Methylene blue therapy for vasoplegia after cardiac surgery
*Katarzyna Skuza1, Sergiusz Chmielniak1, Wojciech Dziuk1, Ewa Kucewicz1, Szymon Pawlak2, Piotr Knapik1
1Department of Cardiac Anaesthesia and Intensive Therapy, Silesian Medical University, Silesian Centre for Heart Diseases in Zabrze
2Department of Cardiac Surgery and Transplantology, Silesian Medical University, Silesian Centre for Heart Diseases in Zabrze
Background. Systemic inflammatory response syndrome (SIRS) may be associated with critically decreased vascular resistance (vasoplegia syndrome) and become resistant to noradrenaline. Such a condition may be successfully treated with intravenous methylene blue.
Case report. A 73-year-old patient with acute myocardial infarction and cardiogenic shock was admitted to our centre after failed percutaneous coronary interventions to the left anterior descending coronary artery and underwent emergency coronary revascularisation. After surgery, his ejection fraction was 25%. X-ray revealed pulmonary oedema. The patient became severely hypotensive with marked vasoplegia and metabolic acidosis, despite incremental doses of adrenaline and noradrenaline. 2 mg kg-1 of methylene blue was administered, which quickly stabilized the patient`s general condition.
Conclusion. Methylene blue applied to vasoplegic patients can effectively increase systemic vascular resistance and restore satisfactory organ perfusion.
The systemic inflammatory response syndrome (SIRS) may develop as a complication of cardiac surgery . According to the guidelines of the American College of Chest Physicians and Society of Critical Care Medicine, the diagnosis of SIRS requires the presence of at least two of the following six symptoms: body temperature >38° C (or <36° C), HR >90 min-1, f >20 min-1, PaCO2 <32 mm Hg, WBC >12 G L-1 or <4 G L-1) or presence of at least 10% of immature leukocytes. SIRS may be caused by infectious and non-infectious factors. Infectious SIRS is most commonly caused by Gram-negative bacteria. Liposaccharide, an element of the cell wall, is the factor strongly activating the inflammatory response . The non-inflammatory form of SIRS results from surgical trauma and shock .
Patients undergoing cardiac surgery are at particularly high risk of SIRS. On contact with artificial surfaces of extracorporeal circulation devices, leukocytes are activated and proinflammatory cytokines are released. This is one of the essential factors predisposing to SIRS. The other factors include transient ischaemia of the intestinal wall with endotoxaemia, reperfusion of ischaemic myocardium, transfusion of blood and blood preparations, tissue trauma. The intensified inflammatory response may lead to vasoplegia syndrome and ultimately to multi-organ failure .
The paper presents a case of effective methylene blue therapy in a patient with vasoplegia syndrome in the early postoperative period.
A 73-year-old patient with myocardial infarction of the anterior wall with ST elevation was admitted to the district hospital equipped with the invasive haemodynamics unit. Emergency angioplasty of the anterior descending artery was attempted yet failed complicated by total closure of the vessel. The patient`s condition deteriorated, cardiogenic shock developed. The patient was transferred to the cardiac surgery department for emergency surgery. Intaaortal balloon counterpulsation was initiated due to symptomatic cardiogenic shock and then the patient underwent life saving off pump coronary artery bypass (OPCAB) surgery.
In the early postoperative period, the patient was haemodynamically unstable. The following abnormalities were observed: low systemic blood pressure (MAP <50 mm Hg), radiographic features of lung oedema, low left ventricular ejection fraction (25%) on echocardiography and increasing metabolic acidosis. The continuous infusion of adrenaline 0.1 µg kg-1 min-1 was started. The cardiovascular function was monitored using the Swan-Ganz catheter. The haemodynamic profile revealed elevated values of CO and CI and extremely low systemic vascular resistances. The continuous infusion of noradrenalin was initiated. Within several hours, clinical symptoms of visceral hypoperfusion developed (pain, abdominal muscle guarding on palpation). The level of lactates reached 20 mmol L-1. The dose of noradrenalin was increased to 0.4 µg kg-1 min-1, yet the systemic pressure was not stabilized. The patient needed mechanical lung ventilation (FIO2 1.0). No oliguria was observed. Since the treatment outcome was not positive, the methylene blue infusion was administered (2 mg kg-1 over 60 min) . During the infusion, peripheral vascular resistance and arterial blood pressure increased, which enabled us to reduce the dose of noradrenalin (Fig. 1).
At subsequent examinations, the level of lactates significantly decreased and normalized within 24 h (Table 1). Broad-spectrum antibiotics were instituted to prevent the spread of bacteria from the intestines. FIO2 was gradually reduced in the respiratory mixture. Mechanical ventilation had to be prolonged because of coexisting chronic obstructive lung disease. At postoperative day 6, ventilation was discontinued, at day 8 the infusion of catecholamines was stopped and at day 9 the intaaortal balloon was removed. At day 8, abdominal pain re-developed. The concentration of pancreatic amylase was markedly elevated; acute pancreatitis was diagnosed whose conservative treatment was successful. At day 14, the patient was transferred to the department of cardiac surgery in general good condition for further treatment and rehabilitation. At day 20, he was sent to the district hospital; his condition was satisfactory.
