Apnea Test for Brain-Death Determination: A Seven-Years Retrospective Study in a French University Hospital

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Apnea Test for Brain-Death Determination: A Seven-Years Retrospective Study in a French University Hospital | 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 Apnea Test for Brain-Death Determination: A Seven-Years Retrospective Study in a French University Hospital Baptiste Hirsinger , Laurent Martin-Lefèvre , Karim Lakhal , Alexandre Bourdiol , Thierry Lepoivre , RN Matthieu Delahaye , Emmanuel Canet , View ORCID Profile Jean-Baptiste Lascarrou doi: https://doi.org/10.1101/2025.10.14.25337990 Baptiste Hirsinger 1 Medecine Intensive Reanimation, Nantes University Hospital , Nantes, France MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Laurent Martin-Lefèvre 2 Organ Donation Department, Nantes University Hospital , Nantes, France MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Karim Lakhal 3 Department of Anesthesiology and Critical Care at Laennec Hospital, Nantes University Hospital , Nantes, France MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Alexandre Bourdiol 4 Surgical Intensive Care Unit, Nantes University Hospital , Nantes, France MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Thierry Lepoivre 5 Cardiothoracic Surgery Intensive Care Unit, Nantes University Hospital , France MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site RN Matthieu Delahaye 1 Medecine Intensive Reanimation, Nantes University Hospital , Nantes, France Find this author on Google Scholar Find this author on PubMed Search for this author on this site Emmanuel Canet 1 Medecine Intensive Reanimation, Nantes University Hospital , Nantes, France MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jean-Baptiste Lascarrou 6 Medecine Intensive Reanimation, Motion-Interactions-Performance Laboratory (MIP) , UR 4334, Nantes University Hospital , Nantes, France MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Jean-Baptiste Lascarrou For correspondence: jeanbaptiste.lascarrou{at}chu-nantes.fr Abstract Full Text Info/History Metrics Data/Code Preview PDF ABSTRACT Background The apnea test is essential for the diagnosis of death by neurologic criteria but clinical data are scarce. Research Question How often and why apnea testing was not done or was aborted, how often the apnea test was completed, and the results of aborted and completed tests (positive/negative/inconclusive). Study Design and Methods This retrospective observational cohort study enrolled patients screened for death by neurologic criteria in four intensive care units at a French university hospital in 2015–2022. The main outcomes were the proportion of patients in whom the apnea test was not done due to safety concerns, the proportion of tested patients in whom the test was aborted because of adverse events, completed tests, and the results of tests. Adverse events were described. We measured arterial pH, PaO 2 , and PaCO 2 at the start and end of each test. In patients with multiple tests, only the first was considered for the study. Results Of 371 patients screened for death by neurologic criteria, 52 (14%) did not undergo apnea testing, mainly because of respiratory or hemodynamic instability. Among all apnea tests, 94% were positive, 2% negative, and 4% inconclusive. The test was aborted in 34 (11%) patients due to adverse events, of which the most common was hypoxemia; five other severe adverse events were recorded. Test duration varied substantially even when considering only completed tests. The proportion of patients who became donors was not significantly different across the groups with completed tests, aborted tests, or no test. Interpretation Our data confirm that in most cases, the apnea test is conducted, completed and generally safe for diagnosing death by neurologic criteria. However, further research is needed to identify risk factors for adverse events during testing, contraindications to testing, and the optimal protocol for conducting the apnea test according to the characteristics of each patient. BACKGROUND Brain death (BD), or death by neurological criteria (DNC), is now widely accepted as a definition of death. BD/DNC can occur in a patient with persistent cardiac output, which maintains oxygen and nutrient delivery to the organs, making them potentially suitable for transplantation. In 1995, the American Academy of Neurology stated that BD/DNC can be diagnosed when three clinical criteria are met simultaneously: unresponsive coma, abolition of brainstem reflexes, and absence of spontaneous breathing. 1 , 2 This last criterion must be verified by an apnea test, in which the patient is disconnected from the ventilator to determine whether spontaneous breathing then occurs in response to hypercapnia. The apnea test must be performed in patients with catastrophic brain injury, in the absence of confounding factors (e.g., sedatives, neuromuscular blocking agents, hypothermia, and severe hydroelectrolytic disorders) and after a period of preoxygenation. Passive oxygenation should be provided during the test to ensure sufficient oxygen delivery to the organs. The most widely accepted level of hypercapnia required to confirm the abolition of spontaneous breathing is now 60 mmHg. Adverse events have been reported during 15% to 50% of apnea tests and consist chiefly of hypotension, cardiac arrest, arrhythmias, hypoxemia, and pneumothorax. 