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Good evening. My name is Katrina Cali. I'm a consultant in critical care. Um, it's and a neuro anesthesia working in the Belfast. Tough in social characterised. On this evening, I've been asked to review the hot ice you trial, which is published last month in the New England Journal of Medicine. At this point, like to declare a conflict of interest. I am on the organizing committee for critical Care reviews on the E critical care of you. Meeting off 2021 on one of our platinum sponsors is Armstrong Medical. I've also in the past received at speaker fees from Armstrong. Magical. I was a bit of disclaimer at this point. I'm not a researcher. I am a job inclination on. Really. For the past 12 months, my work has been exclusively focused on the cool. But I see you in the Belfast City Hospital. The element we know I know was Oxygen was first discovered and 17 72 by the Swedish chemist car Sheila and then in 17 74 juice of priestly and English chemist, independently discovered and oxygen unpublished his work first. So he is often notice being the first and to discover it, but it wasn't until 17 75. Antoine Loren Levadia named the actual element oxygen on his commissions, especially in intensive care. Stabbing we administer am oxygen every day to our patients with right, Actually, a lot of evidence bs. What high? We should target our therapies. And often it is a balance between avoiding hypoc CIA on them. The Converse Avoiding hyperoxia They have been relatively few large center trials. Looking at high, we deliver oxygen to your patients in the intensive care sounding. But in recent years the number that has been growing interest in this subspecialty specialist area and with the publication of several trials First Trial of Notes his Oxygen I See, which was published in the Journal of the American Medical Association and 2016 This was a single center trial conducted in an Italian medical surgical intensive care unit on and ruled 480 patients. The intervention arm was looking at targeted saturation of auction of 94 to 98% and why the control arm? The patients have a target of 97 200% saturations their primary. I come showed that the ice you mortality was significantly lower in their intervention group 11.6% versus 20.2%. Equipment to this trial was stopped early because of damage the hospital because of an earthquake. This was a single center. Study on the authors themselves recognized the need for a multi center trial to be performed. The Icy Rocks Trial was published in the New England Journal of Medicine in 2019. This is a trial conducted by the on sex Trogir it encompassing that work and 21 attempts of carries across the street Lawyer and you Zealand. A name on it just to reiterate it. 965 patients An intervention arm. The targeted auction saturations, off 97% or lower under feet saturation was above 97%. The fraction of inspired oxygen introduce for 10% every five minutes until the target saturation was reached in the control group, there was no upper limit set for oxygen. Saturations on their primary outcome, looked a friendly or three days. Remanded is a shin until day 28. 4 wing admission and they find no difference between the intervention on control groups with ventilator. Three days, 21.3 days in the intervention group, compared to 23.1 days in the control and 2020 also in the New England Journal of Medicine. Local, too published, gets results. This was a trial conducted in 13 80 years in fronts where they recruited 201 patients and in the intervention or, um, they targeted a PA or two of 7.3 to 9.3 killer Paschal's and in the control group that a targeted Pa Oh two of 12 to 14 Killer Pascal's their primary. Or it calms record of his death from any calls at 28 days. And there was no significant difference in these events between the intervention and control group. But it is worthy of note that this trial was stopped early at in in drum analysis stage because of the Avonex of increased recent Erica Ski Me A. And the intervention or the most recent trial on the one record focus on this evening, has been that the lower higher oxygenation targets for acute ischemic respiratory failure trial or Hot Ice You, which was published in January of this year in the New England Journal of Medicine on the trial results. Annoyance to the critical care of use meeting online. This is one of the largest randomized control trials, something in oxygenation in intensive care to do it. This was a randomized control trial with Wonder one. The allocation into the Controller Intervention Arms, which took please across 35 European and tons of care units between June 2017. On August 2000 and 20 in total, 2920th adult patients were in. Ruled into this trial I'm had popped ASUs of the investigators. At the outset, WAAS would targeting a pa or so tree off it kill a Pascal's reduced 90 day mortality by 5% points as compared with the pa Oh to 12. Kill a Pasquale's in intensive care patients who were admitted with Hypoc