In this case, four multimodal neuromonitoring techniques were jointly applied to continuously assess cerebral blood flow, cortical electrical activity, cerebral tissue oxygenation, and intracranial pressure–related indices.

Transcranial Doppler ultrasonography (TCD) was used to monitor the pulsatility index (PI) and resistance index (RI), with commonly accepted reference ranges of PI < 1.2 and RI 0.5–0.7 (5). PI reflects the pulsatile characteristics of cerebral blood flow and is associated with vascular resistance and arterial elasticity (6), whereas RI primarily reflects distal vascular resistance (7); both parameters are classic noninvasive indicators of cerebrovascular compliance (8). In this patient, PI ranged from 0.5 to 1.06 and RI from 0.5 to 0.8, values close to the normal range. When interpreted together with stable regional cerebral oxygen saturation (rScO2 65%–80%) and the absence of sustained intracranial pressure elevation on cross-validation with ONSD, these findings supported preserved cerebrovascular autoregulation.

Regional cerebral oxygen saturation (rScO2) monitoring showed values ranging from 65% to 80%, within or slightly above the commonly reported reference range of approximately 55%–75% (9–11), indicating adequate regional cerebral oxygen delivery during the monitoring period.

Ocular ultrasonography assessed optic nerve sheath diameter (ONSD), with a reference threshold of <5 mm. The initial ONSD exceeded 5 mm, a finding commonly associated with elevated intracranial pressure in traumatic brain injury (6, 12); therefore, ONSD measurements were interpreted in conjunction with TCD-derived indices to reduce false-positive interpretation and avoid overtreatment (13).

Continuous electroencephalography (EEG) was used to evaluate cortical electrical activity. EEG demonstrated diffuse bilateral slow-wave activity predominantly in the delta frequency range, with moderate amplitude, symmetric distribution, and no epileptiform discharges, providing supportive information for post-traumatic epilepsy risk assessment (14, 15).

Based on integrated multimodal neuromonitoring findings, osmotherapy was initiated using alternating 12-h infusions of mannitol (125 mL) and 3% hypertonic saline (100 mL), together with analgesia–sedation and controlled mild hypothermia to reduce cerebral metabolic demand. Normoxemia and normocapnia were maintained, and nimodipine was administered by continuous intravenous infusion to mitigate cerebral vasospasm.

➀ Glucose: The patient’s blood glucose on the admission day was 8.29 mmol/L. Given that patients with severe ultra-severe TBI are prone to blood glucose fluctuations, we measured blood glucose every 4 h and set the target blood glucose range at 4–10 mmol/L (4). Considering the potential risks of aspiration and gastrointestinal nutritional intolerance, a jejunal feeding tube was placed under bedside ultrasound guidance on the 2nd day after admission, and 500 mL of Nutrison was administered as enteral nutrition at a rate of 20 mL/h. The enteral nutrition tolerance score was 1 point. Hypoglycemia (blood glucose level: 2.8 mmol/L) occurred 1 week after the patient’s admission, which was considered to be related to skull base fracture and diffuse axonal injury. For treatment, precise glucose supplementation was performed with 50% glucose injection infused via intravenous pump at a rate of 10 mL/h based on the target blood glucose value.

➁ Hemoglobin: In accordance with the requirements of the GHOST-CAP strategy, the hemoglobin level of patients with acute brain injury should be maintained at ≥70 g/L (16). The patient’s hemoglobin level on admission was 153 g/L, and it remained between 135 and 153 g/L during hospitalization, with no abnormal values or clinical manifestations of bleeding observed.

➂ Oxygen Saturation (SpO₂) and Partial Pressure of Carbon Dioxide (PaCO2): Given the patient’s profoundly depressed level of consciousness (GCS score of 4) accompanied by clinical signs of brain herniation, invasive mechanical ventilation was initiated immediately after admission, in accordance with the European Society of Intensive Care Medicine consensus, which recommends endotracheal intubation in patients with acute TBI when the GCS score is ≤8 and signs of brain herniation are present (17). Ventilatory management was guided by predefined cerebral and systemic targets, including maintenance of adequate oxygenation and normocapnia (18). Ventilator modes and parameters were adjusted dynamically according to blood gas analysis, patient–ventilator interaction, and cerebral monitoring findings.