3 Ancillary tests can also be used to confirm BD/DNC. They include brain angiography, brain computed tomography angiography (CTA), electroencephalography (EEG), and ultrasound-based techniques. As shown in a recent studies, 4 , 5 the use of ancillary tests varies across the world. In most countries, these tests are performed when confounding factors are present, the apnea test cannot be performed safely, or the results are inconclusive. However, legislation in some countries requires routine ancillary tests in addition to the apnea test to confirm brain death despite their utility has been matter of controversy 6 . In France, the diagnosis of BD/DNC requires three steps ( eFigure 1 ). First, BD/DNC is suspected based on the medical history and clinical findings (unresponsive coma of known origin and abolition of brainstem reflexes). Second, an apnea test is required by law without the need for informed consent 7 and must show absence of spontaneous breathing in response to hypercapnia. According to French guidelines, the recommended PaCO 2 level by arterial blood gas analysis at the end of the apnea test was 50 to 60 mmHg from 2005 to 2019. 8 However, since 2019, a level of 60 mmHg is required. 9 , 10 The third step is confirmation of the diagnosis by an EEG or CTA (BD/DNC can be affirmed on the basis of step 1 and step 3 only, if the patient was judged too unstable to receive apnea test). Download figure Open in new tab Figure 1: Patient flowchart MOF: multiorgan failure; ECMO: extracorporeal membrane oxygenation The apnea test is traditionally performed by physically disconnecting the tracheal tube from the ventilator and providing oxygen through a cannula at a constant flow, either via a T-piece or by direct insertion into the trachea. This method can cause barotrauma and/or pneumothorax. Modifications have been suggested, such as adding a pH target to the PaCO 2 target, 11 limiting the test to 5 min instead of 10 min, 12 or using continuous positive airway pressure (CPAP) for oxygenation during the test, a method reported to decrease adverse effects and improve lung-function biomarkers. 13 , 14 Another modification consists in keeping the patient on the ventilator and decreasing the tidal volume and/or respiratory rate to reach the PaCO 2 target then checking for respiratory movements. 15 , 16 None of these methods has been proven optimal to affirm absence of brainstem function. In addition, organs retrieved from extended-criteria donors are being increasingly transplanted, and these donors are more likely to experience adverse events during apnea testing. In France, the mean age of donors was 38 years in 1998 and 58 years in 2023, 17 with 43% of donors being older than 65 years. A single standardized protocol may not be optimal for all potential donors, and personalization may be desirable. Descriptive clinical data on apnea-test practices is crucial to determine which methods ensure maximal efficacy and minimal harm to potential transplants. A single-center retrospective study from the USA described 228 apnea tests done in 1996–2007, 18 and the same group reported 147 additional tests done in 2008–2018. 19 , 20 At another center, 512 tests were done, including 484 successfully. Acidosis and a high alveolar-arterial O 2 gradient predicted failure in this study and in another. 21 , 22 A test that is aborted due to adverse events may still be valid if the PaCO 2 level at test termination is sufficient, but the results of aborted tests are rarely reported. No published data on apnea test practices in France are available. The objective of this retrospective cohort study was to collect data on the conduct and results of apnea tests done in several ICUs at a single center in France. METHODS Study design We conducted a retrospective study in four intensive care units (ICUs): a medical ICU, a surgical ICU and trauma center, a mixed neurologic ICU, and a thoracic- and cardiovascular-surgery ICU. We searched the ICU databases to identify all patients in whom BD/DNC was suspected between 2015 and 2022. Exclusion criteria were age<18 y and contraindication to organ donation before an extensive neurological assessment due, for instance, to refusal of the next-of-kin or to multiorgan failure. Data collection For each patient, data was extracted from the ICU electronic medical records and recorded into case report form (Excel, Microsoft, Redmond, USA). The collected data included demographics, cause of brain injury, and clinical parameters. For each apnea test, we recorded the changes in pH, PaO 2 , and PaCO 2 during the test; test duration; and whether the test was aborted, with the reason (hypoxemia, pneumothorax, hemodynamic instability, ventricular arrhythmia, or cardiac arrest). For patients who had multiple apnea tests performed, only the first test was considered. Apnea Test No specific written protocol was available to guide clinicians in performing the apnea test. The traditional method involved preoxygenating the