Fn3.sites.medinfo.ufl.edu
IV. Cardiovascular Support and HIESection ContentsWhat is the goal Mean Arterial Blood Pressure (MAP) for infants with HIE?What is the optimal method to manage hypotension with HIE?How does hypothermia affect hemodynamic status post asphyxia?When should an echocardiogram be obtain for infants with HIE?Should serum markers of cardiac injury be obtained in infants with HIE, whatmarkers, and when should they be obtained?How should bradycardia associated with hypothermia be managed?VII. References I. What is the goal Mean Arterial Blood Pressure (MAP) for infants with HIE?Blood pressure must remain in a safe range post HIE with the goals of avoiding hypotensive associate cerebral ischemia while ensuring the infant is not hypertensive with subsequent intra-cerebral hemorrhage. The ideal MAP for term infants with HIE has not been established. Since infants operate over a narrow blood pressure range, and hypoxic-ischemia impairs cerebral autoregulation, it is recommended to maintain MAP within the critical margin of 40mmHg to 60mmHg ADDIN EN.CITE <EndNote><Cite><Author>Volpe</Author><Year>2008</Year><RecNum>102</RecNum><DisplayText>[1]</DisplayText><record><rec-number>102</rec-number><foreign-keys><key app="EN" db-id="0e5wpxtvj2v5x4ewattvp2z4ww05zzez0svv">102</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>Volpe, JJ</author></authors><secondary-authors><author>Volpe, JJ</author></secondary-authors></contributors><titles><title>Neurology of the Newborn</title></titles><edition>Fifth</edition><section>400-480</section><dates><year>2008</year></dates><pub-location>Philadelphia</pub-location><publisher>Saunders</publisher><urls></urls></record></Cite></EndNote>[1] unless the hemodynamics suggest a more optimal MAP.Recommendations: Attempt to maintain MAP between 40mmHg and 60mmHg. Cerebral oximetry may be used to identify the optimal blood pressure for the patient. 2. Infants with pulmonary hypertension may require a MAP on the -higher end of this scale3. Attempt to avoid acute fluctuations in blood pressure Level of Evidence: V- Expert opinion based on current review of literature.II. What is the optimal method to manage hypotension with HIE?There is minimal documentation regarding the ideal method to augment MAP for infants with HIE. If there is clinical or historical evidence of hypovolemia (i.e. severe anemia, placenta abruption, cord compression) than volume may be indicated. The unwarranted use of fluids may exacerbate cerebral edema ADDIN EN.CITE <EndNote><Cite><Author>Kimelberg</Author><Year>1995</Year><RecNum>160</RecNum><DisplayText>[2]</DisplayText><record><rec-number>160</rec-number><foreign-keys><key app="EN" db-id="0e5wpxtvj2v5x4ewattvp2z4ww05zzez0svv">160</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kimelberg, H. K.</author></authors></contributors><auth-address>Division of Neurosurgery, Albany Medical College, New York, USA.</auth-address><titles><title>Current concepts of brain edema. Review of laboratory investigations</title><secondary-title>J Neurosurg</secondary-title></titles><periodical><full-title>J Neurosurg</full-title></periodical><pages>1051-9</pages><volume>83</volume><number>6</number><edition>1995/12/01</edition><keywords><keyword>Amino Acids/metabolism</keyword><keyword>Animals</keyword><keyword>Astrocytes/metabolism</keyword><keyword>Brain Edema/*physiopathology</keyword><keyword>Cells/metabolism</keyword><keyword>Electrolytes/metabolism</keyword><keyword>Extracellular Space/metabolism</keyword><keyword>Neurons/metabolism</keyword></keywords><dates><year>1995</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>0022-3085 (Print)
0022-3085 (Linking)</isbn><accession-num>7490620</accession-num><urls><related-urls><url>;[2]. A 2002 Cochrane systemic review evaluating Dopamine for the prevention of morbidity and mortality with HIE was found to be inconclusive ADDIN EN.CITE <EndNote><Cite><Author>Hunt</Author><Year>2002</Year><RecNum>1569</RecNum><DisplayText>[3]</DisplayText><record><rec-number>1569</rec-number><foreign-keys><key app="EN" db-id="vrrvp2a0wvapdbefva5pvzz30v0xfpxade0t" timestamp="0">1569</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hunt, R.</author><author>Osborn, D.</author></authors></contributors><auth-address>Neonatal Neurology, Royal Women's and Royal Children's Hospitals, Melbourne, Level 2, Royal Children's Hospital, Flemington Road, Parkville, VIC, Australia, 3052. huntr@cryptic.rch.unimelb.edu.au</auth-address><titles><title>Dopamine for prevention of morbidity and mortality in term newborn infants with suspected perinatal asphyxia</title><secondary-title>Cochrane Database Syst Rev</secondary-title></titles><periodical><full-title>Cochrane Database Syst Rev</full-title></periodical><pages>CD003484</pages><number>3</number><edition>2002/07/26</edition><keywords><keyword>Asphyxia Neonatorum/*prevention & control</keyword><keyword>Cardiotonic Agents/*therapeutic use</keyword><keyword>Dopamine/*therapeutic use</keyword><keyword>Humans</keyword><keyword>Infant, Newborn</keyword><keyword>Randomized Controlled Trials as Topic</keyword></keywords><dates><year>2002</year></dates><isbn>1469-493X (Electronic)
