65: Hypotension and Shock

The nurse reports that an infant may be hypotensive and is showing signs of shock. Hypotension (diminished blood pressure [BP]) is distinct from shock, a clinical syndrome of inadequate tissue perfusion with the clinical signs noted in Section II.B. While hypotension frequently accompanies shock, there is no consensus on the exact definition of hypotension in the neonate. Normal BP values for extremely premature infants are also debated. Data are conflicting for the exact BP that requires treatment for every gestational, postnatal age, and infant weight. Some define hypotension as a BP >2 standard deviations below normal for age or below the fifth percentile. For a rapid reference for premature and term infants BP ranges, see Table 65–1 and for more detailed BP values, see Appendix C.

1. What method of measurement was used? If a BP cuff was used, be certain that it was the correct width (ie, covering two-thirds of the upper arm). A cuff that is too large gives falsely low readings. If measurements were obtained from an indwelling arterial catheter, a “dampened” waveform suggests air in the transducer or tubing or a clot in the system, and the readings are inaccurate (see also Selected Reference).

2. Are signs of shock present? Signs of shock include tachycardia, poor/reduced perfusion, prolonged capillary refill time (>3–4 seconds), respiratory distress, poor tone, poor color, cold extremities (with a normal core temperature), lethargy, narrow pulse pressure, apnea and bradycardia, tachypnea, metabolic acidosis, and weak pulse.

3. Is the urine output acceptable? Normal urine output is ∼1–2 mL/kg/h and is decreased in shock due to decreased renal perfusion. If the BP is low but the urine output is adequate, aggressive treatment may not be necessary as renal perfusion is adequate. (Note: An exception involves the infant with septic shock and hyperglycemia with osmotic diuresis.)

4. Is there a history of birth asphyxia? Birth asphyxia may be associated with myocardial dysfunction and cardiogenic shock.

5. At the time of delivery, was there maternal bleeding (eg, abruptio placentae or placenta previa) or was clamping of the cord delayed? These factors may be associated with loss of blood volume in the infant.

Types of shock are hypovolemic, cardiogenic, distributive (septic, neurogenic, adrenal, anaphylactic), obstructive, and dissociative. Some of the causes are in more than one category. Note: Some inborn errors of metabolism resulting in hypoglycemia or hyperammonemia can mimic the presentation of shock in a newborn (eg, galactosemia, maple syrup urine disease, and others). (See Chapter 101.)

1. Hypovolemic shock. The most common type of shock in a neonate and results from an inadequate blood volume and can be secondary to hemorrhagic shock (antepartum or postpartum blood loss) or nonhemorrhagic shock (fluid and electrolyte losses). The majority of very low birthweight (VLBW) infants that are hypotensive are not hypovolemic.

   1. Antepartum/intrapartum blood loss (often associated with asphyxia)

      1. Abruptio placentae.

      2. Placenta previa.

      3. Twin-twin transfusion.

      4. Fetomaternal hemorrhage.

      5. Others. Difficult delivery, umbilical cord tear, birth injuries (rupture of spleen and liver).

   2. Postpartum blood loss

      1. Coagulation disorders (disseminated intravascular coagulation [DIC], coagulopathies).

      2. Vitamin K deficiency

      3. Iatrogenic causes (eg, loss of an arterial catheter).

      4. Birth trauma (eg, liver injury, adrenal hemorrhage, intraperitoneal hemorrhage).

      5. Pulmonary hemorrhage.

      6. Intracranial hemorrhage.

      7. Circumcision wound. Frenular artery bleed with death as the quantity of blood loss in diaper was concealed.

   3. Fluid and electrolyte losses. Volume depletion is common in premature infants. Besides insensible water loss and diuretic use, sepsis, heat stress, vomiting, diarrhea, gastrointestinal (GI) abnormalities, and iatrogenic are other causes.

2. Cardiogenic shock. Inadequate tissue perfusion secondary to myocardial dysfunction. It implies primary failure of the heart as a pump and is relatively uncommon in the neonate.