patient for 10 minutes with an FiO□ of 1.0, then disconnecting the patient from the ventilator and administering oxygen at a rate of 3 to 5 L/min using a T-piece. Arterial blood gases were drawn at 10 minutes before reconnecting the patient to the ventilator. Definition of apnea test results The recruitment period overlapped two sets of French guidelines, with a final PaCO 2 of 50–60 mmHg recommended until 2019 and a final PaCO 2 of at least 60 mmHg subsequently. We therefore defined a positive test as PaCO 2 >50 mmHg with no respiratory movements, a negative test as PaCO 2 >50 mmHg with respiratory movements, and an inconclusive test as failure to reach PaCO 2 >50 mmHg after 10 minutes of disconnecting. Outcomes The study outcomes were the proportion of patients with suspected BD/DNC but no apnea test; the proportion of patients with aborted tests due to adverse events; and, among patients with apnea tests, the proportions with positive, negative, and inconclusive results. Statistical analysis The data were described as mean±SD if normally distributed and as median [interquartile range] otherwise. Continuous variables were compared using Student’s t -test or the Mann-Whitney test as appropriate. Categorical variables were compared using the chi-square test. We first compared patients with vs. without an attempted apnea test. Among patients with an attempted test, we compared those in whom the test was completed (≥10 minutes) to those in whom the test was aborted. A sensitivity analysis in which a completed test was defined as PaCO 2 >60 mmHg instead of >50 mmHg was performed. All statistical analyses were done using STATA version 14 (StataCorp, College Station, TX). Missing data were not imputed. We did not correct the alpha risk for multiple comparisons. Ethics committee The study protocol was approved by the appropriate ethics committee (French Intensive Care Society Ethics Committee 24-012). This study report complies with STROBE guidelines. 23 RESULTS Patients Figure 1 is the patient flowchart. Of 459 identified patients, 88 were excluded due either to age <18 years (n=37) or, in adults, to refusal by relatives, contraindication to organ donation before an extensive neurological examination, or cardiac arrest. This left 371 patients for the study, including 95 (25.6%) with traumatic brain injury, 165 (44.4%) with intracranial bleeding, 32 (8.6%) with ischemic stroke, 68 (18.6%) with prolonged anoxic injury due to cardiac arrest or severe shock, and 10 (2.7%) with other causes of brain injury (hyponatremia, central nervous system infection, or complications of neurosurgery). Groups with vs. without an attempted apnea test No apnea test was attempted in 52 (14%) patients. The main reasons were respiratory failure (n=26, 50.0%), multiorgan failure (n=11, 21.1%), and being on extra-corporeal membrane oxygenation (ECMO) (n=6, 11.5%). Table 1 compares the patients with vs. without an attempted apnea test. View this table: View inline View popup Table 1: Comparison of patients with vs. without an attempted apnea test View this table: View inline View popup Table 2: Comparison of patients completed vs. aborted apnea test Groups with an aborted vs. completed apnea test Of the 319 patients with at least one apnea test, 36 (11.3%) had the test aborted due to adverse effects including hypoxemia (n=26), cardiac arrest (n=3), hypotension (n=1), pneumothorax (n=1), and ventricular arrythmias (n=1); in two patients, the reason for aborting the test was not reported. Aborted tests were significantly shorter than completed tests (5 min vs. 10 min, P <0.001). The final pH was higher (7.24 vs. 7.20, P =0.03), the final PaCO 2 was lower (57 vs. 68 mmHg, P =0.001), and the final PaO 2 was lower (59 vs. 167 mmHg, P <0.001) ( Figure 2 ). Download figure Open in new tab Figure 2: Changes in arterial pH (a), PaO 2 (b), and PaCO 2 (c) during completed and aborted apnea tests Two pretest characteristics were associated with apnea test abortion, namely, the pretest PaO 2 (278 vs. 338 mmHg for completed tests, P =0.02) and not receiving desmopressin within 12 h before the test (29% vs 52% for completed tests, P =0.002). Half the aborted tests could be interpreted as positive for BD. The proportion of positive tests was significantly smaller for the aborted tests (50% vs. 94% of completed tests, P <0.001). Figure 2 shows the PaCO 2 increase from the beginning to the end of the test for completed vs. aborted tests. Results of completed apnea tests The median duration of the 285 apnea tests not aborted was 10 [10–15] min. However, test duration varied substantially ( Figure 3 ). The result was positive in 268 (94%) patients, inconclusive in 11 (4%) patients, and negative in 6 (2%) patients. Blood gas analyses showed a decrease in pH from 7.42 [7.36–7.46] at baseline to 7.20 [7.14–7.23] at completion), a decrease in PaO 2 from 338 [240–398] mmHg at baseline to 117 [92–262] mmHg at completion, and an increase in PaCO 2 from 38 [34–41] mmHg at baseline to 68 [62–79] mmHg at completion ( Figure 2 ). Of the 268 positive tests, 56 ended with a final PaCO 2 between 50 and 60 mmHg. Download figure Open in new tab Figure 3: PaCO 2 changes according to apnea test duration The passive oxygenation