eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Neonatology

Shock and Hypotension in the Newborn

Samir Gupta, MD, MRCP, FRCPCH, Consulting Neonatologist, University Hospital of North Tees
Sunil K Sinha, MBBS, MD, MRCP, PhD, FRCP, FRCPCH, Director of Neonatal Services, South Cleveland Hospital, UK; Steven M Donn, MD, Professor of Pediatrics, Director, Neonatal-Perinatal Medicine, Department of Pediatrics, University of Michigan Health System

Updated: Jun 25, 2008

Introduction

Background

Shock is a complex clinical syndrome caused by an acute failure of circulatory function and is characterized by inadequate tissue and organ perfusion. When this occurs, inadequate amounts of oxygen and nutrient substrate are delivered to body tissues, and removal of metabolic waste products is inadequate. This results in cellular dysfunction, which may eventually lead to cell death. Failure of perfusion may involve isolated organs or the entire organism. Hypotension (ie, lower than expected blood pressure) frequently, but not always, accompanies shock.

Pathophysiology

Maintenance of adequate tissue perfusion depends on a combination of 3 major factors: (1) cardiac output; (2) integrity and maintenance of vasomotor tone of local vascular beds, including arterial, venous, and capillary; and (3) the ability of the blood to perform its necessary delivery of metabolic substrates and removal of metabolic wastes.

Cardiac output is the product of heart rate and stroke volume. Neonatal cardiac output depends more on heart rate than stroke volume; therefore, both very high (>180 beats per minute [bpm]) and very low (<80 bpm) heart rates are likely to compromise cardiac output if prolonged. However, not all infants with subnormal heart rates have impaired perfusion. At higher rates, ventricular filling time and end-diastolic volume are diminished, and myocardial oxygen consumption is increased. Because myocardial perfusion occurs during diastole, further increases in heart rate may produce undesirable cardiac ischemia, leading to ventricular dysfunction. Stroke volume, the other major determinant of cardiac output, is influenced by 3 factors: preload, afterload, and myocardial contractility.

• Preload corresponds to the myocardial end-diastolic fiber length and is determined by the amount of blood filling the ventricles during diastole. Increases in preload increase stroke volume up to a maximum value, beyond which stroke volume falls according to the Starling law.
• Afterload is the force that the myocardium generates during ejection against systemic and pulmonary vascular resistances (for the left and right ventricles, respectively). Reductions in afterload increase stroke volume if other variables remain constant.
• Contractility is a semiquantitative measure of ventricular function. An increase in contractility produces an increase in stroke volume if preload and afterload are unchanged. This is determined by the percentage of fractional shortening, which depends on the ventricular end diastolic and end systolic diameter.
• Clinically significant alterations in preload, afterload, and contractility may be achieved by the use of vasoactive pharmacologic agents, administration of inotropic agents, changes in blood volume, or a combination of these methods.

Blood flow to tissues and organs is influenced by their vascular beds, which are under the control of central and local vasoregulation, also referred to as autoregulation. This provides different organs with the ability to maintain internal blood flow over a wide range of arterial blood pressure fluctuations. When autoregulation is lost, blood flow becomes pressure passive, and this may lead to ischemic or hemorrhagic consequences. The biochemical mediators of vasomotor tone for each vascular bed are different, and their complex interactions are not yet fully understood.

The ability of the blood to impart delivery of oxygen and nutrients and to remove metabolic excretory products is largely determined by adequate lung ventilation and perfusion, oxygen-carrying capacity, and oxygen extraction by the tissues. Although each gram of hemoglobin can bind 1.36 mL of oxygen, fetal hemoglobin binds oxygen more tightly than adult hemoglobin and, thus, has a relatively reduced oxygen-unloading capacity at the tissue level. This results in a leftward shift of the oxygen-hemoglobin dissociation curve. Other factors that may also cause a significant leftward shift of this curve frequently accompany shock and include hypothermia and hypocarbia. Under these circumstances, oxygen extraction by tissues may be decreased despite adequate oxygen delivery.

Inadequate tissue perfusion may result from defects of the pump (cardiogenic), inadequate blood volume (hypovolemic), abnormalities within the vascular beds (distributive), flow restriction (obstructive), or inadequate oxygen-releasing capacity (dissociative). These are summarized in History.

Hypotension refers to a blood pressure lower than the expected reference range. Although the normal physiologic range for blood pressure (defined by the presence of normal organ blood flow) is not well studied in the newborn population, in clinical practice, the reference range blood pressure limits are defined as the gestational age–dependent and postnatal age–dependent blood pressure values between the 5^th (or 10th) and 95th (or 90th) percentiles.