   1. Severe birth asphyxia can cause low cardiac output.

   2. Metabolic problems (eg, severe hypoglycemia [infant of diabetic mother], hypocalcemia, acidemia) can cause decreased cardiac output with a decrease in BP. Adrenal insufficiency and inborn errors of metabolism can present with cardiac involvement including congestive heart failure, arrhythmias, cardiomyopathy, and conduction disturbances.

   3. Congenital heart disease with left-sided obstructive lesions are the most common to present with shock after the patent ductus arteriosus (PDA) closes: hypoplastic left heart syndrome, congenital aortic stenosis, coarctation of the aorta, interruption of the aortic arch, and others with systemic outflow obstruction. Other congenital heart diseases can present with shock but are not as common.

   4. Cardiomyopathies.

   5. Persistent pulmonary hypertension.

   6. PDA in a premature infant can cause cardiac failure and hypotension. Extremely low birthweight (ELBW) infants often present only with hypotension without a murmur.

   7. Arrhythmias/dysrhythmias can cause a decrease in cardiac output. Examples include supraventricular tachycardia (SVT), ventricular tachycardia, ventricular fibrillation, complete atrioventricular (AV) block, atrial flutter, and others.

   8. Infectious agents (bacterial, viral, or protozoan) can cause myocarditis and myocardial dysfunction in addition to septic shock.

3. Distributive shock includes septic, neurogenic, adrenal, anaphylactic, and others. There are abnormalities within the vascular beds that can cause blood volume to be distributed inadequately to organs and tissues. There is not a definite volume loss but inappropriate vasodilatation, dysfunction of the endothelium with a capillary leak, loss of vascular tone, or a combination of the above. Because the intravascular fluid volume is maldistributed, signs of shock appear. The most common form of distributive shock in the neonate is sepsis.

   1. Septic shock. Endotoxemia occurs, with release of vasodilator substances and resulting hypotension. It usually involves gram-negative organisms such as Escherichia coli, Klebsiella spp., Enterobacter, Pseudomonas, and Proteus but can also occur with gram-positive organisms. Viruses such as herpes simplex and enteroviruses can also cause septic shock. Fungal infections such as Candida primarily occur in ELBW infants and can cause sepsis and shock. DIC can be a consequence of sepsis.

   2. Neurogenic shock. Rare in neonates, this is secondary to decreased sympathetic activity and leads to a lack of vascular tone and vasodilation with decreased tissue perfusion. Birth asphyxia and intracranial hemorrhage can both cause hypotension.

   3. Anaphylactic shock. Very rare in neonates, this is caused by a hypersensitivity response. There is vasodilation, increased capillary permeability, and fluid shifts with severe hypotension and circulatory collapse. Typical causes include food (through breast milk), cow's milk, formulas, medications (β-lactam antibiotics), penicillin (PCN), antipyretics (ibuprofen and neuromuscular blockers), intravenous immune globulin, hepatitis B immune globulin (HBIG; mom was a hepatitis B virus [HBV] carrier), parenteral nutrition, hepatitis B vaccine, cold exposure, latex, vaccinations, and idiopathic anaphylaxis, and all have been reported in infants.

   4. Adrenal shock. Caused by endocrine disorders; complete 21-hydroxylase deficiency and adrenal hemorrhage are the most common. Suspect adrenogenital syndrome with low serum sodium, high serum potassium, and hypotension.

   5. Other causes of abnormal peripheral vasoregulation. Necrotizing enterocolitis (NEC), extracorporeal membrane oxygenation/extracorporeal life support (ECMO/ECLS), respiratory distress syndrome (RDS), major surgery, asphyxia, and hydrops fetalis, and others.

4. Obstructive shock. Any obstruction of venous blood return (tension pneumothorax, pericardial tamponade, diaphragmatic hernia, severe pulmonary interstitial emphysema, air embolism, specific obstructive congenital heart disease [critical aortic stenosis, coarctation of the aorta, hypoplastic left heart syndrome, interrupted aortic arch, and others]).

