Inotropic therapies in asphyxiated neonates: The clinical and laboratory facts

Current Pediatric Reviews

Volumn 5, Issue 2, 2009, Pages 71-78

  Joynt, Chloe ^a   Cheung, Po Yin ^a,b  

^a UNIVERSITY OF ALBERTA   (Canada)

^b ROYAL ALEXANDRA HOSPITAL   (Canada)

Author keywords

Asphyxia; Blood pressure; Catecholamines; Inotropes; Newborn

Indexed keywords

ADENYLATE CYCLASE; ADRENALIN; BETA 2 ADRENERGIC RECEPTOR; BETA ADRENERGIC RECEPTOR; CYCLIC AMP; DOBUTAMINE; DOPAMINE; HYDROCORTISONE; INOTROPIC AGENT; LEVOSIMENDAN; MILRINONE; PLACEBO; REACTIVE OXYGEN METABOLITE;

ACIDOSIS; BRAIN BLOOD FLOW; CARDIOVASCULAR DISEASE; CARDIOVASCULAR FUNCTION; CLINICAL TRIAL; DEVELOPMENTAL DISORDER; DOWN REGULATION; DRUG DOSE TITRATION; DRUG MEGADOSE; DRUG RESPONSE; FLUID RESUSCITATION; HEART DILATATION; HEART MUSCLE CONTRACTILITY; HEART OUTPUT; HEART RATE; HEART STROKE VOLUME; HUMAN; HYPOTENSION; INOTROPISM; LOW DRUG DOSE; MEAN ARTERIAL PRESSURE; NEWBORN HYPOXIA; NONHUMAN; PRIORITY JOURNAL; PULMONARY HYPERTENSION; REOXYGENATION; REVIEW; SHOCK; SYSTOLIC BLOOD PRESSURE; VASOCONSTRICTION;

EID: 68549083785     PISSN: 15733963     EISSN: None     Source Type: Journal    
DOI: 10.2174/157339609788185712     Document Type: Review

References (119)

