Effects of hypotensive treatment with α₂‐agonist and β₁‐antagonist on cerebral haemodynamics in severely head injured patients

Abstract

Therapy of post-traumatic brain oedema often includes preservation of high arterial blood pressure to avoid secondary ischaemic injuries to the brain. This practice can be questioned since high arterial blood pressure may aggravate brain oedema through raised hydrostatic capillary pressure, causing fluid filtration across the damaged blood-brain barrier. This latter view is in agreement with our clinical experience and therefore hypotensive therapy with an alpha 2-adrenergic agonist (clonidine) and a beta 1-adrenergic antagonist (metoprolol) has become part of our treatment protocol for severely head injured patients to decrease the post-traumatic brain oedema. The present study is an attempt to analyse whether there are any direct local cerebrovascular effects of the hypotensive agents used, which also might influence intracranial pressure. Severely head injured patients were investigated. Heart rate, mean arterial blood pressure, intracranial pressure, cerebral blood flow and arteriovenous difference in oxygen content were measured before and after a bolus dose of clonidine (six patients) and metoprolol (nine patients). Clonidine decreased mean arterial blood pressure and cerebrovascular resistance without affecting other parameters measured. Metoprolol decreased heart rate and mean arterial pressure, but had no effect on the cerebrovascular parameters. The results show that clonidine and metoprolol have no, or only minor, direct influence on local cerebral haemodynamics in severely brain injured patients. This implies that if there is an intracranial pressure reducing effect of these drugs, as suggested, this must be due to other mechanisms, namely a reduction in capillary hydrostatic pressure secondary to decreased arterial blood pressure and heart rate.

The role of α2-agonists in neurosurgery

“…43 Fale et al 44 further demonstrated in dogs, that dexmedetomidine limits the vasodilatory effect of raised PaCO 2 . No human studies have been performed to examine cerebral protection or ischaemia, however in rabbits and rats, dexmedetomidine conveys dose related cerebral protection from ischaemia, 45,46 and in dogs there was no evidence of cerebral ischaemia despite reductions of cerebral blood flow.…”

“…a 2 -agonists have been implicated in the uncoupling of cerebral blood flow and cerebral metabolic requirement for oxygen, however other studies have shown that a 2 -agonists have no effect on cerebral metabolic requirement for oxygen. 41,43 Therefore, the clinical relevance of these findings is still unclear when reasonable blood pressure is maintained. Our application of this information has led to the safe and successful use of these agents for intracranial surgery over the last decade, with the caveats of particular care to maintain an adequate MAP with preoperative volume replacement and avoidance in patients with suspected acute raised ICP.…”

Severe traumatic brain injury in pediatric patients: treatment and outcome using an intracranial pressure targeted therapy—the Lund concept

“…The Lund concept includes reduction in systemic arterial pressure to decrease capillary hydrostatic pressure [11]. It has been well documented that hypotensive episodes can be deleterious in severe TBI [32,33,34].…”

“…0.8 g/kg per 24 h) was used. Decreased hydrostatic capillary pressure in combination with preservation of normal colloid osmotic pressure induces transcapillary fluid absorption [10,11].…”

“…The physiological and biochemical effects of the treatment protocol have been evaluated in experimental and clinical studies since 1994 [10,11,12,13,14]. Decreased mortality in combination with increased favorable outcome has been reported in clinical studies [15,16,17].…”