All right. Good afternoon, everyone. Thanks for having me here. So I have no disclosures to make. And in the next 15 minutes, I'm going to take us through four trials published in the last year looking at cardiac arrest management or post-cardiac arrest management and blood pressure, oxygen targets, and temperature management. Starting off with blood pressure management. So post-resuscitation care requires active blood pressure management to maintain a perfusion pressure to the brain, heart, and kidneys and other organs. After an arrest, most patients have some element of cardiac dysfunction, but evidence for specific blood pressure targets still remains limited. There have been some small trials that weren't powered to evaluate clinical or safety endpoints that showed neutral results for different blood pressure targets after cardiac arrest. Some argue for a higher MAP target post-cardiac arrest in order to account for a lower perfusion at any given pressure. And in patients with sepsis, there has been shown that those with pre-existing hypertension targeting a higher MAP can be associated with a lower rate of dialysis. The Box trial, which looked at blood pressure and oxygenation targets in post-resuscitation care, looked to ask if a higher or lower target mean arterial pressure was superior in preventing death or brain injury following cardiac arrest. This was a two-center randomized control trial in Denmark looking at two interventions, blood pressure management and oxygen target. Eligible patients included comatose adults after an out-of-hospital cardiac arrest of presumed cardiac cause. Patients with unwitnessed asystole, suspected stroke, or intracranial bleeding were excluded, as well as any of those with refractory shock or limitations in their care. Patients were randomized after their hospital arrival to either a higher target mean arterial pressure of 77 millimeters mercury or to a lower MAP target of 63 millimeters mercury. The intervention was particularly unique in that the intervention was blinded, so the invasive blood pressure monitoring device was calibrated to report a blood pressure that was either a MAP 10% lower or higher than the actual so that the team targeted a MAP of 70 for all patients enrolled in the trial. Their primary outcome was a composite score or hazard of death or discharge from the hospital with severe neurologic disability or coma up to 90 days from randomization. A total of 789 patients were enrolled in the trial with 393 in the high blood pressure target group and 396 in the low target group. 81% of the participants were male and 85% had a shockable arrest and a mean time to return a spontaneous circulation of 21 minutes. In the high blood pressure target group, 133 patients or 34% had the primary outcome of death or discharge from the hospital with severe neurologic disability. And in the low blood pressure target group, 127 patients or 32% had the primary outcome. I've shown here the Kaplan-Meier survival curve for the primary outcome, so survival free from death or discharge with severe neurologic disability at 90 days and a hazard ratio of 1.08 with a confidence interval that clearly includes 1. Highlighted here are some key secondary outcomes that showed no difference, including death from any cause at 90 days, need for renal replacement therapy, and median neuron specific enolase levels, as well as there was no difference in any neurocognitive ability at 90 days between the two groups. They did several pre-specified subgroup analyses and there was no difference in any of these subgroups, including those patients with pre-existing hypertension. So this was a fairly robust trial with a unique method of blinding for blood pressure targets. They did achieve good separation in the blood pressure targets and vasopressor use between both groups. However, overall the population was very selective. It was two large referral centers in Denmark and the patients coming in had a low risk of a poor outcome at the outset, a high prevalence of acute coronary syndrome. Additionally, the trial was powered for a 30% relative risk reduction, which for anyone doing critical care trials, that's a fairly high relative risk reduction. Additionally, their protocol recommended use of dopamine as their second line vasopressor use after norepinephrine to achieve the target map, which may limit its generalizability. Lastly, the mean difference between the two groups and their maps was about 10 millimeters of mercury, which some may argue is not maybe a clinically significant difference. This study didn't show a difference in the risk of death or poor neurologic outcome between two clinically relevant map targets, adding to the smaller open-label trials previously that showed a neutral result. Including in those patients with pre-existing hypertension, there was no benefit of a higher blood pressure target. However, this trial may provide a roadmap for future studies to test a higher than