Traumatic Brain Injury: Outcome and Pathophysiology
Clemens Pahl FRCA DICM
Consultant Intensivist King’s College Hospital
Focus on outcome from traumatic brain njury
Traumatic brain injury (TBI) is graded as follows:
• Mild GCS 14-15
• Moderate GCS 9 -13
• Severe GCS 8 and below
Evidence from observational studies shows that outcome after severe TBI is highly dependent on the quality of the critical care management. Patel et al. collected prospective data from the Trauma Audit and Research Network database on patients presenting with blunt trauma between 1989 and 2003. This network includes 60% of the trauma-receiving hospitals in England and Wales, and is the largest trauma registry in Europe. Patel and his co-authors found that 6921 patients presented with severe head injury (GCS<9) between 1996 and 2003. Nearly two-thirds of these patients (2305) were managed solely by non-neurosurgical centres. Interestingly, management in a non-neurosurgical centre was associated with a 26% increase in mortality and a 2.15-fold increase in the odds ratio of death (adjusted for case mix) compared with treatment in specialist neurosurgical centres. The results of this survey suggest that patients are twice as likely to survive a severe head injury if they are treated in a specialist neurosurgical centre. This poses a particular challenge for both neurosurgeons and intensivists involved in the management of TBI.
Evidence from the current literature demonstrates that 30-40% of patients presenting with TBI have a favourable outcome, defined as a Glasgow Outcome Scale score of 4 or 5 (Table 1). In neurosurgical centres, the mortality of isolated severe TBI is approximately 30-40%.
Table 1. The Glasgow Outcome Scale
2. Persistent vegetative state
3. Severe disability
'Dependent for some support in activities of daily living'
4. Moderate disability
'Independent, but disabled. May or may not be able to return to work'
5. Good recovery
The following factors are associated with a poorer prognosis in patients with TBI:
• GCS (the lower the worse)
• Increased age (above 45 years)
• Additional injuries
• Duration that ICP >20 mmHg
• Management in a non-neurosurgical centre
Focus on the pathophysiology of TBI
Primary brain injury
The primary impact to the brain and skull may cause bony fractures, intracranial haematomas, brain contusion, axonal injury and disruption of the blood-brain barrier.
Secondary brain injury
Secondary brain injury occurs as a consequence of cerebral ischaemia and inflammatory and cytotoxic processes.
Cerebral ischaemia is the key secondary insult following TBI. Ischaemic brain damage can be identified on histology in up to 90% of patients who die following closed head injury. There is increasing evidence that cerebral blood flow (CBF) is significantly reduced following severe TBI. The resultant CBF may be appropriately low to match reduced cerebral metabolism (flow-metabolism coupling). However, a reduced CBF is generally considered to be the main cause of cerebral ischaemia. For this reason, restoring and preserving adequate CBF is the major principle underlying the management of patients with severe TBI.
The aetiology of post-traumatic cerebral ischaemia is likely to be multifactorial. TBI leads to an increased resistance to CBF driven by the formation of brain oedema, microvascular pathology, focal compression by haematomas or by cerebral vasospasm. TBI is also associated with a loss or impairment of cerebrovascular autoregulation. This means that CBF becomes directly proportional to the cerebral perfusion pressure (CPP). It is difficult to determine the exact CPP above which an adequate CBF is maintained if cerebrovascular autoregulation is lost. Moreover, the value is likely to differ from individual to individual. However, a CPP below 50 mmHg has been shown to increase significantly mortality from TBI. Other important causes of cerebral ischaemia are systemic hypoxaemia and systemic arterial hypotension.
Brain oedema following TBI is broadly classified as cytotoxic or vasogenic in origin. Cellular cytotoxicity is the initial mechanism of oedema formation, whereby fluid accumulates within cells following the breakdown of cell membrane sodium-potassium ATPase pumps. Vasogenic oedema results both from the disruption of the blood-brain barrier (commonly occurring 48 hours after TBI) and from brain hyperaemia. The result is extravasation of fluid into the brain parenchyma.
Intracranial oedema and haemorrhage has such devastating effects on cerebral function because the brain is encased in a rigid skull (‘Monroe-Kelly doctrine’). Any increase in the volume of one of the skull’s internal components (e.g. parenchymal swelling through oedema formation) will cause intracranial hypertension once compensatory mechanisms are exhausted (Figure 1). Important compensatory mechanisms include displacement of CSF into the spinal subarachnoid space, increased CSF absorption and reduced CSF production.
Cytotoxic and inflammatory processes
Cytotoxic and inflammatory processes that have been implicated in driving secondary brain injury include release of excitatory amino acids (e.g. glutamate), influx of excessive calcium ions into cells via glutamate-mediated ion channels, injury mediated by oxygen-free radicals, accumulation of neutrophils, lymphocytes and macrophages, and the deposition of amyloid protein.
Haemodynamic phases after traumatic brain injury
CBF may show significant variations in the days after the TBI. There is also a significant patient-to-patient variation in the haemodynamic response to TBI. However, a pattern of three distinct haemodynamic phases can be distinguished:
Hypoperfusion phase (phase 1; day 0)
The first 24 hours after TBI are characterised by cerebral hypoperfusion. Although CBF is reduced, there is a normal velocity in the middle cerebral artery (VMCA) as assessed by transcranial Doppler and a normal cerebral arteriovenous oxygen difference (AVDO2) and hence normal jugular venous bulb oxygen saturations (SjO2). During this hypoperfusion phase, cerebral metabolic rate for oxygen (CMRO2) is about 50% of normal. It has been suggested that pathological microcirculatory resistance is responsible for the reduced blood flow. Given the normal AVDO2, it is also plausible that the CBF during this stage represents physiological flow-metabolism coupling.
