Advertisement

Neonatal Hypotension: What Is the Efficacy of Each Anti-Hypotensive Intervention? A Systematic Review

  • Felipe Y. Matsushita
  • Vera L. J. Krebs
  • Werther B. de CarvalhoEmail author
Pediatrics in South America (L Landry and WB de Carvalho, Section Editors)
  • 7 Downloads
Part of the following topical collections:
  1. Topical Collection on Pediatrics in South America

Abstract

Purpose of review

There is no consensus in the treatment of hemodynamic instability in the preterm newborn. Blood pressure is one of the few measurable objective parameters for hemodynamic evaluation in this population. However, little is known about the efficacy of anti-hypotensive treatments in newborns. The objective of this review is to identify and analyze the efficacy of a given anti-hypotensive intervention in improving the hypotensive preterm newborn.

Recent findings

With the increase in survival of the preterm newborns, there was an augmentation in the interest for the treatment of hypotension in this population. However, as there are doubts regarding the efficacy in anti-hypotensive treatment, new drugs are being used to reverse the hypotensive state in preterm infants: epinephrine, norepinephrine, vasopressin, and steroids.

Summary

We have identified that classically used medications in the treatment of hypotension have little evidence of efficacy in rescuing the preterm infant from the hypotensive state. New therapies are emerging with potential benefits, especially in refractory hypotension such as epinephrine and norepinephrine, but more prospective studies are needed. Literature review should be careful, considering the definition used for hypotension, the time of onset, the intravascular volume status of each patient, and if the drug was used as a first or second line of treatment.