5. Dissociative shock. Inadequate oxygen-releasing capacity such as in severe anemia or methemoglobinemia.

6. Drug-induced hypotension. Drugs such as tolazoline, tubocurarine, nitroprusside, sedatives, magnesium sulfate, digitalis, and barbiturates may cause vasodilation and a drop in BP. Transient hypotension has been seen after exogenous surfactant administration.

7. Extreme prematurity and hypotension. Hypotension is very common in ELBW infants (60–100% at 24–26 weeks) and VLBW infants (40% at 27–29 weeks). Hypotension in this group of infants is rarely secondary to hypovolemia and more likely due to adrenocortical insufficiency, poor vascular tone, immature catecholamine responses, and transient left ventricular dysfunction. Hypotension with evidence of end-organ dysfunction in ELBW infants is associated with intraventricular hemorrhage/periventricular leukomalacia (IVH/PVL). Blood pressure usually improves spontaneously during the first 24 hours in an ELBW infant. In VLBW infants in the first 3 days of life a mean arterial pressure <30 mm Hg or a mean arterial pressure with a number less than the gestational age in weeks of the infant is used to define hypotension (eg, mean BP <27 for a 27-week neonate). See Appendix Figure C–1 for mean blood pressure for infants <1000 g.

1. Physical examination. Particular attention is given to signs of blood loss (eg, intracranial or intra-abdominal bleeding), sepsis, or clinical signs of shock (cool extremities, mottling of the skin, tachycardia, decreased urine output). Anaphylaxis in an infant is hard to diagnose. Sudden onset of lethargy or hypotonia can be seen. Normal symptoms of itching cannot be evaluated, and signs may be nonspecific. Check the weights and fluid intake and output (I&O) status. A loss of >15% of birthweight during the first week of life should be considered excessive, and body water balance may be excessive and contributing to low BP. Phototherapy and radiant warmers may increase insensible fluid losses (see Chapter 9). Peripheral edema, heart murmur, and hepatomegaly can be seen in cardiogenic shock. Assess capillary refill time in the newborn. Measure it by pressing on the sternum for 5 seconds and noting the time it takes for the color to return. Normal upper limit is 3 seconds. Is there low systemic blood flow? Is the infant in early or late stage of shock? Shock can be divided into two phases: early (warm) or late (cold) shock. Shock can also be classified as compensated, uncompensated, or irreversible.

   1. Warm shock (early stage of shock). Extremities are warm with loss of vascular tone, peripheral vasodilation, tachycardia, bounding peripheral pulses, increase in systemic blood flow, and a decrease in blood pressure.

   2. Cold shock (late stage of shock). Extremities are cold and mottled with a prolonged capillary refill time (>3–4 seconds), decreased peripheral pulses, an increase in vascular tone, vasoconstriction, decrease in systemic blood flow, and a decrease in blood pressure.

   3. Low systemic blood flow (LSBF). When the systemic end organs receive a decreased amount of blood, causing a decrease in oxygen delivery and results in shock.

   4. Compensated shock. Blood flow to the vital organs is maintained. Infant presents with tachycardia, pallor, and cool extremities. Vital signs are normal.

   5. Uncompensated shock. Blood flow to the vital organs is compromised. Infant has metabolic acidosis, rapid breathing, and decreased blood pressure and urine output.

   6. Irreversible shock. Irreversible damage to the vital organs. Profound failure resulting in death.

2. Laboratory studies

   1. Complete blood count (CBC) with differential. Decreased hematocrit (Hct) identifies blood loss; however, the Hct can be normal in patients with acute blood loss. Elevated/decreased white blood cell count and differential may help identify sepsis as the cause.

   2. Coagulation studies (prothrombin time [PT]/partial thromboplastin time [PTT]) and platelet count. If DIC is suspected.