Usually, mean blood pressure, rather than systolic pressure, is used to judge the normality of data obtained from the indwelling arterial line. Mean blood pressure is thought to be free of the artifact caused by resonance, thrombi, and air bubbles, but this may not always be true. Based on these data, the statistically defined lower limits of mean blood pressure during the first day of life are approximately numerically similar to the gestational age reference range of the infant. However, most preterm infants, even at 24-26 weeks' gestation, have a mean blood pressure of 30 mm Hg or greater by the third day of life. The systolic blood pressure correlates with the gestational age reference range 4-24 hours after birth; only 3% of babies with normal long-term outcome have systolic blood pressures below the reference range for the gestational age.¹

A low upper body blood flow is common in first day of life in preterm infants younger than 30 weeks' gestation; this has strong correlation with periventricular or intraventricular hemorrhage. Blood pressure measurement is limited to assessing the systemic flow, particularly in the presence of physiologic shunts; thus, the estimation of superior vena cava (SVC) flow is observed to correlate with the low flow states rather than the left ventricular output (LVO). The low flow states are also associated with hyperkalemia in premature infants.

A linear relationship between blood pressure and both gestational age or birthweight and postnatal age is recognized; however, only preliminary data are available on the gestational age–dependent and postnatal age–dependent organ blood flow autoregulatory range and on the relation among blood pressure and systemic blood flow, cardiac output, and neonatal mortality and morbidity. Oxygen delivery to the tissues is influenced by cardiac output and blood flow more so than blood pressure; hence, values of blood pressure that are statistically abnormal are not necessarily pathologic. This is true for systolic, diastolic, and mean arterial blood pressures. Similarly, hypotension is not synonymous with shock but may be associated with the later stages of shock.

Frequency

United States

The true frequency of neonatal shock is unknown because it is primarily a clinical syndrome.

International

In one study of the variation in prevalence of hypotension, authors noted that, among low–birth-weight infants, 16-52% received volume expansion and 4-39% received vasopressors.²

Mortality/Morbidity

Shock remains a major cause of neonatal morbidity and mortality. Because shock accompanies other primary conditions, specific figures are unavailable. Morbidity as a consequence of end-organ injury and organ dysfunction is similar.

Race

No predilection based on race has been reported.

Sex

No predilection based on sex has been reported.

Clinical

History

• Causes of neonatal shock include the following:
  • Hypovolemic shock is caused by acute blood loss or fluid and electrolyte losses.
  • Distributive shock is caused by sepsis, vasodilators, myocardial depression, or endothelial injury.
  • Cardiogenic shock is caused by cardiomyopathy, heart failure, arrhythmias, or myocardial ischemia.
  • Obstructive shock is caused by tension pneumothorax or cardiac tamponade.
  • Dissociative shock is caused by profound anemia or methemoglobinemia.
• Risk factors for neonatal shock include the following:
  • Umbilical cord accident
  • Placental abnormalities
  • Fetal or neonatal hemolysis
  • Fetal or neonatal hemorrhage
  • Maternal infection
  • Maternal anesthesia, hypotension
  • Intrauterine asphyxia, intrapartum asphyxia
  • Neonatal sepsis
  • Pulmonary air leak syndromes
  • Lung overdistension during positive pressure ventilation
  • Cardiac arrhythmias

Physical

Clinical manifestations of hypotension include prolonged capillary refill time, tachycardia, mottling of the skin, cool extremities, and decreased urine output. Carefully observe heart sounds, peripheral pulses, and breath sounds.

The physical examination should also carefully assess these factors, as well as accurately assess blood pressure. Measurement of neonatal blood pressure can be completed directly through invasive techniques or indirectly through noninvasive techniques. Invasive methods include direct manometry using an arterial catheter or use of an in-line pressure transducer and continuous monitor. Noninvasive methods include manual oscillometric techniques and automated Doppler techniques. A good correlation between the systolic blood pressure measured by Doppler and by direct manometry using an intra-arterial catheter is observed.

Causes

Shock is a progressive disorder but can generally be divided into 3 phases: compensated, uncompensated, and irreversible. Each phase has characteristic clinicopathologic manifestations and outcomes; however, in the neonatal setting, distinguishing them may be impossible. Initiate aggressive treatment in all cases where shock is suspected.

• Compensated shock
  • In compensated shock, perfusion to vital organs, such as the brain, heart, and adrenal glands, is preserved by sympathetic reflexes, which increase systemic arterial resistance.
  • Derangement of vital signs, such as heart rate, respiratory rate, blood pressure, and temperature, is absent or minimal.
  • Increased secretion of angiotensin and vasopressin allows the kidneys to conserve water and salt. The release of catecholamines enhances myocardial contractility, and decreased spontaneous activity reduces oxygen consumption.
  • Clinical signs at this time include pallor, tachycardia, cool peripheral skin, and prolonged capillary refill time. As these homeostatic mechanisms are exhausted or become inadequate to meet the metabolic demands of the tissues, the uncompensated stage ensues.
• Uncompensated shock
  • During uncompensated shock, delivery of oxygen and nutrients to tissues becomes marginal or insufficient to meet demands. Anaerobic metabolism becomes the major source of energy production, and lactic acid production  is excessive, which leads to systemic metabolic acidosis. Acidosis reduces myocardial contractility and impairs its response to catecholamines.
  • Numerous chemical mediators, enzymes, and other substances are released, including histamine, cytokines (especially tumor necrosis factor and interleukin-1), xanthine oxidase (which generates oxygen free radicals), platelet-aggregating factor, and bacterial toxins (in the case of septic shock). This cascade of metabolic changes further reduces tissue perfusion and oxidative phosphorylation.
  • A further result of anaerobic metabolism is the failure of the energy-dependent sodium-potassium pump, which maintains the normal homeostatic environment in which cells function. The integrity of the capillary endothelium is disrupted, and plasma proteins leak, with the resultant loss of oncotic pressure and extravasation of intravascular fluids into the extravascular space.
  • Sluggish flow of blood and chemical changes in small blood vessels lead to platelet adhesion and activation of the coagulation cascade, which may eventually produce a bleeding tendency and further deplete blood volume.
  • Clinically, patients with uncompensated shock present with falling blood pressure, very prolonged capillary refill time, tachycardia, cold skin, rapid breathing (to compensate for the metabolic acidosis), and reduced or absent urine output. If effective intervention is not promptly instituted, progression to irreversible shock follows.
• Irreversible shock: A diagnosis of irreversible shock is actually retrospective. Major vital organs, such as the heart and brain, are so extensively damaged that death occurs despite adequate restoration of the circulation. Early recognition and effective treatment of shock are crucial to prevent inevitable progression to this stage.

