Traumatic brain injuries in children represent a major cause of morbidity and mortality worldwide and it is the main cause of death in children older than one years of age. The majority of children who survives a life threatening brain trauma have new disabilities that affect how they function throughout the rest of their lives. This also has great impact on their carers and societies. Currently the best option to improve survival and recovery of children with life threatening brain trauma is to improve their early hospital treatments including intensive care because none of the new experiemental therapies tested in the laboratory is useful in clinical practice. The current best therapeutic option to improve paediatric TBI outcome is to optimise physiological support in the intensive-care to minimise secondary physiological insults which are proven to negatively affect outcome. However therapeutic thresholds for abnormal physiology vary between units and are implemented clinically without validation. To give these patients the best possible recovery, we urgently need clinically relevant and readily translatable research that optimises paediatric brain trauma treatment and reduces inequality between different centres.
Secondary ischaemic injury from reduced brain perfusion is the main insult neuro-intensive care management aims to prevent and we need to monitor cerebral blood flow (CBF) and metabolism continuously to prevent brain ischaemia. Intact cerebrovascular autoregulation means having the ability to maintain a stable brain perfusion for varying mean arterial blood pressure (MAP). In clinical practice, we know cerebrovascular autoregulation is intact when a patient retains the pressure active pattern while considering the relationship between MAP and ICP. Optimal CPP (CPPopt) is the CPP level that maintains the pressure active pattern. Cerebro-vascular autoregulation is known to be impaired after severe TBI and the degree and range of this dysfunction vary between patients and over time within the same patient. Continuous real-time physiological monitoring is a recognised standard in TBI intensive-care management and ICP-lowering therapy is recommended when ICP is elevated above 20 mmHg or more, but this treatment threshold is only based upon clinical experience.
We hypothesize that having measured CPP within calculated CPPopt provide better tolerance to raised ICP and improve recovery in childhood brain trauma.
Children aged 2 to 16 years who require intensive care management after sustaining accidental TBI are eligible for inclusion. The contributing units ( UK, Belgium, Spanish, and Romanian centres) have similar treatment protocols, which include: defined raised ICP treatment guidelines using osmo-diuretics as a first line medical treatment; using intravenous infusions of vasopressive drugs to drive mean arterial blood pressure to achieve a target CPP; sedation and muscle relaxant protocol; mechanical ventilation to control PaCO2 to low normal values; actively controlling core body temperature to normothermia.
Patients’ anonymised clinical data are collected; it includes the cause and nature of injury, age, Glasgow Coma Score (GCS) on admission and after acute non-surgical resuscitation, pupillary responses, initial radiological and computerized tomography (CT), operative and other treatment details. Each patient’s anonymised clinical data is linked to their physiological and outcome data in the KidsBrainIT data-bank using an anonymous study ID. Routinely measured physiological data in minute-resolutions are captured from the bedside monitors prospectively. All physiological data are anonymised prior to exporting, and then stored in the KidsBrainIT central data-bank Outcome assessments are performed by each local team.
CPPopt calculation and ICP dose-response visualisation analyses are performed to test our hypotheses and determine if TBI patients with favourable outcome have longer periods of measured CPP within the calculated CPPopt ranges and an enhanced tolerance of raised ICP. The accordance between CPPopt and actual CPP is calculated to evaluate the association with survival (GOS > 1) and favorable outcome (GOS >3):
‐ the percentage of time for which the actual CPP is within the recommended CPPopt range;
‐ the average difference between actual CPP and CPPopt;
‐ the average absolute difference between actual CPP and CPPopt;
‐ the average absolute difference when actual CPP is outside CPPopt range;
‐ the average difference where actual CPP is below CPPopt;
‐ the average difference where actual CPP is above CPPopt;
‐ the previous criteria are used in a multivariate logistic regression model.
The findings from our study and any treatment target recommendations are directly transferable back to a wider clinical audience because no special equipment or software is required beyond that is currently used for the routine minute-by-minute physiological bedside monitoring.