in uncertain cases to prevent respiratory failure or cardiac arrest.23 Administer 0.01 mg/kg of a 1:1,000 [1 mg/mL] epinephrine solution into the anterolateral thigh, with a maximum of 0.5 mg in adults and 0.3 mg in children, repeated every five to 15 minutes.22
Refractory anaphylaxis requires an IV infusion of epinephrine at the concentration of 0.1 mg/mL at 0.2 mcg/kg up to 10 mcg/dose. Delayed use of epinephrine has been associated with increased mortality in observational and case report studies.22
Control the airway with intubation if signs of airway compromise occur, especially if obstructive symptoms are worsening despite management.23 In the event that anaphylaxis completely resolves with continued resolution after four to six hours of observation, the patient must be discharged with a weight-based epinephrine auto-injector and education on trigger avoidance and biphasic reactions.22,23
Hemorrhagic Shock
For all patients presenting in shock following traumatic mechanisms of injury, there are additional aspects of care to consider for shock management. The first goal is to achieve hemostasis in bleeding patients using pressure, tourniquet, hemostatic gauze, or operative management, as in the case of intra-abdominal bleeding.15 Address long-bone fractures and evaluate for retained foreign bodies, since these both can cause significant vascular injury/hemorrhage. Do not place IVs/IOs in an injured extremity, and ensure that a patient with an injury below the diaphragm has vascular access in the upper extremities that can drain into the SVC.15
Start with 20 mL/kg crystalloid transfusion, but if blood loss is suspected, switch to blood transfusion early. Massive transfusion (more than 40 mL/kg of blood product) has not been well studied in critically injured pediatric patients requiring blood transfusion.5,15 Between 5% and 15% of pediatric trauma patients fall into the category of massive transfusion when requiring blood products.15 To determine which children might need a large-volume blood resuscitation, recent research has applied a modified Assessment of Blood Consumption with age-adjusted shock index (ABC-S) score that was dubbed the “ABCD” score (Assessment of Blood Consumption with SIPA with inclusion of base defect and lactate measurement). This score is derived from the adult ABC trauma score that assigns a point each for: a positive FAST, penetrating trauma, systolic blood pressure > 90 mmHg, and heart rate > 120 beats/minute. The ABCD score substitutes SIPA (> 1.22 for children ages 4-6 years, > 1.0 for children ages 7-12 years, and > 0.9 for children ages 13-16 years) for the adult vital signs and adds base deficit >- 8.8 and lactate > 3.5. An ABCD ≥ 3 was 77% sensitive and 78% specific for massive transfusion requirements.5
In nontraumatic causes of bleeding, similar principles apply with a few additions. Gastrointestinal bleeding requires endoscopy or angiography.15 Variceal bleeding requires octreotide at 1-2 mcg/kg/hour for splanchnic blood flow reduction and gastric acid secretion antagonism.14
The transfusion threshold, derived from adult hemorrhagic literature, is a hemoglobin of 7 g/dL. Recognize that ongoing bleeding can have a delayed presentation of anemia on lab work. After one equivalent blood volume of packed red blood cells (pRBCs) is given, move to a 1:1:1 (pRBC:fresh frozen plasma [FFP]:platelets) transfusion, since dilution of platelets and clotting factors can worsen bleeding.15 Restrictive transfusion is recommended and has held up in pediatric intensive care unit (PICU) patients and pediatric burn studies, but it requires further study in acutely injured children.
Complications with transfusion include fluid overload and transfusion reactions. Be alert for both. Permissive hypotension cannot be applied directly to pediatric populations because of increased cardiovascular reserve, but monitoring lactate, SVO2, and hemoglobin in unison with clinical picture is a reasonable approach.15 Evaluate for and actively treat metabolic derangements, such as hyperkalemia or hypocalcemia due to citrate-binding from transfused blood.14,15
Cardiogenic Shock
After recognition of cardiogenic shock, the two primary goals of ED management are to balance preload, afterload, and heart rate to maintain adequate oxygen delivery to critical organ systems and to reduce the metabolic demands of these systems. Inotropic agents, such as dopamine and dobutamine, lead to increased contractility and larger stroke volumes. Cardiogenic shock patients do not require as much fluid or respond as well to arrhythmogenic vasopressors.11
Dobutamine treatment between
5-20 mcg/kg/min traditionally is favored in pediatric patients in cardiogenic shock because of its ability to improve the cardiac index similar to dopamine, without increasing pulmonary vascular resistance.75,76 Norepinephrine has potent vasoconstrictive effects that can worsen afterload; however, in patients with reduced cardiac output, low systemic vascular resistance, and persistent hypertension, combination with another inotrope is recommended. Replace norepinephrine with epinephrine in situations of inotropic-resistant cardiogenic shock.
