Use of methylene blue in the reversal of vasoplegia refractory to the use of catecholamines after aortobifemoral bypass

Abstracts

Há evidências de que o óxido nítrico (NO) tem importância na vasodilatação associada a reações vasoplégicas. O objetivo deste relato de caso é documentar um caso de vasoplegia refratária ao uso de catecolaminas após bypass aortobifemoral revertida com o uso de azul de metileno. Mulher, 50 anos, submetida a bypass aortobifemoral. Sem comorbidades. Saiu de sala cirúrgica extubada, estável e com pulsos distais presentes. Duas horas após a cirurgia, evoluiu com choque circulatório. Iniciada noradrenalina e investigadas causas de choque. Manteve-se com necessidades crescentes de aminas e parâmetros estáveis. No sexto dia pós-operatório, com a hipótese de vasoplegia refratária, optou-se pelo uso do azul. Resposta imediata, com queda nos níveis de aminas, sendo desligada a noradrenalina no dia seguinte. O azul de metileno inibe a guanilato ciclase, produtora de guanosina monofosfato cíclico. Especula-se que haja um sinergismo entre essas drogas, já que a sua associação permite a atuação do sistema adenosina monofosfato.

Azul de metileno; vasoplegia; bypass aortobifemoral; óxido nítrico

CASE REPORT

Use of methylene blue in the reversal of vasoplegia refractory to the use of catecholamines after aortobifemoral bypass

Mariana Raphaela Garcia de Araújo dos Santos; Luis Gustavo Campos da Silva; Paulo Roberto Barbosa Evora; Carlos Eli Piccinato; Edwaldo Edner Joviliano

Departamento de Cirurgia e Anatomia, Hospital das Clínicas de Ribeirão Preto, Medicine School of Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil

Correspondence

ABSTRACT

There is evidence that the nitric oxide plays an important role in the vasodilation associated with vasoplegic reactions. The objective of this case report is to document a case of catecholamine-refractory shock after aortobifemoral bypass treated with methylene blue. A 50-year-old woman was admitted for aortobifemoral bypass graft surgery. She did not present with any comorbidities. At the end of the surgery, she was breathing spontaneously, with palpable pedal pulses. Two hours later, the patient presented shock. Noradrenaline infusion was initiated and the causes of shock were investigated. She required increasing doses of amines and her parameters were stable. On the sixth day after surgery, methylene blue was administered due to the hypothesis of refractory vasoplegia. There was immediate response, with decrease in the catecholamine infusion levels until its withdrawal on the next day. Methylene blue inhibits the enzyme guanylate cyclase that produces GMPc. There might be a synergism between these two drugs, since their association allows the action of the AMPc system.

Keywords: Methylene blue, vasoplegia, aortobifemoral bypass, nitric oxide.

Introduction

There is important evidence that nitric oxide (NO) plays a progressively significant role in vasodilation associated to various forms of circulatory shock. NO is a short-lived substance, formed from amino acid L-arginine by a group of enzymes called NO synthases (NOS), whose regular production is maintained by a series of antigens acting on the surface of the endothelial cell, among others (Figure 1). O NO ativa a guanilil ciclase solúvel, diminuindo a quantidade de cálcio intracelular e facilitando o relaxamento do músculo liso. NO activates soluble guanylyl cyclase, diminishing the amount of intracellular calcium and facilitating relaxation of the smooth muscle. Currently it is known that NO is associated with vasoplegic reactions related to sepsis^1-3 and anaphylaxis.^4,5

The objective of this case report is to document a case of cathecolamine-refractory vasoplegia, probably secondary to a systemic inflammatory response syndrome (SIRS), after aortobifemoral bypass, which was reversed by the use of methylene blue, a competitive inhibitor of the enzyme guanylyl cyclase.

Case report

A 50-year-old female patient was submitted to an aortobifemoral bypass due to aortoiliac obstruction. She smoked regularly during 30 years and had dislypidemia. She did not present with hypertension, cardiopathy, or diabetes mellitus. The drugs being used were acetylsalicylic acid and simvastatin. After the surgery, she was breathing spontaneously, conscious and oriented. Distal pulses, previously absent, were present and palpable, with an ankle - brachial index (ABI) of 1.0.

Around 2 hours after the surgery, the patient evolved with hypertension (60 x 40 mm Hg), cardiac frequency (CF) of 100 bpm and central venous pressure (CVP) of 13 cm H2O. Noradrenaline was initiated in 0.5 mL/kg/min. Causes for hypovolemic, and cardiogenic shock, and pulmonary thromboembolism were investigated (follow up to hematimetric levels, thorax x-ray, ecocardiography, in addition to all the routine postoperative biochemical exams after an important surgery). All the complementary exams were normal, except for a leukocytosis (white blood cell count = 13.000 Gpt/L). In the subsequent hours, the patient had a progressive need for vasoactive amines to maintain hemodynamic parameters.

On the third postoperative day, all parameters stable (diuresis, no decrease in hematimetric levels), she presented with a fever peak of 38°C.

