- Email: [email protected]
Pro: Vasopressin is the vasoconstrictor of choice after cardiopulmonary bypass
PRO AND CON Paul G. Barash, MD Section Editor
Pro: Vasopressin Is the Vasoconstrictor of Choice After Cardiopulmonary Bypass John V. Booth, MB, ChB, FRCA, David Schinderle, MD, and Ian J. Welsby, MB, BS
H
OMEOSTASIS IS the process whereby physiologic balance is preserved by neurohormonal feedback mechanisms. Cardiac surgery requiring cardiopulmonary bypass (CPB) activates a variety of neurohormonal, metabolic, and immunologic processes within the body that disrupt normal physiology and are balanced by processes designed to bring physiology back into balance. Maintenance of systemic blood pressure and perfusion in organ systems is one of the endpoints of homeostasis. The vasodilatory shock state sometimes seen after CPB is often a result of an imbalance in that homeostatic mechanism, and this imbalance is an inability to increase arginine vasopressin (AVP) levels in response to stress. AVP therapy restores homeostasis, resulting in sufficient organ perfusion without deleterious effects. AVP therapy becomes the logical first-line treatment to restore adequate mean arterial pressure in vasodilatory shock after CPB. PATHOPHYSIOLOGY OF VASODILATION AFTER CARDIOPULMONARY BYPASS
CPB results in the activation of a complex system of neurohormonal, endocrine, and immunologic mediators, the balance of which is designed to create homeostasis in a system under stress. When the system is in balance, blood pressure and essential organ perfusion are preserved without compromising at-risk organs, such as the gastrointestinal tract or kidney. When imbalance occurs during CPB, it often results in systemic vasoconstriction that sometimes requires vasodilator therapy because of temporary elevations in epinephrine, norepinephrine, serotonin, and AVP.1 CPB has been shown to cause 6-fold increased circulating AVP levels 12 hours after surgery.2 Sometimes, imbalance results in a relative deficiency of AVP, however, occasionally resulting in diabetes insipidus.3,4 Clinically, this syndrome has been described as a vasodilatory state that is often poorly responsive to phenylephrine but responsive to octreotide and angiotensin II.5,6 Argenziano et al showed that the incidence of vasodilatory shock in the early post-CPB period is 8% to 10% and is significantly more common in patients with low ejection fraction and patients who used angiotensin-converting enzyme (ACE) inhibitors.6 Patients with post-CPB vasodilatory shock had AVP levels in the normal range for resting adults (5 to 15 pg/mL), but inappropriately low levels for the degree of arterial hypotension. AVP levels during and after CPB are usually ⬎35 pg/mL and often ⬎100 pg/mL. The cause of poor AVP response to CPB is unknown, but hyponatremia and activated
atrial stretch receptors are known to blunt AVP responses. Patients in heart failure with elevated atrial filling pressures and resultant increased atrial natriuretic peptide levels could be partly responsible for poor AVP responsiveness.7 Another potential cause of AVP hyporesponsiveness is autonomic dysfunction, a process also known to occur in patients with heart failure.8 PHYSIOLOGY OF VASOPRESSIN
AVP is also known as antidiuretic hormone and is essential for cardiovascular homeostasis. That AVP is essential for survival is attested by its teleologic persistence. The oxytocinAVP protein superfamily is found in vertebrates and invertebrates with conserved sequences. The gene encoding AVP predates the divergence of vertebrates and invertebrates that occurred about 700 million years ago.9 AVP is a nonapeptide synthesized in the hypothalamus. After synthesis, the protein migrates to the posterior pituitary so that it can be readily released. Only 10% to 20% of the total AVP pool can be readily released. When this amount is discharged into the circulation, AVP continues to be secreted in response to appropriate stimuli but at a greatly reduced rate, resulting in a biphasic response of AVP release.9 AVP release is stimulated by osmotic and nonosmotic factors. Osmotic factors include hyperosmolality, detected at central and peripheral osmoreceptors whereby small increases in plasma osmolality are quickly sensed; this results in AVP release and increased urine osmolality. Nonosmotic stimuli include hypovolemia, such as hypotension and decreased intravascular volume, and hormonal regulation with acetylcholine, histamine, dopamine, prostaglandins, angiotensin II, and catecholamines.9 AVP acts on AVP receptors (VRs) and oxytocin receptors (OTRs). VRs are G protein– coupled receptors of the 7-trans-