1361-6137 (Linking)</isbn><accession-num>12137696</accession-num><urls><related-urls><url> [pii]
10.1002/14651858.CD003484</electronic-resource-num><language>eng</language></record></Cite></EndNote>[3]. Further, Dopamine may not be the ideal first line agent for infants with evidence of pulmonary hypertension (PPHN) and HIE because it increases both systemic (SVR) and pulmonary vascular resistance (PVR) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGV1bmc8L0F1dGhvcj48WWVhcj4yMDAxPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA [4]. Dobutamine, at high doses, can also increase pulmonary artery pressure while reducing afterload and therefore would not be an ideal agent for infants with HIE and PPHN ADDIN EN.CITE <EndNote><Cite><Author>Cheung</Author><Year>1999</Year><RecNum>163</RecNum><DisplayText>[5]</DisplayText><record><rec-number>163</rec-number><foreign-keys><key app="EN" db-id="0e5wpxtvj2v5x4ewattvp2z4ww05zzez0svv">163</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cheung, P. Y.</author><author>Barrington, K. J.</author><author>Bigam, D.</author></authors></contributors><auth-address>Department of Pediatrics, University of Alberta, Edmonton, Canada.</auth-address><titles><title>The hemodynamic effects of dobutamine infusion in the chronically instrumented newborn piglet</title><secondary-title>Crit Care Med</secondary-title></titles><periodical><full-title>Crit Care Med</full-title></periodical><pages>558-64</pages><volume>27</volume><number>3</number><edition>1999/04/13</edition><keywords><keyword>Analysis of Variance</keyword><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>Cardiotonic Agents/administration & dosage/*pharmacology</keyword><keyword>Dobutamine/administration & dosage/*pharmacology</keyword><keyword>Dose-Response Relationship, Drug</keyword><keyword>Hemodynamics/*drug effects</keyword><keyword>Infusions, Intravenous</keyword><keyword>Random Allocation</keyword><keyword>Renal Circulation/drug effects</keyword><keyword>Swine</keyword><keyword>Thermodilution</keyword></keywords><dates><year>1999</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0090-3493 (Print)
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ADDIN EN.CITE.DATA [6, 7]. Recommendations: 1. If infant is hypotensive, start treatment with a pressor which supports the clinical need of the neonate. 2. Obtain an Echocardiogram to assist in management. If myocardial dysfunction is evident on echocardiogram, consider the addition of epinephrine. 3. This is the recommended approach for hypotensive, encephalopathic infants with or without PPHN. Of note, the addition of Milrinone as a single agent may be beneficial in PPHN when normotensive or a combination of Milrinone with low dose epinephrine to prevent systemic hypotension with Milrinone infusion or if the patient had hypotension and PPHN PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NY05hbWFyYTwvQXV0aG9yPjxZZWFyPjIwMDY8L1llYXI+
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ADDIN EN.CITE.DATA [6, 7].4. In the case of refractory hypotension to pressor support, consideration should be given to the addition of steroids with hydrocortisone the steroid of choice. Consider checking serum cortisol prior to starting hydrocortisone. 5. A majority of neonates with HIE do not have acute volume or blood loss. Unless there is a history of volume or blood loss, caution should be used in volume expansion for hypotension given the risk of cerebral edema and renal insufficiency due to hypoxic-ischemic injury. Level of Evidence: IV- Case Series and Expert opinion based on current review of the literature.III. How does hypothermia affect hemodynamic status post asphyxia?Mild systemic hypothermia in itself appears to have minimal clinical effects on hemodynamic status. The CoolCap Trial which utilized mild systemic hypothermia to a rectal temperature of 34.5°C did not demonstrate affects on arterial blood pressure or initial treatment with inotropes or volume in infants with moderate to severe HIE ADDIN EN.CITE <EndNote><Cite><Author>Battin</Author><Year>2009</Year><RecNum>166</RecNum><DisplayText>[8]</DisplayText><record><rec-number>166</rec-number><foreign-keys><key app="EN" db-id="0e5wpxtvj2v5x4ewattvp2z4ww05zzez0svv">166</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Battin, M. R.</author><author>Thoresen, M.</author><author>Robinson, E.</author><author>Polin, R. A.