1. Perinatal morbidity. Report of the Health Care Committee Expert panel on Perinatal Morbidity. National Health and Medical Research Council. Australian Government Publishing Service, 1995.
2. American Heart Association. Neonatal Resuscitation. 5th ed. Kattwinkel J, Ed. 2006; pp. 1-2.
3. World Health Organization. Child health and development: health of the newborn. 2003. who.int/reproductive health/publications/ interagency_manual_on_RH-in_refugee_situations/a3.pdf
4. Van Bel F, Walther FJ. Myocardial dysfunction and cerebral blood flow velocity following birth asphyxia. Acta Paediatr Scand 1990; 79: 756-62.
5. Martin-Ancel A, Garcia-Alix A, Gaya F, et al. Multiple organ involvement in perinatal asphyxia. J Pediatr 1995; 127: 786-93.
6. Shah P, Riphagen S, Beyene J, Perlman M. Multiorgan dysfunction in infants with post asphyxial hypoxic ischemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 2004; 89: 152-5.
7. Perlman JM, Tack Ed, Martin T, Shackelford G, Amon E. Acute systemic organ injury in term infants after asphyxia. Am J Dis Child 1989; 143: 617-20.
8. Rowe RD, Hoffman T. Transient myocardial ischemia of the newborn infant: a form of severe cardiorespiratory distress in full term infants. J Pediatr 1972; 28: 243-5.
9. Leuthner SR, Das UG. Low Apgar scores and the definition of birth asphyxia. Ped Clin N Am 2004; 51: 737-45.
10. Evans N, Kluckow M, Currie A. Range of echocardiographic findings in term neonates with high oxygen requirements. Arch Dis Child Fetal Neonatal Ed 1998; 78: F105-11.
11. Evans N. Which inotrope for which baby. Arc Dis Child Fetal Neonatal Ed 2006; 91: F213-20.
12. Osborn D, Evans N, Kluckow M. Diagnosis and treatment of low systemic blood flow in preterm infants. Neoreviews 2004; 5: e109-21.
13. Tapia-Rombo C, Carpio-Hernandez JC, Herminia Salazar-Acuna A, et al. Detection of transitory myocardial ischemia secondary to perinatal asphyxia. Arch Med Res 2000; 31: 377-83.
14. Bolli R, Jeroudi MO, Patel BS, et al. Direct evidence that oxygen-derived free radicals contribute to postischemic myocardial dysfunction in the intact dog. Proc Natl Acad Sci USA 1989; 86: 4695-9.
15. Brown JM, Terada LS, Grosso MA, et al. Hydrogen peroxide mediates reperfusion injury in the isolated rat heart. Mol Cell Biochem 1988; 84: 173-5.
16. Zweier JL, Kuppusamy P, Williams R, et al. Measurement and characterization of postischemic free radical generation in the isolated perfused heart. J Biol Chem 1989; 264: 18890-5.
17. Liu P, Hock CE, Nagele R, Wong PY. Formation of nitric oxide, superoxide and peroxynitrite in myocardial ischemia-reprfusion injury in rats. Am J Physiol 1997; 272: H2327-36.
18. Fernández-Checa JC, García-Ruiz C, Colell A, et al. Oxidative stress: role of mitochondria and protection by glutathione. Biofactors 1998; 8: 7-11.
19. Cornette L, Levene MI. Post resuscitative management of the asphyxiated term and preterm infant. Semin Neonatol 2001; 6: 271-82.
20. Wessel D. Managing low cardiac output syndrome after congenital heart surgery. Crit Care Med 2001; 29: S220-30.
21. Lister GT, Walter TK, Versmold HT, et al. Oxygen delivery in lambs: cardiovascular and hematologic development. Am J Physiol 1979; 237: H668-75.
22. Fisher DJ. Acidaemia reduces cardiac output and left ventricular contractility in conscious lambs. J Dev Physiol 1986; 8: 23-31.
23. Merante F, Mickel DA, Weisel RD, et al. Myocardial aerobic metabolism is impaired in a cell culture model of cyanotic heart disease. Am J Physiol 1998; 275: H1673-81.
24. Itskovitz J, La Gamma EF, Rudolph AM. The effect of reducing umbilical blood flow on fetal oxygenation. Am J Obstet Gynecol 1983; 145: 813-8.
25. Downing SE. Wall tension and myocardial dysfunction after ischemia and reperfusion. Am J Physiol 1993; 264: H386-93.
