Vasoplegic Syndrome after Off-Pump Coronary Artery Bypass Surgery

Abstract

We report the case of a 65-year-old man who developed norepinephrine-resistant vasoplegic syndrome after elective off-pump coronary artery bypass surgery (OPCAB). The failure of norepinephrine to improve the patient's hemodynamics prompted us to start treatment with vasopressin; within 30 minutes, the hemodynamics began to improve. After 12 hours, the patient was stable enough to be weaned from the vasopressin. He was discharged from the hospital on the 10th postoperative day. To our knowledge, ours is the 1st report of vasopressin use for vasodilatory shock after OPCAB in the English-language medical literature. Herein, we discuss the pathophysiology and management of vasoplegic syndrome—which is controversial—with special emphasis on the use of vasopressin in this situation.

Vasoplegic syndrome is characterized by a severe and persistent form of hypotension, tachycardia, normal or increased cardiac output, and decreased systemic vascular resistance (SVR) and low filling pressures, and is poorly responsive or unresponsive to volume increase with fluid infusion. This condition is a potentially lethal complication in patients undergoing cardiac surgery on cardiopulmonary bypass (CPB).^1–3 This manifestation of systemic inflammatory response to cardiac surgery with CPB^4–6 has resulted in the use of high-dose norepinephrine and experimental drugs such as methylene blue to save the lives of affected individuals.^2,3,7

Concerns regarding the complications and costs surrounding the use of CPB have led to renewed interest in off-pump coronary artery bypass grafting (OPCAB) techniques. Available evidence suggests that OPCAB reduces the elaboration of key mediators of the systemic inflammatory response, attenuates the cellular inflammatory response, and thereby decreases the degree of postoperative organ dysfunction.⁸ Contrary to available evidence, however, we report the case of a patient who developed norepinephrine-resistant vasoplegic syndrome after OPCAB. We discuss the pathophysiology and management of vasoplegic syndrome with special emphasis on the role of vasopressin in this situation.

Case Report

In March 2002, a 65-year-old hypertensive and nondiabetic man with a history of anterolateral myocardial infarction (MI) was admitted to our institution for elective coronary artery bypass surgery. Coronary angiography revealed 70% blockage of the left main coronary artery and more than 50% blockage of the right coronary artery. Electrocardiography showed changes corresponding to the MI, and 2-dimensional echocardiography revealed moderate left ventricular dysfunction with anterior wall hypokinesia. The patient was taking aspirin, atorvastatin, ramipril, atenolol, isosorbide dinitrate, and nicorandil; these were taken along with premedication on the day of surgery.

A radial arterial line, central venous line, peripheral venous cannulae, Swan-Ganz catheter, and urinary catheter were inserted. The anesthetic technique included administration of fentanyl, propofol, and isoflurane, with controlled mechanical ventilation. In addition, heparin was administered to achieve an activated clotting time longer than 250 seconds and was not reversed at the completion of the operation. Triple-vessel, total arterial revascularization was performed off-pump by sequential anastomoses of skeletonized left internal mammary artery-to-left anterior descending and diagonal arteries and radial artery-to-right coronary artery. At the end of the procedure, the patient was transferred to the intensive care unit (ICU) in a hemodynamically stable condition on minimal inotropic support (dopamine, 5 μg/kg per min), from which he was weaned over the next 3 hours.

An hour later, the patient developed severe hypotension, tachycardia, and oliguria, which were initially treated unsuccessfully with fluid infusion. Hemodynamic measurements revealed a systemic vascular resistance (SVR) of 685 dyne · sec · cm⁻⁵; cardiac output (CO), 6.8 L/min; and pulmonary capillary wedge pressure (PCWP), 13 mmHg. The mean arterial pressure was 40 to 45 mmHg, and the heart rate was 145 to 150 beats/min. A provisional diagnosis of septic shock was made. Samples were collected for microbiologic screening, broad-spectrum antibiotics were given, and norepinephrine infusion was started at 0.025 μg/kg per min. The dose of norepinephrine was gradually increased to 0.2 μg/kg per min in an effort to treat persistently low SVR, hypotension, and inadequate urine output. However, during the next 4 hours, the hemodynamic variables did not change much.

The failure of norepinephrine to improve the hemodynamics prompted us to start vasopressin infusion at a rate of 5 U/hr. Within 30 minutes of beginning the vasopressin infusion, an improvement in hemodynamics was noticed. Over the next 6 hours, the SVR increased to 1,109 dyne · sec · cm⁻⁵, the CO stabilized to 5.2 L/min, and the mean arterial pressure increased to 60 to 65 mmHg. The urine output also improved and remained at 0.5 mL/kg per min or more. The associated electrolyte imbalance and metabolic acidosis were appropriately managed, and norepinephrine was gradually stopped. Serial electrocardiograms were obtained throughout this period to exclude myocardial ischemia secondary to vasopressin use. The creatine kinase-MB and troponin T levels remained unchanged from those measured upon the patient's arrival at the ICU.

After 12 hours of stable hemodynamics, vasopressin infusion was tapered at a rate of 1 U/hr until the patient was weaned. The patient was extubated 24 hours after surgery. Results of microbiologic screens were negative, and antibiotics were stopped. The patient was transferred to the ward on postoperative day 2 and was discharged from the hospital on the 10th postoperative day. Six weeks later, follow-up in the outpatient clinic suggested prompt recovery, and the patient was released from surgical care.

