Vasoplegia during radical prostatectomy: Methylene blue to rescue

Dear Editor,

A 65-year-male known case of hypertension on medical management (Tablet Amlodipine 5 mg once daily) and of chronic obstructive pulmonary disease was operated upon for laparoscopic radical prostatectomy. Preoperative laboratory investigations and pulmonary function tests were within normal limits. Cardiology workup was indicative of low risk for adverse cardiac event. Prostate biopsy was suggestive of adenocarcinoma of prostate. Patient was accepted for surgery under general anaesthesia with invasive monitoring as ASA Class II.

General anaesthesia was induced using midazolam, propofol, fentanyl, and cis-Atracurium and maintained with isoflurane in oxygen and air. Monitoring included electrocardiogram (EKG), non-invasive blood pressure (NIBP), and pulse oximetry (SPO2). Radial artery was cannulated and transduced to monitor blood pressure. Pneumoperitoneum was created and surgical ports were established. Surgery commenced in extreme Trendelenburg position. During dissection around dorsal venous complex (DVC) bleeding was troublesome in view of which surgery was converted to open. During this time, hypotension with sinus tachycardia was observed. Response to fluid boluses, crystalloid and then colloid (Human Albumin, HAlb, 4%) was insufficient and ill sustained. Baseline hemoglobin (Hb) was 11 gm/dl. Trigger for blood transfusion at our hospital is Hb of 8 gm/dl. Blood loss was accordingly replaced with packed red blood cells and Hb was maintained at all points of time in excess of 8 gm/dl. A total of 3 packed red blood cells and 4 liters of crystalloid and 1000 ml of 4% Human Albumin were transfused by this time. Nor-Adrenaline infusion was started but was not proving helpful even in incremental doses. Ionized calcium levels were corrected guided by serum electrolytes using arterial blood gas (ABG) analysis. Blood pH was within normal range at all the times. Vitamin C, 2 gm was added hoping for better response to vasopressors. Transesophageal echocardiography (TEE) was done and depicted adequate volume status with hypercontractile left ventricle, suggestive of decreased systemic vascular resistance (SVR). Adrenaline and then vasopressin infusion were added sequentially. Blood pressure, however, continued to be non-responsive and remained around systolic of 60-65 and diastolic of 30-35 mmHg. A diagnosis of catecholamine resistant hypotension (CRH) or severe vasoplegia was then made.[1] Methylene blue 100 mg was administered in 100 ml saline over 20 minutes. Blood pressures responded within minutes of completion of infusion. Vasopressors could be tapered off in next 1 hour. Surgery was concluded and patient was shifted to intensive care unit for elective mechanical ventilation overnight, following which he was weaned off mechanical ventilation. Rest of the clinical course was uneventful and patient was discharged to home.

Malignant prostate tissue unlike normal prostate tissue is known to manifest Cyclooxygenase-2(COX-2) and inducible nitric oxide syanthase-2(iNOS) and their expression is considered a prognostic marker.[2,3] NOS among other things, causes vasodilatation by acting on vascular smooth muscle cells. Studies have revealed that nitric oxide synthase (NOS) activity is human prostate is greater in peripheral zones than in the transition zone. Inducible from of cyclooxygenase, COX-2, converts arachidonic acid to prostaglandins (PG). COX-2 is an important contributor to inflammation and its overexpression is associated with uncontrolled cell proliferation, neovascularization, and angiogenesis mediated via COX-2 derived PGE2. PGE2 thus formed, also perpetuates iNOS activity.

PGE2 mediated inflammation and iNOS mediated vasodilatation, we suspect was the reason for occurrence of vasoplegia in our patient. These mediators of inflammation and vasoplegia were probably released into systemic circulation during dissection around DVC of prostate and that manifested as severe vasoplegia, refractory to inotropes and vasopressors. Methylene blue is of proven value in management of catacholamine refractory vasoplegia.[4] It acts by inhibiting the activity of enzyme guanylate cyclase and decreases the Cyclic GMP to reverse the consequent smooth muscle relaxation. Methylene blue usage in our patient rescued the hemodynamics, otherwise unresponsive to fluids and to the escalating doses of vasopressors and also confirmed the diagnosis.

Authors believe that awareness about possibility of such haemodynamic consequence in prostate surgery and its pathophysiology is important and that should such is witnessed, methylene blue may be used sooner.

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Conflicts of interest

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