Role of a non-invasive multimodal brain monitoring approach in supplementing the clinical diagnosis of brain death: Observations from a case series

INTRODUCTION The irreversible cessation of brain and brainstem function characterises brain death.[1] While clinical evaluation remains the primary method for brain death diagnosis, ancillary tests may be required in cases with physiological confounders or clinical dilemmas. The ancillary tests require considerable technical expertise which restrict their use. Brain death determination may be expedited if ancillary tests are available at the bedside to supplement clinical criteria. Role of non-invasive bedside multimodality neuromonitoring (NI-MMM), including transcranial Doppler (TCD), bilateral regional cerebral oxygen saturation (rSO2) measured by near-infrared spectroscopy (NIRS), optic nerve sheath diameter (ONSD), and bilateral bispectral index (BIS) monitoring, is being increasingly studied in neurocritical care. In this case series, we highlight our findings of NI-MMM in three patients with challenging apnoea tests. METHODS We conducted a retrospective interpretation of the clinical and acquired monitored de-identified patient data after obtaining an exemption from the Institute Ethics Committee (NIMHANS/IEC/2023 dated 06.03.2023). Three severe acute brain injury patients with poor Glasgow Coma Scale (GCS) scores were admitted to a tertiary care hospital’s neuro-intensive care unit (NICU). Patient demographics and clinical details are presented in Table 1. All had an extraventricular drain (EVD), were mechanically ventilated with fractional inspiratory oxygen (FiO2) of 40%, and received high-dose vasopressors to maintain systolic blood pressure (SBP) >100 mmHg and peripheral oxygen saturation >97%. Despite maximal treatment, no improvement occurred, and clinical signs suggested brain death with absent brainstem reflexes. Apnoea tests were attempted but deemed unfeasible due to hypotension/arrhythmias in all the cases. As a part of the routine NICU management, NI-MMM (bilateral TCD, BIS, NIRS, and ONSD) was initiated. Supportive care was provided, and all patients followed the natural course of death.Table 1: Demographic details and findings of non-invasive multimodal monitoring modalities once patients were considered clinically brain-deadRESULTS The key findings of NI-MMM in these three cases are summarised [Table 1 and Figure 1]. TCD revealed flow reversal in the anterior and posterior cerebral circulations, consistent with brain death diagnosis. BIS showed bilateral BIS values of 0 with 100% burst suppression in all cases, indicating electrical silence. ONSD as measured bilaterally in succession revealed the mean ONSD of 0.69 cm in all the patients. This finding provides supportive evidence of elevated intracranial pressure (ICP) despite EVD. NIRS revealed a baseline rSO2 values in the 50%–60% range, except for case 3, where the rSO2 on the left side was 66%. However, due to extracranial contamination, the interpretation of NIRS findings can be complex.Figure 1: Findings of case 3: Left panel: a and b. Computed tomographic findings of case 3; Right panel: c. Transcranial Doppler images showing middle cerebral artery flows at 60 mm of depth; d. Basilar artery at a depth of 70 mm showing oscillating flow pattern; e. Regional cerebral oxygen saturation - Right (channel 1): 54 and Left (channel 2): 66; f. After 10 minutes of giving fractional inspiratory oxygen of 100% - Right (channel 1): 100 and Left (channel 2): 80; g. Optic nerve sheath diameter of 0.70 cm; h. Bilateral bispectral inde × 30-min recording showing iso-electricity and values of 0Detailed NIRS observations Case 1 At SBP >100 mmHg, rSO2 values were 50%–60%. To eliminate the effect of extracranial contamination, a surgical bandage tourniquet was applied around the forehead (ensuring no gaps) for 10 minutes to blanch the scalp. NIRS sensors were placed bilaterally to record rSO2 after removing the tourniquet. A significant drop in rSO2 by 40% from baseline (35% from 54%) was observed. These values are similar to those observed in post-cardiac arrest (24%–25%) patients. Case 2 The patient suffered cardiac arrest, at which point the rSO2 values reduced by 40%–50% from baseline to around 24%–35% and remained stable at this value. Case 3 In the third patient, rSO2 values were lower on the right side compared to the left side, with a hemicranial difference of 12%. During the apnoea test, administering 100% FiO2 resulted in a passive increase in the right rSO2 value from 54% to 100% and the left rSO2 value from 66% to 80% [Figure 1]. The rise in rSO2 values was more pronounced on the right side, where saturation was initially lower. DISCUSSION The diagnosis of brain death is fundamentally based on clinical criteria, and ancillary tests are legally not required in the Indian scenario. However, their need arises when the panel of specialists are in doubt and have disagreements. These tests are based on distinct alterations in the cerebral physiology and the internal milieu after brain death, which can be identified using various neuromonitoring modalities, which are mainly invasive, such as microdialysis, cerebral oxygenation using brain tissue oxygen (PbtO2) and invasive ICP. Rajagopalan et al.