Beneficial Effects of Vasopressin Compared With Norepinephrine on Renal Perfusion, Oxygenation, and Function in Experimental Septic Acute Kidney Injury

Nobuki Okazaki, Naoya Iguchi, Roger G Evans, Sally G Hood, Rinaldo Bellomo, Clive N May, Yugeesh R Lankadeva, Nobuki Okazaki, Naoya Iguchi, Roger G Evans, Sally G Hood, Rinaldo Bellomo, Clive N May, Yugeesh R Lankadeva

Abstract

Objectives: To compare the effects of restoring mean arterial pressure with vasopressin or norepinephrine on systemic hemodynamics, renal blood flow, intrarenal perfusion and oxygenation, and renal function in ovine septic acute kidney injury.

Design: Interventional Study.

Setting: Research Institute.

Subjects: Adult Merino ewes.

Interventions: Flow probes were implanted on the pulmonary and renal arteries (and the mesenteric artery in sheep that received vasopressin). Fiber-optic probes were implanted in the renal cortex and medulla to measure tissue perfusion and oxygen tension (PO2). Conscious sheep were administered Escherichia coli to induce septic acute kidney injury. Vasopressin (0.03 IU/min [0.03-0.05 IU/min]; n = 7) or norepinephrine (0.60 μg/kg/min [0.30-0.70 μg/kg/min]; n = 7) was infused IV and titrated to restore baseline mean arterial pressure during 24-30 hours of sepsis.

Measurements and main results: Ovine septic acute kidney injury was characterized by reduced mean arterial pressure (-16% ± 2%) and creatinine clearance (-65% ± 9%) and increased renal blood flow (+34% ± 7%) but reduced renal medullary perfusion (-44% ± 7%) and PO2 (-47% ± 10%). Vasopressin infusion did not significantly affect renal medullary perfusion or PO2 and induced a sustained (6 hr) ~2.5-fold increase in creatinine clearance. Vasopressin reduced sepsis-induced mesenteric hyperemia (+61 ± 13 to +9% ± 6%). Norepinephrine transiently (2 hr) improved creatinine clearance (by ~3.5-fold) but worsened renal medullary ischemia (to -64% ± 7%) and hypoxia (to -71% ± 6%).

Conclusions: In ovine septic acute kidney injury, restoration of mean arterial pressure with vasopressin induced a more sustained improvement in renal function than norepinephrine, without exacerbating renal medullary ischemia and hypoxia or reducing mesenteric blood flow below baseline values.