clinically relevant map target to reach those maps where cerebral autoregulation may be affected following cardiac arrest. At my bottom line for this trial, I'm still going to target a map of greater than 65 post-cardiac arrest. Moving on to oxygen targets following cardiac arrest, so reperfusion to the hypoxic brain after spontaneous circulation is restored can cause further injury. Some observational studies have shown an increased risk of ischemic encephalopathy and death with liberal oxygenation, and animal models of cardiac arrest can suggest that reperfusion and hyperoxia can worsen brain damage through oxygen-free radicals. On the flip side, restrictive oxygenation can increase your risk for tissue hypoxia. Similar to the blood pressure target trials, prior studies have been small and not powered for clinical or safety endpoints. In the ICU ROCKS trial, there was a post-hoc subgroup analysis in patients with ischemic encephalopathy that suggested that conservative oxygen therapy may be beneficial over usual care. So the second part of the ROCKS trial aimed to evaluate if a restrictive or a liberal oxygen target was superior in once again preventing death or discharge with severe neurologic injury after cardiac arrest. Again, this is the same trial we just presented out of hospital of cardiac arrest, adults who are comatose after spontaneous circulation is restored. Patients were also randomized in a two-by-two factorial design to either a restrictive oxygen target, targeting a PaO2 of 68 to 75 millimeters mercury, or to a liberal target targeting a PaO2 of 98 to 105 millimeters mercury after arrival to the ICU. To achieve their target oxygenation, FiO2 was set at 30% initially in the restrictive group and 60% in the liberal group, and then further titrations made for the assigned target. If the peripheral O2 saturation fell below 93%, the FiO2 was adjusted for the participants. Other ventilator settings, including PEEP, were actually left to the treating physician's discretion, and this part of the study was unblinded. So once again, of the 789 patients, there were 394 in the restrictive target group and 395 in the liberal oxygen target group. Baseline characteristics were similar between the two groups, and at initial arrival in the ICU before the intervention was started, they had similar PaO2 and FiO2 levels with separation of their oxygenation at about two to four hours in the ICU. In the restrictive group, 126 patients, or 32%, had the primary outcome of death or severe neurologic disability by 90 days, and in the liberal group, 134, or 34%, of the patients. Once again, this led to a hazard ratio of close to 1.95 with a 95% confidence interval, including one, and I've shown here, once again, the Kaplan-Meier curves for survival free from death or disability. There was no interaction with the blood pressure group, or intervention, notably. Once again, I've just highlighted a few of the key secondary outcomes, and there was no difference in those as well as no difference in other neurologic abilities at 90 days, and there was no difference in any adverse events or in any of the pre-specified subgroups. Limitations, so obviously this part of the study was unblinded, but additionally, the restrictive group, actually, during their period of intervention, had high PaO2 levels that neared the upper limit of the target, and in overall, in both groups, the P to F ratio was fairly high. At time of enrollment and randomization, most of the patients had similar PaO2 levels, and these were actually higher than even the upper limit in the liberal groups, so the average PaO2 level at time of enrollment was about 113 millimeters mercury. Overall, this suggests that there was a lower risk of illness and lower severity and decreased frequency of hypoxic respiratory events and failure in this group, so in other words, this population may have been too healthy for the actual intervention to show any benefit. Lastly, the patients in the liberal group actually were shown to have higher PEEP levels during the intervention period compared to the restrictive group. I'm going to, in very briefly, discuss one other article, the exact trial that actually looked if oxygen, targeting a lower oxygen saturation in earlier post-resuscitation care improved survival in cardiac arrest, so one of the issues raised by the box trial is the intervention started after patients presented to the ICU, raising the question if we were to intervene and target a different oxygen saturation earlier, i.e. in pre-hospital care or a more aggressive target, would that end up leading to a difference in survival? The study was performed in 15 hospitals in Australia and two EMS services, once again including comatose adults after return of spontaneous circulation without a hospital cardiac arrest and included only those adults with an initial saturation of 95%. They were randomized either to a target low oxygen saturation of 90 to 94% via peripheral