For afterload reduction using vasodilatory medications, nitrated derivatives are not strongly recommended at this time. Other interventions, such as therapeutic hypothermia and anticoagulation, are not well studied and do not have expert recommendations of their effectiveness.77 Consider reducing the metabolic demand of skeletal tissue in fussy or agitated infants, as well as maintaining relative normothermia to reduce metabolic demand for heat production.17
Neonatal cardiogenic shock is nuanced. Treat neonates with ductal-dependent lesions presenting in shock or distress with prostaglandin E1 to maintain patency of the ductus arteriosus.17 Conversely, a moderate to large patent ductus arteriosis (PDA) can negatively affect cardiovascular stability and lead to reduced cardiac output and hypotension. PDA-associated hypotension may be difficult to treat, and hypoperfusion may be resistant to both inotropes and fluid resuscitation.78 Be mindful of hypoglycemia, hypocalcemia, and possible pulmonary hypertension in neonates.11
Septic Shock
Recognizing septic shock early with goal-directed therapy has been proven to improve mortality.11 Basic principles are:
• monitoring: IV/IO access, supplemental oxygen, cardiac and pulse oximetry monitoring, temperature measurement;
• initial laboratory: CBC, glucose, chemistry panel, lactate, urine, cultures;
• IV fluid bolus: initial 20 mL/kg NS or LR, may repeat × 2;
• initial broad-spectrum antibiotics;
• reassess: normalization of vital signs adjusted for age, improved mental status, capillary refill, normal urine output
> 1 mL/kg per hour;
• for fluid refractory shock: initiate norepinephrine for “warm shock” and epinephrine for “cold shock”;
• consider treatment for adrenal suppression and/or hypothyroidism if refractory to vasopressors.
Neurogenic Shock
Loss of autonomic tone differentiates neurogenic shock from other types of shock caused by spinal cord injuries at or above the level of T6.25 Initiate resuscitation with fluid loading but know that blood pressure support may require both alpha and beta agonism to treat peripheral decrease in SVR and prevent reflex bradycardia. Norepinephrine, epinephrine, and dopamine all are reasonable choices.24 Monitor for hypothermia secondary to vasodilation. Aggressive treatment with elevated MAP goals decreases secondary ischemic injury to the spinal cord.
Goals for blood pressure are unknown, but aim for higher than the minimum for the age group.25 Do not permit hypotension, especially in patients with traumatic brain injury, and avoid mannitol as a way to reduce intracranial pressure. Hypertonic saline is recommended now as first-line therapy.25 Steroids remain controversial and are not recommended in the treatment of pediatric spinal cord injury.24 Consider glycopyrrolate (4 mcg/kg/dose [max. 100 mcg/dose] at two to three-minute intervals) for continued bradycardia.25,79 Lastly, continue spinal immobilization until spinal cord injury can be ruled out or addressed. This may require sedation in smaller children.24,25
Obstructive Shock
Treatment for obstructive shock is geared toward reversing the underlying pathology, since myocardial function and intravascular volume both are normal despite the reduction in the cardiac output.11
The first treatable cause of obstructive shock is tension pneumothorax. It requires immediate needle decompression with a sterile needle in the second intercostal space along the midclavicular line, followed by a tube thoracostomy for definitive management.80
Secondly, for patients with suspected cardiac tamponade as a cause of obstruction, perform bedside echocardiogram to assess for diastolic RV collapse. Fluid resuscitation in hypovolemic patients has been shown to be beneficial, but use caution in normovolemic or hypervolemic patients, since increased fluid administration could lead to increased intracardiac pressure causing worsening tamponade.81 For unstable patients with cardiac tamponade, do not wait for a comprehensive echocardiogram to perform an ultrasound-guided pericardiocentesis.80
Thirdly, pediatric pulmonary embolisms obstruct the cardiac outflow tract, causing shock. In the ED, there are limited data and no consensus statement for PE treatment at this time. Some institutions have created multidisciplinary PE response teams. If there are strong suspicions of PE for the patient, consider consulting hematology, intensive care, and interventional cardiology early. The decision to initiate recombinant tissue plasminogen activator (rtPA; alteplase) should be considered in consultation with these services, since although the American College of Clinical Pharmacy has dosing guidelines, an optimal dosing regimen has not yet been established.80,82
Special Circumstances
