Hello everybody. Well, I'm sorry I just get confused. So my name is Nuria Yala. I'm from Mexico, from Guadalajara, and I'm going to talk a little bit about this trial that we that we were doing there. It's an ejected methylene blue for patients in septic shock. We call the shock and blue trail, okay? And I'm sorry for my English. I'm just learning, okay? Okay, I'm an emergency physician, and I'm in the second year in my fellowship in intensive care, and my interests there include mechanical ventilation, burn injury, and sepsis. So I have no disclosure for this trial. Okay, let's let's talk about methylene blue. So as you know, there are just only two randomized clinical trials addressing the use of methylene blue in patients with septic shock with limited sample size. I mean, we're talking about 20 years ago. One is with 20 patients and the other one with 30. So this is like the most biggest trial recently with methylene blue and septic shock. Okay, so our hospital is one is in western Mexico. It's a reference center with capacity of 1,000 beds, and it's a or ICU some medical and surgical intensive care, and the intravenous methanol blue was provided by the institution. So we included patients more than 18 or at least 18 years old with septic 3 criteria and with a highly suspect or confirmed infection requiring norepinephrine to maintain and map at least or or greater than 65 millimeters of mercury and serum lactate more than 2 millimoles per liter after an adequate fluid resuscitation. We used fluid resuscitation, I mean, was guided by dynamic test for predictor of volume responsiveness before any IV fluid load, and the most common methods that we that we use is arctic velocity time integral, change after a passive leg rising, arterial pulse pressure variation, and tidal volume change. Respiratory variation in carotid peak flow velocity also. So the exclusion criteria were more than 24 hours since initiation of norepinephrine, pregnancy, current hemorrhagic obstructed or hypovolemic shock, pending damage control surgery, major burn, allergy to methyl and blue, phenothiazine or food dyes, recent intake, I mean talking about four weeks, or selective teratonin reuptake inhibitors and refusal to participate in this trial. So the randomization was stratified by center with 101 allocation radio, permuted blocks with a size of four, and the blighting was performed by covering fusion bags and PVC lines with opaque envelopes. It was a parallel trial and second blinding trial. So we have the two groups, the intervention group was given like a hundred milligrams of methylene blue in 500 milliliters of saline solution in an infusion of for six hours once daily, but we used three doses. I mean in the difference of the other studies where they're used like just one infusion for the four or six hours. This is different in our trial. And in the control group we use the same amount of milliliters and in an infusion of six hours and the same doses three days. So patients were follow-up until 28 days of enrollment with a time resolution shock as a primary outcome. We define shock resolution as a discontinuation of vasopressor for at least 84 hours and consecutive. Okay and the secondary outcomes was like vasopressor three days at 28 days, all-cause mortality at 28 days, time to lactate normalization less than two millimeters per liter, Langenstein ICU, change in serum creatinine, bilirubin, aspartate, alanine, amino transferase, PO2 radio and ejection fraction after intervention, and the dose reduction of norepinephrine requirement after the first dose of intervention. We take care, I mean, about these things because we know all the adverse effects that could have with methylene blue. So we got 308 patients. They were assessed for eligibility but the ethic commit, they didn't allow to include patients with COVID-19, so they were not eligible. So we just ran with 92 patients and 46 in each group. In the intervention group, one of them just decided to withdraw the concept before the, I mean, after the first dose, so there was 46 versus 49 patients. We have the baseline characteristics right here, so you can see in the tables they are pretty similar both groups like in the methylene blue and the control group. There's no significant differences between them. So we have a couple of major graphic here where you can see the time of 2-vasopressor discontinuation in the methylene group was 69 hours versus 94 hours in the control group. And 11% of the methylene blue group and 28% in the control group required reinitiation of norepinephrine within 48 hours after discontinuation. So we have like preference here in the, not preference, but better outcomes in the methylene blue group. So you can see in the tables, patients in the methylene blue group had one more day of vasopressor-free days at day 8, and serolactate normalizes 14 hours faster in patients in the methylene blue group. And they had a shorter ICU length on day 5, one day, too. Okay, the most common adverse effect was green-blue discoloration of urine in 90% of the patients in methylene group. And the maximum values of methamoglobin were significantly higher in patients in the methylene blue, but with no risk. So you can see here, we evaluate the eject fraction and the bilirubins and the POF102 radio very close, and there was no difference between groups. We built a ROC curve, including all the patients in methylene blue group, for analysis of the change in norepinephrine requirement after the first dose of methylene blue and shock reversal. A decrease of norepinephrine dose by at least or equal 32% has a highly high sensibility, 100%, and a specificity of 92% for prediction of shock reversal, with a positive likelihood radio of 13 and a negative likelihood radio of 0. With an area under the curve, 0.98. So almost to conclude this conversation, we can see that this is the largest randomized control trial addressing the early use of methylene blue in patients with septic shock. The other studies that we already read, and we know they're using in like in the vasoplasmic shock causes by cardiopulmonary bypass, and here's with septic shock. And the long period of observation allow us to identify the benefit of patient-centered outcomes, and unlikely previous studies allow intermediate doses like 1.2 milligrams per kilo, but repeated doses in three times of methylene blue could have been a key component of the efficacy and safety profile that we found in this study. The response to initial doses of methylene blue could be useful to discriminate the patients who will benefit more from his use. So in conclusion, methylene blue administered in three daily doses reduced vasopressor duration, cumulative fluid balance, and ICU and hospital length of stay among patients with septic shock has compared with standard care. There were no severe adverse effects related to use even in patients with RSO or acute kidney injury. Our results support the continuous research of methylene blue as an early adjective therapy in patients with septic shock to confirm the potential benefit in a larger multicenter randomized clinical trial. So thank you. I know you have some questions.

Dr. Nuria Yala

methylene blue

septic shock

Shock and Blue Trial

vasopressor use