Shock in Neonates PREPARED BY MAGED ZAKARIA NICU RESIDENT
Neonatal Vasoregulation Blood pressure (BP) measures the pressure in the walls of arteries created by the activity of the myocardium. This measurement consists of 2 numerical values: 1. Systole is the force exerted on the vessel wall during the myocardium contraction. 2. Diastole is the pressure that remains on the blood vessels when the myocardium relaxes.
Neonatal Vasoregulation Blood pressure is affected by several factors: 1. The integrity of the myocardium. 2. The elasticity of blood vessels. 3. Blood volume. 4. Blood viscosity. The nervous system maintains adequate organ perfusion through sympathetic/parasympathetic nervous system which is necessary for hormone secretion to maintain homeostasis.
Neonatal Vasoregulation The neonatal myocardium has unique features: 1. It lacks sarcoplasmic reticulum. 2. It has an fibrous non-contractile tissue. 3. It possess diminished sympathetic intervention. These structural differences are evident in the high output and lack of contractile reserve shown by the premature neonatal myocardium. Consequently, the premature neonate displays a relative tachycardia when compared with that of the term neonate.
Neonatal Vasoregulation The Frank–Starling law states that stroke volume (and therefore, COP) is when the myocardium relaxes and stretches to allow more blood to fill in the chambers during diastole. The Frank–Starling law has a limited application to neonatal physiology; because of the amounts of fibrous non- contractile tissue. This fibrous tissue does not have the capacity to stretch adequately to COP.
Neonatal Vasoregulation When the neonate perceives a stressor, hormones that trigger receptors to manipulate vasculature, cardiac contraction, and smooth muscle tone are released. These hormones are known as catecholamines.
Neonatal Vasoregulation The 3 major catecholamines are: 1. Dopamine 2. Epinephrine (adrenaline) 3. Norepinephrine (noradrenaline) These biologically active chemical compounds are released by the adrenal glands during times of stress. The following discussion will be confined to catecholamines effects in relation to blood pressure.
Neonatal Vasoregulation There are 4 types of receptors that accept catecholamine. These “acceptors” are known as α1, α2, β1, and β2 receptors. They are classified according to their location in the body and the alterations elicited by stimulation.
Table 1: ɑ And β ReceptorsCatecholamine Site ActionReceptor Smooth muscles in BVs • VC of coronary arteries • VC of peripheral veins α1 including mesenteric • Smooth muscle motility/blood BVs flow in the GI tract • VC of coronary artery • VC of peripheral veins α2 Pre-postsynaptic nerve • Myocardial conduction velocity terminals • Muscle motility/blood flow in the GI tract • HR β1 Cardiac muscles • Contractility of the atrium • Dilates smaller BVs β2 • Blood vessels • Dilates hepatic artery • Bronchi • Dilates the arteries to skeletal ms • Bronchodilation
Clarifying Terminology Neonatal care does not specifically aim to avoid hypotension but is more concerned in preventing shock. Shock occurs when organs experience inadequate blood flow to meet aerobic, cellular metabolism. Cellular oxygen requirements must be maintained for efficient energy production, and its absence results in cellular death.
Clarifying Terminology When the myocardium fails to produce adequate COP, or the nervous system detects a hypoxic state, catecholamines are released in an attempt to compensate for poor perfusion. This can be observed in patients who exhibit tachycardia and yet have a stable BP. However, without normal COP, a normotensive state can be maintained only for a limited amount of time. In fact, hypotension is a late sign of shock.
Clarifying Terminology The first phase of shock is the “compensated phase.” Signs include HR and UOP with no change in BP. It is important to understand that HR does not mean tachycardia and UOP is not synonymous for oliguria; both are simply deviations from the patient’s baseline.
Clarifying Terminology The second stage of neonatal shock is the “uncompensated phase.” It is in this stage that the blood flow to major organs becomes compromised. The HR remains from the baseline, UOP continues to , and BP as well.
Clarifying Terminology The final stage of shock is known as the “irreversible phase.” The cellular damage encountered leads to cellular death with severe organ damage.
