Many conditions and pathophysiologic disturbances are associated with shock and hypotension in the newborn, ranging from acute blood loss (hypovolemic shock) to heart failure (cardiogenic shock). (See Etiology.)
Shock is a complex clinical syndrome caused by an acute failure of circulatory function and is characterized by inadequate tissue and organ perfusion.[1] 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. (See Pathophysiology and Etiology.)
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]
Physiology
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. (See Treatment and Medications.)
Cardiac output is the product of heart rate and stroke volume. Neonatal cardiac output depends more on heart rate than stroke volume; therefore, 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 preload, afterload, and myocardial contractility, as follows:
Preload - 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 - 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 - Contractility is a semiquantitative measure of ventricular function, and 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 1.36mL 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 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.
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 30mm 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.[3]
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.
In premature babies, the presence of fetal shunts such as patent ductus arteriosus (PDA) and patent foramen ovale (PFO) further affects the systemic and pulmonary blood flow. Depending on the size of these shunts, blood may be shunted to lower downstream pressure bed, which, in turn, can cause volume overloading of the left side of the heart (PDA) and could lead to cardiac failure and other complications, including low blood pressure. Shock unresponsive to inotropes in the first few days of life in preterm babies can be caused by a large PDA. Further, it has been observed that estimations of blood pressure (mean and systolic) have poor correlation with cardiac output in babies with a PDA.[4]
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. Determinants of cardiac function and oxygen delivery to tissues are shown in the illustration below.
View Image
Determinants of cardiac function and oxygen delivery to tissues. Adapted from Strange GR. APLS: The Pediatric Emergency Medicine Course. 3rd ed. Elk G....
Complications
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. (See Pathophysiology.)
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.
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. (See Pathophysiology.)
Patient education
Parents should be informed of the risk for neurodevelopmental handicaps as well as the need for intensive follow-up care for medical and neurologic problems. For patient education information, see Shock and Cardiopulmonary Resuscitation (CPR).
Shock is a progressive disorder but can generally be divided into 3 phases: compensated, uncompensated, and irreversible.
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.
A hemodynamically significant patent ductus arteriosus (PDA) in the first postnatal week can account for inadequate tissue perfusion in babies with birth weights below 1000g. This may be due to failure of a compensatory increase in the cardiac output secondary to myocardial immaturity and the ductal steal phenomenon, which accounts for uniform reduction in systolic and diastolic blood pressure.
A significant decrease in systolic blood pressure occurs only when the PDA shunt is moderate or large, yet a decrease in diastolic and mean blood pressure can occur when the shunt is small.
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 5th (or 10th) and 95th (or 90th) percentiles.[5]
Types of shock
Many conditions and pathophysiologic disturbances are associated with shock and hypotension. Causes of neonatal shock include the following:
Hypovolemic shock - Caused by acute blood loss or fluid and electrolyte losses
Distributive shock - Caused by sepsis, vasodilators, myocardial depression, or endothelial injury
Cardiogenic shock - Caused by cardiomyopathy, heart failure, arrhythmias, or myocardial ischemia
Obstructive shock - Caused by tension pneumothorax or cardiac tamponade
Dissociative shock - Caused by profound anemia or methemoglobinemia
Risk factors
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
Shock remains a major cause of neonatal morbidity and mortality, although because it accompanies other primary conditions, specific figures for the frequency of shock are unavailable. Prognosis following neonatal shock is related to the underlying cause (eg, sepsis, heart disease) and the injuries sustained during the period of inadequate perfusion. Early recognition and treatment is essential to maximizing outcome in neonatal shock. Morbidity as a consequence of end-organ injury and organ dysfunction is similar. Frequent sequelae include pulmonary, renal, endocrine, gastrointestinal (GI), and neurologic dysfunction. Delayed diagnosis and treatment can lead to permanent neurologic sequelae such as cerebral palsy, epilepsy, and mental retardation.