From the Division of Cardiothoracic Anesthesia and Critical Care, Department of Anesthesiology, Duke University Medical Center, Durham, NC. Address reprint requests to John V. Booth, MB, ChB, FRCA, Division of Cardiothoracic Anesthesia and Critical Care, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710. E-mail: [email protected] Copyright 2002, Elsevier Science (USA). All rights reserved. 1053-0770/02/1606-0020$35.00/0 doi:10.1053/jcan.2002.128432 Key words: Vasopressin, cardiopulmonary bypass, shock
Journal of Cardiothoracic and Vascular Anesthesia, Vol 16, No 6 (December), 2002: pp 773-775
773
774
BOOTH ET AL
Table 1. Comparison of Vasopressin and Norepinephrine Vasoconstriction
Vasopressin Norepinephrine
Coronary
Cerebral
Pulmonary
Mesenteric
CO
GFR
Cr Cl
⫹ ⫹⫹⫹
⫹/⫺ ⫹⫹⫹
⫺ ⫹⫹
⫺ ⫹⫹⫹
1 or 2 1 or 2
1 2
1 2
NOTE. Vasopressin is at doses ⬍0.1 U/min, the dose commonly used during vasodilatory shock. Abbreviations: CO, cardiac output; GFR, glomerular filtration rate; Cr Cl, creatinine clearance.
membrane domain superfamily and can be subdivided into V1Rs, V2Rs, and V3Rs.10 V1 vascular receptors (V1Rs) are located on vascular smooth muscle and mediate vasoconstriction. Additional receptors are located in the kidney, myometrium, liver, and platelets. V1Rs signal through phospholipase C and cause release of intracellular calcium. V2Rs mediate the antidiuretic effects of AVP and are located in the renal collecting duct system and endothelial cells and mediate effects through adenylyl cyclase activation. V3Rs are pituitary receptors responsible for central regulation and adrenocorticotropic hormone release. OTRs also are activated by AVP and are found in pulmonary artery endothelial cells, aorta, and uterus and mammary glands. AVP-induced OTR activation mediates a calcium-dependent vasodilatory response via the nitric oxide pathway. An important physiologic role of AVP is in the preservation of perfusion during periods of hypotension. AVP has little effect on blood pressure under normal conditions and at normal concentrations but helps maintain arterial blood pressure via V1Rs during hypovolemia, a mechanism similar to catecholamines.11 AVP differs from catecholamines in several respects, however. AVP is a potent vasoconstrictor in skin, skeletal muscle, fat, pancreas, and thyroid gland. In contrast to norepinephrine, AVP causes less vasoconstriction in the coronary and cerebral circulations (Table 1).12 In addition, AVP does not cause mesenteric or pulmonary vasoconstriction in vitro.13 AVP also enhances the sensitivity of vascular smooth muscle to other vasoconstrictive agents and blocks potassium-sensitive adenosine triphosphate (ATP) channels in a dose-dependent manner. This action may be partly responsible for restoring vascular tone in the post-CPB vasodilatory state. Another difference between catecholamine pressor agents and AVP is that AVP may cause vasodilation in selected organs. The receptor subtype involved in this action is uncertain, but the effect varies among different vascular beds in the same organ, such that arteries of the circle of Willis are more sensitive than other intracranial or extracranial arteries. This effect is endothelium dependent and likely mediated via nitric oxide. Specifically, this effect is seen in the pulmonary vasculature, where pulmonary vasodilation is the predominant effect until high concentrations of AVP are achieved, an effect mediated via V1Rs and endothelium-derived nitric oxide production (Table 1). The effects of AVP on the kidney are complex. AVP regulates urine osmolality (increasing urine osmolality) by increasing collecting duct permeability to water via V2Rs and by activating urea transport mechanisms, the classic antidiuretic hormone effect. Paradoxically, low-dose AVP (similar doses to that used during CPB vasodilatory shock) induces diuresis in humans with hepatorenal syndrome and congestive heart failure. The mechanism of this action is poorly understood.14
CLINICAL USE