Keywords

Hypotension Premature Inotrope Volume resuscitation 

Notes

Compliance with Ethical Standards

Conflict of Interest

Felipe Y. Matsushita, Vera L. J. Krebs, and Werther B. de Carvalho declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Noori S, Seri I. Evidence-based versus pathophysiology-based approach to diagnosis and treatment of neonatal cardiovascular compromise. Semin Fetal Neonatal Med. 2015;20:238–45.CrossRefGoogle Scholar
  2. 2.
    Ancel PY, Goffinet F, Kuhn P, Langer B, Matis J, Hernandorena X, et al. Survival and morbidity of preterm children born at 22 through 34 weeks’ gestation in France in 2011 results of the EPIPAGE-2 cohort study. JAMA Pediatr. 2015;169:230–8.CrossRefGoogle Scholar
  3. 3.
    Davis AL, Carcillo JA, Aneja RK, et al. The American College of Critical Care Medicine Clinical Practice Parameters for hemodynamic support of pediatric and neonatal septic shock: Executive Summary. Pediatr Crit Care Med; 2017.  https://doi.org/10.1097/PCC.0000000000001259.
  4. 4.
    Dempsey EM, Al Hazzani F, Barrington KJ. Permissive hypotension in the extremely low birthweight infant with signs of good perfusion. Arch Dis Child Fetal Neonatal Ed. 2009;94:F241–4.CrossRefGoogle Scholar
  5. 5.
    Dempsey E, Barrington K. Treating hypotension in the preterm infant: when and with what: a critical and systematic review. J Perinatol. 2007;27:469–78.CrossRefGoogle Scholar
  6. 6.
    Joynt C, Cheung P-Y. Treating hypotension in preterm neonates with vasoactive medications. Front Pediatr. 2018;6:1–8.CrossRefGoogle Scholar
  7. 7.
    Stranak Z, Semberova J, Barrington K, et al. International survey on diagnosis and management of hypotension in extremely preterm babies. Eur J Pediatr. 2014;173:793–8.CrossRefGoogle Scholar
  8. 8.
    Development of audit measures and guidelines for good practice in the management of neonatal respiratory distress syndrome. Report of a Joint Working group of the British association of Perinatal Medicine and the Research Unit of the Royal College of Phys. Arch Dis Child. 1992;67:1221–7.Google Scholar
  9. 9.
    Faust K, Härtel C, Preuß M, Rabe H, Roll C, Emeis M, et al. Short-term outcome of very-low-birthweight infants with arterial hypotension in the first 24 h of life. Arch Dis Child Fetal Neonatal Ed. 2015;100:F388–92.CrossRefGoogle Scholar
  10. 10.
    • St Peter D, Gandy C, Hoffman SB. Hypotension and adverse outcomes in prematurity: comparing definitions. Neonatology. 2017;111:228–33 This study suggests that hypotension, defined either by MAP less than GA by gestational age or MAP <30 mmHg, is not a risk factor related to an adverse outcome.CrossRefGoogle Scholar
  11. 11.
    Watkins AMC, West CR, Cooke RWI. Blood pressure and cerebral haemorrhage and ischaemia in very low birthweight infants. Early Hum Dev. 1989;19:103–10.CrossRefGoogle Scholar
  12. 12.
    Zubrow AB, Hulman S, Kushner H, Falkner B. Determinants of blood pressure in infants admitted to neonatal intensive care units: a prospective multicenter study. Philadelphia Neonatal Blood Pressure Study Group. J Perinatol. 1994;15:470–9.Google Scholar
  13. 13.
    Weindling AM. Blood pressure monitoring in the newborn. Arch Dis Child. 1989;64:444–7.CrossRefGoogle Scholar
  14. 14.
    Miall-Allen VM, De Vries LS, Whitelaw AG. Mean arterial blood pressure and neonatal cerebral lesions. Arch Dis Child. 1987;62:1068–9.CrossRefGoogle Scholar
  15. 15.
    Munro MJ, Walker AM, Barfield CP. Hypotensive extremely low birth weight infants have reduced cerebral blood flow. Pediatrics. 2004;114:1591–6.CrossRefGoogle Scholar
  16. 16.
    Dempsey EM. What should we do about low blood pressure in preterm infants. Neonatology. 2017;111:402–7.CrossRefGoogle Scholar
  17. 17.
    Limperopoulos C, Bassan H, Kalish LA, Ringer SA, Eichenwald EC, Walter G, et al. Current definitions of hypotension do not predict abnormal cranial ultrasound findings in preterm infants. Pediatrics. 2007;120:966–77.CrossRefGoogle Scholar
  18. 18.
    El-Khuffash A, McNamara PJ. Hemodynamic assessment and monitoring of premature infants. Clin Perinatol. 2017;44:377–93.CrossRefGoogle Scholar
  19. 19.
    •• Durrmeyer X, Marchand-Martin L, Porcher R, Gascoin G, Roze JC, Storme L, et al. Abstention or intervention for isolated hypotension in the first 3 days of life in extremely preterm infants: association with short-term outcomes in the EPIPAGE 2 cohort study. Arch Dis Child Fetal Neonatal Ed. 2017;102:490–7 This study suggests that the treatment of hypotension in the first 3 days of life is associated with higher survival rate without severe morbidities and a lower risk of severe brain damage, in contrast to the strategy of permissive hypotension.CrossRefGoogle Scholar
  20. 20.
    Batton B, Zhu X, Fanaroff J, Kirchner HL, Berlin S, Wilson-Costello D, et al. Blood pressure, anti-hypotensive therapy, and neurodevelopment in extremely preterm infants. J Pediatr. 2009;154:351–8.CrossRefGoogle Scholar
  21. 21.
    Batton B, Batton D, Riggs T. Blood pressure during the first 7 days in premature infants born at postmenstrual age 23 to 25 weeks. Am J Perinatol. 2007;24:107–15.CrossRefGoogle Scholar
  22. 22.