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 accurately assess blood pressure, the existence of any heart murmurs, and the presence of femoral pulses. 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 is observed between the systolic blood pressure as measured by Doppler and this pressure as assessed by direct manometry using an intra-arterial catheter.
Hypovolemic shock
Hypovolemic shock is caused by perinatal blood loss in newborn infants. 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.
Cardiogenic shock
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.
Septic shock
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.[6] In septic shock, cardiac function may be depressed (the left ventricle [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.
Compensated shock
As previously stated, 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 in which shock is suspected.
In compensated shock, derangement of vital signs, such as heart rate, respiratory rate, blood pressure, and temperature, is absent or minimal. 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
Clinically, patients with uncompensated shock present with falling blood pressure, very prolonged capillary refill time, tachycardia, cold skin, rapid breathing (to compensate for 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.
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.
Obtain the patient’s 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, data supporting the diagnosis of shock include metabolic acidosis on an arterial blood specimen in the face of reasonable oxygenation.
Elevated plasma lactate with a normal pyruvate suggests anaerobic metabolism triggered by tissue hypoxia-ischemia.
Specific studies must be performed to determine the causes (eg, sepsis, cardiac lesions, anemia) and sequelae (eg, renal, hepatic, endocrine) of shock.
Other pertinent tests include the following:
Automated Doppler - Automated Doppler provides blood pressure readings through a noninvasive method
Manual oscillometric techniques - Manual oscillometric techniques are used for noninvasive blood pressure testing
Infant blood pressure testing - Invasive methods for infant blood pressure testing include direct manometry using an arterial catheter and the use of an in-line pressure transducer and continuous monitor
A study by Wahab and Saeed indicated that serum levels of mannose-binding lectin (MBL) can be used to predict the development of sepsis and septic shock, as well as their prognosis, in neonates. In a comparison of 62 newborns with sepsis with 35 controls, the investigators found that MBL levels were lower in the infants with sepsis and were lowest in those with septic shock, this being particularly the case in infants with septic shock who died.[7]
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.
Echocardiography and Doppler flow velocimetry may provide semiquantitative and semiqualitative noninvasive analysis of myocardial function.
Assessment of left ventricular output
Echocardiography is increasingly used as an imaging tool to objectively assess and manage hypotension. The left ventricular output (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 the interventricular septum would benefit from dobutamine.
There are noninvasive methods to assess cardiac output now available, which use either Doppler principle or impedance methods to calculate LVO. Echocardiography remains the criterion standard to evaluate cardiac function.
Newer modalities such as functional MRI are being evaluated to assess cardiac function. This technology is promising but is limited to the research findings and is subject to availability of an MRI scanner. It also has the limitation of the inability to perform repeated longitudinal measurements at point of care, such as bedside echocardiography.
Assessment of superior vena cava flow
Superior vena cava (SVC) flow in newborn infants has been reported to be a novel marker of systemic blood flow.[8] Low SVC flow (< 41 mL/kg/min) has been used to diagnose hypotension and to predict long-term outcome.[9]
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.
See the video of assisted ventilation in the newborn, below.
View Video
Assisted ventilation newborn –Intubation and meconium aspiration. Video courtesy of Therese Canares, MD, and Jonathan Valente, MD, Rhode Island Hospital, Brown University.
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.
Patent ductus arteriosus
The patent ductus arteriosus (PDA) is a significant cause of hypotension in preterm infants. Although the increase in left ventricular output (LVO) and other compensatory mechanisms may initially offset the effects of ductal shunt on systemic circulation, effective LVO is reduced over time. This can lead to organ hypoperfusion, and treatment of shock in such situations should be directed towards closing the PDA.
Surgical care
Structural heart disease and 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.
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.
Consultations
Depending on the type of shock, potential consultants include the following pediatric subspecialists: neonatologist, cardiologist, nephrologist, surgeon, infectious disease specialist, and hematologist.
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.
Monitoring
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.
