Editorial

Norepinephrine and the kidneys after cardiopulmonary resuscitation: what is the fuzz all about?

Joseph Varon MD ^a,b,c,?, Pilar Acosta MD ^b

^aThe University of Texas Health Science Center, Houston, TX 77030, USA ^bThe University of Texas Medical Branch, Galveston, TX 77555, USA ^cDorrington Medical Associates, Houston, TX 77030, USA

Received 21 March 2010; accepted 23 March 2010

Norepinepinephrine (NE) is a naturally occurring potent vasopressor and inotrope that is commonly used in Acute care medicine [1]. It is an ?_1,2-?_1,2 adrenergic agonist, with a marked ?₁-sympathomimetic and ?₁-sympathomimetic activi- ty. This agent has been used in cardiopulmonary arrest events and in the immediate postarrest period [2]. The basic rationale of using vasopressors, such as NE, in the context of a cardiac arrest is an attempt to restore the threshold levels of coronary perfusion pressure and myocardial blood flow [3]. Contro- versy exists, however, regarding the use of NE in victims of sudden cardiac death with return of spontaneous circulation (ROSC), specially during the postresuscitation care [4].

Some animal models have shown that the addition of adrenergic agents, such as epinephrine and NE, during cardiac arrest decreases blood flow to the kidneys during cardiopulmonary resuscitation [4,5]. Some of these models have also shown that this effect persists even after ROSC is achieved [5]. Despite the proven fact that high plasma NE levels are found in Canine model of cardiac arrest after successful ROSC, suggesting the protective value of this adrenergic agent in cardiac arrest situations, the use of this agent in this context is limited [6]. Many clinicians are concerned of the potential vasoconstrictive effects of NE on

* Corresponding author. The University of Texas Health Science Center at Houston, Dorrington Medical Associates, The University of Texas Medical Branch at Galveston, 2219 Dorrington Street, Houston, Texas 77030, USA. Tel.: +1 713 669 1670; fax: +1 713 669 1671.

E-mail addresses: [email protected], [email protected] (J. Varon).

the kidney with the resulting renal dysfunction in the postresuscitation period.

Norepinepinephrine has been proven useful, however, in many other settings such as in severe sepsis and septic shock [7]. Norepinepinephrine is recommended by most sepsis guidelines as the drug of choice for the treatment of hypotension, as in these patients; this increases both the renal blood flow and urine output [7-9]. Norepinepinephrine has demonstrated to increase the expression of cycloox- ygenase 2 in the kidney, with the subsequent production of cyclooxygenase 2-derived prostaglandins (PGE₂, PGI₂). By inducing PGE₂ and PGI₂, the alleged renal vasoconstriction induced by NE is blunted [10].

In this issue of The American Journal of Emergency Medicine, Li and coworkers [11], in a swine cardiac arrest model, analyze the effects of NE on the metabolic status, hemodynamics, and renal function of survivors of cardiac arrest. These investigators divided the survivors of cardiac arrest with ROSC in 2 groups to maintain either the prearrest mean arterial pressure (MAP) values or to have a MAP of 130% of the prearrest value by adjusting the dose of NE. These “high” NE and “low” NE groups revealed very interesting physiologic and histologic features. For example, the study reveals that increasing MAP via high-dose NE helps maintain adequate hemodynamic status, thus reflecting a preserved renal function. These authors confirmed that the renal results not only metabolically and physiologically but also by means of histology.

Contrary to clinical misconceptions, this study helps us better understand the “protective effect” of NE to the kidney,

0735-6757/$ - see front matter (C) 2011 doi:10.1016/j.ajem.2010.03.028

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by maintaining hemodynamic stability through high-dose NE. It is interesting that adequate Blood supply to the kidney, assessed by normal mitochondrial function in the glomerular and epithelial cells, was also reflected on laboratory parameters in this study.

Despite the limitations of this animal study, these results are promising and optimistic. Further randomized, controlled trials in humans are warranted to further extend the recommendation of using NE in cardiopulmonary resuscita- tion and the postresuscitation period.

References

1. Paradis NA, Wenzel V, Southall J, et al. Pressor drugs in the treatment of cardiac arrest. Cardiol Clin 2002;20:61-78.
2. ECC Committee, Subcommittees and Task Forces of the American Heart Association. 2005 American heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2005;112:IV1-IV203.
3. Pellis T, Weil MH, Tang W, Sun S, Xie J, Song L, et al. Evidence favoring the use of ?₂-selective vasopressor agent for cardiopulmonary resuscitation. Circulation 2003;108:2716-21.
4. Voelckel WG, Lurie KG, McKnite S, et al. Effects of epinephrine and vasopressin in a piglet model of Prolonged ventricular fibrillation and cardiopulmonary resuscitation. Crit Care Med 2002;30(5):957-62.
5. Cronin RA, Erickson M, De Torrente A, et al. Norepinephrine induced acute renal failure. Kidney Int 1978;14:187-90.
6. Huyghens LP, Calle PA, Moerman EJ, Buylaert WA, Bogaert MG. Plasma norepinephrine concentrations during resuscitation in the dog. Am J Emerg Med 1991;9:426-31.
7. Marik P, Varon J. The hemodynamic derangements in sepsis: resuscitate the gut and not the body? Chest 1998;114(3):854-60.
8. Albanese J, Leone M, Garnier F, et al. Renal effects of norepinephrine in septic and non-septic patients. Chest 2004;126:534-9.
9. Marik P, Varon J. Sepsis: state-of-the-art. Dis Month 2001;42:462-532.
10. Llinas MT, Lopez R, Rodriguez F, et al. Role of COX2 derived metabolites in regulation of renal Hemodynamic response to norepinephrine. Am J Physiol 2001;281:F975-82.
11. Li C, Su Z, Lu Y, et al. Effects of norepinephrine on kidney in a swine model of cardiopulmonary resuscitation. Am J Emerg Med 2010 (in press).