Shock in neonates

Introduction and Definition

• Shock is a clinico-pathological state characterized by compromised energy resources to the body's tissues and organs.
• These energy sources are chiefly oxygen and glucose. A low blood flow to organs is the key determinant of this energy depletion.
• This compromised state triggers a chain of events leading to overwhelming anaerobic metabolism, accumulation of toxic wastes, and organ dysfunction.
• Hypotension is a late manifestation of shock and does not always reflect the organ perfusion status.
• In neonates, hypotension is most often defined as a mean blood pressure (MBP) less than the 5th percentile for postnatal age in days.
• A widely accepted bedside definition defines hypotension as an MBP less than the gestational age in weeks.
• Alternatively, an MBP of less than 30 mmHg in the first postnatal days of life defines hypotension.
• The practice of permissive hypotension is generally not recommended pending robust evidence, especially beyond the initial few hours of life in extremely premature infants.

Operational Definition of Shock

The operational definition of neonatal shock includes the presence of one or more of the following clinical features:

• Poor peripheral and central pulses.
• Tachycardia.
• Mottled appearance to the skin or an ashen gray to pale skin color.
• Prolonged capillary refilling time greater than 3 seconds.
• Cold to touch extremities.
• A core-periphery temperature difference of greater than 3 degrees Celsius.
• Low blood pressure.

Presence of biochemical and laboratory features further strengthens the diagnosis:

• Oliguria defined as urine output less than 0.5 ml/kg/hour in the preceding 6 hours.
• Elevated serum lactate greater than 5 mmol/L.
• Low pH less than 7.25 with a base deficit greater than -5 mEq/L.
• Superior vena cava flow less than 40 ml/kg/min.

Etiology and Classification

The cardiovascular physiology of preterm neonates is unique and continues to change with gestational and postnatal age. The most common mechanism of neonatal shock in preterm neonates is a combination of poor myocardial contractility and loss of vasomotor tone. Factors contributing to hypotension include myocardial immaturity, higher systemic vascular resistance during transition, perinatal asphyxia, left to right shunts, and relative adrenal insufficiency.

Types of Shock

Circulatory Classification

Shock can be categorized into four groups irrespective of etiology:

• Low cardiac output and normal blood pressure indicating compensated shock.
• Low cardiac output and low blood pressure indicating decompensated shock.
• Normal to high cardiac output and low blood pressure indicating hyperdynamic circulation.
• Normal cardiac output and low blood pressure indicating transitional circulation.

Assessment of Circulation

Clinical Signs

• Assess the brachial and femoral pulses using your thumb.
• Radial artery evaluation is generally not suitable in preterm neonates due to smaller caliber.
• Palpation of both right brachial and right femoral pulses is recommended to screen for duct-dependent systemic circulation heart diseases.
• A serial trend of increasing heart rate could be an early and sensitive sign of shock.
• Check capillary refill time by applying pressure over the mid-sternum.
• A refill time of greater than 3 to 4 seconds suggests poor perfusion, though it has a poor predictive value as a surrogate marker of low systemic blood flow.
• Flash refill may indicate the warm phase of septic shock.
• Touch the neonate's hands and feet to look for cold extremities and measure core-periphery temperature difference.
• Check oxygen saturation using a pre-ductal and post-ductal placement.
• A pre-post-ductal saturation difference of greater than 3 percent is abnormal.
• Assess for neurological signs like lethargy, irritability, unresponsiveness to painful stimuli, and generalized hypotonia.

Blood Pressure Measurement

• Systolic blood pressure reflects left ventricular contractility.
• Low systolic blood pressure is due to low preload, high afterload, or reduced myocardial contractility.
• Diastolic blood pressure reflects basal vascular tone and intravascular blood volume.
• The oscillometric non-invasive method is reasonably accurate if the mean blood pressure is in the range of 25 to 50 mmHg.
• In extreme preterm neonates and critically ill low-birth-weight infants, the oscillometric method may overestimate blood pressure.
• Invasive intra-arterial blood pressure measurements are the gold standard for sick preterm neonates.
• Radial artery and umbilical artery lines are suitable for recording invasive pressures.

Point of Care Echocardiography

Point of care echocardiography is recommended to evaluate cardiovascular hemodynamics and rationalize pharmacologic management.

• Inferior vena cava collapsibility indicates reduced intravascular volume and predicts fluid responsiveness.
• Left ventricular output and right ventricular output assess systolic function.
• Superior vena cava flow reflects cerebral venous return and is a better surrogate marker for systemic cardiac output in the presence of shunts.
• A superior vena cava flow of less than 50 ml/kg/min and right ventricular output of less than 150 ml/kg/min represent the lower limits of normal in preterm neonates.
• Fractional shortening and ejection fraction measure cardiac contractility.
• Mitral valve inflow doppler features assess left ventricular compliance and elasticity.