    Batton B, Li L, Newman NS, Das A, Watterberg KL, Yoder BA, et al. Use of antihypotensive therapies in extremely preterm infants. Pediatrics. 2013;131:e1865–73.CrossRefGoogle Scholar
  23. 23.
    Gill AB, Weindling AM. Randomised controlled trial of plasma protein fraction versus dopamine in hypotensive very low birthweight infants. Arch Dis Child. 1993;69:284–7.CrossRefGoogle Scholar
  24. 24.
    Rozé JC, Tohier C, C M, Lefèvre M, Mouzard A. Response to dobutamine and dopamine in the hypotensive very preterm infant. Arch Dis Child. 1993;69:59–63.CrossRefGoogle Scholar
  25. 25.
    Greenough A, F EE (1993) Randomized trial comparing dopamine and dobutamine in preterm infants. Eur J Pediatr 152:925–927.Google Scholar
  26. 26.
    Klarr JM, Faix RG, Pryce CJ, Bhatt-Mehta V. Randomized, blind trial of dopamine versus dobutamine for treatment of hypotension in preterm infants with respiratory distress syndrome. J Pediatr. 1994;125:117–22.CrossRefGoogle Scholar
  27. 27.
    Hentschel R, Hensel D, Brune T, Rabe H, Jorch G. Impact on blood pressure and intestinal pertusion of dobutamine or dopamine in hypotensive preterm infants. Neonatology. 1995;68:318–24.CrossRefGoogle Scholar
  28. 28.
    Bourchier D, Weston PJ. Randomised trial of dopamine compared with hydrocortisone for the treatment of hypotensive very low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 1997;76:174–8.CrossRefGoogle Scholar
  29. 29.
    Pellicer A, Valverde E, Elorza MD, Madero R, Gaya F, Quero J, et al. Cardiovascular support for low birth weight infants and cerebral hemodynamics: a randomized, blinded, clinical trial. Pediatrics. 2005;115:1501–12.CrossRefGoogle Scholar
  30. 30.
    Valverde E. Dopamine versus epinephrine for cardiovascular support in low birth weight infants: analysis of systemic effects and neonatal clinical outcomes. Pediatrics. 2006;117:e1213–22.CrossRefGoogle Scholar
  31. 31.
    Lightburn MH, Gauss CH, Williams DK, Kaiser JR. Observational study of cerebral hemodynamics during dopamine treatment in hypotensive ELBW infants on the first day of life. J Perinatol. 2013;33:698–702.CrossRefGoogle Scholar
  32. 32.
    Catenacci M, Miyagi S, Wickremasinghe AC, Lucas SS, De Alba Campomanes AG, Good WV, et al. Dopamine-resistant hypotension and severe retinopathy of prematurity. J Pediatr. 2013;163:400–5.CrossRefGoogle Scholar
  33. 33.
    Rios DR, Kaiser JR. Vasopressin versus dopamine for treatment of hypotension in extremely low birth weight infants: a randomized, blinded pilot study. J Pediatr. 2015;166:850–5.CrossRefGoogle Scholar
  34. 34.
    So KW, Fok TF, Ng PC, Wong WW, Cheung KL. Randomised controlled trial of colloid or crystalloid in hypotensive preterm infants. Arch Dis Child Fetal Neonatal Ed. 1997;76:F43–6.CrossRefGoogle Scholar
  35. 35.
    Heckmann M, Trotter A, Pohlandt F, Lindner W. Epinephrine treatment of hypotension in very low birthweight infants. Acta Paediatr. 2007;91:566–70.CrossRefGoogle Scholar
  36. 36.
    • Rowcliff K, de Waal K, Mohamed AL, Chaudhari T. Noradrenaline in preterm infants with cardiovascular compromise. Eur J Pediatr. 2016;175:1967–73 This retrospective study suggests that noradrenaline appears to be effective in removing preterm infants from the hypotensive state, and appears to be well tolerated without major side effects.CrossRefGoogle Scholar
  37. 37.
    • Rizk MY, Lapointe A, Lefebvre F, Barrington KJ. Norepinephrine infusion improves haemodynamics in the preterm infants during septic shock. Acta Paediatr Int J Paediatr. 2018;107:408–13 This study shows that in preterm infants with septic shock, norepinephrine was successful in increasing blood pressure and improving urine output, without respiratory worsening.CrossRefGoogle Scholar
  38. 38.
    Ikegami H, Funato M, Tamai H, Wada H, Nabetani M, Nishihara M. Low-dose vasopressin infusion therapy for refractory hypotension in ELBW infants. Pediatr Int. 2010;52:368–73.CrossRefGoogle Scholar
  39. 39.
    Gaissmaier RE, Pohlandt F Ingle-dose dexamethasone treatment of hypotension.Google Scholar
  40. 40.
    Ng PC. 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.CrossRefGoogle Scholar
  41. 41.
    Mizobuchi M, Yoshimoto S, Nakao H. Time-course effect of a single dose of hydrocortisone for refractory hypotension in preterm infants. Pediatr Int. 2011;53:881–6.CrossRefGoogle Scholar
  42. 42.
    Osborn DA, Evans NJ. Early volume expansion for prevention of morbidity and mortality in very preterm infants. Cochrane Database Syst Rev. 2004.  https://doi.org/10.1002/14651858.CD002055.pub2.
  43. 43.
    •• Saini SS, Kumar P, Kumar RM. Hemodynamic changes in preterm neonates with septic shock. Pediatr Crit Care Med. 2014;15:443–50 This study demonstrate that preterm newborns with septic shock have an increased cardiac output with a normal ejection fraction. This suggests that the cause of the shock is more related to a vasoplegia.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Felipe Y. Matsushita
    • 1
  • Vera L. J. Krebs
    • 1
  • Werther B. de Carvalho
    • 1
    Email author
  1. 1.Department of Pediatrics, Neonatology Division, Faculty of Medicine of the University of São PauloInstituto da CriançaSão PauloBrazil

Personalised recommendations