Background and clinical questions
5. Management of ICP
Among patients with severe acute TBI, how do ICP-lowering inter-ventions affect the probability of death or the severity of neurological impairment?
A systematic review done by Roberts et al. [26], analysed the effectiveness of five medical interventions routinely used in the medical management of severe acute TBI patients.
The specific interventions were hyperventilation, mannitol, cerebrospinal fluid (CSF) drainage, barbiturates, and corti-costeroids. On the basis of the available randomized evidence, it is not possible to support or refute the existence of a real benefit on mortality and neurological disability from the use of these therapeutic interventions (Table 15.4).
Hyperventilation is often associated with a rapid fall in ICP, therefore, it has been assumed to be effective in the treatment of severe head injury patients. Hyperventilation reduces raised ICP by causing cerebral vasoconstriction and a reduction in cerebral blood volume. A Cochrane Systematic Review was
performed and published in 2000 [27]; only one trial was which randomized 113 patients [28]. Possible disadvantages of hyperventilation include cerebral vasoconstriction to such an extent that cerebral ischaemia ensues. These investiga-tors hypothesized that the short effect of hyperventilation could be related to the CSF pH decrease, with a loss of HCO3 -buffer. The latter disadvantage might be overcome by the addition of the buffer tromethamine (THAM). Accordingly, a trial was performed with patients randomly assigned to receive normal ventilation, hyperventilation (PaCO2 25 2 mmHg), or hyperventilation plus THAM (PaCO2 25 2 mmHg). Stratification into subgroups of patients with motor scores of 1–3 and 4–5 took place. Outcome was assessed according to the Glasgow Outcome Scale at 3, 6, and 12 months. There were 41, 36, and 36 patients, respectively.
A 100% follow-up was obtained. At 3 and 6 months after injury the number of patients with a favourable outcome was significantly lower in the hyperventilated patients than in the other two groups. This occurred only in patients with a motor score of 4–5. At 12 months post-trauma this differ-ence was not significant (P 0.13). Biochemical data indi-cated that hyperventilation could not sustain alkalinization in the CSF, although THAM could. Accordingly, CBF was lower in the HV THAM group than in the control and HV groups, but neither CBF nor arteriovenous difference of oxygen data indicated the occurrence of cerebral ischaemia in any of the three groups. Although mean ICP could be Table 15.4 Interventions for lowering ICP.
Type of study Intervention Outcome Number of Control Relative Absolute risk Comment
(Reference) patients (number group risk reduction
of trials) risk (range) (95% CI) (95% CI)
SR [27] Hyperventilation Death 77 34% 0.73 9% Hyperventilation better
versus control (1) (0.36–1.49) (ns)
Death or 77 61% 1.14 8% Hyperventilation worse
disability (1) (0.82–1.58) (ns)
SR [29] Barbiturate versus Death 208 42% 1.09 4% Barbiturate worse
control (3) (27–53) (0.81–1.47) (ns)
Death or 135 43% 1.15 7% Barbiturate worse
disability (2) (32–61) (0.81–1.64) (ns)
SR [30] Mannitol versus Death 41 14% 1.75 11% Mannitol worse
placebo (1) (0.48–6.38) (ns)
Death 363 34% 0.56 15% High dose mannitol better
(3) (25–66) (0.39–0.79) (7–24)
Death or 363 63% 0.58 26% High dose mannitol better
disability (3) (54–90) (0.47–0.72) (17–36)
RCT [37] Corticosteroid Death 9673 22% 1.15 3% Corticosteroid worse
versus control (1) (1.07–1.24) (2–5)
Death or 9554 36% 1.05 2% Corticosteroid worse
disability (1) (0.99–1.10) (ns)
SR: systematic review; RCT: randomized controlled trial; CI: confidence intervals; ns: not statistically significant.
Chapter 15: Acute traumatic brain injury 149
kept well below 25 mmHg in all three groups, the course of ICP was most stable in the HV THAM group. It is concluded that prophylactic hyperventilation is deleterious in head-injured patients with motor scores of 4–5. Hyperventilation alone, as well as in conjunction with the buffer THAM showed a beneficial effect on mortality at 1 year after injury, although the effect measure was imprecise (RR 0.73; 95%
CI 0.36–1.49 and RR 0.89; 95% CI 0.47–1.72, respect-ively). This improvement in outcome was not supported by an improvement in neurological recovery. For hyperventila-tion alone, the RR for death or severe disability was 1.14 (95% CI 0.82–1.58). In the hyperventilation plus THAM group, the RR for death or severe disability, was 0.87 (95%
CI 0.58–1.28). The data available are inadequate to assess any potential benefit or harm that might result from hyper-ventilation in severe head injury. RCTs to assess the effect-iveness of hyperventilation therapy following severe head injury are needed.
Mannitol may sometimes dramatically effective in revers-ing acute brain swellrevers-ing, but its effectiveness in the on-gorevers-ing management of severe head injury remains open to ques-tion. There is evidence that, in prolonged dosage, mannitol may pass from the blood into the brain, where it might cause reverse osmotic shifts that increase ICP. A Cochrane Systematic Review was performed on this topic [30]. They included 5 RCTs [31–35]. The authors concluded that high-dose mannitol (fast intravenous mannitol in a high-dose of 1.4 g/kg followed by rapid normal saline infusion 14 mL/kg) appears to be preferable to conventional-dose mannitol in the pre-operative management of patients with acute traumatic intracranial haematomas. However, there is little evidence about the use of mannitol as continuous infusion in patients with raised ICP in patients who do not have an operable intracranial haematoma. Mannitol therapy for raised ICP may have a beneficial effect on mortality when compared to pen-tobarbital treatment. ICP-directed treatment shows a small beneficial effect compared to treatment directed by neurolog-ical signs and physiologneurolog-ical indicators. There are insufficient data on the effectiveness of pre-hospital administration of mannitol to preclude either a harmful or a beneficial effect on mortality. It has to be stressed that three of these five trials did not measure ICP, because the patients were examined in the emergency room, and therefore, mannitol was administered for the treatment of clinical signs of severity.
Cortisteroids have been widely used in treating people with TBI. However the increase in mortality with steroids demonstrated by the Cochrane Systematic Review [36] and the CRASH trial [37] suggest that steroids should no longer be routinely used in people with traumatic head injury.
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Background
Whether to prescribe corticosteroids for central nervous sys-tem infections is a thorny topic for the physician and, as many of these conditions are often fatal and cause long-term neurological deficit in the survivors, is important to get right.
Many organisms that infect the central nervous system cause inflammation. This can cause further local damage through compression of the brain parenchyma. In addition, the associ-ated cerebral oedema can cause raised intracranial pressure, leading to reduced cerebral perfusion and ischaemia which results in further oedema. Ultimately this can lead to brain-stem herniation and death. Corticosteroids may reduce the inflammation in the parenchyma, subarachnoid space, and blood vessels, reduce cerebral and spinal cord oedema, thus reducing this damage [1–4]. On the other hand, corticosteroids suppress the immune system and this could make the illness worse by allowing the infective organism to proliferate. In addition, adverse effects of steroids (such as gastrointestinal haemorrhage, electrolyte changes, hyperglycaemia, psychosis, and opportunistic infections) can contribute to illness and death. In addition, steroids may reduce inflammation of the meninges which could decrease the penetration of drugs used to treat the infection, across the blood brain barrier.