   3. Serum glucose, electrolytes, and calcium levels. May reveal a metabolic disorder.

   4. Cultures. Obtain blood, urine, and spinal fluid for culture and antibiotic sensitivity testing if indicated.

   5. Kleihauer-Betke test. If fetomaternal transfusion is suspected. The test detects the presence of fetal erythrocytes in the mother's blood by a slide elution technique. A smear of maternal blood is fixed and incubated in an acidic buffer. It causes adult hemoglobin to be eluted from erythrocytes; fetal hemoglobin resists elution. After the slide is stained, fetal hemoglobin cells, if present, appear dark, whereas maternal erythrocytes appear clear. Ask the mother's obstetrician to order this test on the mother.

   6. Arterial blood gases. To assess for hypoxia or acidosis. An increasing anion gap acidosis is seen in shock.

   7. Serum/plasma lactate. If increased, may signify anaerobic metabolism and sepsis. It can indicate low tissue perfusion.

   8. Serum histamine levels or tryptase levels. Elevated with anaphylactic shock. A normal level does not rule out anaphylaxis.

   9. Baseline cortisol level. If considering hydrocortisone therapy.

3. Imaging and other studies

   1. Chest radiograph. An anteroposterior chest radiograph assesses the heart and lungs and rules out any mechanical cause of shock (eg, pneumothorax). Cardiomegaly can be seen in heart defects (cardiogenic shock).

   2. Ultrasonography of the head. In infants in whom intracranial hemorrhage is suspected.

   3. Electrocardiography (ECG). If an arrhythmia is suspected. Cardiogenic shock can have wide QRS complexes and T-wave abnormalities on ECG. Evaluate for heart block.

   4. Echocardiography. Useful in birth-asphyxiated infants to assess myocardial function and left ventricular output. If there is myocardial failure, drug therapy is needed to improve cardiac output. Echocardiography is also useful to rule out a congenital heart lesion. Left ventricular output is important to measure in evaluating mean arterial blood pressure and guiding the management of hypotension. This helps determine if fluids or vasopressors are needed. Right ventricular output can also help in assessing systemic blood flow. Superior vena cava flow has also been measured to assess systemic blood flow. See Section V.A.1e.

   5. Central venous pressure (CVP) measurement. A venous umbilical catheter can be placed above the diaphragm (tip at the right atrium) to obtain central venous pressure readings. Normal values are 4–6 (VLBW) and 5–8 (newborn) mm Hg. CVP in VLBW infants may be wider than previously reported in some sources at 2.8–13.9 mm Hg. Readings are higher in ventilated infants. If the readings are low, hypovolemia is present and volume replacement is usually necessary. CVP values in ventilated infants are limited but can be used to guide when used serially. CVP can be high in cardiogenic and obstructive shock. CVP can be normal in early septic shock but high in late septic shock.

   6. Near infrared spectroscopy (NIRS). Allows a noninvasive measurement of venous oxygen saturation in the skin tissues. It can be used in the brain, renal, and mesenteric regions to give an assessment of oxygen delivery (see Chapter 16).

If a blood pressure is felt to be low, evaluate the infant for shock. If the infant is hypotensive without shock (oxygenating, not acidotic, normal urine output, good perfusion, and normal capillary refill time), aggressive treatment is usually not necessary, regardless of the BP. Close observation and reevaluation of the infant is necessary. If the infant is hypotensive and showing clinical signs of shock (acidotic, not oxygenating, decreased urine output, prolonged capillary refill time, and poor peripheral perfusion), the infant is probably not perfusing and has a BP that needs to be treated. Early aggressive management of shock is necessary.

1. General measures

   1. Rapidly assess the infant to determine what is causing the hypotension in order to direct therapy. First rule out causes that require immediate treatment: chest tube for pneumothorax, pericardiocentesis for cardiac tamponade, epinephrine for anaphylactic shock, prostaglandin (PGE1) for ductal-dependent cardiac lesion, and others. Then the basic decision is whether the infant requires volume replacement or administration of inotropic agents. The decision is not difficult in the majority of patients. Five parameters are useful in making this decision:

      1. History. To rule out birth asphyxia, blood loss (antepartum or postpartum), drug infusion, and birth trauma (adrenal hemorrhage or liver injury).