Outpatient care should include neurodevelopmental follow-up testing and other studies, as indicated by the neonatal course.
Hypovolemic shock is caused by perinatal blood loss in newborn infants. 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.
If blood loss is confirmed, initial resuscitation with 20 mL/kg of volume expansion should replace a quarter of the blood volume. Blood transfusion is preferred, but in an emergency, colloids or crystalloids can be used. If circulatory insufficiency persists, this dose can be repeated.
Once 10 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. 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.[10]
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.[6] 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 blood urea nitrogen (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.
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.
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.
The choice of drug for medical management of shock depends on the underlying cause. Table 1, below, lists agents commonly used in the treatment of neonatal shock.
Table 1. Agents Used To Treat Neonatal Shock
View Table
See Table
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.
In premature infants younger than 30 weeks' gestation, poor cardiac contractility is most common; patients benefit from early institution of dobutamine.
Patients with septic shock benefit from dopamine as first-line management; it has been found to be more effective than dobutamine and albumin in correcting blood pressure for short-term treatment in these situations; however, the effect of these drugs on long-term outcome is unknown.
Although adrenaline is used for cardiovascular compromise, its effect on mortality and morbidity has not yet been evaluated.
No evidence suggests that milrinone is beneficial in prevention of low systemic blood flow in ill, very-preterm neonates during the first postnatal day.
Clinical Context:
Dopamine stimulates adrenergic and dopaminergic receptors. Its 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.
Clinical Context:
Dobutamine produces vasodilation and increases the inotropic state. At higher dosages, it may cause increased heart rate, exacerbating myocardial ischemia.
Clinical Context:
Isoproterenol possesses beta1- and beta2-adrenergic receptor activity. It binds to beta receptors of the heart, smooth muscle of the bronchi, skeletal muscle, vasculature, and alimentary tract. Isoproterenol elicits positive inotropic and chronotropic actions.
Clinical Context:
Norepinephrine is used to treat protracted hypotension following adequate fluid-volume replacement. It stimulates beta1- and alpha-adrenergic receptors, increasing cardiac muscle contractility and heart rate, as well as vasoconstriction; this results 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 80-100mm Hg systolic, sufficient to perfuse vital organs.
Cardiovascular performance deteriorates and cardiac output falls if effective therapy is not administered. Adrenergic antagonists improve the patient’s 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.
Clinical Context:
Nitroprusside produces vasodilation and increases inotropic activity of the heart. At higher dosages, it may exacerbate myocardial ischemia by increasing heart rate.
Preload reduction with vasodilators is thought to be helpful in acute decompensated heart failure by reducing congestion and minimizing cardiac oxygen demand. Afterload reduction is also thought to be helpful in some patients with acute decompensated heart failure by decreasing myocardial oxygen demand and improving forward flow.
Clinical Context:
Phentolamine has positive inotropic and chronotropic effects on the heart. Phentolamine is an alpha1- and alpha2-adrenergic blocking agent that blocks circulating epinephrine and norepinephrine action, reducing hypertension resulting from catecholamine effects on alpha receptors.
Clinical Context:
Milrinone is a bi-pyridine positive inotrope and vasodilator with little chronotropic activity. Its mode of actions differs from that of digitalis glycosides and catecholamines. Milrinone selectively inhibits phosphodiesterase type III (PDE III) in cardiac and smooth vascular muscle, resulting in reduced afterload and preload and increased inotropy.
Lactated Ringer solution with isotonic sodium chloride
Clinical Context:
Each fluid is essentially isotonic and has equivalent volume restorative properties. Although some differences between metabolic changes are observed with the administration of large quantities of either fluid, for practical purposes and in most situations, the differences are clinically irrelevant. Importantly, there is no demonstrable difference in hemodynamic effect, morbidity, or mortality with resuscitation.
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.
Clinical Context:
Cefotaxime is a third-generation cephalosporin that possesses antimicrobial effects on a predominantly gram-negative spectrum. Its efficacy against gram-positive organisms is lower.