oximetry or a standard oxygen target of 98 to 100%. To achieve this, patients were either titrated to a low FiO2 at the outset or given standard 100% FiO2 or high flow. And the intervention was continued until the first ABG administration to the ICU. Titration to 100% was allowed for subsequent intubation or hypoxic events after enrollment into the trial. And the primary outcome was survival to hospital discharge and of the 425 patients, about 38% in the intervention group and 47% in the high target group survived to hospital discharge, leading to an unadjusted odds ratio of 0.68 but a confidence interval that did touch one. This study though was limited in its power. It was stopped early due to poor enrollment and then as well as use of peripheral oxygen saturation as their target intervention given known issues with its measurements. Both these studies showed no difference in outcomes with restrictive or liberal oxygenation target following cardiac arrest. The most recent European guidelines recommended target oxygenation of 94 to 98% or a PaO2 of 65 to 100 millimeters of mercury and recommend that hyperoxia should be avoided. However, this question may not yet be closed. Ongoing is the MEGA-ROCS trial which is a set of three registry embedded trials and one arm of the trial is looking at restrictive versus liberal oxygenation therapy in patients with hypoxic ischemic injury post-cardiac arrest. So lastly, looking at fever, so current guide or temperature management in cardiac arrest. Current guidelines recommend to avoid fever in patients who are comatose after cardiac arrest but the optimal temperature is still under debate. In the early 2000s after the HACA trial supported hypothermia, that became standard of care until the TTM1 trial showed that there was no benefit to targeting a temperature of 33 over 36 degrees Celsius. Subsequently, the TTM2 trial showed there was no difference in hypothermia to 33 degrees versus avoidance of fever and showed an increase in adverse events and differences in secondary outcomes to recommend against hypothermia. However, most of these trials were done in out of hospital cardiac arrest patients. This trial sought to ask if hypothermic temperature control after in-hospital cardiac arrest reduced mortality. This was a multi-center randomized control trial of 11 hospitals in Germany. Once again, our patients were adults who were comatose after an in-hospital cardiac arrest irrespective of their initial rhythm. Those adults with a re-arrest or out of hospital cardiac arrest were excluded. The intervention arm targeted mild hypothermia of 32 to 34 degrees Celsius for 24 hours followed by slow re-warming versus standard of care which was normothermia with no active temperature management although they did recommend avoidance of fever. The primary outcome was all-cause mortality at 180 days and they also used a Cox model to generate a hazard ratio model adjusting for age and initial rhythm. There were 249 patients randomized, 126 were assigned to the hypothermia arm, 123 to normothermia. The majority of the patients were men with a mean age of about 73 and 54 of the arrests took place in medical wards. Asystole and PEA were the most common initial rhythm. There didn't appear to be any major differences in their baseline characteristics of the patients in the 126 patients in the hypothermia arm, 87 or 73% died by 180 days and 84 or 71% in the normothermia died by 180 days. The Cox regression model showed adjusting for age and initial rhythm didn't show a reduced hazard of death. And there were no differences in any of their planned secondary outcomes. So this was, even though this was one of the first studies to look solely at in-hospital cardiac arrest and the role of hypothermia or normothermia, the study's enrollment was reduced after an unplanned interim analysis and thereby reducing the power of the study. The study was also unblinded. And one of the things I found interesting is the study took place in about, it was designed and conducted before the TTM1 and TTM2 trials actually came out and was published subsequently only this year, well after those trials have come out. So although this was one of the first articles to look at in-hospital cardiac arrest and the role of hypothermia, they did not show a difference in targeted hypothermia versus normothermia in in-hospital cardiac arrest. Current guidelines recommend active fever avoidance and that there is insufficient evidence to recommend for or against hypothermia in the subgroup of cardiac arrest patients. Once again, for me, this trial is not changing my practice. I'm going to continue to target a temperature of 36 degrees in patients who are comatose post-arrest with fever avoidance for up to 72 hours. Thank you, and unsurprisingly for all cardiac arrest patients, there was no change in management from these trials.

cardiac arrest

blood pressure management

oxygen targets

temperature management

mortality