Acute Renal Failure and Sepsis
http://www.100md.com
《新英格兰医药杂志》
To the Editor: We are concerned that Schrier and Wang's review of septic acute renal failure (July 8 issue)1 overlooks some important data. Norepinephrine does not result in afferent arteriolar vasoconstriction when given by continuous intravenous infusion at clinically relevant doses. It actually increases the global renal blood flow, with little or no vasoconstriction,2,3 and in large-animal models of hyperdynamic sepsis, it also increases medullary renal blood flow.3 In a randomized, controlled study of hyperdynamic sepsis, norepinephrine markedly increased urinary output, as compared with dopamine,4 thus challenging the idea that norepinephrine "may contribute to and prolong the course of acute renal failure," as stated by the authors.
The demonstration of global renal vasoconstriction in sepsis depends on the model used. We recently showed that there is renal vasodilatation, not vasoconstriction, in hyperdynamic sepsis.5 Whether the glomerular filtration rate in clinical studies or animal models of septic acute renal failure decreases because of afferent arteriolar vasoconstriction, efferent arteriolar vasodilatation, or both remains unknown.
Rinaldo Bellomo, M.D.
Austin Hospital
Melbourne 3084, Australia
rinaldo.bellomo@austin.org.au
Clive May, Ph.D.
Florey Institute
Melbourne 3084, Australia
Li Wan, M.D.
Austin Hospital
Melbourne 3084, Australia
References
Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med 2004;351:159-169.
Anderson WP, Korner PI, Selig SE. Mechanisms involved in the renal responses to intravenous and renal artery infusions of noradrenaline in conscious dogs. J Physiol 1981;321:21-30.
Di Giantomasso D, Morimatsu H, May CN, Bellomo R. Intrarenal blood flow distribution in hyperdynamic septic shock: effect of norepinephrine. Crit Care Med 2003;31:2509-2513.
Martin C, Papazian L, Perrin G, Saux P, Gouin F. Norepinephrine or dopamine for the treatment of hyperdynamic septic shock? Chest 1993;103:1826-1831.
Di Giantomasso D, May C, Bellomo R. Vital organ blood flow during hyperdynamic sepsis. Chest 2003;124:1053-1059.
To the Editor: Schrier and Wang use the term "pseudo–acute respiratory distress syndrome," but arguably, there is potential harm from the use of this label. Indeed, the existence of this diagnosis as a distinct entity is dubious.1,2 Aggressive yet measured volume administration is often indicated in distributive shock states such as sepsis,1 and lung compliance may vary widely in acute lung injury, independently of the volume administered. In addition, the authors' suggestion that vasopressin may precipitate the clinical scenario described is debatable, because there is evidence that vasopressin may not affect fluid balance in the lung at doses that increase systemic vascular resistance.3 Adequately resuscitated patients with sepsis in whom there is early, definitive control of infection will usually have an attenuation of vascular permeability as a prelude to recovery. The determination of when a patient has reached this point and requires a change in the fluid prescription that may include restriction and diuresis is key to successful management and warrants emphasis. New terminology seems unnecessary when a description such as "indiscriminate fluid administration" may be applied.
(The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.)
William L. Jackson, Jr., M.D.
Walter Reed Army Medical Center
Washington, DC 20307
william.jackson1@na.amedd.army.mil
References
Jackson WL Jr. Management of acute renal failure. Ann Intern Med 2003;139:529-530.
Stefanec T. Management of acute renal failure. Ann Intern Med 2003;139:530-530.
Gest AL, Moise AA, Hansen TN, Kaplan S. Effects of arginine vasopressin on hemodynamics and lung fluid balance in lambs. Am J Physiol 1989;256:H641-H647.
To the Editor: In their review of acute renal failure and sepsis, Schrier and Wang postulate that arginine vasopressin may have a protective effect on kidney function in patients with sepsis, secondary to its ability to constrict the efferent arteriole. However, this hypothesis remains unsubstantiated, and there is evidence that significant vasoconstriction due to arginine vasopressin is found only in the interlobular and arcuate arteries, not in the glomerular afferent and efferent arterioles.1 Schrier and Wang also implicate the nonosmotic release of arginine vasopressin in the pathogenesis of acute renal failure, only to discuss later its possible renoprotective effect.