Clarifying Terminology A hemodynamically significant PDA in the 1st postnatal week can cause inadequate tissue perfusion due to failure of a compensatory COP secondary to myocardial immaturity and the ductal steal phenomenon, which accounts for uniform reduction in systolic and diastolic blood pressure. A significant in systolic BP occurs only when the PDA shunt is moderate or large, yet a in diastolic and mean BP can occur when the shunt is small.
Clarifying Terminology The classic clinical picture of hypovolemia is that of a baby who is pale, hypotensive and tachycardic with very slow CRT. Each of these signs is non-specific for circulatory compromise and could reflect anything from sepsis to congenital heart disease.
Clinical monitoring of hemodynamics 1. Capillary refill time (CRT) : The accepted upper normal time is < 3 sec. A study of 469 preterm and term healthy neonates at 1-7 days of age demonstrated significant site and observer variations when CRT was measured on the chest, forehead, palm, and heel. CRT is more reliable when measured on the chest but not the forehead, palm or heel.Strozik KS, Pieper CH and Roller J (1997): Capillary refilling time in newborn babies: normal values. ArchDis Child Fetal Neonatal Ed;76(3):F193–6.
Clinical monitoring of hemodynamics A positive predictive value of CRT for SBF was found only when the refill time was over 6 s. When the refill time is this long, the clinician generally does not need to press the skin to know that something is wrong.Tibby SM, Hatherill M, Murdoch IA (1999): Capillary refill and core–peripheral temperature gap asindicators of haemodynamic status in paediatric intensive care patients. Arch Dis Child;80(2):163–6.
Clinical monitoring of hemodynamics2. Central–peripheral temperature difference (CPTd): Under normal conditions, CPTd will be < 1 °C during the 1st postnatal days in ELBW infants. In a thermoneutral environment (secondary to poor peripheral perfusion in shock), peripheral VC will skin temperature and thus lead to an CPTd.
Clinical monitoring of hemodynamics CPTd depends largely on body temperature, environmental temperature and the use of vasoactive drugs. However, no relation was observed between CPTd and SBF or SVR.Tibby SM, Hatherill M, Murdoch IA (1999): Capillary refill and core–peripheral temperature gap asindicators of haemodynamic status in paediatric intensive care patients. Arch Dis Child;80(2):163–6.
Clinical monitoring of hemodynamics3. Blood Pressure: Vascular resistance is increased as a compensatory response to hypovolemia. So, hypotension may be a relatively late sign.
Clinical monitoring of hemodynamics Three different definitions of neonatal hypotension are in widespread use: 1. BP < the 10th (or 5th) percentile of normative BP values derived from a reference population with regard to GA, BW and postnatal age.
Clinical monitoring of hemodynamics 2. The lower border of normal Mean BP equals the numeric value of GA (provided no signs exist of hypoperfusion e.g. a high serum lactate or oliguria). For example, the lowest acceptable Mean BP for a 26 wk neonate would be 26 mmHg. This is only valid during the 1st 3-5 days of life, since Mean BP during the 1st 3 days of life with a magnitude of 2-10 mmHg.Nuntarumit P, Yang W and Bada-Ellzey HS (1999): Blood pressure measurements in the newborn. ClinPerinatol;26(4):981-996.
Clinical monitoring of hemodynamics 3. Mean BP < 30 mmHg. This is based on the assumption that cerebral blood flow becomes pressure dependent at a MAP around 30 mmHg.Dammann O, Allred EN, Kuban KCK, et al. (2002): Systemic hypotension and white matter damage inpreterm infants. Dev Med Child Neurol;44(2):82-90.
Clinical monitoring of hemodynamics BP is not linearly related to systemic blood flow, which is not unexpected, since BP is not only determined by COP, but also by SVR. The consequence of using BP to diagnose low systemic blood flow will be that too many patients will be undertreated or overtreated, both with substantial risk of adverse effects and iatrogenic damage.
Clinical monitoring of hemodynamics When a low Mean BP is detected; test for accuracy of the reading. It is the nurse’s responsibility to ensure that the BP cuff covers two-thirds of the extremity that is used to derive the measurement. When the BP cuff is too large, the BP will be falsely low. Inversely, when the BP cuff is too small, the measurement will be falsely high.