Hyperaemia phase (phase 2; days 1 to 3)
After 24 hours (days 1 to 3) the CBF increases. This is associated by a fall in AVDO2 and hence a rise in the SjO2. CMRO2 remains depressed. There is both a relative hyperaemia (relative to blood flow demand during this stage) and an absolute hyperaemia (CBF above the normal CBF range). VMCA begins to rise rapidly. The pathophysiological mechanism of this hyperaemia is unknown. Possible explanations are increased cerebral glucose metabolism (hyperglycolysis) and a fall in cerebral microvascular resistance because of the generation of vasodilatory metabolites (e.g. lactic acid, adenosine, neuropeptides). Hyperaemia itself can cause significant elevations of ICP. During the hyperaemia phase systemic vasopressors should be used with caution. The therapeutic CPP target may need to be lowered because systemic hypertension and high CPP in association with impaired autoregulation may further increase CBF and contribute to hyperaemia and raised ICP. Potential guides to the management of the hyperaemic phase include SjO2, cerebral microdialysis, transcranial Doppler, or direct measurements of CBF.
Vasospasm phase (phase 3, days 4 to 15)
TBI may also cause spasm of large cerebral vessels similar to vasospasm induced by subarachnoid haemorrhage. VMCA rises further and CBF gradually declines. Interestingly, during the vasospasm phase the AVDO2 remains low (hence the SjO2 remains high).This is probably the result of either the persistently reduced CMRO2 or cell death.
Vasospasm may contribute further to cerebral ischaemia. The therapeutic implications of vasospasm in conjunction with TBI remain open to debate. It has been proposed that the management algorithm should mirror that of the management of vasospasm associated with subarachnoid haemorrhage - that is, triple H therapy (Hypertension, Haemodilution and Hypervolaemia) and the administration of nimodipine.
Focus on the ICP waveform
The ICP waveform is a modified arterial pressure trace and shows characteristic waveforms (Figure 2). The first peak (P1) is called the “percussive” wave and results from arterial pressure transmitted from the choroid plexus. The second peak (P2) is the “tidal” wave and its amplitude varies with brain compliance. Decreasing brain compliance increases P2 amplitude, which may then exceed P1. P3 represents the dicrotic notch, and is therefore caused by closure of the aortic valve.
The ICP waveform can also be analysed in the time domain - i.e. ICP waveform trend over time. This may reveal typical Lundberg waves of ICP (Figure 3). A paper chart record connected to an analogue output from the ICP transducer often provides better resolution than digital recording for detection of Lundberg waves. Lundberg A waves “or plateau waves” are steep increases in ICP lasting for 5 to 10 minutes. They are always pathological and represent reduced intracranial hypertension indicative of early brain herniation. Lundberg B waves are oscillations of ICP at a frequency of 0.5 to 2 waves/min and are associated with an unstable ICP. Lundberg B waves are possibly the result of cerebral vasospasm, because during the occurrence of these waves, increased velocity in the middle cerebral artery can be demonstrated on transcranial Doppler.
Lundberg C waves are oscillations with a frequency of 4-8 waves/min. They have been documented in healthy subjects and are probably caused by interaction between the cardiac and respiratory cycles.
Patel HC, Bouamra O, Woodford M, et al.
Trends in head injury outcome from 1989 to 2003 and the effect of neurosurgical care: an observational study.
Lancet 2005; 366: 1538-1544.
Bulger EM, Nathens AB, Rivara FP, et al.
Management of severe head injury: Institutional variations in care and effect on outcome.
Crit Care Med 2002; 30: 1870-1876.
Marion DW, Puccio A, Wisniewski SR, et al.
Effect of hyperventilation on extracellular concentrations of glutamate, lactate, pyruvate, and local cerebral blood flow in patients with severe traumatic brain injury.
Crit Care Med 2002; 30: 2619-2625.
Robertson CS, Valadka AB, Hannay HJ, et al.
Prevention of secondary ischaemic insults after severe head injury.
Crit Care Med 1999; 27: 2086-2095.
Martin N, Patwardhan RV, Alexander MJ, et al.
Characterization of cerebral haemodynamic phases following severe head trauma: hypoperfusion, hyperaemia, and vasospasm.
J Neurosurg 1997; 87: 9-19.
Gupta AK, Menon DK, Czosnyka M, et al.
Thresholds for hypoxic cerebral vasodilatation in volunteers.
Anesth Analg 1997; 85: 817-820.
Bouma GJ, Muizelaar JP, Stringer WA, et al.
Ultra-early evaluation of regional cerebral blood flow in severely head injured patients using xenon enhanced computed tomography.
J Neurosurg 1992; 77: 360-368.
Robertson CS, Contant CF, Narayan RK, et al.
Cerebral blood flow, AVDO2, and neurologic outcome in head-injured patients.
J Neurotrauma 1992; 9: S349-S58.
Bouma GJ, Muizelaar JP, Choi SC, et al.
Cerebral circulation and metabolism after severe traumatic brain injury: the elusive role of ischaemia.
J Neurosurg 1991; 75: 685-693.
Marion DW, Darby J, Yonas H.
Acute regional blood flow changes caused by severe head injuries.
J Neurosurg 1991; 74: 407-414.
Jaggi JL, Obrist WD, Gennarelli TA, et al.
Relationship of early cerebral blood flow and metabolism to outcome in acute head injury.
J Neurosurg 1990; 72: 176-182.