Effect of Oxygen Saturation Targets on Neurologic Outcomes after Cardiac Arrest: A Secondary Analysis of the PILOT Trial

Effect of Oxygen Saturation Targets on Neurologic Outcomes after Cardiac Arrest: A Secondary Analysis of the PILOT Trial | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Effect of Oxygen Saturation Targets on Neurologic Outcomes after Cardiac Arrest: A Secondary Analysis of the PILOT Trial View ORCID Profile Stephanie C. DeMasi , Alexander T. Clark , Amelia L. Muhs , Jin H. Han , Kipp Shipley , Jared J. McKinney , Li Wang , Todd W. Rice , Ari Moskowitz , Matthew E. Prekker , Nicholas J Johnson , Wesley H. Self , Jonathan D. Casey , Matthew W. Semler , Kevin P. Seitz , Pragmatic Critical Care Research Group doi: https://doi.org/10.1101/2025.01.10.25320197 Stephanie C. DeMasi 1 Department of Emergency Medicine, Vanderbilt University Medical Center , Nashville, TN MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Stephanie C. DeMasi For correspondence: stephanie.demasi{at}vumc.org Alexander T. Clark 2 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School , Ann Arbor, MI, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Amelia L. Muhs 3 Division of Allergy, Pulmonary, and Critical Care Medicine Vanderbilt University Medical Center , Nashville, TN MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jin H. Han 1 Department of Emergency Medicine, Vanderbilt University Medical Center , Nashville, TN 4 Geriatric Research, Education, and Clinical Center, Tennessee Valley Healthcare System , Nashville, TN, USA MD, MSc Find this author on Google Scholar Find this author on PubMed Search for this author on this site Kipp Shipley 5 Department of Anesthesia Vanderbilt University Medical Center , Nashville, TN DNP, AGACNP Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jared J. McKinney 1 Department of Emergency Medicine, Vanderbilt University Medical Center , Nashville, TN MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Li Wang 6 Department of Biostatistics Vanderbilt University Medical Center , Nashville, TN MS Find this author on Google Scholar Find this author on PubMed Search for this author on this site Todd W. Rice 3 Division of Allergy, Pulmonary, and Critical Care Medicine Vanderbilt University Medical Center , Nashville, TN 7 Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center , Nashville, TN MD, MSc Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ari Moskowitz 8 Division of Critical Care Medicine, Montefiore Medical Center , Bronx, NY, USA MD MPH Find this author on Google Scholar Find this author on PubMed Search for this author on this site Matthew E. Prekker 9 Department of Emergency Medicine and Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, Hennepin County Medical Center , Minneapolis, MN, USA MD, MPH Find this author on Google Scholar Find this author on PubMed Search for this author on this site Nicholas J Johnson 10 Department of Emergency Medicine, Harborview Medical Center, University of Washington School of Medicine , Seattle, WA, USA 11 Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Washington , Seattle, WA, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Wesley H. Self 1 Department of Emergency Medicine, Vanderbilt University Medical Center , Nashville, TN 7 Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center , Nashville, TN MD, MPH Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jonathan D. Casey 3 Division of Allergy, Pulmonary, and Critical Care Medicine Vanderbilt University Medical Center , Nashville, TN 7 Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center , Nashville, TN MD, MSc Find this author on Google Scholar Find this author on PubMed Search for this author on this site Matthew W. Semler 3 Division of Allergy, Pulmonary, and Critical Care Medicine Vanderbilt University Medical Center , Nashville, TN 7 Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center , Nashville, TN MD, MSc Find this author on Google Scholar Find this author on PubMed Search for this author on this site Kevin P. Seitz 3 Division of Allergy, Pulmonary, and Critical Care Medicine Vanderbilt University Medical Center , Nashville, TN MD, MSc Find this author on Google Scholar Find this author on PubMed Search for this author on this site Abstract Full Text Info/History Metrics Supplementary