Management of Pediatric Shock

Shock is a life-threatening emergency characterized by circulatory failure and impaired tissue

perfusion. In addition to clinical and hemodynamic condition, oxygen utilization and/or cellular

variables have been used to define shock.(1) Hypotension is neither a constant nor an early finding in pediatric shock and prompt recognition requires clinical assessment for tissue hypoperfusion and a high index of suspicion.(2)(3) Involved pathophysiological mechanisms include a combination of reduced intravascular volume, abnormal myocardial function, reduced vascular tone with inappropriate vasodilatation (vasoplegia) and/or circulatory obstruction associated with conditions such as cardiac tamponade, tension pneumothorax or massive pulmonary embolism. Clinical conditions often associated with shock include hypovolemia (eg bleeding and severe dehydration), severe sepsis, cardiogenic shock and anaphylaxis.(4-8)

Severe sepsis and septic shock represent a dysregulated immune response to an invasive infection. (9) Even without shock, children with infections frequently develop fever, tachycardia and vasodilatation as a result of an inflammatory response. Septic shock should be suspected if these manifestations are associated with a change in mental status, and the diagnosis made when tissue perfusion is impaired. Patients with septic shock may present with predominantly low cardiac output, vasoconstriction, delayed capillary refill and cold extremities (cold shock); or with predominantly vasodilatation, wide pulse pressure, warm extremities and increased cardiac output (warm shock).(1)(5) Contrary to the case in adults and some adolescents, most cases of septic shock in infants and children present as cold shock, with low cardiac output associated with hypovolemia (deficient intake and capillary leak) and/or myocardial insufficiency.(2)(5) The clinical distinction between cold and warm shock is not always clear-cut and has sometimes been disputed as a guide to initial inotropic/ vasopressor support. (10)

While cardiogenic etiology of shock may be quite obvious, such as following cardiac surgery and in those with cardiac disease, cardiogenic shock should be suspected in patients with signs such as a gallop rhythm, heart murmur, evidence of circulatory congestion (pulmonary rales, jugular venous distension, hepatomegaly or worsening with volume expansion) or arrhythmia. (4)

Bedside cardiac ultrasonography can be helpful in diagnosis and assessment of myocardial function. (11)

Anaphylaxis is a life-threatening systemic hypersensitivity reaction to triggers such as parenteral medications, insect venoms and food allergens. Prompt intervention is critical and early injection of epinephrine (adrenaline) is essential as it is the only drug shown to reduce mortality and hospitalization. (12-15)

An immediate stepwise approach with ongoing monitoring and clear end-points is necessary for successful management of shock. (1)(7) Initial evaluation and resuscitation should occur irrespective of patient location (emergency department, intensive care unit, general ward), even if it is clear that transfer to a higher level of care will be needed (5)

While most patients with shock benefit from intravascular volume expansion, the required amount and frequency of fluid administration can vary significantly and should depend on assessment of fluid responsiveness. The role of inotropes, vasopressors and vasodilators also varies depending on the prevailing pathophysiology, which can change even in the same patient. (4)(5)(16)(17) There is an increasing role for objective non-invasive hemodynamic assessment using tools such as point-of care ultrasound, electrical impedance cardiometry and

measurement of central venous oxygen saturation (ScvO2) (10)(11)(16)(18) to supplement clinical assessment and enable treatment appropriate to the actual pathophysiological derangements present. Other critical aspects of management include support of other systems and treatment of the underlying cause. (5)

This guideline focuses on management of Pediatric Shock.

➡️Guideline development process and methods

After reviewing all the inclusion and exclusion criteria and quality appraisal results, the GDG/ GAG recommended using the following source original clinical practice guidelines (CPGs):

1.  American College of Critical Care Medicine Clinical Practice. Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock. Crit Care Med. (2017)

2.   Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children. Pediatr Crit Care (2020)

3.  The International Society for Heart and Lung Transplantation, Guidelines for the management of pediatric heart failure. (2014)

4.  Guidelines for the Appropriate Use of Bedside General and Cardiac Ultrasonography in the Evaluation of Critically Ill Patients.

General Ultrasonography. Crit Care Med. (2015).

Cardiac Ultrasonography. Crit Care Med. (2016)

5.  EAACI Food Allergy and Anaphylaxis Guidelines Group. Anaphylaxis: Guidelines from the European Academy of Allergy and Clinical Immunology. (2014)

6.  Emergency department diagnosis and treatment of anaphylaxis: a practice parameter. Ann Allergy Asthma Immunol. (2014)

We conducted Adolopment for these guidelines: (Adoption, Adaptation, and Development)

         -   Adoption for most of the guideline recommendations.