On the sixth postoperative day, we were faced with the following situation: noradrenaline: 2.4 mcg/kg/min, dopamine: 20 mcg/min, no hematimetric alterations, PVC: 18 cm H20, diuresis: 100mL/hour, AP: 70 x 50, CF: 120 bpm, patient warm and with palpable and broad pulses in the lower limbs.

With the diagnostic hypothesis of amine-refractory vasoplegia, probably secondary to SIRS, methylene blue (2 mL/kg in bolus EV) was chosen, and, 2 hours after, the same dose. During the methylene blue bolus, noradrenaline was reduced to 1.5 mcg/kg/min, and dopamine was interrupted. On the following day, noradrenaline dose was 0.25 mcg/kg/min. Seven days after the surgery, the use of noradrenaline was suspended. The patient remained hospitalized in the Intensive Therapy Center, because she needed ventilatory support.

She was moved to the ward on the 23rd day after the surgery, since it was necessary to finish the treatment for pneumonia. She was stable, had no fever and no surgical wound alterations, accepting diet with present and broad pulses (ITB = 1). Discharge from hospital happened 26 days after the surgery.

She returned to the outpatient clinic after 30 days, feeling well, with no complaints, walking with ITB = 1.0 bilaterally. Surgical wound had no alterations. A return was scheduled 3 months after for clinical re-evaluation.

Discussion

The systemic inflammatory response syndrome is triggered by the production of post-inflammatory kinins and may result in organic dysfunction in more severe cases. It is more frequently observed in postoperative periods of cardiac surgery with extracorporeal perfusion, with the possibility of myocardial reperfusion lesion, pulmonary lesion and profound systemic vasodilation, resulting in a considerable increase in postoperative morbidity. SIRS is defined, according to the American College of Chest Physicians / Society of Critical Care Medicine Consensus Conference, by the occurrence of two or more of the following signs: abnormalities in body temperature (> 38 °C < 36 °C); persistent tachycardia (CF > 90 bpm); tachypnea or hyperventilation (respiratory frequency > 20/min, or CO2 partial pressure < 32 mm Hg), and leukocytosis or leukopenia (leukocytes count > 12,000 Gpt/L or < 4,000 Gpt/L).⁶ SIRS mechanism is not fully understood. The activation of neutrophils and free radicals, endotoxins, and kinins production are mechanisms that participate in the SIRS inflammatory process, as well as in the processes of lesion in muscle-skeletal ischemia-reperfusion.^5,7,8 Vasoplegia observed in the case described had a similar behavior to the one observed in cases described after heart surgery. Winnock et al. have already described a state of circulatory collapse with significant skin erythema resembling anaphylactic shock after aortoiliac surgery.⁶

The mechanism through which vasoplegia is established occurs as in the adverse reactions observed in the cases of protamine use or sepsis. Induction, through specific antigens, of mast cells' surface receptors triggers the liberation of a series of mediators, some of them leading to an increase in mediators' production and some of them leading to an increase in NO production through NOS regulation. Other possibility is that other antigens may directly stimulate the endothelial cell in the conversion of the amino acid L-arginine into NO.⁹

NO synthesis by the organism is regulated by NOS, divided in 3 types: neuronal NOS, constitutive NOS, and inducible NOS (Figure 2). In situations of sepsis, anaphylaxis and vasoplegic syndromes, an activation of inducible NOS occurs, exponentially increasing the amount of NO in the organism. This exaggerated increase leads to a relaxation in smooth muscles, dependent on guanosine monophosphate (cGMP). This mechanism is closely correlated with the adenosin monophosphate system, in which noradrenaline acts (negative feedback). The cGMP pathway, when highly activated, blocks the cAMP pathway (autoregulation).

The use of methylene blue has been described in different clinical situations. Its action on metahemoglobinemia was described, being helpful in the chronic treatment of urolitiasis. More recently its use has been described in the treatment of hemodynamic alterations in refractory vasoplegia, anaphylaxis, and in septic shock.¹⁰ Its toxicity related to dosage includes hemolytic anemia, cardiac arrhythmias, skin desquamation, abdominal pain, bluish skin and urine, in addition to producing hyperbilirubinemia in newborns. Its action consists of competitive inhibition of the enzyme guanylate cyclase, which produces cGMP. This inhibition of the cGMP system would allow a more effective action of the cAMP system induced by noradrenaline. In the case described, we highlighted the occurrence of the vasoplegic phenomenon after aortoiliac surgery, probably secondary to SIRS triggered by aortic clamping and reperfusion. It must be emphasized that noradrenaline is still the drug of choice in situations of vasoplegic shock. What might be reflected upon is the synergism between these two drugs, because their association permits the cAMP system to be free to act, since there is an at least partial block in the cGMP system due to the action of methylene blue (cross-talk).

Referências

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Publication Dates

• Publication in this collection
  30 Apr 2010
• Date of issue
  2010

History

• Received
  17 Apr 2009
• Accepted
  19 Oct 2009