The verification of apnea plays a key role in the clinical declaration of brain death but ventilator autotriggering can mimic an intrinsic respiratory drive where there is none. This phenomenon becomes relevant for the management of intensive care patients with severe cerebral injuries who have the potential of progressing to brain death and may delay or even prevent the diagnosis of brain death. It should be a consistent notable aspect in the national guidelines, especially against the background of the increasing gap between the demand and availability of donor organs.

Diagnosing brain death (in Germany denoted as irreversible brain function failure) is one of the most serious multidisciplinary challenges for intensive care staff. Despite the consensus on the general concept of brain death, there are differences in the national guidelines for its determination, which can be explained by the historical development of the guidelines and recommendations and compliance with country-specific characteristics (e. g., different medico-legal requirements). The differences include the number of physicians required, the degree of experience and academic rank of the physicians, the observation time, the clinical premises, the assessment and the order for confirmatory tests (mandatory vs. optional), the impact of therapeutic hypothermia and therapeutic medication of central nervous system depressing drugs [5, 11, 12, 23, 24, 26, 28]. Moreover, there is also no consistency in the procedure for determining apnea [5, 12, 24]. Objectification of the loss of spontaneous respiration indicates that the medulla, the most rudimentary part of the brain, is damaged and implies that other vital functions requiring control by the central nervous system are also damaged. Therefore, apnea and its testing play a key role in the clinical declaration of brain death and are considered a conditio sine qua non [18]; however, differences in the testing for apnea exist for the pre-oxygenation period, predefined partial pressure of carbon dioxide (PaCO2) levels, the O2-insufflation mode, the observation period, and clinical objectification [12].

The potential occurrence of ventilator autotriggering (VAT) is a further cause for inconsistency in the determination of apnea in the national guidelines. A VAT is defined as a ventilator being triggered in the absence of patient effort, intrinsic respiratory drive or inspiratory muscle activity [2]. The various synonyms for VAT are listed under the search terms in the Methods section of this article. This phenomenon, which is primarily observed with ventilators of newer generations [30], can lead to confusion among intensive care unit (ICU) staff, resulting in a time delay or even the cancellation of the process of brain death diagnosis.

Methods

The national recommendations and guidelines for the diagnosis of brain death of 15 selected European countries (including all 8 Eurotransplant member states) were evaluated by 2 authors with respect to VAT. Additionally, PubMed and Google Scholar were searched for articles on this topic. The search and evaluation included the terms “brain (stem) death”, “cerebral death” combined with “ventilator(y) autotriggering”, “ventilator autocycling”, “respirator autocycling”, “ventilator selfcycling”, “patient-ventilator asynchrony”, “cardiogenic autotriggering”, “cardiogenic ventilator triggering” as well as the term “cardiogenic respiratory oscillations” and analogous content-related wording describing the same phenomenon. The translations of the official recommendations were checked by 7 native speakers and linguistic experts and one additional researcher double checked the search results and made the final decision.

Results

The search for VAT in the official national recommendations and guidelines of the selected European countries showed variability in various aspects (Table 1).

Table 1 National guidelines and recommendations for determination of brain death of 15 European countries in the context of ventilator autotriggering (VAT)
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The phenomenon of VAT is addressed in 3 of the recommendations and guidelines of the 15 selected European countries (Germany, Ireland and Switzerland). In one of these 3 recommendations and guidelines the synonym “ventilator selfcycling” was found and in the other two, this phenomenon could be identified through analogous content-related wording. The fact that VAT can be entirely attributed to cardiac impulses or pulse synchronous impetus and that disconnection of the patient from the ventilator would support the objectification of VAT, are mentioned in 2 national guidelines (Germany and Ireland). The causal importance of the trigger sensitivity setting of the respirator is mentioned in the recommendations of Germany and Switzerland (Table 1).