Clinical monitoring of hemodynamics4. Heart Rate: Ventricular output is determined by SV and HR. SV is considered to be at a fixed level in neonates without much variation. Supposing that, COP is almost entirely dependent on HR.
Clinical monitoring of hemodynamics HR for compensation of COP can only be effective when EDV is maintained. When the HR is too high, diastolic coronary blood flow can be impeded due to insufficient filling time, which might result in contractility. Children have a limited reserve in HR, because of a basic high HR.
Clinical monitoring of hemodynamics HR can be influenced by many factors, such as body temperature, stress, pain, medication, etc. This means that a single HR value poorly reflects systemic perfusion, but that large changes in HR may indicate relevant changes in COP.
Clinical monitoring of hemodynamics5. Urine Output: UOP is in shock because of renal perfusion. UOP is a poor marker of circulatory failure in the absence of a direct relationship with systemic blood flow. Persistent oliguria after the 2nd day of life or anuria indicates poor renal perfusion after exclusion of congenital malformations and administration of nephrotoxic drugs.
Clinical monitoring of hemodynamics Urine production may be in the normal range, despite a compromised renal perfusion: 1. Renal tubular immaturity. 2. Septic shock with hyperglycemia (osmotic diuresis).
Clinical monitoring of hemodynamics Normally, UOP changes during the 1st days of life with an initial phase of low urine production (first 24 h), followed by a period of transient polyuria (2nd and 3rd days of life), after which diuresis stabilizes and depends on fluid intake. These physiologic changes in UOP are difficult to differentiate from oliguria due to impaired renal perfusion.
Clinical monitoring of hemodynamics6. Lactate: There is an important difference between lactate and lactic acid. Lactic acid is a strong ion, which dissociates into lactate and H+ at the physiological pH. Lactate itself is not an acid. Moreover, the conversion of pyruvate to lactate is not coupled with H+. This means that hyperlactatemia is not synonymous to lactic acidosis.
Clinical monitoring of hemodynamics Only when H+, cannot be recycled in the mitochondria, hyperlactatemia results in lactic acidosis. Possible causes of an lactate production in neonates are anaerobic metabolism (such as in circulatory failure), glycogenolysis, sympathomimetic drugs and IEM.
Clinical monitoring of hemodynamics Blood lactate concentration is not during circulatory failure when lactate clearance is in balance with lactate production and when oxygen delivery meets the oxygen demand in the tissues by oxygen extraction.
Clinical monitoring of hemodynamics Beyond the 1st 6 hrs after birth the lactate concentration in umbilical arterial blood of healthy infants is often < 2.5 mmol/L. There is a good agreement between lactate concentration in arterial, venous and capillary blood, although the difference between arterial and capillary lactate concentration is with the use of vasoactive drugs and in sepsis.
Clinical monitoring of hemodynamics To differentiate between transient dysoxia and IEM in newborns with persistent hyperlactatemia during the 1st 2 days of life, serum alanine concentration can be measured. Neonates with transient hyperlactatemia did not have serum alanine, whereas serum alanine turned out to be a sensitive marker in neonates with an IEM.Morava E, Hogeveen M, De Vries M, Ruitenbeek W, de Boode WP and Smeitink J (2006): Normalserum alanine concentration differentiates transient neonatal lactic acidemia from an inborn error of energymetabolism. Biol Neonate;90: 207–9.
Clinical monitoring of hemodynamics The predictive value of lactate as an isolated indicator of circulatory failure is poor. When lactate is used in conjunction with other markers of poor perfusion it may improve the accuracy of the identification of circulatory failure
Clinical monitoring of hemodynamics7. Acid–base balance: Blood gas parameters, like pH and BE, are used as indirect indicators of tissue acidosis. This is based on the assumption that metabolic acidosis reflects tissue hypoxia secondary to inadequate perfusion and/or oxygenation.
Clinical monitoring of hemodynamics8. Color: The adequacy of peripheral perfusion and/or oxygenation is often evaluated by clinical assessment of the patients color. An infants color is influenced by many factors, such as oxygenation, Hb concentration, skin temperature, skin thickness, peripheral perfusion, race, GA, ambient temperature and light.