      2. Physical examination. Often reveals which organ systems are involved. Check ECG to rule out complete heart block or other arrhythmias.

      3. Chest radiograph. A small heart is seen in volume depletion; a large heart is seen in cardiac disease. Evaluate for pneumothorax. Transillumination of the chest may help detect pneumothorax.

      4. Central venous pressure. If it is low (<4 mm Hg in VLBW or 5 mm Hg in newborn), the infant is volume depleted. If it is high (eg, >6 mm Hg in VLBW or >8 mm Hg in newborn), the infant probably has cardiogenic shock.

      5. Echocardiogram. Left ventricular output (LVO)/right ventricular output can be assessed by echocardiogram. Left ventricular output can measure systemic blood flow but is affected by left-to-right ductal shunting in the first few days after birth. Right ventricular output is less affected by ductal shunting but can be affected by left-to-right foramen ovale shunting. Right ventricular output may be a better assessment of low flow in the first couple of days of life. Superior vena cava flow has also been measured to assess systemic blood flow.

         1. If LVO is normal or high with no patent ductus arteriosus (PDA). A vasopressor (dopamine) is indicated. If a PDA is present, it should be treated.

         2. If LVO is low and the left ventricle shows under-filling. Volume expansion is indicated.

         3. If LVO is normal but the left ventricle shows impaired contractility. Dobutamine is indicated.

         4. Right ventricular (RV) dysfunction. Right ventricular output by echocardiography can help in the measurement of systemic blood flow. Agents to reduce RV afterload are inhaled nitric oxide, milrinone, and sildenafil.

         5. Superior vena cava flow (SVC flow). Measured by Doppler echocardiogram, can assess systemic blood flow, and is low with low systemic blood flow. Superior vena cava flow <40 mL/kg/min is considered low and abnormal.

   2. If cause is uncertain. Start empiric volume expansion with crystalloid (eg, normal saline [NS] 10 mL/kg intravenously over 30 minutes).

      1. If there is a response. Continue volume expansion.

      2. If there is no response or if it worsens (think cardiogenic shock). An inotropic agent (eg, dopamine) should be started.

      3. In cases where volume expansion and inotropic agents do not help. Glucocorticoids can be tried and have been effective.

   3. Provide respiratory support as needed. High-flow heated and humidified oxygen by nasal cannula or continuous positive airway pressure (CPAP) should be provided initially until a blood gas determination and clinical examination is done. Deciding whether the infant requires intubation and mechanical ventilation depends on blood gases and clinical assessment on supplemental oxygen or CPAP.

   4. Correct metabolic acidosis, hypoglycemia, or hypocalcemia.

   5. Begin antibiotics if infection is suspected. Antibiotics should be administered as soon as possible (recommended within the first hour in neonatal septic shock).

   6. Start PGE₁. If ductal-dependent cardiac lesion is suspected.

2. Specific measures

   1. Hypovolemic shock. Treat if there are signs of intravascular volume depletion, but recall that volume depletion is not a common reason for postnatal hypotension in premature infants. Early volume expansion in preterm infants is controversial and increases risks such as intracranial hemorrhage in the first days after birth.

      1. Volume expansion using intravenous crystalloid such as normal saline or lactated Ringer's solution should be given. Crystalloids are preferred over colloids because of the lack of risk of infection, availability, and lower cost. If blood loss has occurred and the patient is severely hypovolemic, immediate volume expansion is essential and should be continued until adequate tissue perfusion is attained, as indicated by good urinary output and central nervous system function. Meanwhile, a blood sample should be sent to the laboratory for Hct value, which is used to guide specific blood products for replacement therapy. Term infants: Give 10 mL/kg bolus over 5–10 minutes; this can be repeated once, then reassess the infant. Boluses up to 40–60 mL/kg can be given until perfusion improves or hepatomegaly develops. Preterm infants: Give 10 mL/kg over 10–30 minutes, then reassess the infant. Higher doses may be needed.

      2. Blood replacement therapy if severe hemorrhage has occurred (hemorrhagic shock). Treat the cause and stop the bleeding if possible. Transfuse if significant blood loss has occurred.

