Traumatic brain injury (TBI) is a major cause of death and disability. TBI is frequently followed by cerebral ischemia which is a great contributor to secondary brain damage. The main causes of cerebral ischemia are pathophysiological changes in cerebral blood flow and metabolism. Treatment of TBI patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted treatment protocols. However, ICP and CPP alone do not provide information of the oxygen availability in the brain. Monitoring of brain tissue oxygenation (BtipO2) may give additional and valuable information about the risk for development of ischemia in TBI patients. The aims of this thesis were to study BtipO2 monitoring devices in-vitro regarding accuracy and stability, to detect threshold level of cerebral ischemia in-vivo and finally to examine the cerebral oxygen levels and cerebral metabolism in TBI patients. The BtipO2 probes performed with high accuracy and stability at different clinically relevant oxygen concentrations. A pig TBI model was developed by step-wise intracranial volume/pressure increase. Volume increase resulted in a gradual increased ICP, decreased CPP, intracranial compliance and BtipO2, respectively. Brain death (BD) was confirmed by negative CPP and negligible amount of previously injected microspheres in the brain tissue. The model simulated the clinical development of BD in humans with a classical pressure-volume response and systemic cardiovascular reactions. The model should be suitable for studies of brain injury mechanisms. From the same in-vivo model it was also possible to detect the threshold level of cerebral ischemia in the pig, where BtipO2 below 10 mmHg and CPP below 30 mmHg was associated with an impaired cerebral metabolism (microdialysis lactate to pyruvate ratio >30). BtipO2 together with cerebral microdialysis were studied in 23 severe TBI patients. We observed different patterns of changes in BtipO2 and cerebral microdialysis biomarkers in focal and diffuse TBI.  Increased cerebral microdialysis levels of glutamate, glycerol or the lactate/pyruvate ratio were observed at BtipO2 < 5 mmHg, indicating increased vulnerability of the brain at this critical level of tissue oxygenation in TBI patients.

The neurological wake-up test, NWT, is a clinical monitoring tool that can be used to evaluate the level of consciousness in patients with traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH) during neurocritical care (NCC). Since patients with severe TBI or SAH are often treated with mechanical ventilation and sedation, the NWT requires that the continuous sedation is interrupted. However, interruption of continuous sedation may induce a stress response and the use of the NWT in NCC is controversial. The effects of the NWT on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were evaluated in 21 patients with TBI or SAH. Compared to baseline when the patients were sedated with continuous propofol sedation, the NWT resulted in increased ICP and CPP (p<0.05). Next, the effects of the NWT on the stress hormones adrenocorticotrophic hormone (ACTH), cortisol, epinephrine and norepinephrine were evaluated in 24 patients. Compared to baseline, the NWT caused a mild stress response resulting in increased levels of all evaluated stress hormones (p<0.05). To compare the use of routine NCC monitoring tools, the choice of sedation and analgesia and the frequency of NWT in Scandinavian NCC units, a questionnaire was used. The results showed that all 16 Scandinavian NCC units routinely use ICP and CPP monitoring and propofol and midazolam were primary choices for patient sedation in an equal number of NCC units. In 2009, the NWT was not routinely used in eight NCC units whereas others used the test up to six times daily. Finally, intracerebral microdialysis (MD), brain tissue oxygenation (PbtiO2) and jugular bulb oxygenation (SjvO2) were used in 17 TBI patients to evaluate the effect of the NWT procedure on focal neurochemistry and cerebral oxygenation. The NWT did not negatively alter interstitial markers of energy metabolism or cerebral oxygenation. In conclusion, the NWT induced a mild stress response in patients with TBI or SAH that did not result in a detectable, significant secondary insult to the injured brain. These results suggest that the NWT may safely be used as a clinical monitoring tool in the NCC of severe TBI and SAH in a majority of patients.

Outcome after traumatic brain injury (TBI) depends on the extent of primary cell death and on the development of secondary brain injury. The general aim of this thesis was to find strategies and quality systems to minimize the extent of secondary insults in neurointensive care (NIC). An established standardized management protocol system, multimodality monitoring and computerized data collection, and analysis systems were used. The Uppsala TBI register was established for regular monitoring of NIC quality indexes. For 2008-2010 the proportion of patients improving during NIC was 60-80%, whereas 10% deteriorated. The percentage of ‘talk and die’ cases was < 1%. The occurrences of secondary insults were less than 5% of good monitoring time (GMT) for intracranial pressure (ICP) > 25 mmHg, cerebral perfusion pressure (CPP) < 50 mmHg and systolic blood pressure < 100 mmHg. Favorable outcome was achieved by 64% of adults. Nurse checklists of secondary insult occurrence were introduced. Evaluation of the use of nursing checklists showed that the nurses documented their assessments in 84-85% of the shifts and duration of monitoring time at insult level was significantly longer when secondary insults were reported regarding ICP, CPP and temperature. The use of nurse checklist was found to be feasible and accurate.  A clinical tool to avoid secondary insults related to nursing interventions was developed. Secondary brain insults occurred in about 10% of nursing interventions. There were substantial variations between patients. The risk ratios of developing an ICP insult were 4.7 when baseline ICP ≥ 15 mmHg, 2.9 when ICP amplitude ≥ 6 mmHg and 1.7 when pressure autoregulation ≥ 0.3. Hyperthermia, which is a known frequent secondary insult, was studied. Hyperthermia was most common on Day 7 after admission and 90% of the TBI patients had hyperthermia during the first 10 days at the NIC unit. The effects of hyperthermia on intracranial dynamics (ICP, brain energy metabolism and BtipO2) were small but individual differences were observed. Hyperthermia increased ICP slightly more when temperature increased in the groups with low compliance and impaired pressure autoregulation. Ischemic pattern was never observed in the microdialysis samples. The treatment of hyperthermia may be individualized and guided by multimodality monitoring.