On day 9, the development of patient–ventilator asynchrony, accompanied by agitation and increased respiratory demand, prompted reassessment of both sedation strategy and ventilatory mode. Following optimization of analgesia and sedation, the ventilation strategy was transitioned to airway pressure release ventilation (APRV) to improve synchrony and lung recruitment while maintaining cerebral oxygenation (19). After neurological improvement and successful spontaneous breathing testing, the patient was extubated on day 11. The complete ventilatory settings and adjustments throughout the ICU stay are provided in Supplementary Table 2.

➃ Sodium: Patients with neurocritical illness are prone to both hyponatremia and hypernatremia, so the control of serum sodium concentration is of great importance. In accordance with the requirements of the GHOST-CAP strategy, we set the target serum sodium concentration for the patient at 135–155 mmol/L (20). The patient’s fluid infusion volume was calculated using the formula: (physiological requirement + additional loss − endogenous water production); meanwhile, the proportion of sodium-containing fluids was reasonably allocated, with isotonic saline accounting for approximately 50%–70% of the daily fluid infusion volume to maintain stable serum sodium levels. Serum sodium levels were monitored every 6 h, and no hypernatremia or hyponatremia occurred during the treatment period.

➄ Temperature: On the admission day, the patient’s body temperature was 38.4°C, with a white blood cell count of 11.73 × 10⁹/L, neutrophil count of 6.46 × 10⁹/L, lymphocyte count of 4.81 × 10⁹/L, and cerebrospinal fluid otorrhea. Considering the possibility of infection, to reduce the cerebral metabolic burden and mitigate the inflammatory response after brain injury, we implemented targeted temperature management (TTM) for the patient. Setting TTM goals: Bladder temperature was monitored, with the target range of 34.0°C ≤ bladder temperature < 36.0°C, maintained for more than 5 consecutive days (21); Cranial CT results on June 20, 2025, showed improved cerebral edema and good cerebral compliance, indicating that the patient met the rewarming criteria. Slow rewarming was performed by adjusting the temperature of the cooling blanket (initially set 0.5°C higher than the target temperature, then adjusted according to the rewarming rate) at a rate of 0.1–0.25°C/h. The body temperature was rewarmed to 36.0°C–37.5°C within 24 h, with strict avoidance of temperatures exceeding 38°C (22). During the rewarming process, the doses of hibernation mixture, midazolam, remifentanil, and other drugs were gradually reduced, and short-acting propofol was added. The patient was successfully rewarmed after 26 h, with the body temperature rising to 37.1°C.

➅ Comfort: Increased ICP can compress brain tissue, leading to local ischemia and hypoxia. We set the sedation and analgesia goals for the patient as follows: RASS score of −4 to −3, and CPOT score ≤ 3 (23). Actively sedative and analgesic treatments were administered with drugs such as remifentanil, midazolam, esketamine, and hibernation mixture. During the treatment period, dynamic assessments of the sedative and analgesic effects were performed every 4 h. On the 8th day of the disease course, the patient’s hypothermia therapy was completed. Midazolam was gradually reduced and discontinued, and sedative treatment was switched to propofol and dexmedetomidine. Subsequently, the patient’s RASS score ranged from −3 to 0, and the CPOT score ranged from 0 to 1.

Given that the patient had a GCS score < 10, ultra-severe TBI, and subdural hematoma shown on CT–all of which are risk factors for post-traumatic epilepsy (PTE) (24), continuous electroencephalographic (EEG) monitoring was performed after admission. The EEG activity showed diffuse slow-wave activity in both cerebral hemispheres, predominantly delta waves, with moderate amplitude, basically symmetrical on the left and right sides, and no obvious focal abnormalities. In accordance with guideline recommendations (25), we initiated prophylactic anti-epileptic treatment via nasogastric feeding on the 3rd day of the disease course, including sodium valproate tablets (0.2 g, twice daily) and levetiracetam tablets (0.5 g, twice daily). No pathological discharge waveforms such as spikes, sharp waves, spike-and-slow complexes, or sharp-and-slow complexes were recorded during the entire course of EEG monitoring.

➆ Arterial Pressure: Arterial blood pressure is the primary determinant of CBF. The patient was diagnosed with severe TBI, with an admission blood pressure of 155/86 mmHg. In accordance with the GHOST-CAP strategy, we maintained the patient’s mean arterial pressure (MAP) ≥ 80 mmHg and systolic arterial pressure (SAP) > 100–110 mmHg (26, 27). No significant abnormalities were observed in the SAP and MAP during the treatment period, and both were maintained within the target range.