26. Finkel MS, Oddis CV, Jacob TD, et al. Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science 1992; 257: 387-9.
27. Vento M, Sastre J, Asensi MA, Viña J. Room-air resuscitation causes less damage to heart and kidney than 100% oxygen. Am J Respir Crit Care Med 2005; 172: 1393-8.
28. Lahaie I, Hardy P, Hou X, et al. A novel mechanism for vasoconstrictor action of 8-isoprostaglandin F2 alpha on retinal vessels. Am J Physiol 1998; 274: R1406-16.
29. Greenough A, Khetriwal B. Pulmonary hypertension in the newborn. Paediatr Respir Rev 2005; 6: 111-6.
30. Ranjit MS. Cardiac abnormalities in birth asphyxia. Indian J Pediatr 2000; 67: S26-9.
31. Greisen G. Autoregulation of cerebral blood flow in newborn babies. Ear Hum Dev 2005; 81: 423-8.
32. Tsuji M, Saul PJ, du Plessis Adre, et al. Cerebral intravascular oxygenation correlates with mean arterial pressure in critically ill premature infants. Pediatrics 2000; 106: 625-32.
33. Pryds O, Greisen G, Lou H, Fris-Hansen B. Vasoparalysis is associated with brain damage in asphyxiated term infants. J Pediatr 1990; 117: 119-25.
34. Fanaroff JM, Fanaroff AA. Blood pressure disorders in the neonate: hypotension and hypertension. Sem Fetal Neonatal Med 2006; 11: 174-81.
35. Bennet L, Booth L, Malpas SC, et al. Acute systemic complications in the preterm fetus after asphyxia: Role of cardiovascular and blood flow responses. Clin Exper Pharm Phys 2006; 33: 291-9.
36. Weindling AM, Kissack CM. Blood pressure and tissue oxygenation in the newborn baby at risk of brain damage. Biol Neonate 2001; 79: 241-5.
37. Mace TP, Azar GJ, Lee RD, et al. Effects of severe hypoxemia on mesenteric blood flow in neonatal piglets. J Surg Res 1998; 80: 287-94.
38. Touloukian RJ, Posch JN, Spencer R. The pathogenesis of ischemic gastroenterocolitis of the neonate: selective get mucosal ischemia in asphyxiated neonatal piglets. J Pediatr Surg 1972; 7: 194-205.
39. Alward CT, Hook JB, Helwrath TA, et al. Effects of asphyxia on cardiac output and organ blood flow in the newborn piglet. Pediatr Res 1978; 12: 824-7.
40. 2 uptake in newborn piglets. Pediatr Res 1986; 20: 929-32.
41. Haase E, Bigam DL, Nakonechny QB, et al. Resuscitation with 100% oxygen causes intenstinal glutathione oxidation and reoxygenation injury in asphyxiated newborn piglets. Ann Surg 2004; 240: 364-73.
42. Fisher DJ. Comparative effects of metabolic acidemia and hypoxemia on cardiac output and regional blood flows in unanesthetized newborn lambs. Pediatr Res 1986; 20: 756-60.
43. Kecskes Z, Healy G, Jensen A. Fluid restriction for term infants with hypoxic-ischaemic encephalopathy following perinatal asphyxia. Cochrane Database Syst Rev 2005; 20: CD004337.
44. Piazza AJ. Postasphyxial management of the newborn. Clin Perinatol 1999; 26: 749-65.
45. Lundstrom K, Pryds O, Greisen G. The haemodynamic effects of dopamine and volume expansion in sick preterm infants. Ear Hum Dev 2000; 57: 157-63.
46. Pladys P, Wodey E, Bétrémieux P, Beuchée A, Ecoffey C. Effects of volume expansion on cardiac output in the preterm infant. Acta Paediatr 1997; 86: 1241-5.
47. Kloner RA, Jennings RB. Consequences of brief ischemia: stunning, preconditioning and their clinical implications: part 1. Circulation 2001; 104: 2981-9.
48. Gerhardstein BL, Puri TS, Chien AJ, et al. Identification of the sites phosphorylated by cyclic AMP dependent protein kinase on the beta 2 subunit of L-type voltage dependent calcium channels. Biochemistry 1999; 38: 10361-70.
49. Seri I. Cardiovascular, renal, and endocrine actions of dopamine in neonates and children. J Pediatr 1995; 126: 333-44.
50. Seri I, Evans J. Controversies in the diagnosis and management of hypotension in the newborn infant. Curr Opin Pediatr 2001; 12: 116-23.
51. Chatterjee K, De Marco T. Role of nonglycoside inotropic agents: indications, ethics and limitations. Med Clin N Am 2003; 87: 391-418.
