The effects of norepinephrine on hemodynamics and renal function in severe septic shock states

Redl-Wenzl, E. M.; Armbruster, Christine; Edelmann, G; Fischl, E.; Kolacny, M.; Wechsler-Fördös, Agnes; Sporn, P.

doi:10.1007/bf01720530

Cited by 191 publications

(69 citation statements)

References 23 publications

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“…The renal effects of NE are surprising because this drug usually improves diuresis without changing renal function in human septic shock and in other experimental designs (22). Despite an increase in perfusion pressure, NE did not change diuresis in the present model, suggesting that the effect on renal vascular resistances was more pronounced than on systemic resistances.…”

Section: Effects Of Drug Treatment On Diuresis and Renal Functioncontrasting

confidence: 53%

Comparative effects of vasopressin, norepinephrine, and l-canavanine, a selective inhibitor of inducible nitric oxide synthase, in endotoxic shock

Lévy

Vallée²,

Lauzier³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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. Comparative effects of vasopressin, norepinephrine, and L-canavanine, a selective inhibitor of inducible nitric oxide synthase, in endotoxic shock. Am J Physiol Heart Circ Physiol 287: H209 -H215, 2004. First published February 26, 2004 10.1152/ajpheart.00946.2003, a standard of care, AVP, an alternative candidate, and L-canavanine (LC), a selective inhibitor of inducible nitric oxide synthase, were compared for efficacy and innocuousness on global and regional hemodynamics, plasmatic and tissue lactate-to-pyruvate ratio (L/P), tissue high-energy phosphates, renal function, and tissue capillary permeability in a rat model of endotoxic normokinetic shock. Mean arterial pressure (MAP) decreased (ϳ35%) but aortic blood flow increased during endotoxin infusion (P Ͻ 0.05 vs. control). Additionally, there was a decrease in mesenteric (MBF) and renal (RBF) blood flows along with regional-to-systemic ratio (P Ͻ 0.05 vs. control). All tested drugs restored MAP to basal levels but slightly decreased abdominal aortic flow; however, RBF and MBF remained unchanged. Endotoxin significantly decreased diuresis and inulin clearance (ϳ3-to 4-fold), whereas AVP or LC attenuated this drop (P Ͻ 0.05 vs. control). In contrast, NE did not improve endotoxininduced renal dysfunction. Endotoxin induced gut and lung hyperpermeability (P Ͻ 0.05 vs. control). Endotoxin-induced gut hyperpermeability was inhibited by AVP, LC, and NE. Endotoxin-induced lung hyperpermeability was further worsened by NE (ϳ2-fold increase) but not AVP infusion (P Ͻ 0.05 vs. endotoxin). LC significantly improved endotoxin-induced pulmonary hyperpermeability. Endotoxin increased renal lactate and decreased renal ATP. NE did not change renal lactate or renal ATP. AVP and LC decreased renal lactate and normalized renal ATP. Finally, endotoxin was associated with increased lactate levels and L/P (ϳ2-and 1.5-fold increases vs. control, respectively), whereas AVP and LC, but not NE, normalized both parameters after endotoxin challenge. These results suggest that, in a short-term endotoxic shock model, AVP improves systemic hemodynamics without side effects and has particular beneficial effects on renal function. septic shock; vascular permeability; renal function THE HUMAN RESPONSE to septic challenge usually includes increased cardiac output, decreased peripheral resistance, low arterial pressure, and increased vascular permeability. AVP, also known as "the" antidiuretic hormone (ADH), is an emerging alternative candidate for management of redistributive shock (7). Indeed, AVP exhibits strong vasoconstrictor effects through stimulation of the V1 receptor leading to arterial pressure improvement (28). Moreover, low concentrations of exogenous AVP mediate vasodilatation in coronary, cerebral, and pulmonary arterial circulation (20). The recognized effects of AVP on renal function are complex and include association of an antidiuretic effect through stimulation of V2 receptors, an increase of diuresis/natriuresis through V1 receptors by efferent arteriolar vasoconstric...