Simic. Respiratory failure. Researchers satellite five eligibility criteria prior to commencing the trial. All patients have to be adults so greater than 18 years they had to have been admitted acutely to in intensive care unit with hypoxic respiratory failure on they had to be within 12 hours of the intensive care admission to be enrolled in the trial. You also needed to have a heart Erie align present and because obviously it's gonna be regular arterial blood gas sampling on. Of course, they had to have auction administered if they were on open system or venous mass. That had to be greater than 10 liters per minute or in a closed system with an F i 02 greater than 0.5 on. There it comes that they were looking at her primary. I comes of death from any calls with the 90 days of randomization on secondary, I comes of one arm or serious adverse event. Look also looking at the percentage of days the patient Amanda live with right life support on the percentage of days the patient was alive after hospital discharge. At the 90 day follow up review, 4192 patients were assassin eligibility. One person, 264 patients were excluded at 712. Couldn't undergo randomization as they were with the 12 are free. Um, for enrollment 395. No provisions for consent. 125 already received home oxygen supplementation 99 were withdrawn from active therapy or were three and dad's during this admission. 49. We're required to receive hyper bark oxygen treatment on $44 going solid organ transplantation during that salsa, but admission also 20 It's were poisoned with carbon dioxide, cyanide or park wanting so could not be enrolled. Getting we're receiving long term mechanical ventilation for were previously been treated bleomycin three pregnant ladies were excluded on. One patient has maximum global. Name me on one patient at sickle cell disease, which meant that they were executed, which left the remainder of 2928 patients he underwent randomization. As you can see from the table 1441 patients in the intervention gripper, including the primary analysis on 1447 patients in the control group of kids included in the primary analysis. The characteristics between both groups were fairly similar and the median age was 70 in both arms else. As usual in the many of these intensive care trials, there's a higher number of male patients admitted to the intensive care, and I'm looking at Coreg. Cystic illnesses. They were all fairly much in terms of off the comorbid ease of the patients percent thing. The look specifically it's chemical heart disease, chronic heart failure, active metastatic concert, long term dialysis and interesting of the Androgel patients who suffer from COPD and active hematologic, a cancer of oxygenation strategies or particular interest in many of these groups. Given the M time period over we were, these patients were in rules not surprising, that there was a higher medical proportion off patients admitted, with 85.9 in the lower extremity Shin Target Group and 85.1% and medical admissions in the higher Oxygenation Target group. Unsurprisingly, the greatest calls for admission Sam's a constant care unit, was pneumonia. It was 57.7% patients in the lower oxygenation grip presenting with pneumonia, compared to 57.4% of patients in the higher oxygenation group. Use of mechanical ventilation prone positioning and healed reinserted, liters, extracorporeal memory in oxygenation, circulatory support, renal replacement therapy and blood transfusions were similar in both groups, and there was no substantial between group. Difference is regarding the positive and expert pressure. He conspired to pressures or tired of volumes amongst those patients. We were undergoing mechanical ventilation, a nose substantial between group difference and and expertise pressure among those who are undergoing no no obvious of Fanta, a shin of 90 days, 618 of the 1441 patients in the lower oxygenation grip on 613 of the 1447 patients and the higher auction a Shin Group had died. It was cocky. There's an adjusted restoration of 1.2, with 95% confidence intervals of 0.94 to 1.1 on 90 days. There was no significant Queen group difference and the percentage of days patients were alive with our life support or in the percentage of days that they were alive after hospital discharge. Percentage of patients who have new episodes of short myocardial ischemia, a scheming stroke or intestinal intestinal ischemia were similar in the two groups. The Coppola mayor estimates of survival shoe initial separation early on in the days, well, one randomization between the two groups, but the two you survival lines converged again, a 90 day follow up and so the conclusion drawn from the investor better grip waas lure oxygenation target did not result in lower mortality of 90 days than the higher target amongst those ice you patients admitted with acute hypoc Simic, Risperdal refigure. As with any trial, it's important to look strength limitations off the trials of they were conducted. This was a well conducted, randomized