Laboratory Investigations

• Complete blood count with differential evaluates the degree of anemia and infection.
• Prothrombin time and activated partial thromboplastin time evaluate for disseminated intravascular coagulation or liver failure.
• Electrolytes, blood sugar, blood urea nitrogen, and creatinine assess renal compromise and metabolic derangements.
• Arterial blood gases measure the adequacy of oxygenation and ventilation.
• Serum lactate evaluates the degree of tissue hypoperfusion.
• Chest radiographs help identify abnormal cardiopulmonary pathology.
• Cranial ultrasounds in preterm neonates rule out acute intracranial hemorrhage.

Clinical Settings of Neonatal Shock

Sepsis and Shock

• Sepsis causes vasoplegia, leading to peripheral vasodilation and capillary vascular bed leakage.
• The early warm phase manifests with an increase in heart rate, low diastolic blood pressure, and a hyperdynamic left ventricle.
• Increased left ventricular contractility can quickly deteriorate, leading to increased systemic vascular resistance.
• The late cold phase involves low systolic and diastolic blood pressures, multiorgan dysfunction, and poor cardiac output.
• A state of relative adrenal insufficiency is frequently described in severe neonatal sepsis.

Perinatal Asphyxia

• Asphyxia typically presents with shock in the initial 48 hours of life.
• Shock results from hypoxic-ischemic myocardial injury leading to poor myocardial contractility.
• This condition presents with reduced stroke volume, low systolic blood pressure, and poor cardiac output.
• Adrenal hemorrhage can additionally complicate the presentation.

Late Onset Glucocorticoid Responsive Circulatory Collapse

• This condition occurs in relatively stable very low birth weight neonates after the first week of life.
• It is characterized by the sudden onset of hypotension or oliguria.
• The shock state is resistant to fluids and inotropes but responds rapidly to intravenous glucocorticoids.
• The underlying cause is attributed to relative adrenal insufficiency.

Management of Neonatal Shock

General Supportive Care

• Initial stabilization includes the temperature, airway, breathing, and circulation protocols of resuscitation.
• Administer the first dose of antibiotics within one hour for suspected septic shock.
• Provide early support of airway and breathing through noninvasive or invasive mechanical ventilation.
• Establish reliable vascular access early via an umbilical venous catheter.
• Correct metabolic derangements such as hypoglycemia, hypocalcemia, and hypokalemia.
• Withhold enteral feeds during the acute phase of shock to prevent gut ischemia.
• Optimize continuous positive airway pressure to 5 to 7 cm H2O.

Volume Expansion

• Shock management in neonates begins with at least one 0.9 percent saline bolus at 10 ml/kg infused over 30 to 60 minutes.
• Crystalloids are preferred over colloids.
• Additional boluses up to 20 to 30 ml/kg may be necessary for proven blood loss and distributive shock.
• Fluid boluses in extreme preterm babies should be used cautiously due to the heightened risk of intraventricular hemorrhage.
• Limit volume expansion to one bolus and plan further fluid replacement based on blood pressure and echocardiographic assessment.

Pathophysiology-Based Management

Systolic Hypotension

• Defined as systolic arterial pressure less than the third centile.
• Results from a decrease in left ventricular stroke output.
• In cardiogenic shock, start dobutamine or epinephrine to improve myocardial systolic performance.
• In septic shock, optimize sepsis treatment and initiate dobutamine or epinephrine.
• In persistent pulmonary hypertension, utilize pulmonary vasodilators like inhaled nitric oxide or milrinone.
• Increase preload with fluid boluses and vasopressin to increase systemic vascular resistance.

Diastolic Hypotension

• Defined as diastolic arterial pressure less than the third centile.
• Results from a decrease in systemic vascular resistance.
• For systemic hypovolemia and warm shock, optimize preload with fluid boluses up to a maximum of two 10 ml/kg boluses.
• Start vasopressin, dopamine, or norepinephrine to increase systemic vascular resistance.
• For a patent ductus arteriosus, close the ductus medically or surgically and start dobutamine to improve left ventricular systolic function.

Combined Systolic-Diastolic Hypotension

• Defined as both systolic and diastolic arterial pressures less than the third centile due to cardiac systolic dysfunction.
• If presenting with low systolic arterial pressure, utilize dobutamine or epinephrine.
• If presenting with low diastolic arterial pressure, optimize fluids and begin dopamine, norepinephrine, or vasopressin.
• In severe warm shock with left ventricular dysfunction, optimize preload, initiate vasopressors, and consider early hydrocortisone.

Pharmacotherapy

Common Clinical Scenario-Based Management

Therapeutic Endpoints and Weaning Plan

• Therapeutic endpoints require normalization of clinical signs of shock such as warm extremities, normal pulses, and mental status.
• Normalization of biochemical parameters including pH, base deficit, and lactate must be achieved.
• Blood pressure should approach or remain above the 50th centile on blood pressure charts.
• Cardiac function parameters on echocardiography should normalize.
• Trophic feeds at 10 to 20 ml/kg/day may be initiated once therapeutic endpoints are met.
• Weaning frequency depends on blood pressure stability; wean every 2 hours if blood pressure is between the 5th and 50th centile, and every 1 hour if above the 50th centile.
• Follow the first in, first out principle when weaning off multiple inotropes and vasoactive agents.
• Tapering should start once the blood pressure remains stable for at least 6 hours.