Effect of mannitol on ICP and CBF and correlation with pressure autoregulation in severely head-injured patients

Abstract

In a previous paper, the authors showed that mannitol causes cerebral vasoconstriction in response to blood viscosity decreases in cats. The present paper describes the changes in intracranial pressure (ICP) and cerebral blood flow (CBF) after mannitol administration in a group of severely head-injured patients with intact or defective autoregulation. The xenon-133 inhalation method was used to measure CBF. Autoregulation was tested by slowly increasing or decreasing the blood pressure by 30% and measuring CBF again. Mannitol was administered intravenously in a dose of 0.66 gm/kg; 25 minutes later, CBF and ICP were measured once again. In the group with intact autoregulation, mannitol had decreased ICP by 27.2%, but CBF remained unchanged. In the group with defective autoregulation, ICP had decreased by only 4.7%, but CBF increased 17.9%. One of the possible explanations for these findings is based on strong indications that autoregulation is mediated through alterations in the level of adenosine in response to oxygen availability changes in cerebral tissue. The decrease in blood viscosity after mannitol administration leads to an improved oxygen transport to the brain. When autoregulation is intact, more oxygen leads to decreased adenosine levels, resulting in vasoconstriction. The decrease in resistance to flow from the decreased blood viscosity is balanced by increased resistance from vasoconstriction, so that CBF remains the same. This might be called blood viscosity autoregulation of CBF, analogous to pressure autoregulation. Vasoconstriction also reduces cerebral blood volume, which enhances the effect of mannitol on ICP through dehydration of the brain. When autoregulation is not intact there is no vasoconstriction in response to increased oxygen availability; thus, CBF increases with decreased viscosity. With the lack of vasoconstriction, the effect on ICP through dehydration is not enhanced, so that the resulting decrease in ICP is much smaller. Such a mechanism explains why osmotic agents do not change CBF but decrease ICP in normal animals or patients with intact vasoconstriction, but do (temporarily) increase CBF in the absence of major ICP changes after stroke.

Hypertonic saline reduces cumulative and daily intracranial pressure burdens after severe traumatic brain injury

“…27,37,40 Although mannitol also increases CPP and CBF and reduces ICP, the increases in CPP and CBF are smaller than those seen with HTS and are not associated with an increase in cerebral oxygenation. 16,31,33,37 There have been no large randomized controlled trials (RCTs) comparing HTS and mannitol in severe TBI. A few small RCTs using equimolar and/or isovolumic dose comparisons provide limited data from heterogeneous groups of patients.…”

Cerebral autoregulation following minor head injury

“…[6,9,21,22,25,26] Muizelaar and colleagues [21,22] evaluated autoregulation in head-injured patients by obtaining CBF values and either raising or lowering MABP to a new steady state and repeating the CBF measurement. They defined intact autoregulation as the •% CPP/ %• CVR ¾ 2 following the change in MABP, where CVR = CPP/CBF.…”

“…[14,26] Cerebral autoregulation can be impaired or absent following severe closed head injury. [4][5][6]8,9,21,22,25,26] Impairments in autoregulation may contribute by several mechanisms to secondary neuronal injury following head injury. Lowered cerebral perfusion pressure (CPP) caused by arterial hypotension or increased intracranial pressure (ICP) can occur and may cause critical reductions in cerebral blood flow (CBF) to ischemic levels more easily in head-injured patients who have poorly functioning or absent autoregulation.…”

“…[32] It has also been demonstrated experimentally and in head-injured patients that mannitol is less effective in reducing ICP when autoregulation is impaired. [21] Although information is available about autoregulation in severely head injured patients, there is little or no information about autoregulation in patients with minor or moderate head injury. The purpose of this study was to measure the cerebral autoregulatory response in patients after minor head injury defined by Glasgow Coma Scale (GCS) scores of 13 to 15 and to determine if any patients in this injury severity category experience significant impairments in the autoregulatory response.…”

Critical care management of head injury – current concepts

“…Immediate reduction in ICP with mannitol (0.25-1g/kg), probably result from restoration of CPP and rheological changes in cerebral blood flow, rather than specific cerebral dehydration 13 . Empirical and regular use of mannitol is not recommended, as repeated doses may cause rebound increase in ICP especially in presence of damaged blood brain barrier.…”