Indian Journal of Critical Care Medicine

Register      Login



Volume / Issue

Online First

Related articles

VOLUME 20 , ISSUE 10 ( 2016 ) > List of Articles


Early norepinephrine decreases fluid and ventilatory requirements in pediatric vasodilatory septic shock

Niranjan Kissoon, Suchitra Ranjit, Rajeswari Natraj, Sathish Kandath, Paul Marik

Keywords : Critical illness, fluid infusion, morbidity, mortality, norepinephrine, pediatrics, sepsis, septic shock, vasodilatory, venous return

Citation Information : Kissoon N, Ranjit S, Natraj R, Kandath S, Marik P. Early norepinephrine decreases fluid and ventilatory requirements in pediatric vasodilatory septic shock. Indian J Crit Care Med 2016; 20 (10):561-569.

DOI: 10.4103/0972-5229.192036

License: CC BY-ND 3.0

Published Online: 01-09-2017

Copyright Statement:  Copyright © 2016; The Author(s).


Aims: We previously reported that vasodilatation was common in pediatric septic shock, regardless of whether they were warm or cold, providing a rationale for early norepinephrine (NE) to increase venous return (VR) and arterial tone. Our primary aim was to evaluate the effect of smaller fluid bolus plus early-NE versus the American College of Critical Care Medicine (ACCM) approach to more liberal fluid boluses and vasoactive-inotropic agents on fluid balance, shock resolution, ventilator support and mortality in children with septic shock. Secondly, the impact of early NE on hemodynamic parameters, urine output and lactate levels was assessed using multimodality-monitoring. Methods: In keeping with the primary aim, the early NE group (N-27) received NE after 30ml/kg fluid, while the ACCM group (N-41) were a historical cohort managed as per the ACCM Guidelines, where after 40-60ml/kg fluid, patients received first line vasoactive-inotropic agents. The effect of early-NE was characterized by measuring stroke volume variation(SVV), systemic vascular resistance index (SVRI) and cardiac function before and after NE, which were monitored using ECHO + Ultrasound-Cardiac-Output-Monitor (USCOM) and lactates. Results: The 6-hr fluid requirement in the early-NE group (88.9+31.3 to 37.4+15.1ml/kg), and ventilated days [median 4 days (IQR 2.5-5.25) to 1day (IQR 1-1.7)] were significantly less as compared to the ACCM group. However, shock resolution and mortality rates were similar. In the early NE group, the overall SVRI was low (mean 679.7dynes/sec/cm5/m2, SD 204.5), and SVV decreased from 23.8±8.2 to 18.5±9.7, p=0.005 with NE infusion suggesting improved preload even without further fluid loading. Furthermore, lactate levels decreased and urine-output improved. Conclusion: Early-NE and fluid restriction may be of benefit in resolving shock with less fluid and ventilator support as compared to the ACCM approach.