AVP has been used in high doses (⬎0.1 U/min) to cause gastrointestinal vasoconstriction in patients with variceal bleeding. Low-dose AVP (0.02 to 0.08 U/min) has been used in vasodilatory shock syndromes, such as septic shock, post–left ventricular assist device vasodilatory shock, and post-CPB vasodilatory shock. Although hypotension seen during sepsis usually is associated with appropriately high levels of AVP, a subgroup of patients have inappropriately low plasma AVP levels (⬍5 pg/mL). Landry et al15 showed that AVP infusion at 0.01 U/min increased AVP levels to appropriately high levels in sepsis (⬎25 pg/mL), indicating that a relative deficiency of AVP secretion as opposed to increased clearance is responsible for the low AVP levels. Patel et al14 and Landry et al15 showed that restoration of physiologically appropriately high levels of AVP in sepsis results in increased blood pressure and systemic vascular resistance. The effects of AVP on cardiac index in the setting of shock are conflicting and probably represent the mixed effect of any pressor agent whereby cardiac index is dependent on the balance of restored coronary perfusion and increased contractility versus increased afterload. It is becoming clear that AVP use can spare conventional catecholamine use in septic patients, but does it have additional benefits? Patel et al14 showed in a double-blind, controlled trial of AVP versus norepinephrine that AVP infusion resulted in a 75% increase in creatinine clearance and doubling of urine output when both agents were titrated against the same mean arterial blood pressure. A plausible mechanism behind this effect is that although norepinephrine constricts afferent and efferent arterioles in the kidney contributing to decreased glomerular filtration rate, AVP constricts only the efferent arteriole, increasing glomerular perfusion pressure and glomerular filtration rate (Table 1). AVP had no adverse impact on gastric-arterial PCO2 gradient and cardiac output. VASOPRESSIN AND CARDIAC SURGERY
Initial reports of AVP use were primarily case reports. Many cases have been described whereby AVP was used for hypotension refractory to catecholamine pressors in patients while on CPB.16-18 Patients who develop post-CPB vasodilatory shock are predicted by preoperative low ejection fraction, ACE inhibitor use, and a relative deficiency of AVP secretion during CPB.19 The first randomized trial comparing AVP with saline placebo was performed in patients after left ventricular assist device placement.20 In this study, 10 patients with post-CPB vasodilatory states were randomized to AVP (0.1 U/min) or placebo. AVP increased mean arterial blood pressure in all patients regardless of plasma AVP levels. Argenziano et al21 further investigated this phenomenon by investigating hypoten-
PRO AND CON
775
sive vasodilated patients after heart transplantation. AVP administration at 0.1 U/min resulted in improved mean arterial blood pressure. The magnitude of the effect was proportional to the degree of hypotension, in that the most severely hypotensive patients derived greatest effect.21 Although no randomized trial has been published investigating AVP therapy after coronary artery bypass graft surgery, a retrospective review of 40 patients receiving AVP for post-CPB vasodilatory shock showed significant improvements in mean arterial pressure and a reduction of norepinephrine requirements.21 CONCLUSIONS
A vasodilatory state requiring vasoconstrictor agents has been well described after cardiac surgery. The cause of this state is multifactorial, and predictors of this state include use of
ACE inhibitors, low ejection fraction, and inappropriately low AVP levels. Catecholamine vasoconstrictor agents often are used to provide adequate perfusion pressure, but a common concern when using these agents is the potential for adverse effects on renal and splanchnic perfusion. In contrast to norepinephrine, AVP significantly improves creatinine clearance and urine output at the same systemic blood pressure, while having minimal effect on mesenteric vasculature at the doses used (⬍0.1 U/min). One small randomized, controlled trial has been conducted in patients with post-CPB vasodilatory shock and showed improved mean arterial pressure without any deleterious effects. The evidence to date suggests that AVP improves mean arterial pressure in patients with post-CPB vasodilatory shock and that this may occur with fewer adverse effects on renal perfusion compared with the use of catecholamine vasocontrictors.