         -  Development of Good Practice Statements

➡️Recommendations and Good Practice Statements (GPS)

This version of the CPG includes recommendations and good practice statements on the following four sub-sections:

➡️ Management of Pediatric Shock

This section includes recommendations and good practice statements on

1)  promotion of effective and timely management of pediatric patients with shock.

2)  improve survival of pediatric patients with shock.

We can summarize the guidelines’ recommendations for management of pediatric shock in the following:

·   Shock should be recognized when there are clinical signs of inadequate tissue perfusion; including:
Prolonged capillary refill greater than 2 seconds, diminished pulses, mottled cool extremities (or flash capillary refill, bounding peripheral pulses and wide pulse pressure), decreased or altered mental status, decreased urine output.

Hypotension is not necessary; however, its presence is confirmatory (weak (conditional) recommendation).

·  Consider hypovolemic shock when there is intravascular fluid loss (eg., hemorrhage, vomiting, diarrhea, osmotic diuresis or capillary leak) (Good practice statemen)t.

·  The clinical diagnosis of septic shock is made in children who have clinical signs of inadequate tissue perfusion AND have a suspected infection (weak (conditional) recommendation).

· Consider cardiogenic shock in patients with signs such as a gallop rhythm, heart murmur, evidence of circulatory congestion (pulmonary rales, jugular venous distension, hepatomegaly or worsening with volume expansion) or arrhythmia. Arrhythmias should be appropriately managed (Good practice statement).

·  The use for cardiac ultrasonography is recommended to assess the etiology of cardiogenic shock (weak (conditional) recommendation).

·  Base the diagnosis of anaphylaxis on the history and physical examination, using scenarios described by the National Institutes of Allergy and Infectious Disease (NIAID) Panel (fig 2, p 28 ), recognizing that there is a broad spectrum of anaphylaxis presentations that require clinical judgment (weak (conditional) recommendation).

·  Life-threatening obstructive causes of shock should be identified and treatment initiated for the underlying cause:

Pericardiocentesis for cardiac tamponade, anticoagulation and thormbectomy for pulmonary embolus, chest tube thoracostomy or needle thoracentesis for pneumothorax, or prostaglandin E1 for ductal dependent circulation (Good practice statement).

·  The use of cardiac ultrasonography is recommended to recognize/ rule out cardiac Tamponade (Strong recommendation).

·   Airway and breathing should be rigorously monitored and maintained. Supplemental oxygen should be given as initial therapy (weak (conditional) recommendation).

·  In children with anaphylaxis, prepare for airway management,including intubation if necessary, if there is any suggestion of airway edema (eg, hoarseness or stridor) (weak (conditional) recommendation).

·   The decision to intubate and ventilate should be based on clinical assessment of

increased work of breathing, hypoventilation, or impaired mental status. Waiting for confirmatory laboratory tests is discouraged (weak (conditional) recommendation).

·  Intubation may be performed for children with fluid-refractory, catecholamine resistant

shock without respiratory failure (Good practice statement).

· If possible, volume loading and peripheral or central inotropic/vasoactive drug support is recommended before and during intubation;

because of relative or absolute hypovolemia, cardiac dysfunction, and the risk of suppressing endogenous stress hormone response with agents that facilitate intubation.

Etomidate is not recommended. Ketamine with atropine pretreatment should be considered the induction combination of choice.

A short-acting neuromuscular blocking agent can facilitate intubation if the provider is confident and skilled (weak (conditional) recommendation).

·  Vascular access should be rapidly attained. Intraosseous access should be established if reliable intravenous line cannot be attained in minutes (weak (conditional) recommendation).

·  The use of ultrasonography is recommended for central venous access (Strong recommendation).

·  Real-time, single operator approach is recommended (Strong recommendation).

Ultrasonography is operator dependent and vascular access should not be delayed in shocked patients (weak (conditional) recommendation).

·   A dilute concentration of the initial vasoactive medication (including epinephrine or norepinephrine) may be administered through a peripheral vein or intraosseous line if central venous access is not readily accessible (Good practice statement).