PDF Share
  1. Ranjit S, Aram G, Kissoon N, Ali MK, Natraj R, Shresti S, et al. Multimodal monitoring for hemodynamic categorization and management of pediatric septic shock: A pilot observational study. Pediatr Crit Care Med 2014;15:e17-26.
  2. Ranjit S, Kissoon N. Bedside echocardiography is useful in assessing children with fluid and inotrope resistant septic shock. Indian J Crit Care Med 2013;17:224-30.
  3. Funk DJ, Jacobsohn E, Kumar A. The role of venous return in critical illness and shock-Part I: Physiology. Crit Care Med 2013;41:255-62.
  4. Funk DJ, Jacobsohn E, Kumar A. Role of the venous return in critical illness and shock: Part II-shock and mechanical ventilation. Crit Care Med 2013;41:573-9.
  5. Foland FA, Fortenberry JD, Warshaw BL, Naipaul A, Jefferson LS, Loftis LL. Fluid overload before continuous hemofiltration and survival in critically ill children; a retrospective analysis. Crit Care Med 2004;32:1771-6.
  6. Sinitsky L, Walls D, Nadel S, Inwald DP. Fluid overload at 48 hours is associated with respiratory morbidity but not mortality in a general PICU: Retrospective cohort study. Pediatr Crit Care Med 2015;16:205-9.
  7. Arikan AA, Zappitelli M, Goldstein SL, Naipaul A, Jefferson LS, Loftis LL. Fluid overload is associated with impaired oxygenation and morbidity in critically ill children. Pediatr Crit Care Med 2012;13:253-8.
  8. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013;39:165-228.
  9. Maas JJ, Geerts BF, van den Berg PC, Pinsky MR, Jansen JR. Assessment of venous return curve and mean systemic filling pressure in postoperative cardiac surgery patients. Crit Care Med 2009;37:912-8.
  10. Monnet X, Jabot J, Maizel J, Richard C, Teboul JL. Norepinephrine increases cardiac preload and reduces preload dependency assessed by passive leg raising in septic shock patients. Crit Care Med 2011;39:689-94.
  11. Persichini R, Silva S, Teboul JL, Jozwiak M, Chemla D, Richard C, et al. Effects of norepinephrine on mean systemic pressure and venous return in human septic shock. Crit Care Med 2012;40:3146-53.
  12. Hamzaoui O, Georger JF, Monnet X, Ksouri H, Maizel J, Richard C, et al. Early administration of norepinephrine increases cardiac preload and cardiac output in septic patients with life-threatening hypotension. Crit Care 2010;14:R142.
  13. Brierley J, Carcillo JA, Choong K, Cornell T, Decaen A, Deymann A, et al. Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine. Crit Care Med 2009;37:666-88.
  14. Dey I, Sprivulis P. Emergency physicians can reliably assess emergency department patient cardiac output using the USCOM continuous wave Doppler cardiac output monitor. Emerg Med Australas 2005;17:193-9.
  15. The USCOM and Haemodynamics. Available from: [Last accessed on 2016 Feb 13].
  16. Marik PE, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest 2008;134:172-8.
  17. Marik PE, Lemson J. Fluid responsiveness: An evolution of our understanding. Br J Anaesth 2014;112:617-20.
  18. Vergnaud E, Vidal C, Verchère J, Miatello J, Meyer P, Carli P, et al. Stroke volume variation and indexed stroke volume measured using bioreactance predict fluid responsiveness in postoperative children. Br J Anaesth 2015;114:103-9.
  19. Smith BE, Madigan VM. Non-invasive method for rapid bedside estimation of inotropy: Theory and preliminary clinical validation. Br J Anaesth 2013;111:580-8.
  20. Brierley J, Peters MJ. Distinct hemodynamic patterns of septic shock at presentation to pediatric intensive care. Pediatrics 2008;122:752-9.
  21. Tibby SM, Hatherill M, Marsh MJ, Murdoch IA. Clinicians′ abilities to estimate cardiac index in ventilated children and infants. Arch Dis Child 1997;77:516-8.
  22. Hunter JD, Doddi M. Sepsis and the heart. Br J Anaesth 2010;104:3-11.
  23. Merx MW, Weber C. Sepsis and the heart. Circulation 2007;116:793-802.
  24. Kumar A, Haery C, Parrillo JE. Myocardial dysfunction in septic shock: Part I. Clinical manifestation of cardiovascular dysfunction. J Cardiothorac Vasc Anesth 2001;15:364-76.
  25. Rabuel C, Mebazaa A. Septic shock: A heart story since the 1960s. Intensive Care Med 2006;32:799-807.
  26. Vieillard-Baron A. Septic cardiomyopathy. Ann Intensive Care 2011;1:6.
  27. Khilnani P, Singhi S, Lodha R, Santhanam I, Sachdev A, Chugh K, et al. Pediatric sepsis guidelines: Summary for resource-limited countries. Indian J Crit Care Med 2010;14:41-52.
  28. De Backer D, Aldecoa C, Njimi H, Vincent JL. Dopamine versus norepinephrine in the treatment of septic shock: A meta-analysis. Crit Care Med 2012;40:725-30.
  29. Ventura AM, Shieh HH, Bousso A, Góes PF, Fernandes I, de Souza DC, et al. Double-blind prospective randomized controlled trial of dopamine versus epinephrine as first-line vasoactive drugs in pediatric septic shock. Crit Care Med 2015;43:2292-302.
  30. Choong K, Bohn D, Fraser DD, Gaboury I, Hutchison JS, Joffe AR, et al. Vasopressin in pediatric vasodilatory shock: A multicenter randomized controlled trial. Am J Respir Crit Care Med 2009;180:632-9.
  31. Redl-Wenzl EM, Armbruster C, Edelmann G, Fischl E, Kolacny M, Wechsler-Fördös A, et al. The effects of norepinephrine on hemodynamics and renal function in severe septic shock states. Intensive Care Med 1993;19:151-4.
  32. Bellomo R, Wan L, May C. Vasoactive drugs and acute kidney injury. Crit Care Med 2008;36 4 Suppl:S179-86.
  33. Santhanam I, Sangareddi S, Venkataraman S, Kissoon N, Thiruvengadamudayan V, Kasthuri RK. A prospective randomized controlled study of two fluid regimens in the initial management of septic shock in the emergency department. Pediatr Emerg Care 2008;24:647-55.
  34. Beale R. Echoes of the past? Crit Care Med 2008;36:1950-1.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.