Discussion

Cardiac surgery provokes a vigorous inflammatory response, which has important clinical implications. Factors influencing the incidence, severity, and clinical outcome of the inflammatory response, and, in particular, the reasons why certain patients develop life-threatening perioperative complications, are not well understood. Vasoplegic syndrome is a newly recognized manifestation commonly occurring during the early postoperative period after cardiac surgery with CPB.¹ Although the cause of the syndrome is unclear, it is attributed mainly to the systemic inflammatory response activated specifically by CPB,^1–3 as well as to nonspecific activators such as surgical trauma, blood loss or transfusion, and hypothermia.⁸

Available evidence suggests that despite comparable surgical trauma, the OPCAB revascularization procedure (without the use of CPB and cardioplegic arrest) significantly reduces the systemic inflammatory response syndrome.⁹ This positive outcome may contribute to improved organ function, subsequently resulting in better postoperative recovery from surgical revascularization procedures, particularly in critically ill patients. However, despite the reduced systemic inflammatory response after OPCAB, another center has reported vasoplegic syndrome as an unusual complication after this technique of myocardial revascularization.¹⁰

The occurrence of vasoplegic syndrome after OPCAB necessitates theorizing about possible causes in the absence of extracorporeal circulation. It is possible that the generation of proinflammatory mediators due to surgical stress,¹¹ the use of resterilized disposable devices,¹² the neutralization of heparin with protamine,¹³ the transfusion of blood products,¹⁰ or the occurrence of endotoxemia secondary to repeated episodes of hypotension throughout OPCAB surgery as a result of mobilization and displacement of the heart¹⁴ might precipitate the systemic inflammatory response and vasoplegic syndrome. Additional factors contributing to the initiation of vasoplegic syndrome include preoperative chronic congestive heart failure with low ejection fraction (<0.35), preoperative use of angiotensin-converting enzyme inhibitors and β-blocking agents, and the pre- and postoperative use of amiodarone and phosphodiesterase inhibitors (milrinone).2,7,15,16

The management of vasoplegic syndrome is controversial. Pressor catecholamines are commonly administered to support the systemic arterial pressure in these cases,¹⁷ but their effectiveness is limited by frequent catecholamine resistance¹⁸ and by severe toxic effects at high doses.¹⁹ Recently, the use of vasopressin has been reported for the treatment of vasoplegic syndrome after cardiopulmonary bypass, especially in cases that are refractory to norepinephrine.²⁰ To the best of our knowledge, ours is the 1st report of vasopressin use for vasodilatory shock after OPCAB in the English-language medical literature.

Vasopressin, an endogenous hormone that is formed primarily in the supraoptic nuclei of the hypothalamus and secreted by the posterior pituitary gland, has shown promise in the management of refractory hypotension and vasodilatory shock after cardiac and noncardiac surgery and sepsis.^20–24 The rationale for using vasopressin stems from the observation that there is a deficiency of arginine vasopressin (AVP) in patients with vasoplegic syndrome.²⁵ Blunting of the AVP response to baroreceptor-mediated stimuli due to hyponatremia after cardiopulmonary bypass,²⁶ activation of atrial stretch receptors, higher serum atrial natriuretic peptide (ANP) levels, and autonomic dysfunction leading to the inhibition of AVP release—as seen in patients with heart failure—may be some of the mechanisms explaining deficiency of AVP in vasodilatory shock.²⁷

Different dosages of vasopressin have been used by various investigators for treating refractory hypotension.^7,20–23 However, a dose of 6 U/hr provides a steady-state plasma concentration of at least 150 pg/mL,²⁴ and increasing the dose provides no further benefit.^7,24 In our patient, we were able to discontinue norepinephrine and achieve stable hemodynamics with a dose of 5 U/hr.

The mechanisms by which AVP acts as a pressor in patients resistant to catecholamines are not clear, but there are several possibilities. Pathologic activation of several vasodilator mechanisms results in vasodilatory shock. Elevated levels of interleukin 1 and ANP due to inflammation induced by CPB promote vasodilation through increased levels of intracellular cyclic guanosine monophosphate.²⁸ Also, adenosine triphosphate-activated potassium channels of vascular smooth muscle are activated by tissue hypoxia and hypoperfusion (and presumably by CPB), and this activation causes vasodilation by inducing cellular hyperpolarization and inhibiting voltage-gated calcium channels.²⁹ Both catecholamines and AVP effect vasoconstriction by increasing intracellular calcium levels in vascular smooth muscle through activation of voltage-gated calcium channels; the activation of vasodilator pathways could impair this calcium-dependent mechanism. In contrast to catecholamines, however, AVP also inhibits the production of cyclic guanosine monophosphate by interleukin 1 and by ANP³⁰ and inhibits the adenosine triphosphate-activated potassium channels of vascular smooth muscle.²⁹ Thus the efficacy of AVP as a pressor in a variety of clinical scenarios in which catecholamines are ineffective may rest on its ability to specifically counteract pathologically activated vasodilatory mechanisms. The restoration of catecholamine sensitivity observed after AVP administration may also be explained on this basis.⁷

It must be stressed that there are limitations regarding the widespread use of vasopressin for the management of refractory vasodilatory shock after cardiac surgery. These limitations include the lack of a dose-response investigation; the risk of complications such as decreased coronary blood flow, cardiac output, and gut perfusion at high doses; and a paucity of evidence from large, prospective, randomized controlled trials using a continuous infusion of arginine vasopressin in patients experiencing vasodilatory shock after cardiac surgery.

Conclusion

Vasodilatory shock is an unusual complication after off-pump coronary artery bypass surgery. A high index of suspicion, along with prompt therapy with vasopressin, can be lifesaving in a patient who presents with severe and persistent hypotension, tachycardia, normal or increased cardiac output, and decreased systemic vascular resistance and low filling pressures, and who is poorly responsive to fluid infusion and routine vasopressors.