Differential Diagnoses

Workup

Laboratory Studies

• Obtain hematocrit level, electrolyte levels, blood culture, blood gases (for acid/base status), and glucose level as soon as vascular access is obtained.
• Among laboratory investigations, supportive data to the diagnosis of shock include metabolic acidosis on an arterial blood specimen in the face of reasonable oxygenation.
• Mixed venous blood gases may be more helpful than arterial measurements because mixed venous blood gases reflect oxygen extraction and waste products at the tissue level. Conversely, arterial blood reflects lung function and the gas composition of blood before it is delivered to the tissues.
• Comparison of simultaneous arterial and mixed venous blood gas determinations may be more useful in assessing cardiac output, tissue oxygenation, and acid-base balance.
• The value of capillary blood gas determinations is severely limited because they may only reflect diminished perfusion to the periphery and not reflect central perfusion.
• Elevated plasma lactate with a normal pyruvate also suggests anaerobic metabolism triggered by tissue hypoxia-ischemia.
• Specific studies must be performed to determine both the causes (eg, sepsis, cardiac lesions, anemia) as well as the sequelae (eg, renal, hepatic, endocrine) of shock.

Imaging Studies

• Echocardiography and Doppler flow velocimetry may provide semiquantitative and semiqualitative noninvasive analysis of myocardial function.
  • Assessment of LVO
    • Echocardiography is increasingly used as an imaging tool to objectively assess and manage hypotension. The LVO can be quantified to guide the management of hypotension.
    • If the LVO is normal or high and patent ductus arteriosus (PDA) is not evident, a vasopressor (eg, dopamine) can initially be instituted. If a hemodynamically significant PDA is diagnosed, additional treatment should be directed toward the PDA.
    • If the LVO is low and the left ventricle (LV) is underfilled, volume expansion is the first-line management.
    • If the LVO is normal and the contractility of the LV is impaired, dobutamine should be the initial choice. Additionally, a low LVO with paradoxical movement of interventricular septum would benefit from dobutamine.
  • Assessment of SVC flow: SVC flow in newborn infants has been reported to be a novel marker of systemic blood flow.³ Low SVC flow (<41 mL/kg/min) has been used to diagnose hypotension and to prognosticate long-term outcome.⁴
• Automated Doppler provides blood pressure readings through a noninvasive method.

Other Tests

• Manual oscillometric techniques are used for noninvasive blood pressure testing.

Procedures

• Infant blood pressure testing through invasive methods includes direct manometry using an arterial catheter or use of an in-line pressure transducer and continuous monitor.

Treatment

Medical Care

Once shock is suspected in a newborn, appropriate supportive measures must be instituted as soon as possible. These include securing the airway and assuring its patency, providing supplemental oxygen and positive-pressure ventilation, achieving intravascular or intraosseous access, and infusing 10 mL/kg of colloid or crystalloid (to repeat the same volume if needed). Use of crystalloid or colloid solutions is appropriate, unless the source of hypovolemia is hemorrhage, in which case whole or reconstituted blood is more appropriate.

Obtain hematocrit level, electrolyte levels, blood gases and pH level, blood culture, and glucose level as soon as vascular access is obtained. At this stage, attempt to determine the type of shock (eg, hypovolemic, cardiogenic, maldistributive) because each requires a different therapeutic approach. In neonates who are hypotensively compromised, the authors encourage the early use of a bladder catheter. Hourly urine output is one of the few objective methods of evaluating hypoperfusion that leads to specific organ failure, and its accurate objective measurement can augment clinical decision making.

Hypovolemic shock is the most common cause of shock in infancy. The key to successful resuscitation is early recognition and controlled volume expansion with the appropriate fluid. The estimated blood volume of a newborn is 80-85 mL/kg of body weight. Clinical signs of hypovolemic shock depend on the degree of intravascular volume depletion, which is estimated to be 25% in compensated shock, 25-40% in uncompensated shock, and more than 40% in irreversible shock. Initial resuscitation with 20 mL/kg of volume expansion should replace a quarter of the blood volume. If circulatory insufficiency persists, this dose should be repeated. The Table below lists agents commonly used in the treatment of neonatal shock.