52. Subhedar NV. Treatment of hypotension in newborns. Semin Neonat 2003; 8: 413-23.
53. Taketomo CK, Hodding JH, Kraus DM. Lexi-Comp's Pediatric Dosage Handbook. Lexi-Comp. Hudson, Ohio, 2005, 12th ed. pp. 446-7.
54. Seri I, Rudas G, Bors Z, Kanyicksa B, Tulassay T. Effects of low dose dopamine infusions in cardiovascular and renal functions, cerebral blood flow and plasma catecholamine levels in sick preterm neonates. Pediatr Res 1993; 34: 742-9.
55. Dempsey EM, Barrington KJ. Treating hypotension in the preterm infant: when and with what: a critical and systematic review. J Perinatol 2007; 27: 469-78.
56. Engle WD, Leflore JL. Hypotension in the neonate. Neoreviews 2002; 3: e157-62.
57. Osborn DA. Diagnosis and treatment of preterm transitional circulatory compromise. Ear Hum Dev 2005; 81: 413-22.
58. Noori S, Freidlich P, Seri I. Developmentally regulated cardiovascular, renal and neuroendocrine effects of dopamine. Neoreviews 2003; 4: e283-8.
59. DiBona GF. Hemodynamic support: volume management and pharmacological cardiovascular support. Semin Nephrol 1994; 12: 33-40.
60. Seri I. Management of hypotension and low systemic blood flow in the very low birth weight neonate during the first postnatal week. J Perinatol 2006; 26(Suppl 1): S8-13.
61. Padbury J, Agata Y, Baylen B, et al. Dopamine pharmacokinetics in critically ill newborn infants. J Pediatr 1987; 110: 293-8.
62. DiSessa TG, Leitner M, Ti CC, et al. The cardiovascular effects of dopamine in the severely asphyxiated neonate. J Pediatr 1981; 99: 772-6.
63. Padbury JF, Agata Y, Baylen BG, et al. Pharmacokinetics of dopamine in critically ill newborn infants. J Pediatr 1990; 117: 472-6.
64. Walther FJ, Siassi B, Ramadan NA, Wu PYK. Cardiac output in newborn infants with transient myocardial dysfunction. J Pediatr 1985; 107: 781-5.
65. Barrington KJ, Finer NN, Chan W. A blind, randomized comparison of the circulatory effects of dopamine and epinephrine infusions in the newborn piglet during normoxia and hypoxia. Crit Care Med 1995; 23: 740-8.
66. O'Laughlin MP, Fisher DJ, Dreyer WJ, Smith EO. Augmentation of cardiac output with intravenous catecholamines in unanesthetized hypoxemic newborn lambs. Pediatr Res 1987; 22: 667-74.
67. Cheung PY, Barrington KJ. The effects of dopamine and epinephrine on hemodynamics and oxygen metabolism in hypoxic anesthetized piglets. Critical Care 2001; 5: 158-68.
68. Hunt R, Osborn D. Dopamine for prevention of morbidity and mortality in term newborn infants with suspected perinatal asphyxia. Cochrane Database Syst Rev 2002; 3: CD003484.
69. Ferrera JJ, Dyess DL, Peeples GL, et al. Effects of dopamine and dobutamine on regional blood flow distribution in the neonatal piglet. Ann Surg 1995; 221: 531-42.
70. Osborn DA, Kluckow M, Evans N. Randomized trial of dobutamine versus dopamine in preterm infants with low systemic blood flow. J Pediatr 2002; 140: 83-91.
71. Hentschel R, Hensel D, Brune T, Rabe H, Jorch G. Impact on blood pressure and intestinal perfusion of dobutamine or dopamine in hypotensive preterm infants. Biol Neonate1995; 68: 318-24.
72. Subhedar NV, Shaw NJ. Dopamine versus dobutamine for hypotensive preterm infants. Cochrane Database Syst Rev 2003; 3: CD001242.
73. Devictor D, Verlhac S, Pariente D, Huault G. Hemodynamic effects of dobutamine in asphyxiated newborn infants. Arch Fr Pediatr 1988; 45: 467-70.
74. Martinez AM, Padbury JF, Thio S. Dobutamine pharmacokinetics and cardiovascular responses in critically ill neonates. Pediatrics 1992; 89: 47-51.
75. Gebauer CM, Knuepfer M, Robel-Tillig E, et al. Hemodynamics among neonates with hypoxic-ischemic encephalopathy during whole-body hypothermia and passive rewarming. Pediatrics 2006; 117: 843-50.
76. Cheung PY, Barrington KJ, Bigam D. The hemodynamic effects of dobutamine infusion in the chronically instrumented newborn piglet. Crit Care Med 1999; 27: 558-64.
