Does a group of drugs known as calcium channel blockers reduce mortality and unfavourable complications in patients with traumatic brain injury?

Acute traumatic brain injury is a major cause of death and disability. Not all damage to the brain occurs at the moment of injury; reduction of blood flow and oxygen supply to the brain can occur afterwards and cause further brain damage, which is an important cause of avoidable death and disability. In the early stages after injury it is therefore important that efforts are made to minimise secondary brain damage and to provide the best chances of recovery from established brain damage.

The use of calcium channel blockers has been proposed for the prevention or treatment of cerebral vasospasm (that is, sudden narrowing of blood vessels in the brain), which can occur after brain injury and cause secondary brain damage due to a reduction in blood flow.

It is important to determine whether or not calcium channel blockers might be effective in reducing mortality and unfavourable outcomes in head-injured patients.

This review looked at all high quality trials comparing the use of calcium channel blockers with a control, in head-injured patients of any age. The authors also looked at trials involving patients suffering from subarachnoid haemorrhage (that is, bleeding into the space between the brain and the skull) caused by an injury, as a subgroup.

The authors found six eligible trials involving 1862 patients. The results indicate that there is insufficient evidence to support the use of calcium channel blockers. The authors conclude that there is some evidence that a calcium channel blocker called nimodipine may be beneficial for some patients with subarachnoid haemorrhage. However, there is also an indication of certain adverse reactions amongst patients treated with nimodipine which may mean that the drug is harmful for some individuals.

The authors recommend that the promising results in patients with subarachnoid haemorrhage are replicated in a larger well designed trial, before any firm conclusions about the effectiveness of the drug can be drawn. In future trials, data on outcomes other than death and severe disability, such as quality of life of the survivors and the economic utility of the drug, should be measured; such outcomes have not been considered in existing research.

Authors' conclusions: 

This systematic review of randomised controlled trials of calcium channel blockers in acute traumatic head injury patients shows that considerable uncertainty remains over their effects. The effect of nimodipine in a subgroup of brain injury patients with subarachnoid haemorrhage shows a beneficial effect, though the increase in adverse reactions suffered by the intervention group may mean that the drug is harmful for some patients.

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Background: 

Acute traumatic brain injury is a major cause of death and disability. Calcium channel blockers (calcium antagonists) have been used in an attempt to prevent cerebral vasospasm after injury, maintain blood flow to the brain, and so prevent further damage.

Objectives: 

To estimate the effects of calcium channel blockers in patients with acute traumatic brain injury, and in a subgroup of brain injury patients with traumatic subarachnoid haemorrhage.

Search strategy: 

We searched the Cochrane Injuries Group's Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and the reference lists of relevant articles. We also contacted experts in the field. The searches were updated in November 2005.

Selection criteria: 

Randomised controlled trials (RCTs) in patients with all levels of severity of clinically diagnosed acute traumatic brain injury.

Data collection and analysis: 

Two authors independently assessed the identified studies for eligibility and extracted data from each study. Summary odds ratios were calculated using the Mantel-Haenszel method.

Main results: 

Six RCTs involving 1862 participants were included. The effect of calcium channel blockers on the risk of death was reported in five of the RCTs. The pooled odds ratio (OR) for the five studies was 0.91 (95% confidence interval [95% CI] 0.70 to 1.16). For the five RCTs that reported death and severe disability (unfavourable outcome), the pooled OR 0.97 (95%CI 0.81 to 1.18). In the two RCTs which reported the risk of death in a subgroup of traumatic subarachnoid haemorrhage patients, the pooled OR 0.59 (95% CI 0.37 to 0.94). Three RCTs reported death and severe disability as an outcome in this subgroup, and the pooled OR 0.67 (95% CI 0.46 to 0.98).

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