Dopamine has been found to be more effective than dobutamine and albumin in correcting blood pressure for short-term treatment, but the effect of these drugs on long-term outcome is unknown. Although adrenaline is used for cardiovascular compromise, its effect on mortality and morbidity is not yet evaluated.

Once 20 mL/kg of blood volume is replaced, a decision to provide any further volume expansion should prompt the clinician to ascertain the cause of hypotension and to evaluate circulatory status (see Imaging Studies). The information regarding central venous pressure (CVP) values in stable ventilated newborns is limited; therefore, interpretation of readings in ill neonates is problematic. Its role in the management of systemic hypotension is uncertain, but serial measurements through an appropriately placed umbilical venous or other central venous catheter may help to guide volume expansion in suspected hypovolemia.⁵

In the absence of CVP, titration against clinical parameters should be completed. Use of crystalloid or colloid solutions is appropriate unless the source of hypovolemia has been hemorrhage, in which case whole or reconstituted blood is more appropriate. If blood is needed in an emergency, type-specific or type O (Rh-negative) blood can be administered. Frequent and careful monitoring of the infant's vital signs with frequently repeated assessment and reexamination is mandatory.

Cardiogenic shock usually occurs following severe intrapartum asphyxia, structural heart disease, or arrhythmias. Global myocardial ischemia reduces contractility and causes papillary muscle dysfunction with secondary tricuspid valvular insufficiency. Clinical findings suggestive of cardiogenic shock include peripheral edema, hepatomegaly, cardiomegaly, and a heart murmur suggestive of tricuspid regurgitation. Inotropic agents, with or without peripheral vasodilators, are warranted in most circumstances. Structural heart disease or arrhythmia often requires specific pharmacologic or surgical therapy. Excessive volume expansion may be potentially harmful.

The most common form of maldistributive shock in the newborn is septic shock; this is a source of considerable mortality and morbidity. In sepsis, cardiac output may be normal or even elevated but may still be too small to deliver sufficient oxygen to the tissues because of the abnormal distribution of blood in the microcirculation, leading to decreased tissue perfusion. In septic shock, cardiac function may be depressed (the LV is usually affected more than the right). The early compensated phase of septic shock is characterized by an increased cardiac output, decreased systemic vascular resistance, warm extremities, and a widened pulse pressure. If effective therapy is not provided, cardiovascular performance deteriorates and cardiac output falls. Even with normal or increased cardiac output, shock develops. The normal relationship between cardiac output and systemic vascular resistance breaks down, and hypotension may persist as a result of decreased vascular resistance.

Newborns, who have little cardiac reserve, often present with hypotension and a picture of cardiovascular collapse. These critically ill infants represent a diagnostic and therapeutic challenge, and sepsis must be presumed and treated as quickly as possible. Survival from septic shock depends on maintenance of a hyperdynamic circulatory state. In the early phase, volume expansion with agents that are likely to remain within the intravascular space is needed, whereas inotropic agents with or without peripheral vasodilators may be indicated later. In early onset neonatal sepsis, ampicillin and gentamicin are the empiric antimicrobials of choice until a specific infectious agent is identified. Cefotaxime is sometimes substituted for gentamicin, although studies have raised concerns about this practice. In the face of renal failure, serum levels of gentamicin should be closely monitored to minimize iatrogenic renal toxicity.

During and following restoration of circulation, varying degrees of organ damage may remain and should be actively sought and managed. For example, acute tubular necrosis may be a sequela of uncompensated shock. Once hemodynamic parameters have improved, consider fluid administration according to urine output and renal function as assessed by serum creatinine, electrolyte, and BUN levels.

Despite adequate volume restoration, myocardial contractility may still be compromised due to the prior poor myocardial perfusion. In this scenario, inotropic agents and intensive monitoring may need to be continued. During the process of shock, production of chemical mediators may initiate disseminated intravascular coagulopathy (DIC), which requires careful monitoring of coagulation profiles and management with fresh frozen plasma, platelets, and/or cryoprecipitate. The liver and bowel may be damaged by shock, leading to GI bleeding and increasing the risk for necrotizing enterocolitis, particularly in the premature infant. However, the extent of irreversible brain damage is probably most anxiously monitored following shock because the brain is so sensitive to hypoxic-ischemic injury once compensation fails.

In circumstances in which volume expansion and vasoactive and inotropic agents have been unsuccessful, glucocorticoids (eg, dexamethasone, hydrocortisone) have been shown to be effective. The findings that steroids rapidly up-regulate cardiovascular adrenergic receptor expression and serve as hormone replacement therapy in cases of adrenal insufficiency explain their effectiveness in stabilizing the cardiovascular status and decreasing the requirement for pressure support in the critically ill newborn with volume-resistant and pressure-resistant hypotension.

The use of milrinone in premature infants is still not established and is limited to babies with low output cardiac failure (eg, postoperative states) or in refractory hypotension (with other inotropic drugs). Its use for prevention of low SVC flow in very preterm infants was not substantiated in a randomized controlled trial.