         1. Hct <30–35%. Consider transfusion if Hct is <35% (some institutions recommend <40%) and the infant has severe cardiopulmonary disease with acidosis or if the Hct is <30% and the infant has moderate cardiopulmonary disease and is acidotic. Packed red blood cells should be given, 5–10 mL/kg. The following formula may also be used to calculate the volume of packed red blood cells needed. This formula assumes that the total blood volume is 80 mL/kg and the Hct of the packed red blood cells is 70%.

            

         2. Hct >50%. Normal saline can be given. If coagulation studies are abnormal, fresh frozen plasma can be given for volume replacement.

      3. Hypovolemic shock in a VLBW infant. In VLBW infants with hypovolemia or acute blood loss, a single bolus of NS, lactated Ringer's solution, or whole blood (O Rh-negative blood) of 10 mL/kg over 10 minutes can be given and then the infant reevaluated. A repeat dose can be given. Carefully titrated dopamine can be considered.

   2. Cardiogenic shock. First, treat any obvious cause.

      1. Arrhythmia. Recognize the arrhythmia and treat it.

      2. Metabolic cause. Metabolic problems need to be corrected.

      3. Asphyxia. The hypotension usually responds to inotropic agents. Treat respiratory failure with oxygen and assisted ventilation. Do not give volume loading (see the following).

      4. Congenital heart disease with left-sided obstructive lesion. Should be treated with prostaglandin infusion (for dosing see Chapter 148).

      5. Cardiogenic shock. The goal is to improve cardiac output. Inotropic agents should be used IV. Use of volume expansion is not warranted and may be harmful. Balancing fluid therapy and inotropic agents is difficult. Echocardiogram helps guide therapy (assess LVO and RV dysfunction).

         1. Dopamine. The drug of choice and is superior to dobutamine, especially in the short-term treatment of preterm infants. Studies suggest that higher than traditionally used dosages (≥30–50 mcg/kg/min) may be used without causing α-adrenergic side effects (decreased renal perfusion and urine output). One review found that infants with perinatal asphyxia who were treated with low-dose dopamine (2.5 mcg/kg/min) did not show improvement in mortality or long-term developmental outcome.

         2. Dobutamine. If dopamine fails to improve BP, dobutamine is recommended as second-line therapy. In neonates, it is usually given together with dopamine infusion. Note: Dobutamine causes peripheral vasodilation.

         3. Other agents. If dopamine or dobutamine do not work.

            • (a) Epinephrine has also been used. Discontinue dopamine if epinephrine is used.

            • (b) Milrinone, a phosphodiesterase type III inhibitor, can be used as second- or third-line therapy. It increases cardiac contractility and output, decreases RV afterload, and has been used postoperatively. There is no evidence to support use in VLBW infants.

            • (c) Vasopressin, inhaled nitric oxide, milrinone, and/or sildenafil may be used.

            • (d) Consider thyroid replacement if hypothyroidism (can present in cardiogenic shock).

         4. ECMO/ECLS. Found to improve survival for postcardiotomy cardiogenic shock.

      6. Cardiogenic shock in a VLBW infant with myocardial dysfunction. Give dobutamine as first-line therapy; second treatment should be with dopamine at low doses. If hypotension continues, use epinephrine (stop dopamine).

   3. Distributive shock

      1. Septic shock. Hypotension is primarily caused by systemic vasodilation.

         1. Obtain cultures (blood and urine [unless in the first 72 hours of life, in which case obtain only blood]), cerebrospinal fluid (CSF).

         2. Initiate empiric antibiotic therapy after culture specimens have been obtained. Antibiotics should be administered within the first hour. Intravenous ampicillin and gentamicin are recommended. Vancomycin may be substituted for ampicillin if staphylococcal infection is suspected (usually infants >3 days old with invasive monitoring catheters or chest tubes). Some institutions are advocating the use of cefotaxime (especially with central nervous system [CNS] infection) with vancomycin instead of gentamicin to avoid the nephrotoxicity (see Chapter 148). Consider using more specific gram-negative coverage based on local resistance patterns. For bowel perforation or NEC, consider Zosyn and gentamicin.

