This study analyzed the results of apnea tests conducted by a single institution in South Korea and suggests a rational and unified international guide to the apnea test protocol.
According to the results, PaCO2 exceeded 60 mmHg in ABGA within 4 min of starting the apnea test (Figs. 1 and 2). This result met the positive criteria for the apnea test suggested by the AAN guidelines. In this study, the increase in PaCO2 over time was significant within 5 min. The short-term apnea test is considered an essential test for brain death determination.
Elevation of PaCO2 causes an additional increase in intracranial pressure in patients with potential brain death, as well as complications such as weakening of myocardial contractility, arrhythmias, and respiratory acidosis [16]. According to a review of apnea test complications reported in 2013, hypotension was observed in 111 (18%) of 608 patients who underwent the test [17]. However, maintaining proper blood pressure in the management of brain death is important to prevent ischemic changes in organ(s) for donation and to increase transplant success rates. Therefore, according to the AAN guidelines, the systolic blood pressure should be ≥ 100 mmHg and the mean ABP should be ≥ 60 mmHg before starting the apnea test for brain death determination. In this study, we aimed to maintain a mean ABP of ≥ 65 mmHg before the apnea test and during the entire management period. In fact, the pH from the ABGA during or immediately after the apnea test decreased significantly over time. There were no significant differences in the mean ABP and pulse rate over time. Cardiovascular dysfunction, which is a common complication during the short-term apnea test and lasted for 1 to 5 minutes, was not severe. Therefore, a short apnea test should be considered for safer outcomes.
The vasopressor infusion rate was significantly increased between the 1st pre- and post-apnea tests. However, the increase in vasopressor infusion rate in the 1st apnea test was as small as 0.02 µg/kg/min. According to the brain death management protocol of our institution, we checked the mean ABP before the apnea test and, in some cases, preemptively increased the vasopressor injection rate when a borderline mean ABP of approximately 65 mmHg was observed. Therefore, it might have acted as a bias due to the external factors of the study. In addition, it is possible that these results were observed because fluid resuscitation was not sufficiently administered to manage potential brain death patients before the 1st apnea test for brain death determination. In fact, the increase in vasopressor infusion rate was not significant between the 2nd pre- and post-apnea tests.
During the apnea test, there was no significant difference in mean ABP fluctuations between the normal and abnormal finding groups on chest radiography; therefore, a short-term apnea test seems safe even in patients with poor lung conditions.
MAT is a method for preventing lung damage without affecting hypercapnia by maintaining PEEP even after removing the mechanical ventilator from the patient [11, 18]. In the 1st apnea test in this study, PaO2 was significantly changed every minute, but its value was ≥ 90 mmHg (Table 2). Previous studies have confirmed that MAT did not negatively affect apnea test results and allowed a safer completion of the tests [19, 20]. MAT was also performed in the present study. Changes in plateau pressure in the pre- and post-apnea tests were checked as a parameter to confirm the presence or absence of lung damage, and no significant changes were observed. Changes in plateau pressure disproved the changes in lung compliance. Although the degree of change was not significant in this study, if the duration of the apnea test is prolonged, lung compliance may worsen. If lung donation is planned, caution is required during the apnea test.
If a normal body temperature is maintained and there is no lung disease, only 5 min of apnea can raise PaCO2 from 40 mmHg to 60 mmHg [21]. Nevertheless, a global consensus has not yet been reached. Although the apnea test in South Korea can be considered to be a relatively weak standard compared to the AAN guideline, EEG is mandatory for all brain death determinations, and TCD is also performed in some cases. However, according to the AAN guidelines and a publication by the World Brain Death Project in 2020, EEG was excluded from the mandatory tests because of its high false-positive rate; however, it could be performed as an optional test if the apnea test is unavailable [4, 22]. TCD, which is not an essential test for brain death determination, can also be performed as an optional test if the apnea test is infeasible. The sensitivity and specificity of TCD for determining brain death are 90% and 98%, respectively [23]. The additional use of TCD may help shorten the duration of the apnea test in brain death determination.
In a previous study, we attempted to determine the optimal duration of the apnea test by performing ABGA every minute during the apnea test [10]. In that study, PaCO2 exceeded 60 mmHg 4 min after the removal of the mechanical ventilator; thus, it can be considered that observing the patient's apnea pattern for at least 8 min during the apnea test, as presented by the AAN guidelines, is relatively long. Although many studies have reported that complications such as hemodynamic instability and lung damage can be caused by the apnea test, studies on the possible shortening the apnea test duration are insufficient. The reason may be because of the recognition that more stringent criteria should be applied because the apnea test is valuable as an essential test for brain death determination.
A study of guidelines for brain death in 80 countries found that detailed guidelines were inconsistent, and in the U.S., there was no internal agreement because of differences in laws even between states [3]. Likewise, the implementation patterns of the apnea tests and positivity criteria have not been standardized worldwide. It will be difficult to achieve a consensus regarding the criteria for brain death determination because of differences in legal systems, culture, and medical standards between countries. Nevertheless, for the safety of patients waiting for brain death determination and for organ preservation after brain death determination, there is a need for a global consensus on the implementation pattern of the apnea test, which is generally considered essential in brain death determination. We suggest an optimal apnea test protocol as follows: 1) after removing the mechanical ventilator from the patient, observe the patient's apnea patterns for 5 min; 2) after 5 min, perform the short-term ABGA for 1 or 2 min; and 3) when it is confirmed that PaCO2 exceeds 60 mmHg, terminate the apnea test immediately.
Because this study was conducted in a single institution, the apnea test was not performed on patients of various races, physiques, etc. This is an important limitation with regarding to generalizing our findings. A global multicenter study is necessary to establish a reasonable apnea test that can be widely performed worldwide.