Agents Used to Treat Neonatal Shock

Surgical Care

Structural heart disease or arrhythmias often require specific pharmacologic or surgical therapy. The liver and bowel may be damaged by shock, leading to GI bleeding and increasing the risk for necrotizing enterocolitis, particularly in the premature infant.

Consultations

Depending on the type of shock, potential consultants include the following pediatric subspecialists: neonatologist, cardiologist, nephrologist, surgeon, infectious disease specialist, and hematologist.

Diet

Infants in shock should not be fed, and feedings should not be resumed until GI function has recovered. Initiate total parenteral nutrition as soon as possible.

Medication

Adrenergic agonists

Cardiovascular performance deteriorates and cardiac output falls if effective therapy is not administered. These agents improve the hemodynamic status by increasing myocardial contractility and heart rate, resulting in increased cardiac output. They also increase peripheral resistance by causing vasoconstriction. Increased cardiac output and increased peripheral resistance lead to increased blood pressure.

Dopamine (Intropin)

Stimulates both adrenergic and dopaminergic receptors. Hemodynamic effect is dependent on the dose. Lower doses predominantly stimulate dopaminergic receptors that, in turn, produce renal and mesenteric vasodilation. Cardiac stimulation and peripheral vasoconstriction is produced by higher doses.

Dosing

Adult

5-20 mcg/kg/min IV

Pediatric

Administer as in adults

Interactions

Phenytoin, alpha- and beta-adrenergic blockers, general anesthesia, and MAOIs increase and prolong effects

Contraindications

Documented hypersensitivity; pheochromocytoma; ventricular fibrillation

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Closely monitor urine flow, cardiac output, pulmonary wedge pressure, and blood pressure during infusion; prior to infusion, correct hypovolemia with either whole blood or plasma, as indicated; monitoring central venous pressure or LV filling pressure may be helpful in detecting and treating hypovolemia

Dobutamine (Dobutrex)

Produces vasodilation and increases inotropic state. At higher dosages, may cause increased heart rate, exacerbating myocardial ischemia.

Dosing

Adult

5-20 mcg/kg/min IV

Pediatric

Administer as in adults

Interactions

Beta-adrenergic blockers antagonize effects of dobutamine; general anesthetics may increase toxicity

Contraindications

Documented hypersensitivity; idiopathic hypertrophic subaortic stenosis; atrial fibrillation or flutter

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Following MI, use with extreme caution; correct hypovolemic state before using drug

Epinephrine (Adrenaline)

Elicits alpha-agonist effects that include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. Beta-agonist effects include bronchodilatation, chronotropic cardiac activity, and positive inotropic effects.

Dosing

Adult

1-10 mcg/min IV

Pediatric

0.05-1 mcg/kg/min IV

Interactions

Increases toxicity of halogenated inhalational anesthetics and beta- and alpha-blocking agents

Contraindications

Documented hypersensitivity; cardiac arrhythmias; angle-closure glaucoma; local anesthesia in areas such as fingers or toes (vasoconstriction may produce sloughing of tissue); use during labor (may delay second stage of labor)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in elderly patients, prostatic hypertrophy, hypertension, cardiovascular disease, diabetes mellitus, hyperthyroidism, and cerebrovascular insufficiency; rapid IV infusions may cause death from cerebrovascular hemorrhage or cardiac arrhythmias

Hydralazine (Apresoline)

Decreases systemic resistance through direct vasodilation of arterioles.

Dosing

Adult

10-20 mg IV prn q4-6h

Pediatric

0.1-0.5 mg/kg IV q3-6h

Interactions

MAOIs and beta-blockers may increase toxicity; pharmacologic effects may be decreased by indomethacin

Contraindications

Documented hypersensitivity; mitral valve rheumatic heart disease

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Implicated in MI; caution in suspected coronary artery disease

Isoproterenol (Isuprel)

Possesses beta1- and beta2-adrenergic receptor activity. Binds beta-receptors of heart, smooth muscle of bronchi, skeletal muscle, vasculature, and alimentary tract. Elicits positive inotropic and chronotropic actions.

Dosing

Adult

2-10 mcg/min IV; titrate to desired heart rate and blood pressure

Pediatric

0.05-0.5 mcg/kg/min IV

Interactions

Bretylium increases action of vasopressors on adrenergic receptors, which may, in turn, result in arrhythmias; guanethidine may increase effect of direct-acting vasopressors, possibly resulting in severe hypertension; tricyclic antidepressants may potentiate pressor response of direct-acting vasopressors

Contraindications

Documented hypersensitivity; tachyarrhythmias; tachycardia or heart block caused by digitalis intoxication; ventricular arrhythmias that require inotropic therapy; angina pectoris

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

By increasing myocardial oxygen requirements while decreasing effective coronary perfusion, may have a deleterious effect on the injured or failing heart; in patients with organic disease of the AV node and its branches, paradoxically worsens heart block or precipitates Adams-Stokes attacks; caution in coronary artery disease, coronary insufficiency, diabetes or hyperthyroidism, and sensitivity to sympathomimetic amines; if heart rate >110 bpm, may decrease infusion rate or temporarily discontinue infusion

Nitroprusside (Nitropress)

Produces vasodilation and increases inotropic activity of the heart. At higher dosages, may exacerbate myocardial ischemia by increasing heart rate.