</author><author>Edwards, A. D.</author><author>Gunn, A. J.</author></authors></contributors><auth-address>Newborn Services, National Women's Health, Auckland City Hospital, Private Bag 92 024, Auckland, New Zealand. malcolmb@t.nz</auth-address><titles><title>Does head cooling with mild systemic hypothermia affect requirement for blood pressure support?</title><secondary-title>Pediatrics</secondary-title></titles><periodical><full-title>Pediatrics</full-title></periodical><pages>1031-6</pages><volume>123</volume><number>3</number><edition>2009/03/04</edition><keywords><keyword>Blood Pressure/*physiology</keyword><keyword>Electroencephalography</keyword><keyword>Female</keyword><keyword>Fluid Therapy</keyword><keyword>*Head</keyword><keyword>Heart Rate/*physiology</keyword><keyword>Homeostasis</keyword><keyword>Humans</keyword><keyword>Hypothermia, Induced/*methods</keyword><keyword>Hypoxia-Ischemia, Brain/physiopathology/*therapy</keyword><keyword>Infant, Newborn</keyword><keyword>Male</keyword><keyword>Monitoring, Physiologic</keyword><keyword>Rewarming</keyword></keywords><dates><year>2009</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1098-4275 (Electronic)
0031-4005 (Linking)</isbn><accession-num>19255036</accession-num><urls><related-urls><url> [pii]
10.1542/peds.2008-1610</electronic-resource-num><language>eng</language></record></Cite></EndNote>[8]. In the NICHD whole body hypothermia trial, there were no differences in the incidence of pulmonary hypertension or cardiac arrhythmias between the treatment and controlled groups. However, there was a trend towards an increase use of inotropes in the hypothermia group PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TaGFua2FyYW48L0F1dGhvcj48WWVhcj4yMDA1PC9ZZWFy
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ADDIN EN.CITE.DATA [9]. In addition, the TOBY Trial did not find any significant difference in the incidence of hypotension, cardiac arrhythmias or pulmonary hypertension between hypothermic and normothermic infants PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BenpvcGFyZGk8L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFy
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ADDIN EN.CITE.DATA [10].Level of Evidence: IA- Based on Randomized Controlled Trials. VI. When should an echocardiogram be obtain for infants with HIE?We recommend an Echocardiogram be performed in any infant with HIE. Echocardiogram may be repeated and used to guide therapy in the following clinical scenarios:1. Elevated cardiac enzymes if performed at your center2. Clinical evidence of cardiac dysfunction3. Clinical evidence of pulmonary hypertension4. Hypotension (MAP < 40mmHg)5. Requiring inotropic support Level of Evidence: V- Expert opinion based on current review of literature.V. Should serum markers of cardiac injury be obtained in infants with HIE, what markers, and when should they be obtained?Myocardial dysfunction is often the direct cause of perinatal brain injury. Myocardial damage may be clinically occult with mild HIE or manifest as a systemic hypoperfusion state in the cases of moderate to severe HIE. Serum cardiac markers may assist in injury detection and guide clinical management. Recent evidence suggests cardiac Troponins are superior to other markers of myocardial injury (LDH, CK, CK-MB) in detecting earlier, cardiac specific injury PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HdW5lczwvQXV0aG9yPjxZZWFyPjIwMDU8L1llYXI+PFJl
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ADDIN EN.CITE.DATA [11, 12]. Cardiac Troponin T (cTnT) and I (cTNI) are structural cytoplasmic proteins of myosites and the most cardiac specific of the troponins in the neonatal period ADDIN EN.CITE <EndNote><Cite><Author>El-Khuffash</Author><Year>2008</Year><RecNum>170</RecNum><DisplayText>[13]</DisplayText><record><rec-number>170</rec-number><foreign-keys><key app="EN" db-id="0e5wpxtvj2v5x4ewattvp2z4ww05zzez0svv">170</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>El-Khuffash, A. F.</author><author>Molloy, E. J.</author></authors></contributors><auth-address>Department of Neonatology, National Maternity Hospital, Dublin, Ireland. afif_faisal@</auth-address><titles><title>Serum troponin in neonatal intensive care</title><secondary-title>Neonatology</secondary-title></titles><periodical><full-title>Neonatology</full-title></periodical><pages>1-7</pages><volume>94</volume><number>1</number><edition>2007/12/22</edition><keywords><keyword>Asphyxia Neonatorum/blood/physiopathology</keyword><keyword>Biological Markers/blood</keyword><keyword>Cardiomyopathies/blood/*physiopathology</keyword><keyword>Echocardiography</keyword><keyword>Humans</keyword><keyword>Infant, Newborn</keyword><keyword>*Intensive Care, Neonatal</keyword><keyword>Respiratory Distress Syndrome, Newborn/blood/physiopathology</keyword><keyword>Troponin/*blood</keyword></keywords><dates><year>2008</year></dates><isbn>1661-7819 (Electronic)