The authors implicate angiotensin II as well. Arima has recently shown that angiotensin II causes more significant vasoconstriction in the efferent arterioles than in the afferent arterioles.2 This may suggest a nephroprotective effect of angiotensin II that is similar to the one postulated for vasopressin, in keeping with evidence of the short-term deterioration of renal function secondary to treatment with angiotensin-converting–enzyme inhibitors in certain groups of patients.3
Gustavo A. Heresi, M.D.
University of Miami School of Medicine
Miami, FL 33101
gheresi@med.miami.edu
References
Cavarape A, Bauer J, Bartoli E, Endlich K, Parekh N. Effects of angiotensin II, arginine vasopressin and thromboxane A2 in renal vascular bed: role of rho-kinase. Nephrol Dial Transplant 2003;18:1764-1769.
Arima S. Role of angiotensin II and endogenous vasodilators in the control of glomerular hemodynamics. Clin Exp Nephrol 2003;7:172-8.
Suki WN. Renal hemodynamic consequences of angiotensin-converting enzyme inhibition in congestive heart failure. Arch Intern Med 1989;149:669-673.
To the Editor: Schrier and Wang present a useful review of sepsis and acute renal failure, but I call attention to three omissions. First, I am sure the authors would agree that a search for the cause of the sepsis, followed by its treatment, is important. This is not mentioned. Second, generalized arterial vasodilatation is central to their septic-shock thesis. However, they fail to indicate how this is determined clinically, with other causes of hypotension ruled out. Third, contrary to what is implied in their review, the mechanism of septic vasodilatation is not well understood and is more complex than a simple induction of nitric oxide synthase.1 This question requires much more study, and the authors should say so.
Francis J. Haddy, M.D., Ph.D.
211 Second St. NW
Rochester, MN 55901-2896
References
Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med 2001;345:588-595.
The authors reply: In a patient with sepsis who has undergone fluid resuscitation, neither measurements of central venous pressure nor measurements of pulmonary-capillary wedge pressure provide an index of interstitial fluid volume in the vasodilated state. If the patient has undergone aggressive resuscitation, the accumulated positive fluid balance frequently ranges between 10 and 15 liters. In a 70-kg man, the extracellular fluid volume is approximately 14 liters; thus, a 100 percent expansion of interstitial fluid volume may have occurred. Early in the course of sepsis, a patient with pulmonary edema and hypoxemia who is receiving ventilatory support in the presence of a large accumulated positive fluid balance frequently has normal lung compliance. We have termed this situation the pseudo–acute respiratory distress syndrome. Although histologic evidence is not available to confirm the absence of the pulmonary-capillary damage and stiff lungs of the acute respiratory distress syndrome, early ultrafiltration with fluid removal can decrease oxygen requirements, permitting earlier removal of ventilatory support. This is important, because the longer the duration of ventilatory support, the higher the mortality among patients with sepsis and acute renal failure and the more likely it is that these patients will have progression to the true acute respiratory distress syndrome.
Vasopressin is a potent constrictor of veins, decreasing splanchnic compliance. Splanchnic venous compliance was not measured in the study cited by Jackson, in which vasopressin was infused into the hind limb of a lamb.1 Vasopressin increases the glomerular filtration rate in patients with cirrhosis, suggesting a vasoconstrictor effect on the glomerular efferent arteriole. We included vasopressin in Figure 1 of our article to indicate the antidiuretic effect of the hormone and the resultant water retention during sepsis.
The systemic effect of norepinephrine in sepsis leads to a positive cardiac inotropic effect and increases systemic vascular resistance. The resultant increase in renal perfusion pressure can lead to a pressure-related diuresis and an increase in renal blood flow, particularly in an already vasoconstricted kidney. The early (six-hour) increase in renal blood flow after the administration of an Escherichia coli bolus in sheep is interesting.2 However, to our knowledge there is no known model of established acute renal failure that involves only glomerular efferent arteriolar dilatation in the absence of afferent arteriolar constriction.
Hypotension in septic shock involves a decrease in systemic vascular resistance and a cardiac output that is less than predicted, given a substantial decrease in cardiac afterload. Although the potent vasodilatation of nitric oxide is important in the arterial vasodilatation of sepsis, other factors are undoubtedly involved.
Robert W. Schrier, M.D.
Wei Wang, M.D.