Clinical monitoring of hemodynamics The determination of the color of newborn infants has been proven to be very subjective with large inter-observer variability.
Clinical monitoring of hemodynamics9. Combination of different clinical hemodynamic variables: Combination of different hemodynamic variables can improve the predictive value for the detection of neonatal circulatory failure.
Echocardiography Ventricular outputs can be assessed using Doppler echocardiography. These outputs may reflect SBF. However, this is not true in the transitional circulation, particularly in very preterm babies, in whom shunts through the ductus arteriosus and foramen ovale may cause ventricular output to overestimate SBF.
Echocardiography Because of this, the measure of superior vena cava (SVC) flow is developed because it is not corrupted by intracardiac shunts. Normal SVC flow in preterm babies is 50-110 ml/kg/min. A low upper body blood flow is common in 1st day of life in preterm infants < 30 weeks gestation; this has strong correlation with periventricular or intraventricular hemorrhage.
Echocardiography The other potential echocardiographic assessment of hypovolemia is ventricular filling, which can be assessed by left ventricular end-diastolic diameter (LVEDD). Normal mean LVEDD increases from 12 mm at 26–28 weeks to 17 mm at term.
EtiologyA. Abnormal peripheral vasoregulation: i. or Dysregulated endothelial nitric oxide (NO) in perinatal period, particularly in preterms ii. Immature neurovascular pathways iii. Pro-inflammatory cascades with vasodilation
EtiologyB. Hypovolemia may be: 1. Absolute; loss of intravascular volume. 2. Relative; vasodilatation (such as in septic shock) and inadequate volume to fill the expanded intravascular compartment. The result is inadequate filling pressure (or preload) on the heart. If the condition is severe enough, COP will fall.
EtiologyB. Hypovolemia: 1. Placental hemorrhage (abruptio placentae, placenta previa or delayed cord clamping). 2. Fetal-to-maternal hemorrhage (diagnosed by the Kleihauer-Betke test of the mothers blood for fetal erythrocytes). 3. Acute twin-to-twin transfusion (the donor twin). 4. Intracranial hemorrhage.
Etiology 5. Massive pulmonary hemorrhage (i.e. PDA). 6. DIC or other severe coagulopathies. 7. Plasma loss into the extravascular compartment, as seen with low oncotic pressure states or capillary leak syndrome (e.g. sepsis). 8. Excessive extracellular fluid losses, as seen with volume depletion from IWL or inappropriate diuresis, commonly seen in ELBW infants.
EtiologyC. Myocardial dysfunction: 1. Intrapartum asphyxia can cause poor contractility and papillary muscle dysfunction with TR, resulting in low COP. 2. Secondary to infectious agents (bacterial or viral) or metabolic abnormalities such as hypoglycemia. 3. Cardiomyopathy can be seen in IDMs with or without hypoglycemia.
Etiology 4. Obstruction to blood flow resulting in COP: a. Inflow obstructions: • Total anomalous pulmonary venous return. • Cor triatriatum. • Tricuspid or Mitral atresia. • Acquired inflow obstructions can occur from IV air or thrombotic embolus, or from intrathoracic pressure caused by high airway pressures or air-leak syndromes (e.g. pneumothorax).
Etiology b. Outflow obstructions: • Pulmonary stenosis or atresia. • Aortic stenosis or atresia. • Hypertrophic subaortic stenosis seen in IDMs with compromised left ventricular outflow, particularly when cardiotonic agents are used. • Coarctation of the aorta or interrupted aortic arch. • Arrhythmias, if prolonged. SVT such as paroxysmal atrial tachycardia are most common.
Treatment Options Correction of negative inotropic factors such as hypoxia, acidosis, hypoglycemia, and other metabolic derangements will improve COP. In clinical practice, the re-establishment of proper organ perfusion is generally approached in a stepwise. The first step is to fill the vasculature by way of volume expanders. The second is to tighten the vasculature with the use of catecholamines. The final step is to compensate for the immature vasculature with steroids.
First Tier: Volume Expanders Fluid boluses are used only when there is physiological evidence of external hemorrhage/fluid loss. An infusion of 10-20 mL/kg isotonic saline solution or Ringer’s lactate over 30-60 min is used to treat suspected hypovolemia if Hct ≥ 40% and cardiogenic process unlikely.