controlled trial and and and in ruled nearly 3000 patients was one of the biggest studies into auction, too. Dear. It was multi centered, looking at 35 intensive care units and across northern Europe. It was pragmatic by that. I mean, it's still avoid the clinician of the bad side. Teo decide on the interventions required and for the patients, rather than following prescriptive ventilator e strategy on In terms of follow up, 98% of the patients were included in the 90 day follow up, which shows the level of dedication on hard work taken to get these results together. The limitations I was expressed by the authors themselves the higher level of oxygenation was not. That would not have been a standard of care routinely tried to be achieved in many of these units. Clinicians patients on the relatives were obviously on blind it which arm the words you could see from that oxygen saturations of the bad side, but the common vest togethers were blinded to what intervention the patient has received. Um, for those patients who were on unopened system, standardized conversion tables were used to em cockatiel. The fracture of inspired auction delivered on this may have been over estimated in some of these systems. So what impact will the findings that the hot ice you try off my current practice? My current popular prep patient population perfectly March is the demographics patients within the trial 100% of my patients are night presenting with acute type proxemics. Risperdal Failure as I work in the well fast trust covert Positive Intensive Care unit, are given the constraints be freest in the last year with a covert palm. Dammit, I'm looking at how we can maximize our oxygen utilization with and the hospital Saturday. My current practice would have being except a pa or two over yet color Pascal's for the majority of my patients, unless there was another clinical indication room I have to re is that threshold. I think with this and study also a lysis is too reassure. Are colleagues working on their spirit reward, which essentially been turned into high dependency units with the high usage of high flow nasal oxygen or say pop, and that they can accept the lure pa or two. You, um, to guide them with their winning reducing of Risperdal. Your support were necessary. Great to be it. Avoid acceptable auction. Asian targets still have been completely answered. The answer groups are currently Rickert recruiting to the mega rocks trial. Mag aerobics is a serious of multi center multinational randomized Parnell group registry about it clinical trials nasty with within an overall 40,000 patient trial sample they had. Prosthesis of the mag Arrakis trial is that a conservative approach to oxygen therapy will reduce mortality compared to a liberal approach given the have a genetic of treatment response. They also prophesized that in patients with the cute breed and pathologies, all of them hypoxic brain injuries on patients with sepsis. Liberal oxygen arm will reduce mortality compared with conservative oxygen in the United Kingdom, It NARC is just a bite to start recruiting patients to their own air oxygenation trial called UK Rocks, the United Kingdom intensive care unit Randomized trial, comparing two approaches to oxygen therapy. Their research question is and mechanically ventilated adult admissions. Two. I See You is a conservative oxygen therapy superior to usual oxygen therapy in terms of oh cause mortality in 90 days on incremental course quality adjusted life years On the net monetary benefit of 90 days, this is going to be a U. K. Wide. Large scale, multi center doctor enables registry embedded randomized clinical trial with an internal pilot Fears on integrative economic evaluation The M is to evaluate the clinical and cost effectiveness of conservative oxygen therapy target in saturation off 92 93% as compared with usual care and McConnell leave out later patients in the United Kingdom. They will be enrolling patients over 18 years receiving invasive mechanical ventilation in the intensive care damn as a consequence of an unplanned intensive care admission or if envious of mechanical ventilation was commenced in the intensive care unit. The predicted sample size will be looking at 16.5 1000 patients in 100 National Health Service adult intensive care units on. They hope to finish your creating these patients in a 24 month recruitment period. So by the spring of 2023 so with so much research going on and a Ryan worked in tow oxygenation therapy strategies. We will surely begin to have unanswered the next couple of years. Many thanks for your attention and like to thank metal. And I'm still medical for inviting me to speak to you this evening. I might also take this opportunity, Teo, make you wear off the next critical curve. Use meeting for 2022 which we hope to hold physically in Titanic. Belfast from the 19th to the 21st off January. Ruby Discussing the best critical care trials from 2021 Many thanks again. Remember going forward to the panel discussion?