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Progress in the understanding of the pathophysiologic process and management of brain injury provides a unique challenge to the young investigator. Currently, there are teams both in the laboratory and clinical settings which may or may not interact as a result of the depth and breadth of the problems before them. For example, laboratory teams may be focused on cellular or molecular mechanisms of injury while the clinical investigator is attempting to deal with refractory ICP and it’s treatment. It is clear that many aspects of biological research must indeed be approached using molecular techniques of neuroscience and much has been learned. However, the translational aspect of this effort may be elusive as it is unclear at present how these molecular techniques translate into the intensive care unit and the patient. For many, the research paths taken in the laboratory and ICU will always remain independent. For those who desire a more direct pathway to treatment, the “bench to bedside” approach is one which is more likely to yield results. Several examples will be given to strengthen the notion that we must not abandon the translational aspect of research but to embrace the process if we are to further improve outcome from brain injury.

This study examined the relationship of cumulative percent time that cerebral perfusion pressure (CPP) fell below set thresholds to outcome in individuals with traumatic brain injury (TBI). The sample included 157 patients (16 to 89 years of age, 79% male) admitted to an intensive care unit at an academic medical center who underwent invasive arterial blood pressure and intracranial pressure monitoring. CPP levels were recorded continuously during the first 96 hours of monitoring. Initial neurologic status was assessed using the post-resuscitation Glasgow Coma Scale. Outcome was evaluated at hospital discharge and at six months post-injury using the Extended Glasgow Outcome Scale (GOSE). The relationship of cumulative periods of low CPP to outcome was evaluated using hierarchical and binary logistic regression analysis, controlling for age, gender, and injury severity.

Patients experiencing less cumulative percent time below specific CPP thresholds were more likely to have better outcome at discharge (55 mm Hg, p=.004; 60 mm Hg, p=.008; 65 mm Hg, p=.024; 70 mm Hg, p=.016). Although differences in GOSE scores at six months were not significant, those with less time below CPP thresholds were more likely to survive. Accumulated episodes of low CPP had a stronger negative relationship with outcome in patients with more severe primary brain injury.

In volunteers, hyperventilation improves autoregulation. However, in head-injured patients, hyperventilation-induced deterioration and improvement of autoregulation have been reported. We have re-examined this question using an index of pressure reactivity. Thirty patients with severe or moderate head-injury were studied. Arterial blood pressure, cerebral perfusion pressure (CPP), and intracranial pressure (ICP) were recorded over 20 minute epochs separated by ten minutes of equilibration at baseline and during moderate (>3.5 kPa) hyperventilation. End-tidal CO was constant during each phase of data acquisition. Pressure reactivity was assessed using an index ‘PRx’ based on the response of ICP to spontaneous blood pressure changes. Hyperventilation decreased PaCO from 5.1±0.4 to 4.4±0.4 kPa (p < 0.0001). ICP decreased by 3.7±2.2 mmHg (p < 0.001). CPP increased by 5.9±8.2 mmHg (p < 0.001). Overall, PRx did not change significantly with hyperventilation. However, there was a significant negative correlation between baseline PRx and the change in PRx (r = −0.71, p < 0.0001). This suggests that patients with disturbed pressure-reactivity may improve, whereas patients with intact pressure reactivity remain largely unchanged. Our data suggest that the response of pressure reactivity to hyperventilation is heterogeneous. This could be due to hyperventilation-induced changes in cerebral metabolism, or the change in CPP.

Severe head injury in childhood continues to be associated with considerable mortality and morbidity. Early surgical decompression may be beneficial and the objective of this study was to examine the relationship between age-related thresholds of mean intracranial pressure (ICP) and cerebral perfusion pressure (CPP) over the first 6 hours and age outcome in paediatric head injury patients.

A total of 209 head injured children admitted to five UK hospitals were studied. Patients aged 2 to 16 years were included if they had a minimum of six hours of invasive pressure monitoring. Mean values of ICP and CPP over this period were calculated and compared to those with independent (good recovery and moderate disability) and poor outcome (severe disability, and death) for different age groups.

There were 148 children with independent outcome (92 good recovery, 56 moderately disabled), and 61 with poor outcome (30 severely disabled, 31 deaths). There was a significant difference between those with independent compared to poor outcome in relation to ICP (p < 0.001) and CPP (p < 0.001). Patients were divided into three groups according to age. The sensitivity of ICP and CPP in predicting outcome was similar for all groups but the specificity differed between groups. At a CPP of 50 mmHg the specificity varied between the age groups (2 to 6 years: 0.47, 7 to 10 years: 0.28 and 11 to 16 years: 0.10) and similarly for an ICP of 25 mmHg (2 to 6 years: 0.53, 7 to 10 years: 0.44 and 11 to 16 years: 0.38).

Younger children may be able to tolerate lower perfusion pressures and still have an independent outcome. Our threshold values for young children are likely to be important in the identification of patients who might benefit from new treatments such as surgical decompression.

This paper describes and validates a new (CPT) which takes into account both duration and degree of cerebral perfusion pressure (CPP) derangement and determines critical thresholds for CPP, in a paediatric head injury dataset.

Sixty-six head-injured children, with invasive minute-to-minute intracranial pressure (ICP) and blood pressure monitoring, had their pre-set CPP derangement episodes (outside the normal range) identified in three childhood age-bands (2–6, 7–10, and 11–16 years) and global outcome assessed at six months post injury.

The new cumulative pressure-time index more accurately predicted outcome than previously used summary measures and by varying the threshold CPP values, it was found that these physiological threshold values (≤48, ≤52 and ≤56 mmHg for 2–6, 7–10, and 11–16 years respectively) best predicted brain insult in terms of subsequent mortality and morbidity.

ICM software was developed in 1986 in Warsaw, Poland and has been in use at the University of Cambridge Neurocritical Care Unit for 10 years collecting data from bed-side monitors in nearly 600 severely head injured patients and calculating secondary indices describing cerebral autoregulation and pressure-volume compensation. The new software ICM+ includes a much extended calculation engine that allows easy configuration and on-line trending of complex parameters.

The program records raw signals, and calculates time trends of summary parameters. Configuration and analysis utilises arithmetic expressions of signal processing functions to calculate various statistical properties for each signal, frequency spectrums and derivatives, as well as correlations/cross-correlations between signals. The software allows configuration of several levels of analysis before calculating the final time trends. The final data are displayed in a variety of ways including simple time trends, as well as time window based histograms, cross histograms, correlations etc. All this allows complex information coming off the bed-side monitors to be summarized in a concise fashion and presented to medical and nursing staff in a simple way that alerts them to the development of various pathological processes.

The system provides a universal tool for clinical and academic purposes. Its flexibility and advanced signal processing is specialized for the needs of multidisciplinary brain monitoring.