Dynamic temperature control: the initiation and termination of TTM were guided by the dual criteria of “injury severity plus radiologic improvement” (21, 22). TTM was instituted on admission because fever (38.4 °C) and cerebrospinal-fluid otorrhoea implied a high infectious risk. After cranial CT demonstrated resolving cerebral edema, improved intracranial compliance and an ONSD < 5 mm, the patient was rewarmed at 0.1–0.25 °C/h to 36.0 °C–37.5 °C within 24 h; Precision control of metabolic targets: blood glucose was checked every 4 h after admission (8.29 mmol/L; target 4–10 mmol/L). One week later, glucose fell to 2.8 mmol/L (below threshold); in the setting of skull-base fracture and diffuse axonal injury, 50% glucose was administered by intravenous infusion and titrated accordingly (34). Concurrent TCD monitoring of cerebral perfusion ensured the safety of combined mannitol/hypertonic-salt dehydration (35) and guided infusion rates during Na⁺ shifts to prevent complications; Integrated cardiopulmonary optimization: On day 9 patient-ventilator asynchrony developed, triggered by “excessive sedation score + falling ventilatory efficiency.” Multimodal checks at that moment showed rScO2 75% and TCD PI 0.87, ruling out raised ICP as the cause; therefore the sedation regimen was adjusted first (remifentanil increased to 0.2 μg/kg/min, dexmedetomidine added) (36). The ventilator was simultaneously switched to APRV, improving lung ventilation and reducing wet-lung injury (37) while avoiding the cerebral oxygen drop that would follow indiscriminate deep sedation, thus achieving a balance between “lung protection” and “brain protection.”

The “dynamic nature” of GHOST-CAP is essentially a closed-loop of “indicator-intervention-feedback”: it is necessary to preferentially deal with the index deviations that “endanger brain function” (such as the decrease of cerebral oxygen, MAP < 80 mmHg), and then coordinate the goals of other systems (such as negative fluid balance); at the same time, it depends on multi-disciplinary collaboration to avoid “neglecting one thing while attending to another” caused by the decision-making of a single department. In this case, all adjustments are based on the premise of “brain function safety.” For example, the rewarming time is delayed until the brain edema is relieved to ensure good brain compliance; the adjustment of ventilator parameters is based on the stability of rScO₂ as the bottom line (38), reflecting the core principle of “brain protection first.”

In the assessment of ICP, although a single ONSD > 5 mm indicates increased ICP, it may be false-positive due to periorbital edema and operation methods; while the PI value monitored by TCD can provide cross-verification. In this case, the ONSD was continuously >5 mm, but the PI monitored by TCD was always within the range of 0.5–1.06, indicating that the degree of increased ICP was mild (35, 39). Therefore, a mild scheme of “alternate infusion of 125 mL of mannitol and 100 mL of 3% hypertonic salt” was adopted to avoid insufficient blood volume and decreased cerebral perfusion caused by excessive dehydration. If only relying on ONSD, the dehydration intensity may be blindly increased, increasing the risks of renal injury and cerebral ischemia.

Even when systemic SpO₂ is normal, local cerebral tissue hypoxia may still occur. On the 5th day of the disease course in this case, SpO2 was 96% but rScO2 decreased to 68%. Combined with a PI of 0.93 monitored by TCD, it was diagnosed as “relative cerebral hypoperfusion.” Immediately, the MAP was increased from 80 to 85 mmHg, and the proportion of protein in enteral nutrition was increased. After 24 h, rScO2 recovered to 73%, avoiding occult cerebral injury caused by “normal systemic oxygenation but local cerebral hypoxia.” In this case, rScO2 monitoring functioned not merely as an observational parameter, but as a trigger for targeted hemodynamic and nutritional interventions.

In the treatment of traumatic wet lung, a reduction in bilateral pulmonary exudation shown by chest CT only reflects improvements in lung morphology and cannot directly verify the benefits to brain function; in contrast, cerebral oxygen monitoring can serve as a bridging indicator for “pulmonary ventilation-cerebral oxygen supply.” On June 24th in this case, chest CT indicated improved bilateral pulmonary exudation and reduced pleural effusion. Concurrently, rScO₂ increased from 65% at admission to 80%, and PI monitored by TCD remained stable. This confirmed that improved pulmonary ventilation effectively enhanced cerebral oxygen supply, providing direct evidence for “brain function safety” to support weaning from the ventilator and endotracheal extubation on June 23rd. This combined assessment of “morphology (CT) + function” is more effective than a single imaging indicator in guiding decisions at key treatment nodes.