First Tier: Volume Expanders In previous years, clinicians have administered colloids, such as albumin, in order to replace the intravascular loss. However, studies have proven that: 1. When albumin and crystalloids (normal saline) are compared in terms of cost, availability, safety, and effective therapeutic outcome, normal saline becomes the agent of choice for volume expansion. 2. Abnormal neurodevelopment is present in neonates who were given albumin as compared to those given crystalloids.Oca MJ, Nelson M and Donn SM (2003): Randomized trial of normal saline versus 5% albumin for thetreatment of neonatal hypotension. J Perinatol;23(6):473-476.Dempsey EM and Barrington KJ (2007): Treating hypotension in the preterm infant: when and with what: acritical and systematic review. J Perinatol;27(8):469-478.
First Tier: Volume Expanders Unwarranted volume expansion has been linked with mortality in the preterm neonate population. Generous fluid administration in preterm infants the likelihood of: 1. PDA 2. NEC 3. Abnormal neurodevelopmental outcomes 4. Death.
First Tier: Volume Expanders When endogenous or exogenous blood loss has occurred, prompt transfusion with “whole blood” is appropriate. It can be administered in aliquots of 5-10 mL/kg over 5 min until signs of adequate perfusion are present.Engle WD and LeFlore JL (2002): Hypotension in the Neonate. NeoReviews;3;157
First Tier: Volume Expanders Measurement of CVP may help fluid management, especially in term or late preterm infants. It is measured using a catheter with its tip in the right atrium or in the intrathoracic SVC. Catheter can be placed through the UV or percutaneously through the EJV, IJV or subclavian vein. CVP should be maintained at 5-8 mmHg. If CVP > 5-8 mmHg, additional volume will usually not be helpful. CVP is influenced by other factors: 1. Noncardiac factors such as ventilator pressures 2. Cardiac factors such as tricuspid valve functionCloherty JP, Eichenwald EC and Stark AR (2008): Manual of Neonatal Care, Lippincott Williams &Wilkins, 6th ed.
First Tier: Volume Expanders Hypocalcemia frequently occurs in infants with circulatory failure, especially if they have received large amounts of volume resuscitation. Calcium gluconate 10% (1 mL/kg) can be infused slowly if ionized calcium levels are low. In this setting, calcium frequently produces a positive inotropic response.Cloherty JP, Eichenwald EC and Stark AR (2008): Manual of Neonatal Care, Lippincott Williams &Wilkins, 6th ed.
Second Tier: Vasoactive Drugs (the Catecholamines) While volume expanders “fill the pump” vasoactive drugs “tighten the pump” to assist the vasculature in providing blood to organ systems. The administration of dopamine, dobutamine, and epinephrine act in accordance with adrenergic receptors to mediate an alteration in vascular tone. Once these receptors are stimulated, changes in blood pressure can be observed in the form of higher Mean BP, shortened CRT, HR, improved oxygenation, and UOP.
Second Tier: Vasoactive Drugs (Dopamine) Dopamine is an endogenous hormone synthesized and released by the nervous tissues and adrenal medulla. The increase in myocardial contractility depends in part on myocardial norepinephrine stores. Low dopamine dosages (0.5-5 μg/kg/min) stimulate dopaminergic receptors, medium dosages (5-10 μg/kg/min) stimulate the β receptors, and high dosages (≥10 μg/kg/min) stimulate the α receptors.Gomella TL, Cunningham MD, Eyal FG and Zenk KE (2004): Neonatology:Management, Procedures, On-Call Problems, Diseases, and Drugs. 5th ed. Stanford, CT: McGraw-Hill.
Second Tier: Vasoactive Drugs (Dopamine) Exogenous dopamine activates receptors in a dose-dependent manner: 1. Low dose dopamine (0.5-2 µg/kg/min) stimulates peripheral dopamine receptors (DA1 and DA2) and renal, mesenteric, and coronary blood flow with little effect on COP. 2. Intermediate dose dopamine (2-6 µg/kg/min) has positive inotropic and chronotropic effects (β1 and β2). 3. High dose dopamine (6-10 µg/kg/min) stimulates α1 and α2 adrenergic receptors and serotonin receptors, resulting in VC and PVR and may VR.Cloherty JP, Eichenwald EC and Stark AR (2008): Manual of Neonatal Care, Lippincott Williams &Wilkins, 6th ed.