REFERENCES 1. Tan CK, Glisson SN, El-Etr AA, Ramakrishnaiah KB: Levels of circulating norepinephrine and epinephrine before, during, and after cardiopulmonary bypass in man. J Thorac Cardiovasc Surg 71:928931, 1976 2. Feddersen K, Aurell M, Delin K, et al: Effects of cardiopulmonary bypass and prostacyclin on plasma catecholamines, angiotensin II and arginine-vasopressin. Acta Anaesthesiol Scand 29:224-230, 1985 3. Kuan P, Messenger JC, Ellestad MH: Transient central diabetes insipidus after aortocoronary bypass operations. Am J Cardiol 52:11811183, 1983 4. Robinson RO, Pagliero KM: Polyuria after cardiac surgery. BMJ 1:265-266, 1970 5. Thaker U, Geary V, Chalmers P, Sheikh F: Low systemic vascular resistance during cardiac surgery: Case reports, brief review, and management with angiotensin II. J Cardiothorac Vasc Anesth 4:360363, 1990 6. Woods WG, Forsling ML, Le Quesne LP: Plasma arginine vasopressin levels and arterial pressure during open heart surgery. Br J Surg 76:29-32, 1989 7. Sehested J, Wacker B, Forssmann WG, Schmitzer E: Natriuresis after cardiopulmonary bypass: Relationship to urodilatin, atrial natriuretic factor, antidiuretic hormone, and aldosterone. J Thorac Cardiovasc Surg 114:666-671, 1997 8. Zerbe RL, Henry DP, Robertson GL: Vasopressin response to orthostatic hypotension: Etiologic and clinical implications. Am J Med 74:265-271, 1983 9. Holmes CL, Patel BM, Russell JA, Walley KR: Physiology of vasopressin relevant to management of septic shock. Chest 120:9891002, 2001 10. Barberis C, Mouillac B, Durroux T: Structural basis of vasopressin/oxytocin receptor function. J Endocrinol 156:223-229, 1998 11. Laszlo FA, Laszlo F, De Wied D: Pharmacology and clinical perspectives of vasopressin antagonists. Pharmacol Rev 43:73-108, 1991
12. Liard JF, Deriaz O, Schelling P, et al: Cardiac output distribution during vasopressin infusion or dehydration in conscious dogs. Am J Physiol 243:663-669, 1982 13. Garcia-Villalon AL, Garcia JL, Fernandez N, et al: Regional differences in the arterial response to vasopressin: Role of endothelial nitric oxide. Br J Pharmacol 118:1848-1854, 1996 14. Patel BM, Chittock DR, Russell JA, Walley KR: Beneficial effects of short-term vasopressin infusion during severe septic shock. Anesthesiology 96:576-582, 2002 15. Landry DW, Levin HR, Gallant EM, et al: Vasopressin pressor hypersensitivity in vasodilatory septic shock. Crit Care Med 25:12791282, 1997 16. Talbot MP, Tremblay I, Denault AY, Belisle S: Vasopressin for refractory hypotension during cardiopulmonary bypass. J Thorac Cardiovasc Surg 120:401-402, 2000 17. Licker M, Schweizer A: Vasopressin and postcardiopulmonary bypass refractory hypotension. Anesth Analg 88:695, 1999 18. Overand PT, Teply JF: Vasopressin for the treatment of refractory hypotension after cardiopulmonary bypass. Anesth Analg 86: 1207-1209, 1998 19. Argenziano M, Chen JM, Choudhri AF, et al: Management of vasodilatory shock after cardiac surgery: Identification of predisposing factors and use of a novel pressor agent. J Thorac Cardiovasc Surg 116:973-980, 1998 20. Argenziano M, Choudhri AF, Oz MC, et al: A prospective randomized trial of arginine vasopressin in the treatment of vasodilatory shock after left ventricular assist device placement. Circulation 96:II-286-II-290, 1997 21. Argenziano M, Chen JM, Cullinane S, et al: Arginine vasopressin in the management of vasodilatory hypotension after cardiac transplantation. J Heart Lung Transplant 18:814-817, 1999
Pro: Vasopressin Is the Vasoconstrictor of Choice After Cardiopulmonary Bypass John V. Booth, MB, ChB, FRCA, David Schinderle, MD, and Ian J. Welsby, MB, BS
H
