The ICEBERG: A score and visual representation to track the severity of traumatic brain injury: Design principles and preliminary results.

BACKGROUND: Establishing neurological prognoses in traumatic brain injury (TBI) patients remains challenging. To help physicians in the early management of severe TBI, we have designed a visual score (ICEBERG score) including multimodal monitoring and treatment-related criteria. We evaluated the ICEBERG scores among patients with severe TBI to predict the 28-day mortality and long-term disability (Extended Glasgow Outcome Scale score at 3 years). In addition, we made a preliminary assessment of the nurses and doctors on the uptake and reception to the use of the ICEBERG visual tool. METHODS: This study was part of a larger prospective cohort study of 207 patients with severe TBI in the Parisian region (PariS-TBI study). The ICEBERG score included six variables from multimodal monitoring and treatment-related criteria: cerebral perfusion pressure, intracranial pressure, body temperature, sedation depth, arterial partial pressure of CO 2 , and blood osmolarity. The primary outcome measures included the ICEBERG score and its relationship with hospital mortality and Extended Glasgow Outcome Score. RESULTS: The hospital mortality was 21% (45/207). The ICEBERG score baseline value and changes during the 72nd first hours were more strongly associated with TBI prognosis than the ICEBERG parameters measured individually. Interestingly, when the clinical and computed tomography parameters at admission were combined with the ICEBERG score at 48 hours using a multimodal approach, the predictive value was significantly increased (area under the curve = 0.92). Furthermore, comparing the ICEBERG visual representation with the traditional numerical readout revealed that changes in patient vitals were more promptly detected using ICEBERG representation ( p < 0.05). CONCLUSION: The ICEBERG score could represent a simple and effective method to describe severity in TBI patients, where a high score is associated with increased mortality and disability. In addition, ICEBERG representation could enhance the recognition of unmet therapeutic goals and dynamic evolution of the patient's condition. These preliminary results must be confirmed in a prospective manner. LEVEL OF EVIDENCE: Diagnostic Tests or Criteria; Level III.

Adrecizumab, a non-neutralizing anti-adrenomedullin antibody, improves haemodynamics and attenuates myocardial oxidative stress in septic rats.

BACKGROUND: Sepsis still represents a major health issue, with persistent high morbidity and mortality rates. Cardiovascular dysfunction occurs frequently during sepsis. Adrenomedullin has been identified as a key mediator in vascular tone regulation. A non-neutralizing anti-adrenomedullin antibody, Adrecizumab, may improve haemodynamic dysfunction during caecal ligation and puncture-induced septic shock in a murine model. Our objective was to determine the role of Adrecizumab on haemodynamics in a rat model of sepsis. METHODS: For the induction of sepsis, caecal ligation and puncture were performed in Wistar male rats. Single blinded administration of Adrecizumab (2 mg/kg) or placebo was injected i.v. 24 h after the surgery, and norepinephrine was infused as the standard of care. There were > 7 animals per group. Invasive blood pressure and cardiac function (by echocardiography) were assessed until 3 h after Adrecizumab injection. RESULTS: A single therapeutic injection of Adrecizumab in septic rats induced rapid haemodynamic benefits with an increase in systolic blood pressure in septic-Adrecizumab rats versus untreated-septic rats (p = 0.049). The shortening fraction did not differ between the untreated-septic and septic-Adrecizumab groups. However, cardiac output increased during the 3 h after a single dose of Adrecizumab compared to untreated septic rats (p = 0.006). A single dose of Adrecizumab resulted in similar haemodynamics to the continuous administration of norepinephrine. Three hours after a single injection of Adrecizumab, there was no change in the inflammatory phenotype (TNFα, IL-10) in the hearts of the septic rats. By contrast, 3 h after a single Adrecizumab injection, free-radical production decreased in the hearts of septic-Adrecizumab vs untreated septic rats (p < 0.05). CONCLUSIONS: In a rat model of sepsis, a single therapeutic injection of Adrecizumab rapidly restored haemodynamic parameters and blunted myocardial oxidative stress. Currently, a proof-of-concept and dose-finding phase II trial (Adrenoss-2) is ongoing in patients with septic shock and elevated concentrations of circulating bio-adrenomedullin.