Second Tier: Vasoactive Drugs (Dopamine) The established dose ranges of 2-20 μg/kg/min have been derived from studies conducted with healthy adults. Interestingly, there are no recorded data regarding administration of dopamine above 20 μg/kg/min having any destructive effects on the neonate.Barrington KJ (2008): Hypotension and shock in the preterm infant. Semin Fetal Neonatal Med;13:16-23. Higher dosages of dopamine (>20 μg/kg/min) are avoided clinically for the theoretical concern of COP occurring because of VC.Roze JC, Tohier C, Maingueneau C, Lefevre M and Mouzard A (1993): Response to dobutamine anddopamine in the hypotensive very preterm infant. Arch Dis Child;69:59-63.
Second Tier: Vasoactive Drugs (Dopamine) There are very serious side effects of dopamine including: 1. Extravasation causes tissue necrosis (infusion site should be monitored). 2. Ventricular arrhythmia, widened QRS complexes, ectopic heartbeats 3. Vomiting 4. Hypertension.
Second Tier: Vasoactive Drugs (Dopamine) Dopamine receptors are also found in the hypothalamus and the pituitary. If dopamine is administered on a continuous basis, the natural balance of the hypothalamic–pituitary–adrenal axis disappears in some patients. This results in of thyroid hormones leading to down-regulation of the receptors that dopamine affects. This leads to dopamine-resistant shock. If this occurs, additional pharmacological agents to maintain organ perfusion should be considered.
Second Tier: Vasoactive Drugs (Dobutamine) Unlike dopamine, dobutamine is not an endogenous catecholamine. Dobutamine have limited effect on the peripheral vasculature. It has a greater affinity for the β receptors on the myocardium producing a stronger left ventricular contraction. This systemic perfusion while only the MAP a negligible amount. Dobutamine is often used with dopamine to improve COP in cases of myocardial function as its inotropic effects, unlike those of dopamine, are independent of norepinephrine stores.
Second Tier: Vasoactive Drugs (Dobutamine) Adverse effects of dobutamine include arrhythmias, hypertension, and VD of the capillary in cutaneous tissue. Neonates may become excessively tachycardic during dobutamine therapy; a reduction in dosage is usually all that is required.
Second Tier: Vasoactive Drugs (Epinephrine) Epinephrine as a pharmacological agent both BP and COP by stimulating the α and β receptors. Like dopamine, animal studies have shown that when epinephrine is administered at a low dose VD occurs together with a positive inotropic action. The VC was not seen until higher dosages. These data have been applied to neonatal medicine with limited human studies.
Second Tier: Vasoactive Drugs (Epinephrine) In clinical practice, low dose epinephrine stimulates the β receptors causing a positive inotropic effect. An elevation in BP may be not seen until higher doses which stimulate the α receptors in the peripheral vasculature.
Second Tier: Vasoactive Drugs (Epinephrine) Epinephrine is widely used in neonatal resuscitation and BP management, but there have been concerns regarding its safety concerning the peripheral VC, in particular of the renal vasculature. So, it is not a first-line drug in newborns.
Second Tier: Vasoactive Drugs (Epinephrine) Some infants who respond poorly to dopamine or dobutamine will respond to a constant infusion of epinephrine at a starting dose of 0.05-0.1 μg/kg/min and can be rapidly as needed while dopamine infusion rates are . Conditions with peripheral VD involved in the circulatory collapse, as in septic shock, may respond to epinephrine.
Second Tier: Vasoactive Drugs (Epinephrine) Epinephrine is an effective adjunct therapy to dopamine because cardiac norepinephrine stores are readily depleted with prolonged and higher rate dopamine infusions. Simultaneous infusions of epinephrine and dopamine BP and UOP in preterm neonates in a state of shock.