Discussion

Prevalence and potential state of knowledge and education

Among 83 neurological and neurosurgical patients who met all clinical criteria for brain death, false triggering was found in a report in 4 patients (4.8%) [29]. In a later report, autotriggering was observed in 9 patients over a period of 15 months, representing an incidence of 10–12% extrapolated from an estimated collective of 50 patients who were declared to be brain dead each year [19]. In a retrospective evaluation of 672 cases (i. e. patients with absent brainstem reflexes except for spontaneous respiration on the mechanical ventilator), an algorithm designed to identify and correct VAT could have been used in 63 cases (9.4%) [13]. It is emphasized that this phenomenon is likely to occur more frequently than estimated and it is believed that VAT may remain undetected in an unknown number of cases; indeed, this clinical scenario does not seem to be uncommon, as other clinical experiences show [19, 29]. A factor for problems in the context with VAT could be the state of education and knowledge about this phenomenon. For example, in a simulation training of brain death determination by critical care fellows and neurology residents, only 22% of the 41 participants checked for spontaneous respirations and/or recognized VAT [15].

Reasons for the occurrence of VAT

There are different causes for VAT, one of which is the improper setting of the trigger thresholds under various constellations [2, 30]. The two main types of ventilator triggers currently available are the flow trigger and the pressure trigger [14, 21]. The flow-triggering mode uses a continuous base flow setting and a flow trigger threshold setting. If the flow measured at the exhalation valve drops below the predefined threshold (flow sensitivity in liters per minute), the ventilator will initiate the inspiratory phase of the breathing cycle [17]. In the pressure-triggering mode, the ventilator maintains a known pressure within the ventilator circuit and if the pressure drops below a predefined threshold (pressure sensitivity in cmH2O) due to a patient inspiratory effort, the ventilator delivers an assisted breath [8]. In comparison, the flow trigger mechanism is more sensitive to cardiogenic autotriggering than the pressure trigger mechanism [14, 16, 29]. If the flow-triggering or pressure-triggering thresholds are decreased on the ventilator, the patient requires lower inspiratory efforts for the delivery of an assisted breath; however, reducing the trigger threshold increases the likelihood of false triggering of the respirator due to inadequate flow and pressure sensitivity [22]. Furthermore, VAT can be observed more frequently on new generation ventilators [29], as some have internal programming that allows assisted breaths to ensure oxygen supply to the patient during longer periods of apnea regardless of the trigger setting selected.

Extrinsic causes for VAT include excessive condensation (occurring in the ventilator circuit, especially when not using a heated-wire circuit), humidification (because secretions within the lungs and airways can be released by a heat and moisture exchanger or external heater humidifier with a heated-wire ventilator), endotracheal tube cuff inflation/endotracheal tube leak, leaks in all other ventilator circuit connections (from proximal or distal airways up to the ventilator sensor at the Y‑piece), malposition of the inline suction catheter, chest tube leaks and random artifacts or noise in the ventilator circuit (due to movement and vibrations) [8, 17].

The predominant intrinsic cause for VAT in connection with brain death are cardiogenic respiratory oscillations (CRO) [1,2,3,4, 6, 22, 29]. The physiological background of CRO is based on the interaction between the cyclic cardiac stroke volumes and the displacement of compliant air-filled lung tissue causing gas movement. As the heart ejects blood during systole, the intrathoracic volume decreases creating a negative intrathoracic pressure. The cardiac cycle and its cyclic variations in pulmonary blood flow [25] can lead to shifts in the intrapulmonary gas volume, which can alter the airway pressure and flow, inducing ventilator self-cycling in brain-dead subjects [1, 3, 6]. The occurrence of CRO in brain-dead patients is often associated with a hyperdynamic precordium [3, 4, 22].

Identification and correction

The procedures for identification and correction of VAT overlap with each other [13]. The spectrum of VAT detection measures ranges from simple but insensitive clinical maneuvers testing the patient for chest wall movements in phase with cardiac cycles, to a close assessment of the graphical waveforms of airway flow or pressure with more detailed waveform analysis [22], up to the more advanced technique of monitoring the neurally adjusted coupling of the bioelectrical diaphragm function to ventilator assistance [9]. A way to terminate false triggering is a change from the flow trigger mechanism to pressure trigger [29] because flow-triggered ventilation is more sensitive than pressure-triggered ventilation. A valuable additional tool for identifying potential VAT could be a differentiated algorithm developed by Henry et al. [13]. In summary, several factors that can be considered to cause VAT should be identified and corrected by various measures [1,2,3, 13, 22, 29] (Table 2).