material Data/Code Preview PDF ABSTRACT Background More than 600,000 adults in the United States experience a cardiac arrest each year. After resuscitation from cardiac arrest, most patients receive mechanical ventilation. The oxygenation target that optimizes neurologic outcomes after cardiac arrest is uncertain. Research Question After cardiac arrest, does a lower oxygen saturation (SpO 2 ) target improve neurologic outcomes compared to a higher SpO 2 target? Study Design and Methods We conducted a secondary analysis of patients who experienced a cardiac arrest before enrollment in the Pragmatic Investigation of optimal Oxygen Targets (PILOT) trial. The PILOT trial assigned critically ill adults receiving mechanical ventilation to a lower (88-92%), intermediate, (92-96%), or higher (96-100%) SpO 2 target. This subgroup analysis compared patients randomized to a lower-or-intermediate SpO 2 target (88-96%) versus a higher SpO 2 target (96-100%) with regard to the primary outcome of survival with a favorable neurologic outcome at hospital discharge (Cerebral Performance Category 1 or 2). The secondary outcome was in-hospital death. Results Of 2,987 patients in the PILOT trial, 339 (11.3%) experienced a cardiac arrest before enrollment: 221 were assigned to a lower-or-intermediate SpO 2 target, and 118 were assigned to a higher SpO 2 target. Overall, the median age was 60 years, 43.5% were female, 58.7% experienced an in-hospital cardiac arrest, and 10.2% had an initial shockable rhythm. Survival with a favorable neurologic outcome occurred in 50 patients (22.6%) assigned to a lower-or-intermediate SpO 2 target and 15 (12.7%) patients assigned to a higher SpO 2 target (P=0.03). In-hospital death occurred in 146 patients (66.1%) assigned to a lower-or-intermediate SpO 2 target and 89 (75.4%) assigned to a higher target (P=0.08). Interpretation Among patients receiving mechanical ventilation after a cardiac arrest, use of a lower-or-intermediate SpO 2 target was associated with a higher incidence of a favorable neurologic outcome compared with a higher target. A randomized trial comparing these targets in the cardiac arrest population is needed to confirm these findings. INTRODUCTION More than 600,000 adults in the United States (US) experience a cardiac arrest each year, of whom only 10-25% survive to hospital discharge. 1 , 2 Among patients who survive cardiac arrest, brain injury is common, is the leading cause of death, and is a major contributor to long-term disability. 3 , 4 After cardiac arrest, nearly all patients receive invasive mechanical ventilation. Clinicians titrate the fraction of inspired oxygen (FiO 2 ) on the mechanical ventilator to achieve a target arterial oxygen saturation, which is commonly measured by pulse oximetry (SpO 2 ). 3 After cardiac arrest, patients may be particularly susceptible to ongoing brain injury from extremes of oxygenation. Hypoxemia may worsen the hypoxic-ischemic injury that commonly occurs during the cardiac arrest. 5 Hyperoxemia may worsen brain injury by inducing cerebral vasoconstriction and creating additional reactive oxygen species. 4 While preclinical and observational studies have suggested that avoiding hyperoxemia may improve neurologic outcomes in survivors of cardiac arrest, 6 – 11 clinical trials evaluating the use of lower oxygenation targets have shown conflicting results, with some suggesting a mortality benefit, 12 , 13 some suggesting no effect, 14 , 15 and some suggesting harm. 16 Currently, the International Liaison Committee on Resuscitation guidelines recommend avoiding hyperoxemia with a low certainty of evidence. 5 Whether use of a lower-or-intermediate SpO 2 target rather than a higher SpO 2 target to avoid hyperoxemia prevents further brain injury and increases survival after cardiac arrest remains uncertain. To address this gap in knowledge, we conducted a secondary analysis of a recent randomized trial that evaluated SpO 2 targets among critically ill adults receiving invasive mechanical ventilation. We sought to examine the effect of using a lower SpO 2 target of 88-92% or an intermediate SpO 2 target of 92-96% compared to a higher SpO 2 target of 96-100% on outcomes in patients after cardiac arrest. We hypothesized that avoiding hyperoxemia by using a lower-or-intermediate SpO 2 target would increase the incidence of a favorable neurologic outcome at hospital discharge. METHODS Study Design This was a pre-planned subgroup analysis of the Pragmatic Investigation of optimal Oxygen Targets (PILOT) trial, which was a cluster-randomized, cluster-crossover trial in adult patients receiving invasive mechanical ventilation in the medical intensive care unit or the emergency department at a single academic medical center. 