·  Patients with hypovolemic shock or distributive shock (including septic & anaphylactic shock) should receive fluid resuscitation:

Amount: 20 mL/Kg per bolus, Type: isotonic crystalloid (eg normal saline) DuraIon: push or rapid infusion over 5-10 min (weak (conditional) recommendation).

·   Patients with cardiogenic shock should only receive fluid resuscitation if they are judged to have preload insufficiency (Good practice statement).

·   Cardiac ultrasonography evaluation is recommended during such assessment (weak (conditional) recommendation).

·  Patients with poor cardiac function may also be volume depleted. Smaller boluses (5-10 mL/kg) should be given more slowly (over 10-20 min) for these patients (Good practice statement).

·   Fluid resuscitation should be avoided or discontinued when there is evidence of intravascular volume overload (weak (conditional) recommendation).

·  During fluid resuscitation, monitor for the development of increased work of breathing, rales, hypoxemia, cardiac gallop rhythm, hepatomegaly or a diminishing MAP-CVP (weak (conditional) recommendation).

·  IniIal volume resuscitaIon requirements may be 0 mL/kg if rales or hepatomegaly are present (weak (conditional) recommendation).

·  Fluid boluses may be repeated with the goal of normal perfusion, cardiac output and blood pressure provided there are no signs of fluid overload (weak (conditional) recommendation).

·  A total of up to 60 mL/Kg may be needed during the first hour (weak (conditional) recommendation).

·  For patients with sepsis In low resource settings with no availability of intensive care: in the absence of hypotension, maintenance fluids should be started without prior bolus fluid administration (Strong recommendation).

·  When children with presumed hypovolemia have not improved after receiving a total of 60 mL/kg over 30 to 60 minutes, the following should be considered:

-The amount of fluid loss may have been underestimated (eg burn injury)

-There may be significant ongoing fluid loss (eg hemorrhage from blunt abdominal trauma or capillary leak with bowel obstruction)

-Other conditions may be causing or contributing to shock (eg spinal cord injury in a child with multiple trauma, sepsis, myocardial dysfunction, etc) (Good practice statement).

·  After the first hour, ongoing fluid replacement should be directed at clinical endpoints including perfusion as well as available tools of hemodynamic monitoring as CO, global end-diastolic volume and PAOP (pulm A occlusion P) (weak (conditional) recommendation).

·   Following shock resuscitation, diuretics, peritoneal dialysis or high flux CRRT can be used to remove fluid in paAents who are 10% fluid overloaded and unable to maintain fluid balance with native urine output/ extra-renal losses (weak (conditional) recommendation).

·  In children with fluid overload and ventricular dysfunction diuretics (such as furosemide) should be used to return to euvolemic state while monitoring clinical criteria and cardiac output (Good practice statement).

·   High-volume hemofiltration (HVHF) is not preferred over standard hemofiltration in children with septic shock or other sepsis-associated organ dysfunction who are treated with renal replacement therapy (weak (conditional) recommendation).

·  Crystalloids, rather than 5% albumin, are recommended for the initial resuscitation of children with septic shock (Weak (conditional) recommendation).

·  Although controversial, colloid is a reasonable option for patients with hypoalbuminemia (albumin <3g /dL) or hyperchloremic metabolic acidosis who have not improved after initial crystalloid volume expansion (Good practice statement).

·  In the acute resuscitation of children with septic shock or other sepsis associated organ dysfunction, it is NOT recommended to use: Starches (Strong recommendation); or Gelatin (Weak (conditional) recommendation).

·  Patients with hemorrhagic shock who have not improved should receive blood and require definitive treatment for the cause of hemorrhage (Good practice statement).

·  Transfusion of RBCs is not routinely indicated if the blood hemoglobin concentration is greater than or equal to 7 g/dL in hemodynamically stabilized children with septic shock or other sepsis-associated organ dysfunction (weak (conditional) recommendation).

·  RBC transfusion may be given to children with Hgb less than 10 g/dL. and poor tissue perfusion despite volume expansion (low CI, low ScvO2) (weak (conditional) recommendation).

·  Prophylactic plasma or platelet transfusions are not routinely recommended in nonbleeding children with septic shock or other sepsis associated organ dysfunction solely on the basis of laboratory abnormalities (weak (conditional) recommendation).

·  IV immune globulin (IVIG) should not be routinely used in children with septic shock or other sepsis associated organ dysfunction (weak (conditional) recommendation).

·   Hypoglycemia must be rapidly diagnosed and promptly treated (weak (conditional) recommendation).