Dosing

Adult

Begin infusion at 0.3-0.5 mcg/kg/min IV, titrate to desired effect using increments of 0.5 mcg/kg/min; average dose is 1-6 mcg/kg/min

Pediatric

0.5-8 mcg/kg/min IV

Interactions

Effects are additive when administered with other hypotensive agents

Contraindications

Documented hypersensitivity; subaortic stenosis; idiopathic hypertrophic and atrial fibrillation or flutter

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in increased intracranial pressure, hepatic failure, severe renal impairment, and hypothyroidism; in renal or hepatic insufficiency, nitroprusside levels may increase and can cause cyanide toxicity; sodium nitroprusside has the ability to lower blood pressure and should use only in patients with mean arterial pressures >70 mm Hg

Norepinephrine (Levophed)

For protracted hypotension following adequate fluid-volume replacement. Stimulates beta1- and alpha-adrenergic receptors, increasing cardiac muscle contractility and heart rate as well as vasoconstriction, resulting in systemic blood pressure and coronary blood flow increases. After obtaining a response, the rate of flow should be adjusted and maintained at a low-normal blood pressure, such as 80-100 mm Hg systolic, sufficient to perfuse vital organs.

Dosing

Adult

4 mcg/min IV; titrate to desired response

Pediatric

0.05-1 mcg/kg/min IV

Interactions

Enhances the pressor response by blocking reflex bradycardia

Contraindications

Documented hypersensitivity; peripheral or mesenteric vascular thrombosis (ischemia may be increased and the area of the infarct extended)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Correct blood-volume depletion, if possible, before administration; extravasation may cause severe tissue necrosis, administer into a large vein; caution in occlusive vascular disease

Phentolamine (Regitine)

Alpha1- and alpha2-adrenergic blocking agent that blocks circulating epinephrine and norepinephrine action, reducing hypertension resulting from catecholamine effects on alpha-receptors.

Dosing

Adult

5-20 mg IV

Pediatric

1-20 mcg/kg/min IV

Interactions

Concurrent administration of epinephrine or ephedrine may decrease effects; ethanol increases toxicity

Contraindications

Documented hypersensitivity; coronary or cerebral arteriosclerosis; renal impairment

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in tachycardia, peptic ulcer, and gastritis; cerebrovascular occlusions and myocardial infarctions can occur following administration

Milrinone (Primacor)

Bi-pyridine positive inotrope and vasodilator with little chronotropic activity. Different in mode of action from both digitalis glycosides and catecholamines. Selectively inhibits phosphodiesterase type III (PDE III) in cardiac and smooth vascular muscle, resulting in reduced afterload, reduced preload, and increased inotropy.

Dosing

Adult

50 mcg/kg IV loading dose over 10 min followed by continuous infusion at 0.375-0.75 mcg/kg/min

Pediatric

Not FDA-approved in children, but commonly used in pediatric ICUs; administer as in adults

Interactions

Incompatible with furosemide when administered within same IV (forms precipitates)

Contraindications

Documented hypersensitivity to milrinone, any component, or inamrinone

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor fluids, electrolyte changes and renal function during therapy (decrease dose with insufficient renal function); excessive diuresis may increase potassium loss and predispose digitalized patients to arrhythmias; important to correct hypokalemia with potassium supplementation prior to treatment; patients showing excessive decreases in blood pressure should have infusion rates slowed or stopped; previous vigorous diuretic therapy has caused significant decreases in cardiac filling pressure, cautiously administer milrinone and monitor blood pressure, heart rate, and clinical symptomatology

Volume expanders

The use of crystalloid or colloid solutions is appropriate, unless the source of hypovolemia is hemorrhage, in which case whole or reconstituted blood is more appropriate.

Sodium chloride 0.9%

Isotonic sodium chloride solution is a low-cost alternative that is readily available.

Dosing

Adult

Pediatric

10-20 mL/kg IV

Interactions

May decrease levels of lithium when administered concurrently

Contraindications

Fluid retention; hypernatremia

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in congestive heart failure, hypertension, edema, liver cirrhosis, renal insufficiency, and sodium toxicity

Albumin 5% (Albumisol, Buminate)

Useful for plasma volume expansion and maintenance of cardiac output.

Dosing

Adult

Pediatric

10-20 mL/kg IV; not to exceed 6 g/kg/d (120 mL/kg/d)

Interactions

None reported

Contraindications

Documented hypersensitivity; pulmonary edema; protein load of 5% albumin

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Although theoretically attractive, no proven benefit of colloid resuscitation over isotonic crystalloids

Lactated ringer solution with isotonic sodium chloride

Each fluid is essentially isotonic and have equivalent volume restorative properties. Although some differences between metabolic changes are observed with administration of large quantities of either fluid, for practical purposes and in most situations, differences are clinically irrelevant. Importantly, no demonstrable difference in hemodynamic effect, morbidity, or mortality with resuscitation.