17 The PILOT trial compared the effects of lower, intermediate, and higher SpO 2 targets on ventilator-free days and in-hospital mortality among critically ill adults receiving mechanical ventilation and has been published previously. 17 Patients were enrolled at the first receipt of mechanical ventilation in a study unit between July 1, 2018, and August 31, 2021. The PILOT trial was approved by the institutional review board at [redacted for peer review]. Population All patients enrolled in the PILOT trial were screened for inclusion. To maximize our sample size, this included patients enrolled during one of the prespecified analytic washout periods in which patients received the assigned SpO 2 target but were not included in the primary analysis of the trial. Patients who experienced a cardiac arrest (defined as the receipt of chest compressions or defibrillation) with sustained return of spontaneous circulation (defined as spontaneous and sustained return of a pulse for 20 or more consecutive minutes) prior to enrollment were included in the analysis. 18 The PILOT trial prespecified cardiac arrest as a subgroup that was expected to modify the effect of the intervention on outcomes. 19 Study Interventions The trial protocol instructed respiratory therapists to adjust the FiO 2 administered in order to achieve an SpO 2 within the assigned target range from initiation of mechanical ventilation until discontinuation or transfer out of the study unit. For this analysis, we reduced the three trial groups in PILOT (SpO 2 88-92%, 92-96%, and 96-100%) to two groups in order to compare the lower-or-intermediate SpO 2 target group (SpO 2 88-96%) versus the higher SpO 2 target group (SpO 2 96-100%). The rationale for combining the lower and intermediate SpO 2 groups was to facilitate the examination of our hypothesis that avoiding hyperoxemia, which was a goal of both the lower and intermediate groups, would improve outcomes. Data Collection Trial personnel collected data on baseline characteristics and in-hospital outcomes from the electronic medical record. These included data on the initial presenting rhythm (shockable or non-shockable), witnessed (bystander, medical team, or unwitnessed) and cause of arrest (defined as the most likely primary cause of the arrest as determined by physician review and classified according to the Ustein guidelines). 20 Cardiac arrests from a medical cause were categorized as being due to respiratory failure, cardiac, shock, or other medical causes. Cardiac arrests not from a medical cause included cardiac arrests due to trauma, drug overdose, drowning, or asphyxia. 20 Data on SpO 2 and FiO 2 after enrollment were automatically extracted from the bedside monitor at a frequency of every one minute. 21 Study Outcomes The primary outcome was a favorable neurologic outcome at hospital discharge, defined as a Cerebral Performance Category of 1 (good cerebral performance) or 2 (moderate cerebral disability) at the time of hospital discharge. 22 – 25 The Cerebral Performance Category scale is a widely-used and validated measure for assessing the functional status of patients after cardiac arrest, and is predictive of long-term outcomes. 22 , 23 , 26 The scale consists of 5 mutually exclusive categories: 1, good cerebral performance; 2, moderate cerebral disability; 3, severe cerebral disability; 4, coma or vegetative state; 5, death. Data regarding patients’ Cerebral Performance Category at hospital discharge were recorded by two independent study physicians blinded to trial group assignment after independent reviews of the entire electronic medical record using a standardized case report form. A third blinded physician resolved cases with a disagreement between the initial two reviewers. Three-way disagreements were resolved by discussion among the three reviewers until a consensus was reached. This method of electronic medical record review and Cerebral Performance Category determination has been previously reported and validated. 