Second Tier: Vasoactive Drugs (Norepinephrine) Norepinephrine use is limited because of its prominent VC activity, which raises concerns about: 1. Possible ischemia 2. Afterload 3. Myocardial oxygen demand 4. RBF and UOPDose in neonates: 20-100 nanograms (base)/kg/min IVI adjustedaccording to response; max. 1 μg (base)/kg/min. BNFC 2010-11
Second Tier: Vasoactive Drugs (Milrinone) This phosphodiesterase III inhibitors possesses inotropic and vasodilating properties. Although a major complication of their use is hypotension, they have been used in conjunction with other inotropic agents such as dopamine or dobutamine in patients who have chronic CHF or septic shock in which VC of some vascular beds is significant.
Third Tier: Steroids Previously therapeutic doses of vasopressor agents may become ineffective with neonates requiring higher doses to maintain organ perfusion “vasopressor-resistant shock”.
Third Tier: Steroids Vasopressor-resistant shock has 2 etiologies: 1. Natural down-regulation of androgenic receptors with the administration of exogenous catecholamines. 2. Neonate’s inherent adrenal insufficiency (especially preterms) that causes a naive cortisol stress response.
Third Tier: Steroids (Glucocorticoids) Hydrocortisone dosage for refractory hypotension: - 1 mg/kg/dose. - If efficacy is noted, the dose can be repeated Q8- 12h for 2-3 days, especially if low serum cortisol levels are documented before hydrocortisone treatment.Cloherty JP, Eichenwald EC and Stark AR (2008): Manual of Neonatal Care, Lippincott Williams &Wilkins, 6th ed.
Third Tier: Steroids (Glucocorticoids) Hydrocortisone, the synthetic version of cortisol, compensates for the neonate’s relative state of adrenal insufficiency. After administering hydrocortisone, nongenomic and genomic responses occur.
Third Tier: Steroids (Glucocorticoids) The immediate response (nongenomic) occur 1-2 hours after drug administration. Nongenomic effects assist the vasculature in 3 ways: 1. Promote hormone availability 2. Alter calcium accessibility 3. Prohibit further circulatory compromise
Third Tier: Steroids (Glucocorticoids) Hydrocortisone promotes hormone availability (more catecholamines available at receptor) by: 1. Catecholamine metabolism 2. Inhibit the reuptake of catecholamines by the sympathetic nervous system.
Third Tier: Steroids (Glucocorticoids) During the shock state, intracellular calcium is depleted because of cellular metabolism. After 1-2 hours of hydrocortisone administration, intracellular calcium is replenished. This the threshold for the action potential, allowing for improved myocardial contractility.
Third Tier: Steroids (Glucocorticoids) Steroids also blunt the effects of local vasodilators, such as nitric oxide, to prevent further circulatory compromise. After nongenomic effects occur, an improvement in the MABP is noticed. However, the patient will still require a high doses of vasopressors to maintain organ perfusion.
Third Tier: Steroids (Glucocorticoids) The prolonged (genomic) response occurs 8-12 hours after hydrocortisone administration. It is the induction of new receptor protein synthesis (upregulation of the adrenergic receptors). After this effect occurs, the vasoactive agents can be titrated back to the initial rate before the neonate experiences vasopressor-resistant shock.
Third Tier: Steroids (Glucocorticoids) A double-blinded control trial results showed that patients who were given prophylactic hydrocortisone 5 days postnatally required fewer rounds of volume expanders and received lower dosages of vasopressors. These cardiovascular effects were not associated with adverse effects of steroids such as hyperglycemia and risk of infection.Ng PC, Lee CH, Bnur FL, et al. (2006): A double-blind, randomized, controlled study of a “stress dose” ofhydrocortisone for rescue treatment of refractory hypotension in preterm infants. Pediatrics;117:367-375
Third Tier: Steroids (Glucocorticoids) While these findings look promising, a recent Cochrane Review was unable to comment on the safety and efficacy of steroid administration in the hypotensive neonate because of a lack of associated research.Subhedar NV, Duffy K and Ibrahim H (2007): Corticosteriods for treating hypotension in preterm infants.Cochrane Database Syst Rev;(1):CD003662. http://www. cochrane.org/reviews/en/ab003662.html.