Dosing

Adult

Pediatric

10-20 mL/kg IV

Interactions

None reported

Contraindications

Pulmonary edema (added fluid promotes more edema and may lead to the development of ARDS)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Major complication of isotonic fluid resuscitation is interstitial edema; edema of extremities is unsightly but is not a significant complication; edema in the brain or lungs is potentially fatal; fluids should be stopped when desired hemodynamic response is observed or pulmonary edema develops

Antimicrobials

In early onset neonatal sepsis, ampicillin and either gentamicin or cefotaxime are the antimicrobials of choice until a specific infectious agent is identified.

Ampicillin (Principen, Omnipen)

Bactericidal activity against susceptible organisms.

Dosing

Adult

1-2 g IV q4-6h

Pediatric

50-100 mg/kg IV q6-8h

Interactions

Probenecid and disulfiram elevate levels; allopurinol decreases effects and has additive effects on ampicillin rash; may decrease effects of PO contraceptives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction

Cefotaxime (Claforan)

Third-generation cephalosporin that possesses antimicrobial effect on a predominantly gram-negative spectrum. Has a lower efficacy against gram-positive organisms.

Dosing

Adult

1-2 g IV/IM q4h

Pediatric

150 mg/kg/d IV divided q8h

Interactions

Probenecid may increase cefotaxime levels; coadministration with furosemide and aminoglycosides may increase nephrotoxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in severe renal insufficiency (high doses may cause CNS toxicity); superinfections and promotion of nonsusceptible organisms may occur with prolonged use or repeated therapy; has been associated with severe colitis

Gentamicin (Garamycin)

Aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes.
Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution. May be administered IV/IM.
Follow each regimen by at least a trough level drawn on the third dose (0.5 h before dosing). Peak levels may be drawn 0.5 h after 30-min infusion. If trough level >2 mg/L, increase dosing interval.

Dosing

Adult

1-1.5 mg/kg IV q8h

Pediatric

Newborn infants:
GA <29 weeks:
Postnatal age 0-7 days: 5 mg/kg IV q48h
Postnatal age 8-28 days: 4 mg/kg IV q36h
Postnatal age >29 days: 4 mg/kg IV q24h

GA 30-34 weeks:
Postnatal age 0-7 days: 4.5 mg/kg IV q36h
Postnatal age >8 days: 4 mg/kg IV q24h

GA >35 weeks: 4 mg/kg IV q24h

Infants and children:
<5 years: 2.5 mg/kg/dose IV q8h
>5 years: 1.5-2.5 mg/kg/dose IV q8h or 6-7.5 mg/kg/d

Interactions

Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents, thus prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)

Contraindications

Documented hypersensitivity; non–dialysis-dependent renal insufficiency

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

Follow-up

Further Inpatient Care

• Infants recovering from neonatal shock are at risk for multiple sequelae and should be intensively screened for neurodevelopmental abnormalities using brain imaging and brainstem audiometric evoked responses. Other tests are determined by the clinical course and complications.

Further Outpatient Care

• Outpatient care should include neurodevelopmental follow-up testing and other studies as indicated by the neonatal course.

Transfer

• Infants presenting with evidence of shock should be transferred immediately to a full-service neonatal intensive care unit with adequate support, personnel, and expertise.

Deterrence/Prevention

• Early recognition and treatment is essential to maximizing outcome in neonatal shock.

Complications

• Complications of neonatal shock are related to both the underlying cause (eg, sepsis, heart disease) and the injury sustained during the period of inadequate tissue perfusion. Frequent sequelae include pulmonary, renal, endocrine, GI, and neurologic dysfunction.

Prognosis

• Prognosis following neonatal shock is related to both the underlying cause (eg, sepsis, heart disease) and the injuries sustained during the period of inadequate perfusion.

Patient Education

• Parents should be informed of the risk for neurodevelopmental handicaps as well as the need for intensive follow-up care of both medical and neurologic problems.
• For excellent patient education resources, visit eMedicine's Shock Center and Public Health Center. Also, see eMedicine's patient education articles Shock and Cardiopulmonary Resuscitation (CPR).

Miscellaneous

Medicolegal Pitfalls

• The major medicolegal pitfall is delayed diagnosis and treatment, leading to permanent neurologic sequelae such as cerebral palsy, epilepsy, and mental retardation.
• Another potential pitfall is the misclassification of shock and subsequent inappropriate treatment.
• Failure to transfer an affected infant to a level III neonatal intensive care unit in a timely manner is another pitfall.

References

1. Northern Neonatal Nursing Initiative. Systolic blood pressure in babies of less than 32 weeks gestation in the first year of life. Arch Dis Child Fetal Neonatal Ed. Jan 1999;80(1):F38-42. [Medline].

2. Al-Aweel I, Pursley DM, Rubin LP, et al. Variations in prevalence of hypotension, hypertension, and vasopressor use in NICUs. J Perinatol. Jul-Aug 2001;21(5):272-8. [Medline].

3. Kluckow M, Evans N. Superior vena cava flow in newborn infants: a novel marker of systemic blood flow. Arch Dis Child Fetal Neonatal Ed. May 2000;82(3):F182-7. [Medline].

4. [Best Evidence] Osborn DA, Evans N, Kluckow M, et al. Low superior vena cava flow and effect of inotropes on neurodevelopment to 3 years in preterm infants. Pediatrics. Aug 2007;120(2):372-80. [Medline].