ECLS application in the pediatric population is rapidly progressing as indications grow and contraindications shrink. Only a supportive measure, ECLS does not treat underlying pathology but simply allows time for temporary life sustainment until the primary problem can be addressed. One benefit is that it can oxygenate and provide hemodynamic support without the necessity of high-dose vasopressors or mechanical ventilation.83 ECMO is recommended in refractory shock without return of adequate perfusion with fluid resuscitation and vasoactive medications, and the ACCM recommends ECLS in refractory septic shock.6,83 The ECLS survival rate in children with severe pneumonia and refractory septic shock is 50%, and it is more than 80% in those with respiratory failure due to a virus.8 Even patients who have undergone cardiac arrest requiring CPR may be ECLS candidates in certain cases.83
Emerging Issues
Multisystem inflammatory syndrome in children (MIS-C) was defined by the Centers for Disease Control and Prevention in 2020 as a patient younger than 21 years of age with fever for more than 24 hours, laboratory evidence of inflammation and multisystem organ involvement without alternative plausible diagnosis, and a recent or current SARS-CoV-2 infection.84,85 Consider the diagnosis in patients with a Kawasaki-like illness, toxic shock syndrome, or macrophage activation syndrome. Hypotension was present in 80% of MIS-C cases reported as of October 2020, and 60% to 80% of patients required ICU admission due to shock requiring vasopressor support.85
Obtain a C-reactive protein, erythrocyte sedimentation rate, D-dimer, fibrinogen, procalcitonin, lactate dehydrogenase, and SARS-Cov-2 antibody or antigen screening as part of the workup.84
Treatment includes immune-suppression under the guidance of specialists, including cardiology, infectious disease, and rheumatology. Reported complications are coronary artery aneurysms in 10% to 20% of cases, coagulopathy abnormalities, and a 1% to 2% mortality.85 ECLS has been used for a miniscule number of COVID-19 or MIS-C patients with varying levels of success, but there are insufficient data to determine its efficacy.83
Disposition
Almost all pediatric shock patients require admission, usually to the PICU. Septic pediatric patients should be transferred to a tertiary care center with pediatric intensivists.6
In the case of resolved anaphylactic shock, otherwise healthy patients who remain symptom free can be discharged after observation, although a specific disposition time has not been clearly established. One hour of observation incurs a 5% chance of biphasic reaction out-of-hospital, while six hours of observation may reduce that risk to 3%.86 Disposition also should consider the child’s family, transportation needs, and the ability for the family to accommodate specific pediatric needs.
While free-standing and critical access EDs have provided easier access to care, pediatric patient transfers have been increasing over time.1 To that end, having specialized pediatric transport systems in place has been shown to improve safety, decrease unplanned adverse events, and lower mortality.87-89 Ensuring that the transport team is composed of a physician, well-experienced nurses, paramedics, and possibly respiratory therapists, and that transport vehicles are equipped with all essential equipment is vital. It also is important to understand that during transport, patients are at increased risk for hypothermia and hypoglycemia; thus, having IV access is imperative.90
Transitions of care, also called hand-offs, are vulnerable situations in which medical errors can occur. The ED is especially vulnerable to mistakes, given the high patient volumes, multiple critically ill patients, ill-timed interruptions, stress, and multiple providers involved in patient care. Compounding factors can be fatigue, inability to obtain an accurate past medical history, and diagnostic uncertainty. In addition, young pediatric patients cannot voice their own issues, placing them at even higher risk. Effective hand-offs should include a summary of patient care, a clear direction of care, and clear authority of orders and treatments.91 The AAP recommends structured hand-offs for consistent continuity of patient care without miscommunication or bias, in a low-distraction environment involving as much of the care-team as possible. The AAP recognizes that having one hand-off method will not apply to every situation, so it is best to have something that works best for each specific environment. A transition of care should occur on transfer, admission, provider change in the ED, and even discharge to family.91
Summary
Pediatric shock presents a clinical challenge in both recognition and management. An appropriate examination should include a comprehensive history, including growth and development issues and eating and voiding status, along with a thorough head-to-toe physical exam. Although pediatric shock cases have been on the rise, having an algorithmic and systematic approach can help reduce errors, improve physician confidence, and provide better care.
REFERENCES
The full list of references is available online: https://bit.ly/3t4k7hV
Pediatric shock carries a high morbidity and mortality, making early recognition key. Recently, pediatric critical care and resuscitation has been the focus of emergency department care improvement.
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.