References

    1. Bagshaw SM, George C, Bellomo R; ANZICS Database Management Committee: Early acute kidney injury and sepsis: A multicentre evaluation. Crit Care 2008; 12:R47
    1. Bagshaw SM, Uchino S, Bellomo R, et al.; Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators: Septic acute kidney injury in critically ill patients: Clinical characteristics and outcomes. Clin J Am Soc Nephrol 2007; 2:431–439
    1. Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 2017; 43:304–377
    1. Russell JA, Walley KR, Singer J, et al.; VASST Investigators: Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 2008; 358:877–887
    1. Gordon AC, Russell JA, Walley KR, et al. The effects of vasopressin on acute kidney injury in septic shock. Intensive Care Med 2010; 36:83–91
    1. Gordon AC, Mason AJ, Thirunavukkarasu N, et al.; VANISH Investigators: Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: The VANISH randomized clinical trial. JAMA 2016; 316:509–518
    1. Bellomo R, Kellum JA, Ronco C, et al. Acute kidney injury in sepsis. Intensive Care Med 2017; 43:816–828
    1. Ma S, Evans RG, Iguchi N, et al. Sepsis-induced acute kidney injury: A disease of the microcirculation. Microcirculation 2019; 26:e12483
    1. Kellum JA, Prowle JR. Paradigms of acute kidney injury in the intensive care setting. Nat Rev Nephrol 2018; 14:217–230
    1. Evans RG, Ince C, Joles JA, et al. Haemodynamic influences on kidney oxygenation: Clinical implications of integrative physiology. Clin Exp Pharmacol Physiol 2013; 40:106–122
    1. Lankadeva YR, Okazaki N, Evans RG, et al. Renal medullary hypoxia: A new therapeutic target for septic acute kidney injury? Semin Nephrol 2019; 39:543–553
    1. Calzavacca P, Evans RG, Bailey M, et al. Cortical and medullary tissue perfusion and oxygenation in experimental septic acute kidney injury. Crit Care Med 2015; 43:e431–e439
    1. Lankadeva YR, Kosaka J, Evans RG, et al. Urinary oxygenation as a surrogate measure of medullary oxygenation during angiotensin ii therapy in septic acute kidney injury. Crit Care Med 2018; 46:e41–e48
    1. Lankadeva YR, Kosaka J, Evans RG, et al. Intrarenal and urinary oxygenation during norepinephrine resuscitation in ovine septic acute kidney injury. Kidney Int 2016; 90:100–108
    1. Lankadeva YR, Ma S, Iguchi N, et al. Dexmedetomidine reduces norepinephrine requirements and preserves renal oxygenation and function in ovine septic acute kidney injury. Kidney Int 2019; 96:1150–1161
    1. Di Giantomasso D, May CN, Bellomo R. Norepinephrine and vital organ blood flow during experimental hyperdynamic sepsis. Intensive Care Med 2003; 29:1774–1781
    1. Di Giantomasso D, Morimatsu H, Bellomo R, et al. Effect of low-dose vasopressin infusion on vital organ blood flow in the conscious normal and septic sheep. Anaesth Intensive Care 2006; 34:427–433
    1. Lankadeva YR, Kosaka J, Evans RG, et al. An ovine model for studying the pathophysiology of septic acute kidney injury. Methods Mol Biol 2018; 1717:207–218
    1. Lankadeva YR, Kosaka J, Iguchi N, et al. Effects of fluid bolus therapy on renal perfusion, oxygenation, and function in early experimental septic kidney injury. Crit Care Med 2019; 47:e36–e43
    1. Calzavacca P, Evans RG, Bailey M, et al. Long-term measurement of renal cortical and medullary tissue oxygenation and perfusion in unanesthetized sheep. Am J Physiol Regul Integr Comp Physiol 2015; 308:R832–R839
    1. Langenberg C, Wan L, Egi M, et al. Renal blood flow in experimental septic acute renal failure. Kidney Int 2006; 69:1996–2002
    1. Hajjar LA, Vincent JL, Barbosa Gomes Galas FR, et al. Vasopressin versus norepinephrine in patients with vasoplegic shock after cardiac surgery: The VANCS randomized controlled trial. Anesthesiology 2017; 126:85–93
    1. Hajjar LA, Zambolim C, Belletti A, et al. Vasopressin versus norepinephrine for the management of septic shock in cancer patients: The VANCS II randomized clinical trial. Crit Care Med 2019; 47:1743–1750
    1. Evans RG, Gardiner BS, Smith DW, et al. Intrarenal oxygenation: Unique challenges and the biophysical basis of homeostasis. Am J Physiol Renal Physiol 2008; 295:F1259–F1270
    1. Edwards RM, Trizna W, Kinter LB. Renal microvascular effects of vasopressin and vasopressin antagonists. Am J Physiol 1989; 256:F274–F278
    1. Nedel WL, Rech TH, Ribeiro RA, et al. Renal outcomes of vasopressin and its analogs in distributive shock: A systematic review and meta-analysis of randomized trials. Crit Care Med 2019; 47:e44–e51
    1. Asfar P, Meziani F, Hamel J-F, et al. High versus low blood pressure target in patients with septic shock. N Eng J Med 2014;370:1583–1593
    1. Undesser KP, Hasser EM, Haywood JR, et al. Interactions of vasopressin with the area postrema in arterial baroreflex function in conscious rabbits. Circ Res 1985; 56:410–417
    1. Russell JA. Bench-to-bedside review: Vasopressin in the management of septic shock. Crit Care 2011; 15:226
    1. Kidney Disease Improving Global Outcomes: A KDIGO clinical practice guideline for acute kidney injury. Kidney Int 2012; 2(Suppl 2):1–138
    1. Iguchi N, Kosaka J, Booth LC, et al. Renal perfusion, oxygenation, and sympathetic nerve activity during volatile or intravenous general anaesthesia in sheep. Br J Anaesth 2019; 122:342–349
    1. Lankadeva YR, Cochrane AD, Marino B, et al. Strategies that improve renal medullary oxygenation during experimental cardiopulmonary bypass may mitigate postoperative acute kidney injury. Kidney Int 2019; 95:1338–1346

Source: PubMed

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