·  In paIents with sepsis, a 10% dextrose containing IV solution can be run at maintenance rate to provide age appropriate glucose delivery and to prevent hypoglycemia (weak (conditional) recommendation).

· Blood glucose levels below 180 mg/dL (10 mmol/L) should be targeted (Good practice statement).

·  Insulin therapy targeting a blood glucose at or below 140 mg/dL (7.8 mmol/L) is NOT recommended (Strong recommendation).

·  Calcium replacement should be directed to normalize ionized calcium concentration (weak (conditional) recommendation).

·  Thyroid replacement can be lifesaving in children with thyroid insufficiency and catecholamine-resistant shock (weak (conditional) recommendation).

·  The routine use of levothyroxine in children with septic shock and other sepsis associated organ dysfunction in a sick euthyroid state is not recommended (weak (conditional) recommendation).

·  The management goals in the first hour should be to maintain/ restore:

*Airway, oxygenation, and ventilation

*Circulation

-normal blood pressure for age (only reliable when pulses palpable)

-normal pulses with no differential between the quality of peripheral & central pulses

-threshold HR

-perfusion: Capillary refill less than or equal to 2 seconds, warm extremities, urine output greater than 1mL/kg/hr, normal mental status

*Normal glucose concentration, normal ionized calcium concentration (weak (conditional) recommendation).

·  The following additional goals are applicable beyond the first hour:

-Perfusion pressure (MAP-CVP or MAP-IAP) appropriate for age.

-ScvO2 greater than 70%

-CI greater than 3.3 and less than 6.0L/min/m2

-Normal INR, anion gap, and lactate. (weak (conditional) recommendation).

·  On-going resuscitation should be guided by hemodynamic assessment & monitoring including:

- Heart rate, blood pressure, pulse pressure, capillary refill/ skin perfusion analysis and temperature

- Pulse-oximetry and continuous ECG monitoring

- CVP

- Urine output

- Laboratory (Arterial blood gases, ScvO2, lactate, glucose and ionized Ca) (weak (conditional) recommendation).

·  Assessment of CI and SVRI using advanced hemodynamic monitoring is recommended when available. Methods include:

- invasive arterial BP monitoring with pulse-contour analysis

- serial ultrasonographic assessment (weak (conditional) recommendation).

·  The use of cardiac ultrasonography to assess the efficacy of fluid resuscitation, ventricular function and inotropic support (weak (conditional) recommendation).

- electrical impedance cardiometry (Good practice statement).

·  In patients with cardiogenic shock, repeated determination of troponin levels can be used to assess the severity of myocardial involvement as well as the response to treatment (Good practice statement).

·  It is reasonable to begin vasoacAve infusions aNer 40–60 mL/kg of fluid resuscitation if the patient continues to have evidence of abnormal perfusion, or sooner if fluid overload develops or other concerns for fluid administration are present (Good practice statement).

·  Use of intravenous inotropic agents in the absence of clinical evidence of hypotension, low CO and/or decreased end-organ perfusion is potentially harmful (Strong recommendation).

·   In septic shock:

-Central epinephrine can be started for “cold shock” (0.05–0.3 μg/kg/min) or

norepinephrine can be titrated for “warm shock”.

-Central dopamine can be Atrated to a maximum of 10 μg/kg/min.

-Epinephrine or norepinephrine is more likely to be beneficial (weak (conditional) recommendation).

·  In cardiogenic shock:

-Milrinone and /or dobutamine can be used as first- line therapy

-It is probably advisable to use milrinone in post- cardiac surgery patients and in

cases with impaired RV function and/or associated pulmonary hypertension (weak (conditional) recommendation).

·  Septic shock With Low CI, Normal Blood Pressure, and High SVR:

- Milrinone is considered the first-line inodilator in patients with epinephrine resistant

shock and normal blood pressure.

- Additional volume loading may be necessary to prevent hypotension.

- Norepinephrine can partly reverse hypotension associated with inodilators.

- Nitroprusside or nitroglycerin may be considered as second-line vasodilators.

- Levosimendan and enoximone may have a role with persistently low CO (weak (conditional) recommendation).

·  Septic shock With Low CI, Low Blood Pressure, and Low SVR:

-Norepinephrine can be added to/or substituted for epinephrine to increase DBP and SVR.

-Once an adequate blood pressure is achieved, dobutamine, milrinone, enoximone or levosimendan may be added to norepinephrine to improve CI and ScvO2 (weak (conditional) recommendation).