Vasoplegia syndrome in the early postoperative period is diagnosed in 8-10% of patients undergoing cardiac surgery. Haemodynamic measurements demonstrate hypotension (MAP <50 mm Hg), reduced filling pressures (CVP<5 mm Hg or/and PCWP <10 mm Hg), normal or elevated CI values, and low systemic vascular resistances (<800 dyne s cm-5 m-2) . Vasoconstricting drugs are required despite supplementation of vascular bed volume.
An important factor triggering vasoplegia is extracorporeal circulation yet it may also develop after OPCAB and is preceded by SIRS . In our case, SIRS resulted from several factors. The generalized inflammatory response was induced by ischaemic trauma and reperfusion resulting from myocardial infarction co-developing with cardiogenic shock. Increased symptoms were strictly associated with the surgical procedure. The bacterial aetiology of the syndrome (spread through the damaged intestinal wall) was not a relevant SIRS-inducing factor, which was evidenced by quick subsidence of symptoms. However, ischaemic and surgical trauma were likely to cause increased synthesis of proinflammatory interleukins (IL-1, IL-6) and TNF-a. The cytokines mentioned modulate the release and activation of further inflammatory factors – interleukin 8, the complement system, histamine and kinins [1, 2]. Moreover, NO synthase is activated, which leads to overproduction of NO. Circulating cytokines additionally sensitize the cells of vascular smooth muscles to NO. The clinical symptom of “cytokine storm” is deep hypotension refractory to standard pharmacotherapy.
Decreased arterial pressure limits organ perfusion leading to hypoxia, which results in activation of the pathway of anaerobic carbohydrate metabolism, whose final product is a lactate anion. Irrespective of its mechanism, hyperlactidemia is always accompanied by low levels of bicarbonates leading to bicarbonate-lactic acidosis. The liver plays a pivotal role in the metabolism of lactates. If its function is normal, excessive lactates are metabolized. Increased levels of lactates indicate their excessive production and metabolism abnormalities due to liver dysfunction (e.g. ischaemia) . Prolonged hypotension, organ hypoperfusion and metabolic acidosis inevitably lead to death.
The therapy of vasoplegia syndrome it to maintain the perfusion pressure; the drug of choice is noradrenalin. If standard therapy fails, vasopressin or methylene blue may be used . Both drugs inhibit the synthesis of cGMP and limit vasoplegia symptoms. Another effective form of treatment is haemofiltration, which eliminates excessive circulating cytokines. The most efficient mechanism of cytokine inactivation is their absorption on the haemofilter.
In the case presented, the methylene blue infusion was decided due to noradrenalin-resistant vasoplegia and symptoms suggestive of abdominal organ ischaemia. During the infusion, haemodynamic parameters gradually improved, thus the dose of noradrenalin was reduced. Spontaneous subsidence of metabolic acidosis was soon observed.
The clinical studies currently carried out confirm the efficacy of methylene blue therapy for vasoplegia syndrome after cardiac surgeries . The recent reports suggest prophylactic administration of methylene blue in patients at risk of vasoplegia . The independent risk factors of vasoplegia syndrome include preoperative intravenous infusions of heparin or angiotensin convertase inhibitors and calcium channel blockers . The use of methylene blue in cardiac surgery is increasingly common. There are reports confirming beneficial effects of this agent in various groups of patients, e.g. in patients with bacterial endocarditis. Intraoperative intravenous infusions of methylene blue provide haemodynamic stabilization . However, its use in septic shock is the subject of much controversy. The drug in question has been found to increase mean arterial pressures and peripheral vascular resistances, yet the methylene blue-related reduction in mortality rates has not been demonstrated. Another special group is patients after heart transplantation. The important factors inducing vasoplegia syndromes in these patients include extracorporeal circulation and release of antigens from the transplanted tissues. The syndrome-associated mortality rates are high.
Moreover, a case was reported, in which methylene blue therapy enabled to maintain the perfusion pressure and shorten the time of noradrenalin administration . Methylene blue in anaphylactic shock is also of interest. The anaphylactic reaction is likely to lead to overproduction of NO resulting in peripheral paralysis. Two cases of anaphylactic reactions following aprotynine and protamine sulphate, administered during cardiac surgery, were described. Neither catecholamines nor vasopressin stabilized the haemodynamic parameters. The use of methylene blue significantly improved the clinical condition of patients. Both were diagnosed with the allergic reaction to protamine and aprotynine .
Methylene blue following cardiac surgical procedures in vasoplegic patients may effectively increase arterial pressures and improve organ perfusion providing that the timing of its institution is appropriate. Its administration after the diagnosis of renal failure and anuria is considered too late. If vasoplegia is accompanied by low cardiac output syndrome, methylene blue is contraindicated. In such cases, haemodynamic parameters should be monitored using the Swan-Ganz catheter; based on the findings, criteria justifying administration of the drug may be verified and effects of therapy controlled.
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