OMEOSTASIS IS the process whereby physiologic balance is preserved by neurohormonal feedback mechanisms. Cardiac surgery requiring cardiopulmonary bypass (CPB) activates a variety of neurohormonal, metabolic, and immunologic processes within the body that disrupt normal physiology and are balanced by processes designed to bring physiology back into balance. Maintenance of systemic blood pressure and perfusion in organ systems is one of the endpoints of homeostasis. The vasodilatory shock state sometimes seen after CPB is often a result of an imbalance in that homeostatic mechanism, and this imbalance is an inability to increase arginine vasopressin (AVP) levels in response to stress. AVP therapy restores homeostasis, resulting in sufficient organ perfusion without deleterious effects. AVP therapy becomes the logical first-line treatment to restore adequate mean arterial pressure in vasodilatory shock after CPB. PATHOPHYSIOLOGY OF VASODILATION AFTER CARDIOPULMONARY BYPASS
CPB results in the activation of a complex system of neurohormonal, endocrine, and immunologic mediators, the balance of which is designed to create homeostasis in a system under stress. When the system is in balance, blood pressure and essential organ perfusion are preserved without compromising at-risk organs, such as the gastrointestinal tract or kidney. When imbalance occurs during CPB, it often results in systemic vasoconstriction that sometimes requires vasodilator therapy because of temporary elevations in epinephrine, norepinephrine, serotonin, and AVP.1 CPB has been shown to cause 6-fold increased circulating AVP levels 12 hours after surgery.2 Sometimes, imbalance results in a relative deficiency of AVP, however, occasionally resulting in diabetes insipidus.3,4 Clinically, this syndrome has been described as a vasodilatory state that is often poorly responsive to phenylephrine but responsive to octreotide and angiotensin II.5,6 Argenziano et al showed that the incidence of vasodilatory shock in the early post-CPB period is 8% to 10% and is significantly more common in patients with low ejection fraction and patients who used angiotensin-converting enzyme (ACE) inhibitors.6 Patients with post-CPB vasodilatory shock had AVP levels in the normal range for resting adults (5 to 15 pg/mL), but inappropriately low levels for the degree of arterial hypotension. AVP levels during and after CPB are usually ⬎35 pg/mL and often ⬎100 pg/mL. The cause of poor AVP response to CPB is unknown, but hyponatremia and activated
atrial stretch receptors are known to blunt AVP responses. Patients in heart failure with elevated atrial filling pressures and resultant increased atrial natriuretic peptide levels could be partly responsible for poor AVP responsiveness.7 Another potential cause of AVP hyporesponsiveness is autonomic dysfunction, a process also known to occur in patients with heart failure.8 PHYSIOLOGY OF VASOPRESSIN
AVP is also known as antidiuretic hormone and is essential for cardiovascular homeostasis. That AVP is essential for survival is attested by its teleologic persistence. The oxytocinAVP protein superfamily is found in vertebrates and invertebrates with conserved sequences. The gene encoding AVP predates the divergence of vertebrates and invertebrates that occurred about 700 million years ago.9 AVP is a nonapeptide synthesized in the hypothalamus. After synthesis, the protein migrates to the posterior pituitary so that it can be readily released. Only 10% to 20% of the total AVP pool can be readily released. When this amount is discharged into the circulation, AVP continues to be secreted in response to appropriate stimuli but at a greatly reduced rate, resulting in a biphasic response of AVP release.9 AVP release is stimulated by osmotic and nonosmotic factors. Osmotic factors include hyperosmolality, detected at central and peripheral osmoreceptors whereby small increases in plasma osmolality are quickly sensed; this results in AVP release and increased urine osmolality. Nonosmotic stimuli include hypovolemia, such as hypotension and decreased intravascular volume, and hormonal regulation with acetylcholine, histamine, dopamine, prostaglandins, angiotensin II, and catecholamines.9 AVP acts on AVP receptors (VRs) and oxytocin receptors (OTRs). VRs are G protein– coupled receptors of the 7-trans-
From the Division of Cardiothoracic Anesthesia and Critical Care, Department of Anesthesiology, Duke University Medical Center, Durham, NC. Address reprint requests to John V. Booth, MB, ChB, FRCA, Division of Cardiothoracic Anesthesia and Critical Care, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710. E-mail: [email protected] Copyright 2002, Elsevier Science (USA). All rights reserved. 1053-0770/02/1606-0020$35.00/0 doi:10.1053/jcan.2002.128432 Key words: Vasopressin, cardiopulmonary bypass, shock
