Anticholinergic Toxidrome as a Possible Explanation for Methylene Blue Toxicity.

BACKGROUND Methylene blue has multiple uses in medicine. It is generally used to treat refractory vasoplegia and methemoglobin toxicity, and can be used as a dye to localize the parathyroid glands intra-operatively. In refractory vasoplegia, methylene blue inhibits endothelial nitric oxide and guanylate cyclase, causing vasoconstriction and potentially stabilizing blood pressure. Multiple complications have been associated with the use of methylene blue. These are related to either the sole effect of methylene blue or the combined effect of methylene blue and certain antidepressants, such as selective serotonin reuptake inhibitors (SSRIs). To the best of our knowledge, in the setting of post-cardiac surgery vasoplegia, there have been no reports of the neurological toxicity of methylene blue in the absence of SSRI use. In this case report, we describe the anticholinergic manifestations associated with the use of methylene blue in post-cardiac surgery vasoplegia. CASE REPORT A male patient in his mid-sixties with severe mitral regurgitation underwent elective mitral valve replacement. Postoperatively, he was hypotensive and required a high dose of vasopressors. Methylene blue was administered to treat refractory vasoplegia. The patient became anuric and febrile, with bilateral mydriasis. Internal cooling and continuous renal replacement therapy were initiated, and symptoms rapidly resolved. The patient was discharged after prolonged hospitalization with a permanent catheter for hemodialysis. CONCLUSIONS Anticholinergic toxidrome may explain the neurological adverse effects associated with high doses of methylene blue. Physicians should be cautious when using methylene blue in combination with other anticholinergic drugs and in conditions of renal failure. The development of methylene blue toxicity warrants the urgent discontinuation of the agent and early drug elimination.

Methylene Blue not Contraindicated in Treating Hemodynamic Instability in Pediatric and Neonate Patients.

The present review was carried out to describe publications on the use of methylene blue (MB) in pediatrics and neonatology, discussing dose, infusion rate, action characteristics, and possible benefits for a pediatric patient group. The research was performed on the data sources PubMed, BioMed Central, and Embase (updated on Aug 31, 2020) by two independent investigators. The selected articles included human studies that evaluated MB use in pediatric or neonatal patients with vasoplegia due to any cause, regardless of the applied methodology. The MB use and 0 to 18-years-old patients with vasodilatory shock were the adopted criteria. Exclusion criteria were the use of MB in patients without vasoplegia and patients ≥ 18-years-old. The primary endpoint was the increase in mean arterial pressure (MAP). Side effects and dose were also evaluated. Eleven studies were found, of which 10 were case reports, and 1 was a randomized clinical study. Only two of these studies were with neonatal patients (less than 28 days-old), reporting a small number of cases (1 and 6). All studies described the positive action of MB on MAP, allowing the decrease of vasoactive amines in several of them. No severe side effects or death related to the use of the medication were reported. The maximum dose used was 2 mg/kg, but there was no consensus on the infusion rate and drug administration timing. Finally, no theoretical or experimental basis sustains the decision to avoid MB in children claiming it can cause pulmonary hypertension. The same goes for the concern of a possible deleterious effect on inflammatory distress syndrome.

Profound Vasoplegia During Sacubitril/Valsartan Treatment After Heart Transplantation.

Vasoplegia occurs in up to 16% of patients who undergo heart transplantation (HT) and is associated with significant morbidity and mortality. We present a case of a 61-year-old man with ischemic cardiomyopathy receiving sacubitril/valsartan (Entresto; Novartis, Cambridge, MA) who developed profound hypotension after HT. He was treated with intravenous methylene blue and high-dose vasopressors, but developed acute kidney injury requiring dialysis and a prolonged stay in the intensive care unit. This case supports a potent vasodilatory effect of sacubitril/valsartan, and if confirmed by other studies, might warrant consideration for withholding treatment while awaiting HT, particularly in patients with risk factors for vasoplegia.

Methylene blue to treat vasoplegia due to a severe protamine reaction: a case report.

Protamine sulfate is used during coronary artery bypass graft surgery to reverse the anticoagulating effects of heparin. Vasoplegic syndrome is a state of endothelial dysregulation that produces profound vasodilatation that is refractory to vasopressors. This syndrome leads to systemic hypoperfusion and may progress to death. Up to 27% of patients after cardiac bypass may experience vasoplegia. Symptoms of vasoplegia may also be present in many different clinical settings. This case report describes a 57-year-old woman who after cardiac bypass experienced a severe protamine reaction with profound hypotension, which was unresponsive to volume resuscitation and vasopressor therapy. A dramatic increase in blood pressure resulted almost immediately after administration of methylene blue. This patient had no prior risk factors for a protamine reaction other than her current cardiac surgery. A review of the pathophysiologic characteristics associated with vasoplegia and the pharmacodynamics of methylene blue will potentially enable anesthesia providers to utilize this lifesaving drug when needed.

Assessment of long-term vasoplegia induced by brachial plexus block: a favorable effect for hemodialysis angioaccess surgery?

PURPOSE: Loco-regional anesthesia, along with the neurosensitive inhibition causes arterial and venous vasodilatation, that could be of interest for vascular access surgery. We evaluated the long term vasoplegia persistence after brachial plexic block. METHODS: Five patients submitted to brachial plexus block for an orthopedic procedure have been observed. Both radial arteries, that of the blocked arm and the opposite as a control, were analyzed by ultrasound examination, at time 0 and 360 minutes after anesthesia induction. All patients were treated with the same anesthesiologic protocol: axillary approach, use of an electroneurostimulator, injection 10 ml of ropivacain 7.5% + 10 ml of mepivacain 2%. The parameters evaluated from the arterial ultrasound flowmetry were: peak systolic velocity (PSV), end diastolic velocity (EDV) and resistance index (RI). RESULTS: No modification of the arterial flow were observed in the control arm at 0 and 360'after block induction. The blocked arm instead showed a significant decrease of the resistive index, stable at 360 minutes. CONCLUSIONS: The vasoplegia accompaning plexic block lasted 6 hours after anesthesia induction. Whereas this longstanding haemodynamic effect is beneficial for early patency of vascular access for hemodialysis, needs to be ascertained by further investigations.