         3. Use volume expansion and inotropic agents as needed to maintain adequate tissue and renal perfusion. Usually early on, volume expansion is indicated; if hypotension continues and there is fluid-refractory shock then inotropic agents are used (dopamine first, then dobutamine and then epinephrine [if fluid and medications don't work]).

         4. In VLBW infants with septic shock, dopamine is considered first, followed by epinephrine. If refractory, consider use of hydrocortisone (see the following).

         5. Use corticosteroids if volume expansion and inotropic agents are ineffective. Obtaining a serum cortisol may be helpful in deciding which infants will benefit. IV corticosteroid therapy for sepsis is controversial. Agents such as dexamethasone and hydrocortisone have been used. Do not use hydrocortisone with indomethacin. Studies have shown that a single dose may be useful in refractory hypotension or a short course of steroids may be beneficial with no adverse effects in neonates. Cochrane review does not support the routine use of hydrocortisone in preterm hypotension. A single dose of hydrocortisone in preterm infants who have refractory hypotension on epinephrine may be effective, but it is not recommended for routine use. Dexamethasone is not recommended (association with cerebral palsy with early postnatal use).

         6. If all of the above do not work the following are options (see definitions of cold and warm shock; recommendations are based on American College of Critical Care Medicine [ACCCM] consensus guidelines):

            • (a) Term infants

              • (i) Cold shock, normal blood pressure, poor LV function. If SVC flow is <40 mL/kg/min, consider volume loading, vasodilator, (milrinone).

              • (ii) Cold shock, low blood pressure, RV dysfunction. If persistent pulmonary hypertension of the newborn (PPHN) with SVC flow <40 mL/kg/min, consider inhaled nitric oxide, milrinone. Consider inhaled Iloprost or IV adenosine.

              • (iii) Warm shock with low blood pressure. Add volume, norepinephrine, consider vasopressin, terlipressin, or angiotensin. Use inotropes to keep SVC flow >40 mL/kg/min.

            • (b) Preterm

              • (i) Cold shock, normal blood pressure, poor LV function. Consider milrinone if normal renal function.

              • (ii) Cold shock, low blood pressure, RV dysfunction. If PPHN, add nitric oxide. Consider milrinone if normal renal function.

              • (iii) Warm shock with low blood pressure. Consider vasopressin or terlipressin with inotropes.

            • (c) Refractory shock. Rule out and treat pneumothorax or pericardial effusion

              • (i) Term infants. Consider hydrocortisone (if adrenal insufficiency is present), correct hypothyroidism if present. Close PDA if present and hemodynamically significant.

              • (ii) Preterm infants. Consider intravenous immune globulin (IVIG); close PDA if present and hemodynamically significant. Consider inhaled nitric oxide for PPH and hypoxemia that persists. Consider pentoxifylline if VLBW.

              • (iii) Consider ECMO/ECLS. If all else fails and shock is not reversed.

         7. Adjunctive therapies. Unclear if beneficial but are used.

            • (a) Naloxone has been used in patients with septic shock and persistent hypotension, but its use is controversial. Naloxone and methylprednisolone may be synergistic in improving the hemodynamics; naloxone is rarely helpful in hypoxic ischemic shock.

            • (b) Methylene blue (controversial) has been used in septic shock unresponsive to colloid, inotropic agents, and corticosteroids.

            • (c) Double-volume exchange transfusion (controversial). Exchange transfusion with fresh whole blood is beneficial in sepsis (see Chapter 30). Because of significant risk and few studies, many institutions have not advocated its use.

            • (d) Intravenous immune globulin (IVIG) (controversial) was found to reduce mortality in 1 review (3% reduction with sepsis). Their conclusion did not support its routine use in sepsis. Some institutions give a single dose in infants with overwhelming sepsis.

            • (e) Fresh frozen plasma. Only indicated in DIC and has no benefit in septic infants.