Journal of Cardiothoracic and Vascular Anesthesia, Vol 16, No 6 (December), 2002: pp 773-775
773
774
BOOTH ET AL
Table 1. Comparison of Vasopressin and Norepinephrine Vasoconstriction
Vasopressin Norepinephrine
Coronary
Cerebral
Pulmonary
Mesenteric
CO
GFR
Cr Cl
⫹ ⫹⫹⫹
⫹/⫺ ⫹⫹⫹
⫺ ⫹⫹
⫺ ⫹⫹⫹
1 or 2 1 or 2
1 2
1 2
NOTE. Vasopressin is at doses ⬍0.1 U/min, the dose commonly used during vasodilatory shock. Abbreviations: CO, cardiac output; GFR, glomerular filtration rate; Cr Cl, creatinine clearance.
membrane domain superfamily and can be subdivided into V1Rs, V2Rs, and V3Rs.10 V1 vascular receptors (V1Rs) are located on vascular smooth muscle and mediate vasoconstriction. Additional receptors are located in the kidney, myometrium, liver, and platelets. V1Rs signal through phospholipase C and cause release of intracellular calcium. V2Rs mediate the antidiuretic effects of AVP and are located in the renal collecting duct system and endothelial cells and mediate effects through adenylyl cyclase activation. V3Rs are pituitary receptors responsible for central regulation and adrenocorticotropic hormone release. OTRs also are activated by AVP and are found in pulmonary artery endothelial cells, aorta, and uterus and mammary glands. AVP-induced OTR activation mediates a calcium-dependent vasodilatory response via the nitric oxide pathway. An important physiologic role of AVP is in the preservation of perfusion during periods of hypotension. AVP has little effect on blood pressure under normal conditions and at normal concentrations but helps maintain arterial blood pressure via V1Rs during hypovolemia, a mechanism similar to catecholamines.11 AVP differs from catecholamines in several respects, however. AVP is a potent vasoconstrictor in skin, skeletal muscle, fat, pancreas, and thyroid gland. In contrast to norepinephrine, AVP causes less vasoconstriction in the coronary and cerebral circulations (Table 1).12 In addition, AVP does not cause mesenteric or pulmonary vasoconstriction in vitro.13 AVP also enhances the sensitivity of vascular smooth muscle to other vasoconstrictive agents and blocks potassium-sensitive adenosine triphosphate (ATP) channels in a dose-dependent manner. This action may be partly responsible for restoring vascular tone in the post-CPB vasodilatory state. Another difference between catecholamine pressor agents and AVP is that AVP may cause vasodilation in selected organs. The receptor subtype involved in this action is uncertain, but the effect varies among different vascular beds in the same organ, such that arteries of the circle of Willis are more sensitive than other intracranial or extracranial arteries. This effect is endothelium dependent and likely mediated via nitric oxide. Specifically, this effect is seen in the pulmonary vasculature, where pulmonary vasodilation is the predominant effect until high concentrations of AVP are achieved, an effect mediated via V1Rs and endothelium-derived nitric oxide production (Table 1). The effects of AVP on the kidney are complex. AVP regulates urine osmolality (increasing urine osmolality) by increasing collecting duct permeability to water via V2Rs and by activating urea transport mechanisms, the classic antidiuretic hormone effect. Paradoxically, low-dose AVP (similar doses to that used during CPB vasodilatory shock) induces diuresis in humans with hepatorenal syndrome and congestive heart failure. The mechanism of this action is poorly understood.14
CLINICAL USE