5. Skinner JR, Milligan DW, Hunter S, et al. Central venous pressure in the ventilated neonate. Arch Dis Child. Apr 1992;67(4 Spec No):374-7. [Medline].

6. Faix RG, Pryce CJ. Shock and hypotension. In: Neonatal Emergencies. Mount Kisco, NY: Futura Publishing Company Inc; 1991:371-386.

7. Keeley SR, Bohn DJ. The use of inotropic and afterload-reducing agents in neonates. Clin Perinatol. Sep 1988;15(3):467-89. [Medline].

8. Laughon M, Bose C, Allred E, et al. Factors associated with treatment for hypotension in extremely low gestational age newborns during the first postnatal week. Pediatrics. Feb 2007;119(2):273-80. [Medline].

9. Noori S, Seri I. Pathophysiology of newborn hypotension outside the transitional period. Early Hum Dev. May 2005;81(5):399-404. [Medline].

10. Nuntnarumit P, Yang W, Bada-Ellzey HS. Blood pressure measurements in the newborn. Clin Perinatol. Dec 1999;26(4):981-96, x. [Medline].

11. Sasidharan P. Role of corticosteroids in neonatal blood pressure homeostasis. Clin Perinatol. 1998;25:723. [Medline].

12. Seri I. Hydrocortisone and vasopressor-resistant shock in preterm neonates. Pediatrics. Feb 2006;117(2):516-8. [Medline].

13. Seri I. Inotrope, lusitrope, and pressor use in neonates. J Perinatol. May 2005;25 Suppl 2:S28-30. [Medline].

14. Seri I, Evans J. Controversies in the diagnosis and management of hypotension in the newborn infant. Curr Opin Pediatr. Apr 2001;13(2):116-23. [Medline].

15. Seri I, Noori S. Diagnosis and treatment of neonatal hypotension outside the transitional period. Early Hum Dev. May 2005;81(5):405-11. [Medline].

16. Seri I, Tan R, Evans J. Cardiovascular effects of hydrocortisone in preterm infants with pressor-resistant hypotension. Pediatrics. May 2001;107(5):1070-4. [Medline].

17. Subhedar NV. Treatment of hypotension in newborns. Semin Neonatol. Dec 2003;8(6):413-23. [Medline].

18. Zubrow AB, Hulman S, Kushner H, et al. Determinants of blood pressure in infants admitted to neonatal intensive care units: a prospective multicenter study. Philadelphia Neonatal Blood Pressure Study Group. J Perinatol. Nov-Dec 1995;15(6):470-9. [Medline].

Keywords

shock, hypotension, hypoperfusion, cardiac ischemia, circulatory collapse, septic shock, hypovolemic shock, distributive shock, cardiogenic shock, obstructive shock, dissociative shock, maldistributive shock, hypothermia, hyperkalemia, end-organ injury, sepsis, vasodilators, myocardial depression, endothelial injury, cardiomyopathy, heart failure, arrhythmias, myocardial ischemia, tension pneumothorax, cardiac tamponade, methemoglobinemia, metabolic acidosis, patent ductus arteriosus, PDA, disseminated intravascular coagulopathy, DIC, acute tubular necrosis

Contributor Information and Disclosures

Author

Samir Gupta, MD, MRCP, FRCPCH, Consulting Neonatologist, University Hospital of North Tees
Samir Gupta, MD, MRCP, FRCPCH is a member of the following medical societies: British Medical Association, European Society for Paediatric Research, Indian Academy of Pediatrics, Royal College of Paediatrics and Child Health, and Royal College of Physicians of Ireland
Disclosure: Nothing to disclose.

Coauthor(s)

Sunil K Sinha, MBBS, MD, MRCP, PhD, FRCP, FRCPCH, Director of Neonatal Services, South Cleveland Hospital, UK
Sunil K Sinha, MBBS is a member of the following medical societies: British Medical Association and Royal College of Physicians
Disclosure: Nothing to disclose.

Steven M Donn, MD, Professor of Pediatrics, Director, Neonatal-Perinatal Medicine, Department of Pediatrics, University of Michigan Health System
Steven M Donn, MD is a member of the following medical societies: American Pediatric Society
Disclosure: Nothing to disclose.

Medical Editor

Steven M Donn, MD, Professor of Pediatrics, Director, Neonatal-Perinatal Medicine, Department of Pediatrics, University of Michigan Health System
Steven M Donn, MD is a member of the following medical societies: American Pediatric Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

David A Clark, MD, Chairman, Professor, Department of Pediatrics, Albany Medical College
David A Clark, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Pediatric Society, Christian Medical & Dental Society, Medical Society of the State of New York, New York Academy of Sciences, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Carol L Wagner, MD, Professor of Pediatrics, Medical University of South Carolina
Carol L Wagner, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American Medical Women's Association, American Public Health Association, American Society for Bone and Mineral Research, American Society for Clinical Nutrition, Massachusetts Medical Society, National Perinatal Association, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Ted Rosenkrantz, MD, Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine
Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Pediatric Society, Connecticut State Medical Society, Eastern Society for Pediatric Research, and Society for Pediatric Research
Disclosure: Nothing to disclose.

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