            • (f) Other agents with potential benefits, but insufficient evidence for routine use. Granulocyte/neutrophil transfusions, cytokines (granulocyte colony-stimulating factor [G-CSF], recombinant human activated protein C (rhAPC), pentoxifylline, nitric oxide inhibitors (milrinone), terlipressin infusion, noradrenaline, arginine vasopressin.

            • (g) ECMO/ECLS has been used in newborns with septic shock with refractory hypotension.

      2. Neurogenic shock. Neurogenic shock is treated with volume expansion and inotropic agents.

      3. Anaphylactic shock. Access ABCs, give oxygen and IV fluids as needed and IV epinephrine (drug of choice). Other therapies include antihistamines and steroids, nebulized albuterol for bronchospasm, and dopamine for blood pressure support. Adjunctive therapy may include H₁ and H₂ receptor blocking agents.

      4. Adrenal shock. For adrenal hemorrhage use volume expansion, blood replacement, and corticosteroids. Congenital adrenal hyperplasia is treated with hydrocortisone and sodium supplementation. Pediatric endocrinologist consultation is recommended.

   4. Obstructive shock. Relief of obstruction is lifesaving. Air leak: If a tension pneumothorax is causing hypotension by obstructing venous return, immediate evacuation of the air is necessary (see Chapter 70). For cardiac tamponade: immediate pericardiocentesis (see Chapter 38).

   5. Dissociative shock. Caused by severe anemia (see Chapter 82) and methemoglobinemia (see Chapter 51). Acute methemoglobinemia can present as shock. Use methylene blue therapy unless the infant has G6PD deficiency.

   6. Drug-induced hypotension. Volume expansion usually maintains the BP in cases of drug-induced vasodilation. If the BP cannot be maintained, the drug causing hypotension may need to be discontinued.

   7. Cause of hypotension unknown. For VLBW infants, consider dopamine first then dobutamine; if ineffective, change to epinephrine. For refractory hypotension use hydrocortisone. For all other infants try a fluid bolus; if no response, use dopamine, then dobutamine, epinephrine, then hydrocortisone.

   8. Hypotension in ELBW infants. Studies have found that blood pressure increases without treatment in 24 hours in the ELBW infant. Infants with good perfusion, even with blood pressures low on standard criterion, had a good outcome compared with those with normal blood pressures. It is difficult to assess normal blood pressure and assess perfusion in the ELBW. Treatment is limited to those with hypoperfusion (low blood pressure with metabolic acidosis, low urine output, and poor capillary refill).

      1. Antenatal steroids decrease the risk of hypotension in ELBW infants.

      2. Dopamine is more effective than normal saline (as long as there is no evidence of myocardial dysfunction) in increasing BP in preterm infants.

      3. Dobutamine if there is evidence of myocardial dysfunction. Epinephrine may also be effective if dopamine or dobutamine do not work.

      4. Physiologic doses of hydrocortisone have been used in refractory hypotension (vasopressor resistant) with uncertainty of long-term side effects. Low-dose dexamethasone increases the blood pressure and also decreases pressor requirements in ELBW infants with volume and pressor-resistant hypotension (see previous discussion concerning recommendations prior to hydrocortisone treatment). Cochrane review does not recommend this. A single dose of hydrocortisone in preterm infants who have refractory hypotension on epinephrine may be effective, but it is not recommended for routine use. Obtaining a baseline serum cortisol may be beneficial.

      5. More studies are needed to evaluate the safety of use of crystalloids/dopamine/dobutamine to treat low BP in preterm infants.

      6. Consider the possibility and role of the left-to-right PDA shunt in hypotension in ELBW infants. Studies have revealed that hypotension not responding to vasopressors was significantly associated with a hemodynamically significant PDA. Echocardiography is recommended early to detect shunting before hydrocortisone is used. Consider closing the PDA.

      7. Indomethacin with hydrocortisone is not recommended because there is an increase in gastric perforations.

      8. Low-dose vasopressin infusion therapy can be considered as rescue therapy when steroid and catecholamine therapy has failed.