22 The secondary outcome was in-hospital death from any cause. Exploratory outcomes included the number of days alive and free of invasive mechanical ventilation to 28 days (ventilator-free days) 27 and the location of discharge, dichotomized as discharge to home (home with or without skilled care) versus all other discharge destinations including death. Power Calculation We calculated that the fixed sample size of 339 patients (221 in the lower-or-intermediate SpO 2 target group and 118 in the higher target group) would provide 80% statistical power at a two-sided alpha level of 0.05 to detect an absolute difference of greater than 12.0% in a favorable neurological outcome at hospital discharge, assuming an incidence of 11% in the higher target group. 28 , 29 Statistical Analysis The primary analysis was an unadjusted, intention-to-treat comparison of the incidence of a favorable neurologic outcome (primary outcome) between patients assigned to a lower-or-intermediate SpO 2 target versus patients assigned to a higher SpO 2 target using a chi-squared test. We performed two additional analyses of Cerebral Performance Category. In the first, we fit a multivariable logistic regression model for the primary outcome with independent variables of trial group assignment and the following prespecified baseline covariates: age, sex, initial shockable rhythm, witnessed (bystander, medical team, or unwitnessed), cause of arrest, and the date of enrollment in the trial. In the second, we analyzed the Cerebral Performance Category as an ordinal outcome ranging from 1 (good cerebral performance) to 5 (death) using a proportional odds model, with an odds ratio (OR) greater than 1.0 indicating a more favorable outcome with a lower-or-intermediate SpO 2 target compared to a higher SpO 2 target. The secondary outcome (in-hospital death) and exploratory outcomes (discharge to home; ventilator-free days) were compared between the two study groups using a chi-squared test for dichotomous outcomes and a proportional odds model for ordinal outcomes. Analyses were performed using STATA version 18.0 and R version 4.1.0 (R Foundation for Statistical Computing). RESULTS Of the 2,987 patients enrolled in the PILOT trial, 378 patients had experienced a cardiac arrest when assessed at enrollment in the trial. Of these, 27 were excluded because the onset of the cardiac arrest was not prior to trial enrollment, 7 were excluded because they did not receive chest compressions or defibrillation, and 5 were excluded because return of spontaneous circulation was not sustained ( Figure 1 ). 18 The remaining 339 patients were included in this analysis, 221 of whom were assigned to the lower-or-intermediate SpO 2 targets and 118 of whom were assigned to the higher SpO 2 target. Overall, the median age was 60 years, 43.5% were female, 58.7% experienced an in-hospital cardiac arrest, and 10.2% had an initial shockable rhythm. The trial groups had similar characteristics at baseline ( Table 1 ). Download figure Open in new tab Figure 1. Number of patients screened, excluded, and included in the analysis. Abbreviations: PILOT = Pragmatic Investigation of Oxygen Targets trial View this table: View inline View popup Table 1. Baseline Characteristics. A total of 864,886 SpO 2 values were measured between enrollment and cessation of mechanical ventilation among the 339 patients, with a median interval between SpO 2 measurements of 1 minute. Oxygen saturation values were lower among patients assigned to the lower-or-intermediate SpO 2 targets than those assigned to the higher SpO 2 target ( Figure 2 ). Download figure Open in new tab Figure 2. SpO 2 and FiO 2 values in each group. Shown are the mean values (colored lines) and 95% confidence intervals (gray shading) for the hourly mean oxygen saturation as measured by pulse oximetry (SpO 2 ) (Panel A) and the fraction of inspired oxygen (FiO 2 ) (Panel B) from enrollment to study day 7. The data were censored at the time that invasive mechanical ventilation was discontinued. SpO 2 and FiO 2 values were obtained approximately every 1 minute, and hourly means were calculated by averaging all measurements obtained during the hour. The number of patients who were alive and receiving invasive