Clinical Context:
Gentamicin is an aminoglycoside antibiotic for gram-negative coverage. It is used in combination with an agent against gram-positive organisms and one that covers anaerobes. Dosing regimens are numerous; adjust the dose based on creatinine clearance (CrCl) and changes in the volume of distribution. The drug may be administered intravenously or intramuscularly.
Follow each regimen by at least a trough level drawn on the third dose (0.5h before dosing). Peak levels may be drawn 0.5 hour after a 30-minute infusion. If the trough level is greater than 2mg/L, increase the dosing interval.
In early onset neonatal sepsis, ampicillin and either gentamicin or cefotaxime are the antimicrobials of choice until a specific infectious agent is identified.
Samir Gupta, MD, DM, MRCP, FRCPCH, FRCPI, Professor of Neonatal Medicine, Director, Research and Development, University of Durham and North Tees University Hospital, UK
Disclosure: Nothing to disclose.
Coauthor(s)
Sunil K Sinha, MBBS, MD, MRCP, PhD, FRCP, FRCPCH, Director of Neonatal Services, South Cleveland Hospital, UK
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
Disclosure: Nothing to disclose.
Acknowledgements
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.
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine
Gupta S, Wyllie J. Correlation of Non-invasive Systolic and Mean Blood pressure (BP) Measurements with Echocardiographic Haemodynamic Assessment. Third Congress of the European Academy of Paediatric Societies (EAPS). Copenhagen, Denmark. October 23-26, 2010.
Determinants of cardiac function and oxygen delivery to tissues. Adapted from Strange GR. APLS: The Pediatric Emergency Medicine Course. 3rd ed. Elk Grove Village, Ill: American Academy of Pediatrics; 1998:34.
Assisted ventilation newborn –Intubation and meconium aspiration. Video courtesy of Therese Canares, MD, and Jonathan Valente, MD, Rhode Island Hospital, Brown University.
Determinants of cardiac function and oxygen delivery to tissues. Adapted from Strange GR. APLS: The Pediatric Emergency Medicine Course. 3rd ed. Elk Grove Village, Ill: American Academy of Pediatrics; 1998:34.
Assisted ventilation newborn –Intubation and meconium aspiration. Video courtesy of Therese Canares, MD, and Jonathan Valente, MD, Rhode Island Hospital, Brown University.
Agent Type
Agent
Initial Dosage
Additional Factors
Volume expanders
Isotonic sodium chloride solution
10-20 mL/kg intravenous (IV)
Inexpensive, available
Albumin (5%)
10-20 mL/kg IV
Expensive
Plasma
10-20 mL/kg IV
Expensive
Lactated ringer solution
10-20 mL/kg IV
Inexpensive, available
Isotonic glucose
10-20 mL/kg IV
Inexpensive, available
Whole blood products
10-20 mL/kg IV
Limited availability
Reconstituted blood products
10-20 mL/kg IV
Use type
O negative
Vasoactive drugs
Dopamine
5-20 mcg/kg/min IV
Never administer intra-arterially
Dobutamine
5-20 mcg/kg/min IV
Never administer intra-arterially
Epinephrine
0.05-1 mcg/kg/min IV
Never administer intra-arterially
Hydralazine
0.1-0.5 mg/kg IV every 3-6 h
Afterload reducer
Isoproterenol
0.05-0.5 mcg/kg/min IV
Never administer intra-arterially
Nitroprusside
0.5-8 mcg/kg/min IV
Afterload reducer
Norepinephrine
0.05-1 mcg/kg/min IV
Never administer intra-arterially
Phentolamine
1-20 mcg/kg/min IV
Afterload reducer
Milrinone
22.5-45 mcg/kg/h continuous IV infusion (ie, 0.375-0.75 mcg/kg/min)
Afterload reducer in cardiac dysfunction; decrease dose with renal impairment
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