University of Colorado Health Sciences Center
Denver, CO 80262
robert.schrier@uchsc.edu
References
Gest AL, Moise AA, Hansen TN, Kaplan S. Effects of arginine vasopressin on hemodynamics and lung fluid balance in lambs. Am J Physiol 1989;256:H641-H647.
Di Giantomasso D, May CN, Bellomo R. Vital organ blood flow during hyperdynamic sepsis. Chest 2003;124:1053-1059.
The demonstration of global renal vasoconstriction in sepsis depends on the model used. We recently showed that there is renal vasodilatation, not vasoconstriction, in hyperdynamic sepsis.5 Whether the glomerular filtration rate in clinical studies or animal models of septic acute renal failure decreases because of afferent arteriolar vasoconstriction, efferent arteriolar vasodilatation, or both remains unknown.
Rinaldo Bellomo, M.D.
Austin Hospital
Melbourne 3084, Australia
rinaldo.bellomo@austin.org.au
Clive May, Ph.D.
Florey Institute
Melbourne 3084, Australia
Li Wan, M.D.
Austin Hospital
Melbourne 3084, Australia
References
Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med 2004;351:159-169.
Anderson WP, Korner PI, Selig SE. Mechanisms involved in the renal responses to intravenous and renal artery infusions of noradrenaline in conscious dogs. J Physiol 1981;321:21-30.
Di Giantomasso D, Morimatsu H, May CN, Bellomo R. Intrarenal blood flow distribution in hyperdynamic septic shock: effect of norepinephrine. Crit Care Med 2003;31:2509-2513.
Martin C, Papazian L, Perrin G, Saux P, Gouin F. Norepinephrine or dopamine for the treatment of hyperdynamic septic shock? Chest 1993;103:1826-1831.
Di Giantomasso D, May C, Bellomo R. Vital organ blood flow during hyperdynamic sepsis. Chest 2003;124:1053-1059.
To the Editor: Schrier and Wang use the term "pseudo–acute respiratory distress syndrome," but arguably, there is potential harm from the use of this label. Indeed, the existence of this diagnosis as a distinct entity is dubious.1,2 Aggressive yet measured volume administration is often indicated in distributive shock states such as sepsis,1 and lung compliance may vary widely in acute lung injury, independently of the volume administered. In addition, the authors' suggestion that vasopressin may precipitate the clinical scenario described is debatable, because there is evidence that vasopressin may not affect fluid balance in the lung at doses that increase systemic vascular resistance.3 Adequately resuscitated patients with sepsis in whom there is early, definitive control of infection will usually have an attenuation of vascular permeability as a prelude to recovery. The determination of when a patient has reached this point and requires a change in the fluid prescription that may include restriction and diuresis is key to successful management and warrants emphasis. New terminology seems unnecessary when a description such as "indiscriminate fluid administration" may be applied.
(The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.)
William L. Jackson, Jr., M.D.
Walter Reed Army Medical Center
Washington, DC 20307
william.jackson1@na.amedd.army.mil
References
Jackson WL Jr. Management of acute renal failure. Ann Intern Med 2003;139:529-530.
Stefanec T. Management of acute renal failure. Ann Intern Med 2003;139:530-530.
Gest AL, Moise AA, Hansen TN, Kaplan S. Effects of arginine vasopressin on hemodynamics and lung fluid balance in lambs. Am J Physiol 1989;256:H641-H647.
To the Editor: In their review of acute renal failure and sepsis, Schrier and Wang postulate that arginine vasopressin may have a protective effect on kidney function in patients with sepsis, secondary to its ability to constrict the efferent arteriole. However, this hypothesis remains unsubstantiated, and there is evidence that significant vasoconstriction due to arginine vasopressin is found only in the interlobular and arcuate arteries, not in the glomerular afferent and efferent arterioles.1 Schrier and Wang also implicate the nonosmotic release of arginine vasopressin in the pathogenesis of acute renal failure, only to discuss later its possible renoprotective effect.
The authors implicate angiotensin II as well. Arima has recently shown that angiotensin II causes more significant vasoconstriction in the efferent arterioles than in the afferent arterioles.2 This may suggest a nephroprotective effect of angiotensin II that is similar to the one postulated for vasopressin, in keeping with evidence of the short-term deterioration of renal function secondary to treatment with angiotensin-converting–enzyme inhibitors in certain groups of patients.3
Gustavo A. Heresi, M.D.
