The primary objective of intensive care is to prevent and treat secondary brain injury (SBI) caused by hypotension, hypoxia, or hyperthermia. We will focus this chapter on traumatic brain injury (TBI) and our objective will be the treatment and prevention of SBI using a neuroprotective strategy to maintain cerebral perfusion in order to meet the brain’s oxygen and metabolic demands. Elevated intracranial pressure (ICP) is an important cause of SBI and associated with very poor outcome after TBI. Elevated ICP can be related to brain edema, vascular engorgement, cerebral contusion, or intracranial mass lesions. The prevention and control of raised ICP and the maintenance of cerebral perfusion pressure (CPP) are essential therapeutic goals after TBI. ICP monitoring has developed an essential role in the treatment of TBI, despite the incredible absence of class-1 studies and its use is only recommended by international consensus guidance .
ICP is a very complex variable. Recent consensus (Brain Trauma Foundation) indication for ICP monitoring in TBI include: patients in coma (Glasgow Coma Scale score of 8 or less) with an abnormal head CT scan; patient in coma with a normal head CT scan but at least two other risk factors for elevated ICP (age over 40 years, pathologic motor posturing, systolic BP under 90 mmHg); and in other head injured patients at the physician’s discretion .
There is around a 60% chance of raised ICP in patients with these risk factors. Although there are again no class-1 studies, there is some clinical evidence supporting the use of ICP to assess prognosis after severe TBI, to guide therapeutic interventions, and to detect earlier intracranial mass lesions. ICP monitoring is accepted as a low-risk procedure, a decisive clinical decision-making tool, and a high-yield and cost-effective intervention during TBI management.
ICP cannot be precisely estimated from any specific clinical feature or CT finding and must be actually measured . Different methods of ICP monitoring have been described (Table 12.1) but two methods are commonly used at the bedside intraventricular catheters and intraparenchymal catheter-tip micro-transducer systems. An intraventricular catheter, connected to a standard pressure transducer via a fluid filled catheter is the “gold standard” method for monitoring ICP. Ventricular catheters measure global ICP and have the additional advantages of allowing periodic external calibration, administration of drugs, and therapeutic drainage of cerebrospinal fluid (CSF). However, installation may be difficult and their use is complicated by an infection rate up to 11% . Micro transducer-tipped ICP monitors can be located in the brain parenchyma or subdural space, either via a cranial access device (skull bolt) or during a neurosurgical procedure. They are almost as accurate as ventricular catheters and are reliable and easy to use at the bedside . Their infection rates are much lower but the measured pressure may not be representative of true CSF pressure, due to the intraparenchymal pressure gradients that are very common after TBI . In vivo calibration is not possible but the zeroing during surgical installation lies within a clinically acceptable range and is usually as low as 1 mmHg after 5 days of continuous use .
Table 1 Intracranial pressure monitoring catheters. Modified from 
Absence of Consensus
There is no general consensus on the benefits of ICP monitoring and intense variability in its application. There are also important differences between different centers regarding treatment modalities guided by ICP levels. In the USA, for instance, ICP monitors were placed in only 58% of patients who fulfilled established criteria for monitoring, and therapies to reduce ICP were routinely applied in those patients in whom ICP was not monitored . In a survey carried out by the European Brain Injury Consortium, ICP monitoring was undertaken in only 37% of eligible patients  and, in a Canadian study of severe TBI, only 20% of neurosurgeons believed that outcome was affected by ICP monitoring . The Latin American Brain Injury Consortium (LABIC) is now conducting a randomized controlled clinical trial (RCCT) comparing TBI patients with and without ICP monitoring.
Treatment of Intracranial Hypertension
High ICP and low CPP result in cerebral ischemia after TBI and are associated with increased mortality and worse outcome in survivors . Consensus guidance recommends that ICP above 20–25 mmHg should be aggressively treated using a multimodal approach .
Sedation and Analgesia
Sedation and analgesia are two crucial components of TBI management . They minimize pain, anxiety and agitation, reduce cerebral metabolic rate, and facilitate mechanical ventilation. Propofol is a widely used sedative agent because it reduces ICP, has profound cerebral metabolic suppressive effects, allows easy control of sedation levels and ICP, and permits rapid wake-up . Other combinations of Midazolam, Fentanyl, and morphine are also very popular.
PaCO2 is a major determinant of cerebral vessel diameter, with its reduction causing cerebral vasoconstriction and therefore a reduction in cerebral blood volume and ICP. Although it has been widely used in the treatment of elevated ICP, it is thought that it can worsen regional ischemia, particularly in the first 24 h after TBI. The routine application of hyperventilation is discouraged and a PaCO2 target of 30–35 mmHg should be used in the first instance. Hyperventilation to lower levels should always be carried out in association with cerebral oxygenation monitoring to avoid cerebral ischemia. Acute hyperventilation is relatively safe only for short-term use (<30 min) and is effective in controlling severely raised ICP while a neurosurgery procedure is prepared. It can also be used in threatened or actual brain herniation.
Mannitol in bolus (0.5 g/kg) effectively treats elevated ICP and improves outcome, although it has never been subject to an RCCT against placebo . It has at least two mechanisms of action: its plasma-expanding effects causes an increase in cerebral microcirculatory flow and is responsible for the rapid onset of action, and its osmotic effect reduces cerebral edema by drawing water across the blood–brain barrier into the vascular space. Treatment driven by ICP increase is much more effective than treatment oriented by clinical signs . Repeated administration could result in high osmolality (>320 mOsm/l), renal, and neurologic complications.