·  Septic shock With High CI and Low SVR:

- When titration of norepinephrine and fluid does not resolve hypotension, vasopressin, angiotensin, or terlipressin can be helpful in restoring blood pressure

- These drugs can reduce CO so CO/ScvO2 monitoring is necessary. Low-dose epinephrine or dobutamine may be added to improve CO (weak (conditional) recommendation).

·   Cardiogenic shock with low CI refractory to milrinone &/or dobutamine:

-Epinephrine has a role in the face of refractory hypotension and poor end-organ perfusion.

-Levosimendan may be considered in children unresponsive to traditional inotropic therapy (weak (conditional) recommendation).

·  Children with refractory shock must be suspected to have unrecognized morbidities; such as:

-Inappropriate source control of infection (remove nidus and use effective antibiotics)

-Pericardial effusion (pericardiocentesis)

-Pneumothorax (thoracentesis)

-Hypoadrenalism (adrenal hormone replacement)

-Hypothyroidism (thyroid hormone replacement)

-Ongoing blood loss (blood replacement/hemostasis)

-Increased IAP (peritoneal catheter or abdominal release)

-Necrotic tissue (nidus removal)

-Excessive immunosuppression (wean immunosuppressants), or immunocompromise (restore immune function; e.g., white cell growth factors/transfusion for neutropenic sepsis) (weak (conditional) recommendation).

· ECMO is an important option to consider in refractory shock when potentially reversible causes are addressed (weak (conditional) recommendation).

·  Venovenous ECMO is suggested in children with sepsis-induced PARDS and refractory hypoxia.

Venoarterial ECMO is suggested in children with septic shock refractory to all other treatments (weak (conditional) recommendation).

·  IV hydrocortisone may be used if adequate fluid resuscitation and vasopressor therapy are not able to restore hemodynamic stability (weak (conditional) recommendation).

· Ideally after attaining a blood sample for subsequent determination of baseline cortisol concentration (weak (conditional) recommendation).

· In septic shock, broad spectrum antibiotics should be initiated within 60 minutes. After obtaining blood culture if it does not delay antibiotic administration (weak (conditional) recommendation).

·  Positioning: patients experiencing anaphylaxis should be positioned supine with elevated lower extremities if they have circulatory instability, sitting up if they have respiratory distress, and in recovery position if unconscious (weak (conditional) recommendation).

·  Adrenaline:

Adrenaline must promptly be administered as the first-line treatment for the emergency management of anaphylaxis (weak (conditional) recommendation).

- By intramuscular injection into the mid-outer thigh (Strong recommendation).

- In patients requiring repeat doses of adrenaline, these should be administered at least 5 min apart (weak (conditional) recommendation).

- If the patient is not responding to epinephrine injections, IV infusion of epinephrine should be given in a monitored setting (Strong recommendation).

- Do not routinely administer antihistamines or corticosteroids instead of epinephrine. There is no substitute for epinephrine in the treatment of anaphylaxis (weak (conditional) recommendation).

· Other therapies:

-Trigger of the anaphylaxis episode should be removed (weak (conditional) recommendation).

- Administer additional vasopressors If parenteral epinephrine and fluid resuscitation fail to restore blood pressure (Strong recommendation).

- Administer an inhaled b-agonist if bronchospasm is a component of anaphylaxis (Strong recommendation).

- Administration of antihistamines and corticosteroids should be considered adjunctive therapy (weak (conditional) recommendation).

- Systemic glucocorticosteroids may be used as they may reduce the risk of late phase respiratory symptoms (weak (conditional) recommendation).

- High-dose nebulized glucocorticoids may be beneficial for upper airway obstruction (weak (conditional) recommendation).

·   Strongly consider observing patients who have experienced anaphylaxis for at least 4 to 8 hours and observe patients with a history of risk factors for severe anaphylaxis (such as asthma, previous biphasic reactions, or protracted anaphylaxis) for a longer period.  Patients who have experienced anaphylaxis should consult an allergist/ immunologist.after discharge (weak (conditional) recommendation).

➡️Guideline Registration

PREPARE (Practice guideline REgistration for transPAREncy), WHO Collaborating Center for Guideline Implementation and Knowledge Translation, EBM Center, University of Lanzhou, Lanzhou, China. Registration Number: ((submitted and in process)). Link: http://www.guidelines-registry.org/