University of Miami School of Medicine
Miami, FL 33101
gheresi@med.miami.edu
References
Cavarape A, Bauer J, Bartoli E, Endlich K, Parekh N. Effects of angiotensin II, arginine vasopressin and thromboxane A2 in renal vascular bed: role of rho-kinase. Nephrol Dial Transplant 2003;18:1764-1769.
Arima S. Role of angiotensin II and endogenous vasodilators in the control of glomerular hemodynamics. Clin Exp Nephrol 2003;7:172-8.
Suki WN. Renal hemodynamic consequences of angiotensin-converting enzyme inhibition in congestive heart failure. Arch Intern Med 1989;149:669-673.
To the Editor: Schrier and Wang present a useful review of sepsis and acute renal failure, but I call attention to three omissions. First, I am sure the authors would agree that a search for the cause of the sepsis, followed by its treatment, is important. This is not mentioned. Second, generalized arterial vasodilatation is central to their septic-shock thesis. However, they fail to indicate how this is determined clinically, with other causes of hypotension ruled out. Third, contrary to what is implied in their review, the mechanism of septic vasodilatation is not well understood and is more complex than a simple induction of nitric oxide synthase.1 This question requires much more study, and the authors should say so.
Francis J. Haddy, M.D., Ph.D.
211 Second St. NW
Rochester, MN 55901-2896
References
Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med 2001;345:588-595.
The authors reply: In a patient with sepsis who has undergone fluid resuscitation, neither measurements of central venous pressure nor measurements of pulmonary-capillary wedge pressure provide an index of interstitial fluid volume in the vasodilated state. If the patient has undergone aggressive resuscitation, the accumulated positive fluid balance frequently ranges between 10 and 15 liters. In a 70-kg man, the extracellular fluid volume is approximately 14 liters; thus, a 100 percent expansion of interstitial fluid volume may have occurred. Early in the course of sepsis, a patient with pulmonary edema and hypoxemia who is receiving ventilatory support in the presence of a large accumulated positive fluid balance frequently has normal lung compliance. We have termed this situation the pseudo–acute respiratory distress syndrome. Although histologic evidence is not available to confirm the absence of the pulmonary-capillary damage and stiff lungs of the acute respiratory distress syndrome, early ultrafiltration with fluid removal can decrease oxygen requirements, permitting earlier removal of ventilatory support. This is important, because the longer the duration of ventilatory support, the higher the mortality among patients with sepsis and acute renal failure and the more likely it is that these patients will have progression to the true acute respiratory distress syndrome.
Vasopressin is a potent constrictor of veins, decreasing splanchnic compliance. Splanchnic venous compliance was not measured in the study cited by Jackson, in which vasopressin was infused into the hind limb of a lamb.1 Vasopressin increases the glomerular filtration rate in patients with cirrhosis, suggesting a vasoconstrictor effect on the glomerular efferent arteriole. We included vasopressin in Figure 1 of our article to indicate the antidiuretic effect of the hormone and the resultant water retention during sepsis.
The systemic effect of norepinephrine in sepsis leads to a positive cardiac inotropic effect and increases systemic vascular resistance. The resultant increase in renal perfusion pressure can lead to a pressure-related diuresis and an increase in renal blood flow, particularly in an already vasoconstricted kidney. The early (six-hour) increase in renal blood flow after the administration of an Escherichia coli bolus in sheep is interesting.2 However, to our knowledge there is no known model of established acute renal failure that involves only glomerular efferent arteriolar dilatation in the absence of afferent arteriolar constriction.
Hypotension in septic shock involves a decrease in systemic vascular resistance and a cardiac output that is less than predicted, given a substantial decrease in cardiac afterload. Although the potent vasodilatation of nitric oxide is important in the arterial vasodilatation of sepsis, other factors are undoubtedly involved.
Robert W. Schrier, M.D.
Wei Wang, M.D.
University of Colorado Health Sciences Center
Denver, CO 80262
robert.schrier@uchsc.edu
References
Gest AL, Moise AA, Hansen TN, Kaplan S. Effects of arginine vasopressin on hemodynamics and lung fluid balance in lambs. Am J Physiol 1989;256:H641-H647.
Di Giantomasso D, May CN, Bellomo R. Vital organ blood flow during hyperdynamic sepsis. Chest 2003;124:1053-1059.