Hypertonic saline is very effective, even better than mannitol, and its actions are not related just to the hyperosmotic effects, but also to hemodynamic, vasoregulatory, endothelial, immunological, and neurochemical actions . It is efficient in controlling ICP resistant to mannitol and is associated with fewer side effects. However, there are no large RCCTs comparing mannitol and hypertonic saline. Furthermore, there are many concentrations available (1.7–29.2%) and the optimal concentration to lower elevated ICP has not been defined . Based on our own data, we suggest a 3 ml/kg loading bolus in a 7.5% concentration.
Moderate hypothermia (33–35°C) has efficient neuroprotective effects in animal studies but human trials have been disappointing, mainly because of infection. We must control this morbidity, which is not that simple, before using it again in humans. In addition, high temperatures are associated with worse outcomes after TBI and are the most important cause of secondary brain injury. Core temperature and cerebral temperature should be continuously monitored and pyrexia must be prevented and aggressively treated.
Barbiturates lower ICP by many mechanisms and, although there is no good evidence that they improve outcome after TBI , there has been a resurgence of interest in the use of high-dose barbiturate therapy for the treatment of refractory intracranial pressure . Hypotension is a frequent complication of treatment, and drug accumulation leads to delayed recovery and difficulties in rapid clinical assessment when the drug is discontinued. Continuous EEG monitoring can be used to titrate barbiturate infusion and minimize side effects.
The removal of an expanding intracranial mass lesion is the goal of neurosurgical treatment after TBI. An external ventricular catheter allows drainage of CSF and, because intracranial compliance is reduced, removal of even small CSF volumes can result in a dramatic decrease in ICP. Decompressive craniectomy is an extensive procedure where a large area of the skull vault is removed, and the dura is opened wide to allow brain expansion, with a consequent ICP reduction. There is divided opinion on the relative benefits and risks of the operation . Our group strongly recommends this method, but it must be performed in a small window of time (<8 h after TBI) and the duraplasty must be large and wide to be effective. This controversial issue is currently being addressed by an RCCT—the Rescue ICP study (www.rescueicp.com).
Like all difficult cases and diseases this issue has many controversies and we will address each one.
What is the Target ICP?
Although it is very well recognized that raised ICP correlates with higher risk of mortality and morbidity, not all patients with intracranial hypertension have poor outcome . There is therefore a fundamental dilemma about which patients should be treated and at what ICP level. Furthermore, recent evidence suggests that the duration of intracranial hypertension and its fast response to treatment could be better predictors of neurological outcome than isolated and absolute ICP values . It has also recently been demonstrated that brain resuscitation after TBI based exclusively on control of ICP levels and CPP does not prevent cerebral hypoxia in more than 20% of patients . This is unsurprising because monitoring of ICP and CPP does not tell the whole story. They are global measurements and sometimes a small but very important cerebral region is suffering very much without global modifications. It is impossible to know in an individual patient whether the targeted ICP or CPP is enough to allow the brain’s metabolic demands to be met at a particular moment in time . There is preliminary evidence that therapy directed towards maintenance of brain tissue oxygenation as well as ICP and CPP is associated with reduced mortality after TBI .
Does ICP Monitoring and Management Improve Outcome?
In a retrospective study, an “aggressive” management protocol was associated with decreased risk of mortality and shorter length of hospital stay, although there were no differences in functional status in survivors after discharge . Another large retrospective study also concluded that ICP monitoring was associated with significantly decreased mortality  but two surveys [19, 20] and one prospective study  did not show benefits from ICP monitoring. In general, all studies demonstrated that the use of ICP increased intensity of treatment without clear evidence of improvement in outcome .
Complications of Treatment
Conventional approaches to the management of TBI have concentrated on a reduction in ICP to prevent secondary cerebral ischemic injury, but there has been a shift in emphasis from primary control of ICP to a multifaceted approach of maintenance of CPP >70 mmHg and brain protection . The Brain Trauma Foundation now recommends that the CPP target after severe TBI should lie between 50–70 mmHg  instead of the previous suggested value >70 mmHg. The previous aggressive attempts to maintain CPP >70 with volume overload and vasopressors caused a fivefold increase in the occurrence of acute lung injury.
In addition to the evidence that the control of ICP and CPP may improve outcome after severe TBI, it is also possible that targeting treatment only towards changes in these two variables might be inappropriate because, when changes do occur in these measurements, irreversible ischemic brain damage may already have occurred . So, besides the pressures, it is also necessary to monitor the adequacy of cerebral perfusion, such as measurements of cerebral oxygenation (jugular venous oximetry and brain tissue oxygen tension) and metabolic status (cerebral micro dialysis). Monitoring of several variables simultaneously, the multimodal monitoring (MM), allows cross validation between monitors, artifact rejection, and greater confidence in making the right clinical decision. Developments of MM have allowed a movement away from rigid physiological target setting after TBI toward an individually tailored, patient-specific approach. This new vision provides early warning of impending brain ischemia, prevents secondary brain injury, and guides targeted therapy.
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