method was reported for 101 patients. A cannula was used in 100 (99%) patients. The position of the cannula was known for only 9 patients, including 2 with the cannula in the trachea and 7 with the cannula on a T-piece. The remaining patient received CPAP with 100% FiO 2 . Figure 3 shows the PaCO 2 level according to test duration, and Figure 4 the proportion of positive apnea tests according to test duration. Download figure Open in new tab Figure 4: Proportion of conclusive apnea tests according to duration Negative apnea tests In 6 patients, the test was aborted due to spontaneous breathing, which consistently occurred within the first 5 min (immediately, n=4; at 3 min, n=1; and at 5 min, n=1). Notably, the highest PaCO2 observed in those patients was 58 mmHg. All 6 patients underwent one or more subsequent apnea tests: four eventually had a positive test, one had an inconclusive test due to hypoxemia, and one had the organ donation procedure aborted at the request of the family after two negative tests (eTable 1). Sensitivity analysis In the sensitivity analysis, absence of breathing with a PaCO 2 cutoff of 60 mmHg defined a positive test. In this analysis, 56 (19.6%) completed tests and 27 (79.4%) aborted tests were considered inconclusive. DISCUSSION Our retrospective cohort study found that at least one apnea test was performed in 86% of patients with suspected BD/DNC. Of the 319 patients with at least one apnea test, only 36 (11.3%) had the first test aborted due to adverse events. Of the 285 patients with a first complete apnea test, 94% (78% with a PaCO2 cut-off at 60mmHg) had a positive result, indicating BD/DNC. Of the 371 patients eligible for the study, 47 (12.7%) were deemed too unstable to undergo apnea testing. In previous studies, the proportion of patients with no apnea test attempts ranged from 4.3% 19 to 30%. 11 Although respiratory or hemodynamic instability was the main reason for not performing an apnea test, the pretest FiO2 was not significantly different between patients with vs. without an apnea test. The vasopressor infusion rate was significantly higher in the untested patients but remained moderate. Conceivably, more subtle markers of instability such as rapid changes in vasopressor doses or O 2 requirements may not have been collected for our study. In France, a positive apnea test is required by law for the diagnosis of BD/DNC (except if patient was judged too instable), and every effort is therefore made to perform the test. 24 One option in unstable patients is to provide organ support until sufficient stability is obtained, allowing an apnea test. Among the patients in whom an apnea test was done, 10.7% had the test aborted due to adverse events, chiefly hypoxemia. In previous studies, only 1% to 5% of patients had aborted tests. 25 More recently, a proportion of 11% was observed in a US cohort of 219 patients 26 . This observation associated with our results might indicate a tendency to discontinue tests earlier nowadays, perhaps driven by the fact – in France - that all patients undergo a confirmatory ancillary test regardless of the result of the apnea test. However, our patients were older than in earlier studies (median, 48 y 21 and 46 y 18 vs. 59 y in our cohort). Moreover, median age in our patients with aborted tests was 65 y. Importantly, half the patients with aborted tests had positive test results confirming BD/DNC (PaCO 2 >50 mmHg without respiratory movements at the time of test termination). Among these patients with aborted tests, the proportion of donors was similar to that among patients with completed test. Thus, an arterial blood gas analysis should be performed before reconnecting the ventilator regardless of test duration or reason for abortion 27 . The six patients with negative apnea tests underwent at least one subsequent apnea test. A positive result was obtained in four patients and an additional patient became a donor. This finding supports repetition of the apnea test after an initial negative result. None of the six patients on ECMO had apnea tests. A review suggests that apnea tests can be performed during ECMO by reducing the sweep flow or providing CO 2 through the ventilator. 28 , 29 However, the test failure rate was high and ancillary tests were usually necessary to diagnose BD/DNC. 11 Contrary to scientific guidelines 10 , French law does not specify a PaCO 2 threshold for the apnea test. In our cohort, 56 (19.6%) of the 285 completed tests ended with a PaCO 2 between 50 and 60 mmHg, i.e. were inconclusive if using the widely accepted threshold of 60 mmHg. One patient presented spontaneous breathing at a PaCO2 of 58mmHg, supporting the use of the higher threshold of 60mmHg to ensure the absence of spontaneous ventilation. Interestingly, PaCO 2 at test initiation was below 33 mmHg in about a quarter of the tests. Normocapnia should be achieved before starting the test to ensure that the PaCO 2 threshold is reached as quickly as possible. Only 11 of the 285 completed tests were inconclusive, with failure to confirm that PaCO 2 was >50 mmHg after ten minutes. For five patients, they had baseline hypocapnia, which should have been corrected before starting the test. In these five