mechanical ventilation in each group on each day is shown on the bottom panel. A single mean SpO 2 value was calculated for each patient; the median of these values was 95% (IQR 93 to 97%) in the combined lower-or-intermediate target group, and 97% (IQR 96 to 99%) in the higher target group. Similarly, values for FiO 2 administered were lower in patients assigned to the lower-or-intermediate SpO 2 targets than those assigned to the higher SpO 2 target ( Figure 2 ). A favorable neurologic outcome at hospital discharge occurred in 50 patients (22.6%) assigned to the lower-or-intermediate SpO 2 targets and 15 patients (12.7%) assigned to the higher SpO 2 target (absolute risk difference, 9.9 percentage points; 95% CI, 1.8 to 18.1; P=0.03) ( Figure 3 ). Results were similar in the adjusted analysis (adjusted odds ratio, 2.24; 95% CI 1.11 to 4.53; P=0.02) and in the analysis treating Cerebral Performance Category scale as an ordinal outcome ranging from 1 (good neurologic outcome) to 5 (death), (odds ratio, 1.63; 95% CI, 0.99 to 2.68; P=0.05). Download figure Open in new tab Figure 3. Results of the primary outcome (favorable neurologic outcome) and secondary outcome (in-hospital death). A favorable neurologic outcome at hospital discharge was defined as a Cerebral Performance Category of 1 (good cerebral performance) or 2 (moderate cerebral disability). Alive with poor neurologic outcome was defined as Cerebral Performance Category of 3 (severe cerebral disability) or 4 (coma or vegetative state). Category 5 was in-hospital death. A favorable neurological outcome occurred in 50 patients (22.6%) assigned to a lower-or-intermediate SpO 2 target and 15 patients (12.7%) assigned to a higher SpO 2 target (P=0.03). At 28 days after enrollment, 146 patients (66.1%) assigned to the lower-or-intermediate SpO 2 targets and 89 patients (75.4%) assigned to the higher SpO 2 target died prior to hospital discharge (absolute risk difference,-9.4 percentage points; 95% CI,-19.3 to 0.6; P=0.08). Additional outcomes are presented in Table 2 . View this table: View inline View popup Download powerpoint Table 2. Outcomes. DISCUSSION Among adult patients receiving invasive mechanical ventilation after cardiac arrest in this secondary analysis of a randomized trial, use of a lower-or-intermediate SpO 2 target (SpO2 88-96%) was associated with a higher incidence of a favorable neurologic outcome at hospital discharge compared to use of a higher SpO 2 target (SpO2 96-100%). Preclinical data suggest that a lower oxygenation target may be associated with improved neurologic outcomes in survivors of cardiac arrest, but recent clinical research has generated conflicting evidence. 6 – 9 , 30 The EXACT trial compared oxygen titration to achieve an SpO 2 of 90-94% versus an SpO 2 of 98-100% among patients in the prehospital or emergency department setting who had experienced an out-of-hospital cardiac arrest and found lower survival in the 90-94% group (absolute risk difference-9.6%; 95% CI-18.9 to-0.2). 16 This trial suggests that early oxygen titration, often before SpO 2 can be reliably measured, may lead to hypoxemia and worse clinical outcomes. The BOX trial compared a restrictive oxygenation target (PaO 2 of 68 to 75mmHg) versus a liberal oxygenation target (PaO 2 of 98-105mmHg) in comatose survivors of out-of-hospital cardiac arrest and found no difference in a composite of death or hospital discharge with severe disability or coma (hazard ratio, 0.95; 95% confidence interval, 0.75 to 1.21; P=0.69). 14 Notably, both the restrictive and liberal PaO 2 targets in the BOX trial correlated with SpO 2 values within the low-or-intermediate target ranges of the PILOT trial; few patients experienced severe hyperoxemia. In the ICU-ROX trial, the suspected hypoxic-ischemic encephalopathy subgroup demonstrated significantly lower death in the conservative-oxygen group (SpO 2 target of less than 97%) than the usual care group (relative risk, 0.73; 95% CI, 0.54 to 0.99) suggesting a potential benefit in this population. Most prior trials of oxygenation targets after cardiac arrest are limited to patients outside of the United States and those with an out-of-hospital cardiac arrest and an initial shockable rhythm. Little evidence is available to inform care for the 300,000 patients each year who experience an in-hospital cardiac arrest and patients with a non-shockable initial rhythm – the patient populations largely represented in the current study. 