77. Penny DJ, Sano T, Smolich JJ. Increased systemic oxygen consumption offsets improved oxygen delivery during dobutamine infusion in newborn lambs. Intensive Care Med 2001; 27: 1518-25.
78. Al-Salam Z, Johnson S, Abozaid S, et al. The hemodynamic effects of dobutamine during reoxygenation after hypoxia: a dose-response study in newborn pigs. Shock 2007; 28: 317-25.
79. Phillipos EZ, Robertson MA. A randomized blinded trial of dopamine versus epinephrine for inotropic support in the sick newborn. Proceedings of 2nd World Congress of PCSS, pp. 897-98.
80. Seri I, Evans J. Addition of epinephrine to dopamine increases blood pressure and urine output in critically ill extremely low birth weight neonates with uncompensated shock. Pediatr Res 1998; 43: 194A.
81. Pellicer A, Valverde E, Elorza MD, et al. Cardiovascular support for low birth weight infants and cerebral hemodynamics: a randomized, blinded clinical trial. Pediatrics 2005; 115: 1501-12.
82. Valverde E, Pellicer A, Madero R, et al. Dopamine versus epinephrine for cardiovascular support in low birth weight infants: analysis of systemic effects and neonatal clinical outcomes. Pediatrics 2006; 117: 1213-22.
83. Paradisis M, Osborn DA. Adrenaline for the prevention of morbidity and mortality in preterm infants with cardiovascular compromise. Cochrane Database Syst Rev 2004; 1: CD003958.
84. Obaid L, Johnson ST, Emara M, Bigam DL, Cheung PY. Epinephrine versus dopamine to treat shock in hypoxic newborn pigs resuscitated with 100% oxygen: epinephrine versus dopamine in asphyxia. Shock 2008; 29: 262-8.
85. Cheung PY, Abozaid S, Al-Salam Z, et al. Systemic and regional hemodynamic effects of high-dose epinephrine infusion in hypoxic piglets resuscitated with 100% oxygen. Shock 2007; 28: 491-7.
86. Caspi J, Coles JG, Benson LN, et al. Age related response to epinephrine induced myocardial stress. A functional and ultrasound study. Circulation 1991; 84: III394-5.
87. Chang AC, Atz AM, Wernovsky G, Burke RP, Wessel DL. Milrinone: systemic and pulmonary hemodynamic effects in neonates after cardiac surgery. Crit Care Med 1995; 23: 1907-24.
88. Hoffman TM, Wernovsky G, Atz AM, et al. Efficacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease. Circulation 2003; 107: 996-1002.
89. Paradisis M, Evans N, Kluckow M, Osborn D, McLachlan AJ. Pilot study of milrinone for low systemic blood flow in very preterm infants. J Pediatr 2006; 148: 306-13.
90. Bassler D, Choong K, McNamara P, Kirpalani H. Neonatal persistent pulmonary hypertension treated with milrinone: four case reports. Biol Neonate 2006; 89: 1-5.
91. Danhaive O, Margossian R, Geva T, Kourembanas S. Pulmonary hypertension and right ventricular dysfunction in growth restricted, extremely low birth weight neonates. J Perinatol 2005; 25: 495-9.
92. McNamara PJ, Laique F, Muang-In S, Whyte HE. Milrinone improves oxygenation in neonates with severe persistent pulmonary hypertension of the newborn. J Crit Care 2006; 21: 217-22.
93. Parr GV, Blackstone EH, Kirklin JW. Cardiac performance and mortality early after intracardiac surgery in infants and young children. Circulation 1975; 51: 867-74.
94. Joynt CA, Bigam D, Charrois G, et al. Dose-response effects of milrinone on hemodynamics of newborn pigs with hypoxiareoxygenation. Intensive Care Med 2008; 34: 1321-9.
95. Figgitt DP, Gillies PS, Goa KL. Levosimendan Drugs 2001; 61: 613-27.
96. Michaelis AD, McKeown B, Kostal M, et al. Effects of intravenous levosimendan on human coronary vasomotor regulation. Left ventricular wall stress, and myocardial oxygen uptake. Circulation 2005; 111: 1504-9.
97. Follath F, Cleland JGF, Just H, et al. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe lowoutput heart failure (the LIDO study): A randomized double-blind trial. Lancet 2002; 360: 196-202.