Table 2 Concept for identification and correction of suspected ventilator autotriggering
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Additional prospective research is, however, needed to determine how many cases of VAT can be identified and corrected by the proposed procedures. In the case of persisting uncertainty, a formal apnea test with disconnection of the patient from mechanical ventilation and observation of whether any respiratory effort or movement of the chest is recognizable is recommended in the literature [6, 19, 20, 29] and by some national guidelines (Table 1). As several complications (e.g. atelectasis, hypoxemia, cardiocirculatory instability) can occur during apnea testing with disconnection from the respirator and adapted procedures (e. g., continuous insufflation of oxygen using a flow-controlled non-rebreathing system and manual ventilation once to twice per minute) can be provided especially in the case of a potential lung donation. Estimation of cerebral blood flow by transcranial Doppler studies or computed tomography (CT) angiography may be considered if the apnea test cannot be performed in patients with a high risk of complications [18].

Potential implications of VAT

The occurrence of VAT can lead to uncertainty and emotional strain for the entire ICU team. Another important implication in the context of organ donation is a possible delay between the occurrence and the pronouncement of brain death [1, 3, 4, 8, 19, 30], as the clinical examination to determine brain death is usually performed only when all brain stem reflexes are absent, which includes the loss of spontaneous breathing due to the lack of an intrinsic respiratory drive [13]. Longer ICU management times for potential organ donors increase the risk of organ loss, mainly due to refractory cardiocirculatory instability [30]. This fact and the prolonged exposition to activated inflammatory mediators secondary to the initial brain lesion and the state of brain death may negatively influence the quality of function of allografts and graft survival [27]. Furthermore, unnecessarily prolonging the ICU experience for patients’ families is an emotional stress that could be accentuated by the risk of raising false hope of patient recovery. Finally, the total ICU resource utilization and the subsequent financial aspects are factors that should also be kept in mind [1, 3].

Role of recommendations and guidelines

The lack of standardization of brain death and organ donation criteria worldwide contributes to a loss of potential donors [7]. The aim of official recommendations for determining brain death is to help healthcare providers to increase their knowledge about brain death diagnosis and to strengthen public confidence that such findings will be made after a thorough and careful evaluation according to accepted medical standards [10]; however, there is variability in European national recommendations and guidelines and VAT is mentioned only in a few of them. Even in the guidelines of countries collaborating within a transnational network that facilitates the allocation and cross-border exchange of deceased donor organs, there is an inconsistency (see Table 1). Therefore, VAT should be addressed and communicated in the national recommendations in a harmonized manner for diagnosing brain death.

Conclusion

Ventilator autotriggering may induce uncertainty in diagnosing brain death because it can falsely indicate central respiratory drive in brain-dead patients where no regular respiratory efforts exist. This topic is addressed inconsistently in the national guidelines for the determination of brain death. In particular, as different countries cooperate in a cross-border exchange of donor organs, it should be the aim for the future to have harmonized brain death codes with the inclusion of VAT. Further prospective studies on algorithms and methods for the identification, avoidance and correction of VAT are necessary.

Practical advice

  • Recognize VAT as a confounder in the determination of brain death that in ventilated brain-dead patients mimics spontaneous breaths where there are none.

  • Consider the main causes for the occurrence of VAT:

    • Cardiogenic respiratory oscillations,

    • Leak in the ventilator circuit,

    • Noise/artifacts,

    • Excessive condensation.

  • VAT can be avoided by appropriate setting of the trigger thresholds of the respirator.

  • Due to its wide-ranging implications, it is important to identify and correct VAT as early as possible using a structured procedure (Table 2).

  • Multidisciplinary clinical information and training should be provided for the entire ICU team.