AVP has been used in high doses (⬎0.1 U/min) to cause gastrointestinal vasoconstriction in patients with variceal bleeding. Low-dose AVP (0.02 to 0.08 U/min) has been used in vasodilatory shock syndromes, such as septic shock, post–left ventricular assist device vasodilatory shock, and post-CPB vasodilatory shock. Although hypotension seen during sepsis usually is associated with appropriately high levels of AVP, a subgroup of patients have inappropriately low plasma AVP levels (⬍5 pg/mL). Landry et al15 showed that AVP infusion at 0.01 U/min increased AVP levels to appropriately high levels in sepsis (⬎25 pg/mL), indicating that a relative deficiency of AVP secretion as opposed to increased clearance is responsible for the low AVP levels. Patel et al14 and Landry et al15 showed that restoration of physiologically appropriately high levels of AVP in sepsis results in increased blood pressure and systemic vascular resistance. The effects of AVP on cardiac index in the setting of shock are conflicting and probably represent the mixed effect of any pressor agent whereby cardiac index is dependent on the balance of restored coronary perfusion and increased contractility versus increased afterload. It is becoming clear that AVP use can spare conventional catecholamine use in septic patients, but does it have additional benefits? Patel et al14 showed in a double-blind, controlled trial of AVP versus norepinephrine that AVP infusion resulted in a 75% increase in creatinine clearance and doubling of urine output when both agents were titrated against the same mean arterial blood pressure. A plausible mechanism behind this effect is that although norepinephrine constricts afferent and efferent arterioles in the kidney contributing to decreased glomerular filtration rate, AVP constricts only the efferent arteriole, increasing glomerular perfusion pressure and glomerular filtration rate (Table 1). AVP had no adverse impact on gastric-arterial PCO2 gradient and cardiac output. VASOPRESSIN AND CARDIAC SURGERY
Initial reports of AVP use were primarily case reports. Many cases have been described whereby AVP was used for hypotension refractory to catecholamine pressors in patients while on CPB.16-18 Patients who develop post-CPB vasodilatory shock are predicted by preoperative low ejection fraction, ACE inhibitor use, and a relative deficiency of AVP secretion during CPB.19 The first randomized trial comparing AVP with saline placebo was performed in patients after left ventricular assist device placement.20 In this study, 10 patients with post-CPB vasodilatory states were randomized to AVP (0.1 U/min) or placebo. AVP increased mean arterial blood pressure in all patients regardless of plasma AVP levels. Argenziano et al21 further investigated this phenomenon by investigating hypoten-
PRO AND CON
775
sive vasodilated patients after heart transplantation. AVP administration at 0.1 U/min resulted in improved mean arterial blood pressure. The magnitude of the effect was proportional to the degree of hypotension, in that the most severely hypotensive patients derived greatest effect.21 Although no randomized trial has been published investigating AVP therapy after coronary artery bypass graft surgery, a retrospective review of 40 patients receiving AVP for post-CPB vasodilatory shock showed significant improvements in mean arterial pressure and a reduction of norepinephrine requirements.21 CONCLUSIONS
A vasodilatory state requiring vasoconstrictor agents has been well described after cardiac surgery. The cause of this state is multifactorial, and predictors of this state include use of
ACE inhibitors, low ejection fraction, and inappropriately low AVP levels. Catecholamine vasoconstrictor agents often are used to provide adequate perfusion pressure, but a common concern when using these agents is the potential for adverse effects on renal and splanchnic perfusion. In contrast to norepinephrine, AVP significantly improves creatinine clearance and urine output at the same systemic blood pressure, while having minimal effect on mesenteric vasculature at the doses used (⬍0.1 U/min). One small randomized, controlled trial has been conducted in patients with post-CPB vasodilatory shock and showed improved mean arterial pressure without any deleterious effects. The evidence to date suggests that AVP improves mean arterial pressure in patients with post-CPB vasodilatory shock and that this may occur with fewer adverse effects on renal perfusion compared with the use of catecholamine vasocontrictors.