1661-7800 (Linking)</isbn><accession-num>18097151</accession-num><urls><related-urls><url> [pii]
10.1159/000112540</electronic-resource-num><language>eng</language></record></Cite></EndNote>[13]. Further, there is only one commercially available assay for Troponin T making standardization between different studies and reference ranges relatively consistent. Although there is not an accepted normal range for cTnT in neonates, a value of ≥ 0.1 ng/ml in the setting of HIE has been considered as elevated in several studies and as a potential indicator of mortality in the neonatal period PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYXR0ZXI8L0F1dGhvcj48UmVjTnVtPjE3MTwvUmVjTnVt
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ADDIN EN.CITE.DATA [11-14]. Recommendations:1. If performed at your center and clinically indicated, obtain an ECG and Echocardiogram if cTnT or cTNI is ≥ 0.1ng/ml to evaluate myocardial ischemia and cardiac function.As stated above, Cardiac Troponin T or Troponin I may also be predictive of outcome and may aid the bedside clinician with additional prognostic information. Level of Evidence: IIC- based on outcome data and case-controlled studies. VI. How should bradycardia associated with hypothermia be managed? Relative bradycardia (70-100 bpm) is not an uncommon occurrence in infants undergoing hypothermia. However, pathologic bradycardia can be a result of cardiac dysfunction, arrhythmias, deep hypothermia and increased intracranial pressure. Clinical intervention should be initiated when bradycardia is associated with evidence of decreased cardiac output, electrolyte abnormalities, elevated cardiac enzymes, and/or ECG abnormalities. Recommendations:1. If heart rate is <70bpm with evidence of reduced cardiac output (worsening metabolic acidosis, ↑lactic acid, prolonged capillary refill time, diminished pulses, low or borderline low MAP) obtain electrolytes including ionized calcium, ECG, echocardiogram, and ensure core temperature is appropriate.2. If heart rate is <70bpm but >60bpm without evidence of reduced cardiac output, normal electrolytes, normal ECG and echocardiogram then close clinical observation is a reasonable approach.3. The bedside clinician may consider decreasing sedation or rewarming by 0.50C to see if the HR increases if below 60 or below 70 with evidence of reduced cardiac output. Level of Evidence: V- Expert opinion based on current review of literature.VII. References: ADDIN EN.REFLIST 1.Volpe, J., Neurology of the Newborn. Fifth ed, ed. J. Volpe. 2008, Philadelphia: Saunders.2.Kimelberg, H.K., Current concepts of brain edema. Review of laboratory investigations. J Neurosurg, 1995. 83(6): p. 1051-9.3.Hunt, R. and D. Osborn, Dopamine for prevention of morbidity and mortality in term newborn infants with suspected perinatal asphyxia. Cochrane Database Syst Rev, 2002(3): p. CD003484.4.Cheung, P.Y. and K.J. Barrington, The effects of dopamine and epinephrine on hemodynamics and oxygen metabolism in hypoxic anesthetized piglets. Crit Care, 2001. 5(3): p. 158-66.5.Cheung, P.Y., K.J. Barrington, and D. Bigam, The hemodynamic effects of dobutamine infusion in the chronically instrumented newborn piglet. Crit Care Med, 1999. 27(3): p. 558-64.6.McNamara, P.J., et al., Milrinone improves oxygenation in neonates with severe persistent pulmonary hypertension of the newborn. J Crit Care, 2006. 21(2): p. 217-22.7.Bassler, D., et al., Neonatal persistent pulmonary hypertension treated with milrinone: four case reports. Biol Neonate, 2006. 89(1): p. 1-5.8.Battin, M.R., et al., Does head cooling with mild systemic hypothermia affect requirement for blood pressure support? Pediatrics, 2009. 123(3): p. 1031-6.9.Shankaran, S., et al., Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med, 2005. 353(15): p. 1574-84.10.Azzopardi, D.V., et al., Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med, 2009. 361(14): p. 1349-58.11.Gunes, T., et al., Troponin-T levels in perinatally asphyxiated infants during the first 15 days of life. Acta Paediatr, 2005. 94(11): p. 1638-43.12.Boo, N.Y., et al., Comparison of serum cardiac troponin T and creatine kinase MB isoenzyme mass concentrations in asphyxiated term infants during the first 48 h of life. J Paediatr Child Health, 2005. 41(7): p. 331-7.13.El-Khuffash, A.F. and E.J. Molloy, Serum troponin in neonatal intensive care. Neonatology, 2008. 94(1): p. 1-7.14.Matter, M., et al., Myocardial performance in asphyxiated full-term infants assessed by Doppler tissue imaging. Pediatr Cardiol. 31(5): p. 634-42. ................
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