98. Moiseyev VS, Poder P, Andrejevs N, et al. Safety and efficacy of a novel calcium sensitizer, levosimendan, in patients with left ventricular failure due to acute myocardial infarction. A randomized, placebo-controlled, double-blind study (RUSSLAN). Eur Heart J 2002; 23: 1422-32.
99. Lechner E, Moosbauer W, Pinter M, Mair R, Tulzer G. Use of levosimendan, a new inodilator, for postoperative myocardial stunning in a premature neonate. Pediatr Crit Care Med 2007; 8: 61-3.
100. Namachivayam P, Crossland DS, Butt WW, et al. Early experience with levosimendan in children with ventricular dysfunction. Pediatr Crit Care Med 2006; 7: 445-8.
101. Egan JR, Clarke AJ, Williams S, et al. Levosimendan for low cardiac output: a pediatric experience. J Intensive Care Med 2006; 21: 183-7.
102. Booker PD. Myocardial stunning in the neonate. Br J Anaesth 1998; 80: 371-83.
103. Fernandez E, Schrader R, Watterberg K. Prevalence of low cortisol values in term and near-term infants with vasopressor-resistant hypotension. J Perinatol 2005; 25: 114-8.
104. Chapados I, Chik C, Cheung PY. Higher cortisol response to adrenocorticotrophin (ACTH) stimulation in hypoxic newborn piglets resuscitated with 21% than 100% oxygen. (Abstract) E-PAS 2007: 617932.17.
105. Aucott SW. Hypotension in the newborn: who needs hydrocortisone? J Perinatol 2005; 25: 77-8.
106. Ng PC, Lee CH, Bnur FL, et al. A double-blind, randomized, controlled study of a "stress dose" of hydrocortisone for rescue treatment of refractory hypotension in preterm infants. Pediatrics 2006; 117: 367-75.
107. Sasidharan P. Role of corticosteroids in neonatal blood pressure homeostasis. Clin Perinatol 1998; 25: 723-40.
108. Stark AR, Carlo WA, Tyson JE, et al. Adverse effects of early dexamethasone in extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med 2001; 344: 95-101.
109. Yeh TF, Lin YJ, Huang CC, et al. Early dexamethasone therapy in preterm infants: a follow-up study. Pediatrics 1998; 101: E7.
110. Kluckow M, Evans N. Low superior vena cava flow and intraventricular haemorrhage in preterm infants. Arch Dis Child Fetal Neonatal Ed 2000; 82: F188-94.
111. Kluckow M, Evans N. Relationship between blood pressure and cardiac output in preterm infants requiring mechanical ventilation. J Pediatr 1996; 129: 506-12.
112. Osborn DA, Kluckow M, Evans N. Blood pressure, capillary refill and central peripheral temperature difference. Clinical detection of low upper body flow in very premature infants. Arch Dis Child 2004; 89: F168-73.
113. Noone MA, Sellwood M, Meek JH, Wyatt JS. Postnatal adaptation of cerebral blood flow using near infrared spectroscopy in extremely preterm infants undergoing high frequency oscillatory ventilation. Acta Pediatr 2003; 92: 1079-84.
114. Quaedackers JS, Roelfsema V, Heineman E, et al. The role of the sympathetic nervous system in post-asphyxial intestinal hypoperfusion in the preterm sheep fetus. J Physiol 2004; 557: 1033-44.
115. Kluckow M, Evans N. Superior vena cava flow in newborn infants: a novel marker of systemic blood flow. Arch Dis Child Fetal Neonatal Ed 2000; 82: F182-7.
116. Hunt RW, Evans N, Reiger I, et al. Low superior vena cava flow and neurodevelopment at 3 years in very preterm infants. J Pediatr 2004; 145: 588-92.
117. Groves AM, Kuschel CA, Knight DB, Skinner JR. Echocardiographic assessment of blood flow volume in the superior vena cava and descending aorta on the newborn infant. Arch Dis Child Fetal Neonatal Ed 2008; 93: F24-8.
118. Seri I. Inotrope, lusitrope and pressor used in neonates. J Perinatol 2005; 25: S28-30.
119. Osborn DA, Paradisis M, Evans N. The effect of inotropes on morbidity and mortality in preterm infants with low systemic or organ blood flow. Cochrane Database Syst Rev 2007; 24(1): CD005090.