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Section: Effects Of Drug Treatment On Diuresis and Renal Functioncontrasting

confidence: 53%

Comparative effects of vasopressin, norepinephrine, and l-canavanine, a selective inhibitor of inducible nitric oxide synthase, in endotoxic shock

Lévy

Vallée²,

Lauzier³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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“…The majority of the studies also find a significant increase in urinary output that may result from an increased GFR but also from pressure diuresis. An increase in GFR is only observed in three uncontrolled studies [56,62,64]. The only prospective randomized trial compares the effect of NE with high-dose dopamine.…”

Section: Clinical Studiesmentioning

confidence: 99%

Vasopressors and the Kidney

Schetz¹

2002

Blood Purif

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The changes in renal perfusion induced by vasopressors depend on their effects on systemic hemodynamics and renal vascular resistance. Both effects are largely influenced by the patient’s underlying condition such as myocardial contractility and vascular responsiveness. A beneficial effect can be expected if mean arterial pressure increases without decreasing cardiac output and if the effect on renal vascular resistance is less pronounced than on systemic vascular resistance. Acute renal failure is associated with loss of renal autoregulation and sepsis is associated with blood pressures below the autoregulatory threshold. Both conditions might therefore benefit from the administration of vasopressors. Many experimental and clinical data indeed suggest a beneficial effect of norepinephrine on the urine output in sepsis. A beneficial effect on renal function (glomerular filtration) is a less consistent finding suggesting that pressure diuresis might be partially responsible for the pressor-induced diuresis. Administration of vasopressors to patients with oliguria should be considered in fluid-resuscitated patients with distributive shock. Whether other vasopressors offer advantages over norepinephrine requires further investigation.

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“…These interventions can be separated into measures designed to improve kidney perfusion and/or glomerular function or to modulate intrarenal pathophysiology. In sepsis-associated AKI, small and uncontrolled studies have shown that vasopressors can improve glomerular filtration (10,11). Renal-dose ("lowdose") dopamine, once widely used, is ineffective in improving kidney function in AKI, with the possible exception of increasing diuresis on the first day of use (12,13).…”

Section: Initial Consideration: Pharmacologic Interventions For Earlymentioning

confidence: 99%

Evaluation and Initial Management of Acute Kidney Injury

Himmelfarb

Joannidis²,

Molitoris

et al. 2008

Clinical Journal of the American Society of Nephrology

126

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The evaluation and initial management of patients with acute kidney injury (AKI) should include: (1) an assessment of the contributing causes of the kidney injury, (2) an assessment of the clinical course including comorbidities, (3) a careful assessment of volume status, and (4) the institution of appropriate therapeutic measures designed to reverse or prevent worsening of functional or structural kidney abnormalities. The initial assessment of patients with AKI classically includes the differentiation between prerenal, renal, and postrenal causes. The differentiation between so-called "prerenal" and "renal" causes is more difficult, especially because renal hypoperfusion may coexist with any stage of AKI. Using a modified Delphi approach, the multidisciplinary international working group, generated a set of testable research questions. Key questions included the following: Is there a difference in prognosis between volume-responsive and volume-unresponsive AKI? Are there biomarkers whose patterns (dynamic changes) predict the severity and recovery of AKI (maximal stage of AKI, need for RRT, renal recovery, mortality) and guide therapy? What is the best biomarker to assess prospectively whether AKI is volume responsive? What is the best biomarker to assess the optimal volume status in AKI patients? In evaluating the current literature and ongoing studies, it was thought that the answers to the questions posed herein would improve the understanding of AKI, and ultimately patient outcomes.

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The effects of norepinephrine on hemodynamics and renal function in severe septic shock states

Abstract: Our results suggest that norepinephrine can be used safely in the treatment of severe septic shock states. Mean arterial pressure and glomerular filtration rate improved markedly without deleterious effects on CI, O2AVI and VO2I.

Cited by 191 publications

References 23 publications

Comparative effects of vasopressin, norepinephrine, and l-canavanine, a selective inhibitor of inducible nitric oxide synthase, in endotoxic shock

Comparative effects of vasopressin, norepinephrine, and l-canavanine, a selective inhibitor of inducible nitric oxide synthase, in endotoxic shock

Vasopressors and the Kidney

Evaluation and Initial Management of Acute Kidney Injury

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