patients, ancillary tests confirmed BD/DNC. The rate of PaCO 2 increase during the apnea test may vary across patients. Point-of-care arterial blood gas assays would allow multiple PaCO 2 measurements with test discontinuation as soon as the PaCO 2 threshold is reached 11 and are therefore recommended by the 2023 American Association of Neurologists guidelines 27 . This would limit the risk of harm in patients whose PaCO 2 increases rapidly. The development of transcutaneous partial CO 2 pressure (TcpCO 2 ) sensors would also allow tracking of the PaCO 2 value during the test. Identifying patients in whom the test will be aborted due to adverse events is challenging. In our cohort, a lower pretest PaO 2 and not having received desmopressin were the only factors significantly associated with test abortion in our univariate analysis. However, neither factor alone can predict test abortion. In other studies, predictors of test abortion were low systolic blood pressure, low pH, and high alveolar-arterial O 2 gradient. 21 , 22 Further studies with larger numbers of aborted tests might allow the identification of additional risk factors and, perhaps, the development of a score for predicting test abortion. Additionally, recent data about the accuracy of ancillary tests 30 highlights the need to secure apnea test methods in the specific context of BD/DNC. The retrospective design is a major limitation of our study as it is associated with missing data about the apnea tests, clinical features, and laboratory results. The predefined duration of 10 minutes is questionable and could be prolonged if patient was stable during the AT. Second, all patients were recruited at the same institution, potentially limiting the generalizability of our findings to other hospitals or other countries. Strengths of our study include the large sample size and the enrollment of consecutive patients to minimize selection bias. The median age of donors (58 y) and the distribution of causes of BD/DNC (stroke, 53%; trauma, 26%, and anoxia, 21%) are consistent with recent national data on donors who died from BD/DNC. 17 CONCLUSION The apnea test proved generally safe and effective for diagnosing BD/DNC in potential organ donors. However, 14% of patients were deemed too unstable to undergo apnea testing and, among tested patients, 15% had an aborted or inconclusive test. Of note, among the aborted tests, half were stopped after the PaCO 2 threshold was reached and were positive. The frequency of severe adverse events was less than 2%. Improvements in apnea test practices would be expected to increase safety and effectiveness. More specifically, normocapnia should be achieved before starting the test and effective oxygenation methods such as CPAP should be used during the test. Tracking PaCO 2 levels during the test by repeated blood gas sampling or by transcutaneous measurement would allow shorter test durations in patients with rapid PaCO 2 increases. Every effort must be made to ensure that apnea testing is performed in all patients with suspected BD/DNC, as no other test can establish the diagnosis with complete certainty. Data sharing statement De-identified dataset will be available upon reasonable request to corresponding author. Data Availability All data produced in the present study are available upon reasonable request to the authors. The manuscript complies with all instructions to authors from Neurocritical Care. The authorship requirements have been met and the final manuscript was approved by all authors. The conceptualization of the study was led by JBL. The methodology was developed by JBL. Formal analysis and data validation were carried out by BH and JBL. Validation was performed by BH and JBL, whereas investigation were managed by KL, EC, MD, AB. Data curation was done by BH and JBL, and the original draft was prepared by BH. and JBL., with review and editing by EC. All authors meet the International Committee of Medical Journal Editors criteria for authorship and have approved the final version of the manuscript. The manuscript has not been published elsewhere and is not under consideration by another journal. The study protocol was approved by the appropriate ethics committee (French Intensive Care Society Ethics Committee 24-012). Conflict of Interest statement for all authors. The authors declare no conflict of interest. This study report complies with STROBE guidelines. eFigure 1: Process in our country for organ donation from donors who died of brain death REFERENCES 1. ↵ Practice parameters for determining brain death in adults (summary statement) . 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Determination of brain death under extracorporeal life support . Intensive Care Med 2019 ; 45 ( 3 ): 364 – 366 . OpenUrl PubMed 30. ↵ Computed Tomography Perfusion and Angiography for Death by Neurologic Criteria | Radiology | JAMA Neurology | JAMA Network [Internet] . [cited 2025 July 1];Available from: https://jamanetwork.com/journals/jamaneurology/fullarticle/2835388 View the discussion thread. Back to top Previous Next Posted October 15, 2025. Download PDF Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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