Journal: J Trauma 62(2):292-298, 2007. 41 References
Reprint: Dept of Neurosurgery, University of Heidelberg, Im Neuenheimer Feld 400 D-69120, Heidelberg, Germany (OW Sakowitz, MD)
Faculty Disclosure: Abstracted by R. Klotz, who has nothing to disclose.
Traumatic brain injury (TBI) remains a leading cause of disability and death, with an incidence of 200-400 cases per 100,000. Osmotic agents are widely used to lower elevated intracranial pressure (ICP). However, little data are available regarding cerebral oxygenation and metabolism in the traumatized brains studied under clinical conditions. The present prospective, open-labeled clinical study was designed to investigate whether administration of mannitol, with the aim of reducing moderate intracranial hypertension, improves cerebral metabolism and oxygenation in patients after severe traumatic brain injury (TBI).
Any increase in ICP can lead to further structural and functional impairment owing to its deleterious effect on the already compromised microcirculation and metabolism seen after severe TBI. Ischemic deterioration, however, can occur with normal and elevated ICP. Therefore, multimodal cerebral monitoring (MCM), consisting of intraparenchymal ICP, tissue oxygenation (ptiO2), and microdialysis (MD), was initiated in 6 male TBI patients (mean age 45 yr).
Only patients suffering from a severe TBI with an initial Glasgow Coma Scale (GCS) score of 25 mL) were evacuated in the OR. Neuromonitoring sensors were placed at this time if desired. To ensure placement in viable brain tissue the frontal lobe of the less injured hemisphere was chosen. All patients remained sedated with treatment directed by protocol based on guidelines for the treatment of severe head injury.
The general aims were to maintain normal physiologic balance and to establish a minimum cerebral perfusion pressure (CPP) of 70 mmHg and a MAP > 80 mmHg. The arterial partial pressure of oxygen (PaO2) was elevated to levels > 100 mmHg by increasing the FiO2 to 0.30 to 0.55 or adjusting the positive end-expiratory pressure (PEEP) settings. Normovolemia was guided by clinical assessment.
The ICP treatment threshold was 20 mmHg. Once ICP exceeded 20 mmHg ventricular catheters, if present, were used for intermittent drainage of CSF. Elevated ICP despite adequate sedation was treated by hyperventilation and intermittent bolus administration of mannitol. In cases in which these first-line measures failed to normalize ICP, second tier therapies were initiated.
A total of 14 episodes of intracranial hypertension treated with mannitol bolus administration were observed in 6 severely head-injured patients. A significant homogenous reduction in ICP by as much as 32% associated with a concomitant increase in CPP by as much as 12.5% was observed in these patients. At the given degree of intracranial hypertension, tissue oxygenation, however, was not affected by mannitol infusion. After mannitol infusion, extracellular concentrations of all intermediary metabolites were uniformly increased by 10% to 20% that only reached statistical significance for glucose and pyruvate.
In this study, mannitol infusions significantly reduced increased ICP in patients with severe TBI. However, ptiO2 remained unchanged. The calculated CPP as such does not exclude local ischemia. Normal or moderately increased ICP is only an indirect indicator of sufficient perfusion. An elevated ICP, however, is not necessarily a herald of impending ischemia.
Acute mannitol administration may lead to hypotension, which could offset the beneficial effects of ICP reduction. Administering a bolus slowly with or without compensatory fluid may counteract hemodynamic compromise. In this study, infusing mannitol for 20 minutes did not require compensatory fluids to maintain normotension that, thus, can be regarded as a safe measure.
At least three mechanisms, however, govern the view of mannitol’s action on traumatized brain tissue. Firstly, tissue dehydration according to the osmotic gradient created by mannitol infusion has been suggested to result in a reduction of intracranial volume content and therefore ICP. Secondly, mannitol actions as a scavenger of hydroxyl-radicals have been known for some time and may therefore inhibit otherwise occurring vasodilation. Thirdly, reductions in blood viscosity could result in improved hemodynamics. Therefore, if autoregulation of cerebral blood flow (CBF) is maintained, vessel diameter decreases with effectively decreased cerebral blood volume (CBV) and ICP.
An ICP exceeding pretreatment levels (rebound phenomenon) is a consequence of cerebral penetration of the applied osmotherapeutic agents. In the current study, no rebound phenomenon was observed. More detailed studies employing monitoring of cerebral oxygenation and metabolism to characterize pharmacodynamic effects of osmotherapy after severe TBI are necessary.
The authors conclude that mannitol is an effective treatment to lower increased ICP, and that at an ICP of 20-30 mmHg, it does not influence cerebral oxygenation. |