REFERENCES 1. Tan CK, Glisson SN, El-Etr AA, Ramakrishnaiah KB: Levels of circulating norepinephrine and epinephrine before, during, and after cardiopulmonary bypass in man. J Thorac Cardiovasc Surg 71:928931, 1976 2. Feddersen K, Aurell M, Delin K, et al: Effects of cardiopulmonary bypass and prostacyclin on plasma catecholamines, angiotensin II and arginine-vasopressin. Acta Anaesthesiol Scand 29:224-230, 1985 3. Kuan P, Messenger JC, Ellestad MH: Transient central diabetes insipidus after aortocoronary bypass operations. Am J Cardiol 52:11811183, 1983 4. Robinson RO, Pagliero KM: Polyuria after cardiac surgery. BMJ 1:265-266, 1970 5. Thaker U, Geary V, Chalmers P, Sheikh F: Low systemic vascular resistance during cardiac surgery: Case reports, brief review, and management with angiotensin II. J Cardiothorac Vasc Anesth 4:360363, 1990 6. Woods WG, Forsling ML, Le Quesne LP: Plasma arginine vasopressin levels and arterial pressure during open heart surgery. Br J Surg 76:29-32, 1989 7. Sehested J, Wacker B, Forssmann WG, Schmitzer E: Natriuresis after cardiopulmonary bypass: Relationship to urodilatin, atrial natriuretic factor, antidiuretic hormone, and aldosterone. J Thorac Cardiovasc Surg 114:666-671, 1997 8. Zerbe RL, Henry DP, Robertson GL: Vasopressin response to orthostatic hypotension: Etiologic and clinical implications. Am J Med 74:265-271, 1983 9. Holmes CL, Patel BM, Russell JA, Walley KR: Physiology of vasopressin relevant to management of septic shock. Chest 120:9891002, 2001 10. Barberis C, Mouillac B, Durroux T: Structural basis of vasopressin/oxytocin receptor function. J Endocrinol 156:223-229, 1998 11. Laszlo FA, Laszlo F, De Wied D: Pharmacology and clinical perspectives of vasopressin antagonists. Pharmacol Rev 43:73-108, 1991
12. Liard JF, Deriaz O, Schelling P, et al: Cardiac output distribution during vasopressin infusion or dehydration in conscious dogs. Am J Physiol 243:663-669, 1982 13. Garcia-Villalon AL, Garcia JL, Fernandez N, et al: Regional differences in the arterial response to vasopressin: Role of endothelial nitric oxide. Br J Pharmacol 118:1848-1854, 1996 14. Patel BM, Chittock DR, Russell JA, Walley KR: Beneficial effects of short-term vasopressin infusion during severe septic shock. Anesthesiology 96:576-582, 2002 15. Landry DW, Levin HR, Gallant EM, et al: Vasopressin pressor hypersensitivity in vasodilatory septic shock. Crit Care Med 25:12791282, 1997 16. Talbot MP, Tremblay I, Denault AY, Belisle S: Vasopressin for refractory hypotension during cardiopulmonary bypass. J Thorac Cardiovasc Surg 120:401-402, 2000 17. Licker M, Schweizer A: Vasopressin and postcardiopulmonary bypass refractory hypotension. Anesth Analg 88:695, 1999 18. Overand PT, Teply JF: Vasopressin for the treatment of refractory hypotension after cardiopulmonary bypass. Anesth Analg 86: 1207-1209, 1998 19. Argenziano M, Chen JM, Choudhri AF, et al: Management of vasodilatory shock after cardiac surgery: Identification of predisposing factors and use of a novel pressor agent. J Thorac Cardiovasc Surg 116:973-980, 1998 20. Argenziano M, Choudhri AF, Oz MC, et al: A prospective randomized trial of arginine vasopressin in the treatment of vasodilatory shock after left ventricular assist device placement. Circulation 96:II-286-II-290, 1997 21. Argenziano M, Chen JM, Cullinane S, et al: Arginine vasopressin in the management of vasodilatory hypotension after cardiac transplantation. J Heart Lung Transplant 18:814-817, 1999