[2] observed that with equalisation of mean arterial pressure and ICP, there was significantly diminished cerebral blood flow, near-zero PbtO2, depletion of cerebral glucose and pyruvate, and elevated cerebral glycerol levels. As against this study, our case series identifies the physiological derangements by using available bedside monitors. Though no modality or combination is superior to another, non-invasive techniques have advantages such as being relatively inexpensive, safe, portable, reproducible, and easy to execute and interpret. Demonstrating the cessation of cerebral circulatory function through TCD examinations in both the anterior and posterior circulatory systems aligns with the diagnostic criteria of brain death,[3] which we observed in our cases. Similarly, the ONSD serves as a metric for assessing elevated ICP, and significantly raised ICP can lead to circulatory arrest and, ultimately, brain death. A mean ONSD exceeding 0.68 cm has been strongly correlated with elevated ICP in patients diagnosed with brain death.[4] Despite an EVD, ONSD measurements consistently exceeded 0.68 cm in our patients. Optic nerve sheath swelling thus can signify a last-resort response to severe brain swelling within the constrained skull, linked to malignant ICP elevation observed during brain death diagnosis. This finding offers supportive evidence for brain death determination, particularly when TCD, BIS, and NIRS values are assessed collectively and concurrently. BIS has been studied in brain death determination; while it can be helpful, it cannot replace valid clinical tests. In our cases, bilateral BIS of 0 with 100% burst suppression suggests complete electrical silence, indicative of brain death.[5] Bilateral rSO2 findings in brain death determination have been inconclusive. Reports show brain-dead patients with rSO2 values exceeding 60%,[6–8] while one study noted a decline from 67% to 55% at brain death onset, stabilising at that level. Post-cardiac arrest, rSO2 levels are around 24%–25%,[7,9] consistent with our case 2. Variability in frontal rSO2 may result from frontal sinus anomalies, pigment contamination, or improper optode positioning.[10] In case 1, applying a forehead tourniquet for 10 minutes reduced values, indicating initial values likely reflected extracranial contamination. In case 3, the FiO2 challenge led to a passive increase in the rSO2 values, unaffected by the forehead tourniquet application. This is likely due to the dead, infarcted, non-metabolising brain tissue beneath the NIRS optode not consuming the available increased oxygen besides the cessation of cerebral circulation. Thus, even after applying the tourniquet and removing the effect of extracranial circulation, the values did not change, suggesting saturated haemoglobin. Contrasting the previous reports, which showed near-zero PbtO2,[2] frontal rSO2 showed variable results as NIRS receives signals even from the deoxygenated blood, which may still be available at the capillary level, leading to the observed fluctuations. Optical contrast using indocyanine green[11] and functional NIRS[12] have been used to address these limitations. Overall, rather than absolute rSO2 values, the trend of change in rSO2 after a FiO2 challenge and using a tourniquet to limit extracranial contamination seem more helpful in decoding the role of NIRS in clinically brain-dead patients. CONCLUSION Our series highlights the possible utility of the NI-MMM in clinically brain-dead patients. Such bedside monitors provide certain advantages- identify patients needing brain death evaluation and perform established clinical tests in a timely manner, conduct ancillary tests when specific parameters of existing brain death determination criteria cannot be met, and provide timely prognosis. These multi-parameter monitors used together may supplement the apnoea test and the routine ancillary tests at the bedside. However, the rSO2 value trends require careful interpretation. With limited literature on the role of NI-MMM in brain death, future studies should focus on assessing if there is any effectiveness of combining these monitors in diagnosing brain death, potentially through larger-scale investigations or the development of predictive models, as these may be useful when a clinical conundrum exists. Declaration of patient consent The authors certify that due to the retrospective nature of data collection, the ethics review board waived the requirement for patient consent. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.