Improving Clinical Outcomes from Acute Subdural Hematomas with the Emergency Preoperative Administration of High Doses of Mannitol: A Randomized Trial

The Comprehensive International Center for Neuroemergencies and Federal University of São Paulo, São Paulo SP 04093-970, Brazil.
Neurosurgery (Impact Factor: 3.62). 10/2001; 49(4):864-71. DOI: 10.1097/00006123-200110000-00016
Source: PubMed


To evaluate clinical outcomes and postoperative physiological findings for comatose patients with acute subdural hematomas who received preoperative high-dose mannitol (HDM) versus conventional-dose mannitol treatment.
One hundred seventy-eight adult patients with non-missile, traumatic, acute, subdural hematomas were prospectively and randomly assigned to receive emergency, preoperative, intravenous HDM treatment (91 patients), compared with a control group treated with a lower preoperative mannitol dose (87 patients).
Preoperative improvement of abnormal pupillary widening was significantly more frequent in the study group than in the control group of patients (P < 0.0001). Preoperative HDM treatment was also associated with significantly better clinical outcomes at 6-month follow-up evaluations (P < 0.01). Postoperative physiological findings revealed statistically significant between-group differences, with higher intracranial pressure and lower cerebral extraction of oxygen (relative cerebral hyperperfusion) in the control group, compared with the HDM group. Postoperative global brain ischemia (abnormally low arteriojugular lactate difference values) was rare and was detected in 2.2 and 3.4% of the patients in the study and control groups, respectively.
Emergency preoperative HDM administration was associated with improved clinical outcomes for patients with acute subdural hematomas. Preoperative improvement of abnormal pupillary widening and better postoperative control of intracranial hypertension and associated relative cerebral hyperperfusion seemed to be relevant factors associated with improved outcomes.

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Available from: Kazuo Okuchi, Jul 16, 2014
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    • "It is a non-permeating molecule, i.e., it cannot cross biological membranes. Mannitol is used clinically to reduce acutely raised intracranial pressure, e.g. after a stroke or head trauma (although significant controversy exists over this use) and to treat patients with renal failure [18]. Propylene Glycol (or propane-1,2-diol) is an organic compound that is hygroscopic and miscible with water [19]. "
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    ABSTRACT: There are several reports suggesting that hyperosmolarity induces inflammation. We recently showed that Dextran Sodium Sulfate causes inflammatory bowel disease due to hyperosmolarity. The aim of this study was to confirm the link between hyperosmolarity and inflammation by assessing osmolarity values in vivo during inflammation, compare the inflammatory potential of different osmotic agents and finally study the long-term consequences of hyperosmolarity on cell fate. Osmotic pressures were measured in inflammatory liquids withdrawn from mice subjected to inflammation caused either by subcutaneous injection of Bacille Calmette-Guérin (BCG) or Freund adjuvant. Three epithelial cell lines (HT29, T24 and A549) were exposed up to 48 hours to increasing osmolarities (300, 600, 900 mOsm) of chemically inert molecules such as Mannitol, Propylene Glycol, and Glycerol and inflammatory response was assessed by Enzyme Linked ImmunoSorbent Assay (ELISA) and RNA Protection Assay (RPA). Finally, normal mouse macrophages were exposed to hyperosmotic conditions for long-term culture. The inflammation caused either by BCG or Freund adjuvant is correlated to hyperosmolarity in inflammatory liquids. The exposure of cells to the different compounds, whatever their molecular weight, has no effect on the secretion of cytokines as long as the osmolarity is below a threshold of 300 mOsm. Higher osmolarities result in the secretion of proinflammatory cytokines (Interleukin-8, Interleukin-6, Interleukin-1beta and Tumor Necrosis factor-alpha). Long-term hyperosmotic culture extends normal macrophage half-life, from 44 days to 102 days, and alters the expression of p53, Bcl-2 and Bax. The present study further suggests inflammation and hyperosmolarity are closely related phenomena if not synonymous.
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    • "Rheology of cerebral blood flow can be improved by mannitol, as it lowers the viscosity and allows better capillary flow (Burke et al., 1981). Although it is still somewhat controversial, high doses of mannitol have been reported to treat acute TBI and reduce elevated intracranial pressure (Cruz et al., 2001, Wakai et al., 2005). Our previous study indicates that the number of hBMSCs that were recruited to the injured site reached a plateau after intravenous infusion of 3 to 8 million hBMSCs, suggesting that the BBB may be one of the rate-limiting steps in hBMSCs reaching the injured site (Seyfried et al., 2006). "
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    ABSTRACT: Previous studies show that intravascular injection of human bone marrow stromal cells (hBMSCs) significantly improves neurological functional recovery in a rat model of intracerebral hemorrhage (ICH). In the present study, we tested the hypothesis that mannitol improves the efficiency of intraarterial MSC delivery (i.e., fewer injected cells required for therapeutic efficacy) after ICH. There were four post-ICH groups (N=9): group 1, negative control with only intraarterial injection of 1 million human fibroblasts in phosphate-buffered saline (PBS); group 2, intravenous injection of mannitol alone in PBS (1.5 g/kg); group 3, intraarterial injection of 1 million hBMSCs alone in PBS; and group 4, intravenous injection of mannitol (1.5 g/kg) in PBS followed by intraarterial injection of 1 million hBMSCs in PBS. Group 4 exhibited significantly improved neurological functional outcome as assessed by neurological severity score (NSS) and corner test scores. Immunohistochemical staining of group 4 suggested increased synaptogenesis, proliferating immature neurons, and neuronal migration. The number of hBMSCs recruited to the injured region increased strikingly in group 4. Tissue loss was notably reduced in group 4. In summary, the beneficial effects of intraarterial infusion of MSCs are amplified with intravenous injection of mannitol. Preadministration of mannitol significantly increases the number of hBMSCs located in the ICH region, improves histochemical parameters of neural regeneration, and reduces the anatomical and pathological consequences of ICH.
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    • "Ces 65 patients sont tous décédés après 1 an quels qu'aient été les traitements à l'hôpital (osmothérapie et/ou chirurgie). Un article récent [Cruz, 2001] permet plusieurs remarques sur l'utilisation du mannitol en préhospitalier. Cet article montre que l'utilisation de mannitol à des doses importantes (1,2 à 2,1 ml/kg) améliore le pronostic des patients présentant un hématome sous-dural (HSD) traumatique. "

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