14 , 16 Our results support the use of a lower SpO 2 target to avoid hyperoxemia in patients after cardiac arrest may be beneficial. 12 , 13 Multiple ongoing randomized trials may help further address oxygenation targets in this population ( NCT05029167 and NCT03138005 ). 31 This secondary analysis has several strengths. The PILOT trial collected SpO 2 and FiO 2 values every minute, which allows for a highly granular assessment of the oxygenation and oxygen therapy experienced by patients in this analysis. Further, this trial enrolled patients at the first receipt of mechanical ventilation in the study emergency department or intensive care unit, capturing the early period in which the harmful effects of hyperoxia are thought to be most pronounced. 32 Most patients (58.7%) in this analysis experienced an in-hospital cardiac arrest, which is a patient group not well represented by most previous trials evaluating oxygenation targets after cardiac arrest. Finally, this analysis assessed functional outcomes such as the Cerebral Performance Category scale (analyzed as both a binary and ordinal outcome) and discharge destination. This study also has several limitations. The pragmatic trial and this secondary analysis used only data available from the electronic medical record, which limits the data available for assessment of baseline characteristics and outcomes available for analysis. The trial enrolled patients from a medical intensive care unit; resulting in a high proportion of patients with in-hospital cardiac arrest and without shockable rhythms. A study of this population fills an important knowledge gap but also limits our ability to compare these findings to prior trials. Sample size limited our ability to definitively evaluate mortality as an outcome. INTERPRETATION Among adults receiving mechanical ventilation after cardiac arrest in a randomized clinical trial of SpO 2 targets, survival with a favorable neurologic outcome occurred more often with use of a lower-or-intermediate SpO 2 target (88-96%), compared to use of a higher SpO 2 target (96-100%). Additional randomized clinical trials are needed to confirm these findings, particularly among patients after cardiac arrest without an initial shockable rhythm. Data Availability All data produced in the present study are available upon reasonable request to the authors. Note this manuscript is currently under peer review at CHEST. Footnotes Authors Contribution: Study concept and design: SCD, JDC, MWS, KPS, WHS. Acquisition of data: SCD, ATC, ALM, WHS, MWS, JDC, KPS. Analysis and interpretation of data: LW, SCD, KPS. Drafting of the initial manuscript: SCD. Critical revision of the manuscript for important intellectual content: all authors. SCD takes primary responsibility for the content of the manuscript. Grant Support : This work was supported in part by grants from the National Institutes of Health. J.D.C. was supported in part by the NIH (K23HL153584). S.C.D was supported in part by the NIH (5T32GM108554). K.P.S. was supported in part by the NIH (5T32HL087738). M.W.S. was supported in part by the NIH (K23HL143053). T.W.R. was supported in part by the NIH (UL1TR002243). W.H.S. was supported in part by the NIH (UL1TR002243). N.J.J. receives funding from NIH, CDC, and American Heart Association (AHA) and serves on guidelines committees for the AHA and International Liaison Committee on Resuscitation. Deanonymized version of the IRB statemen t: The PILOT trial was approved by the institutional review board at Vanderbilt University Medical Center. REFERENCES 1. ↵ Tsao CW , Aday AW , Almarzooq ZI , et al. Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association . Circulation . 2023 ;147(8): e93 – e621 . doi: 10.1161/CIR.0000000000001123 OpenUrl CrossRef PubMed 2. ↵ Merchant RM , Yang L , Becker LB , et al. Incidence of treated cardiac arrest in hospitalized patients in the United States . Crit Care Med . 2011 ; 39 ( 11 ): 2401 – 2406 . doi: 10.1097/CCM.0b013e3182257459 OpenUrl CrossRef PubMed Web of Science 3. ↵ Gräsner J , Wnent J . Survival after out-of-hospital cardiac arrest in Europe - Results of the EuReCa TWO study. Resuscitation . 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