Does a bolus of mannitol initially aggravate intracranial hypertension? A study at various PaCO2 tensions in dogs

In two groups of anaesthetized dogs, with (n = 28) or without (n = 28) induced intracranial hypertension, we compared the effects on intracranial pressure (ICP) of the rapid administration of mannitol 2 g kg-1 i.v. at PaCO2 2.7, 4.0, 5.3, and 6.7 kPa (n = 7). In dogs with no induced intracranial hypertension, ICP increased during the administration of mannitol, reached a peak at 2 min after infusion, and then gradually decreased (P less than 0.05). More marked changes in ICP were observed in response to higher values of PaCO2 (P less than 0.05). In dogs with induced intracranial hypertension, the rapid infusion of mannitol caused an exponential decrease in ICP, without initial increase, which was significantly steeper at higher values of PaCO2 (P less than 0.05). This was followed by a more gradual decrease which achieved pre-balloon inflation values 10 min after infusion. We postulate that the absence of the initial increase in ICP is the result of a concomitant decrease in arterial pressure, a reduction in the volume-pressure response of the brain, the failure of mannitol to dilate further the cerebral arterial vascular bed and a hitherto unnoticed early water-drawing effect. Our study confirmed the safety of rapidly expanding the circulating blood volume with mannitol in circumstances of increased ICP in dogs

The effects of rapid infusions of saline and mannitol on cerebral blood volume and intracranial pressure in dogs

The role of osmotic brain dehydration in the early reduction of intracranial pressure (ICP) following mannitol administration has recently been questioned and a decrease in cerebral blood volume (CBV) proposed as the mechanism of action. To evaluate this hypothesis, relative CBV changes before and after mannitol infusion were determined by collimated gamma counting across the biparietal diameter of the exposed skull in six dogs. Red blood cells were labelled with chromium-51. Cerebral blood volume (CBV), total blood volume (TBV), ICP, mean arterial pressure (MAP), central venous pressure (CVP), haematocrit and osmolality were serially measured after infusions of 10 ml X kg-1 of normal saline (control study) and of 20 per cent mannitol (mannitol study). The solutions were administered over a two-minute period; a 30-minute equilibration period intervened between the saline and mannitol infusions. We demonstrated that the mannitol infusion was associated with significant increases in relative CBV (25 per cent), ICP (7 mmHg), CVP (11 cm H2O), and TBV (50 per cent). MAP declined significantly (14 per cent) after mannitol infusion. The administration of saline, although associated with an increase in TBV (18 per cent), was not associated with any significant change in CBV, ICP, MAP or CVP. The increase in relative CBV persisted for 15 minutes after mannitol infusion, while the ICP returned to control within five minutes and continued to decrease. This study supports the fact that after rapid mannitol infusion, ICP begins to decrease only once the dehydrating effect has counteracted the increase in brain bulk caused by the increase in cerebral blood volume

Changes in CSF pressure after mannitol in patients with and without elevated CSF pressure

In view of the current concern that rapid infusion of mannitol might initially aggravate intracranial hypertension, the effects of a mannitol infusion on lumbar cerebrospinal fluid pressure (CSFP) were investigated in 49 patients. The studies were performed when the patients were under general anesthesia prior to elective craniotomy for tumor resection or intracerebral aneurysm clipping. The patients were divided into two groups: 24 patients with normal CSFP (Group I, mean CSFP 10.5 mm Hg) and 25 with raised CSFP (Group II, mean CSFP 20.8 mm Hg). Measurements of CSFP, mean arterial blood pressure (MABP), and central venous pressure (CVP) were made serially during and after the infusion of 20% mannitol (1 gm.kg-1 infused over a 10-minute interval). In both groups, mannitol infusion provoked a fall in MABP and an increase in CVP. An immediate decrease [corrected] in CSFP was observed in Group II, whereas CSFP increased transiently but significantly in Group I. Analysis of the arterial and venous driving pressures which contribute to CSFP suggests that the transient increase in CSFP after mannitol in Group I was partly due to the increase in CVP. The presence of intracranial hypertension may thus alter the CSFP response to arterial and venous pressure changes. Cerebral blood volume (CBV) was measured in dogs in a separate study analogous to the human protocol. The CBV increased approximately 25% over control values after mannitol infusion both in the normal animals and in those with CSFP raised by an epidural balloon. The response of the CSFP to mannitol infusion differed between both groups in a fashion similar to that observed in the human subjects. Thus, differences in CBV changes after mannitol do not account for the difference in CSFP response between normal subjects and those with raised CSFP

Effects of rapid mannitol infusion on cerebral blood volume. A positron emission tomographic study in dogs and man

Positron emission tomography was used to study the effect of a rapid infusion of mannitol on cerebral blood volume (CBV) in five dogs and in three human subjects. The ability of mannitol to reduce intracranial pressure (ICP) has always been attributed to its osmotic dehydrating effect. The effects of mannitol infusion include increased osmolality, total blood volume, central venous pressure (CVP), and cerebral blood flow, and decreased hematocrit, hemoglobin concentration, serum sodium level, and viscosity. Mannitol's ability to dilate the cerebral vasculature, either directly or indirectly, and thus to transiently increase ICP, is a subject of controversy. By in vivo labeling of red cells with carbon-11, the authors were able to demonstrate an early increase in CBV in dogs of 20%, 27%, and 23% (mean increase, p less than 0.05) at 1, 2, and 3 minutes, respectively, after an infusion of 20% mannitol (2 gm/kg over a 3-minute period). The animals' muscle blood volume increased by 27% (mean increase, p less than 0.05) 2 minutes after infusion. In the human subjects, lower doses and a longer duration of infusion (1 gm/kg over 4 minutes) resulted in an increase in CBV of 8%, 14% (p less than 0.05), and 10% at 1, 2, and 3 minutes, respectively, after infusion. In dogs, ICP increased by 4 mm Hg (mean increase, p less than 0.05) 1 minute after the infusion, before decreasing sharply. The ICP was not measured in the human subjects. Hematocrit, hemoglobin, sodium, potassium, osmolality, heart rate, mean arterial pressure (MAP), and CVP were measured serially. Results of these measurements, as well as the significant decrease in MAP that occurred after mannitol infusion, are discussed. This study demonstrated that rapid mannitol infusion increases CBV and ICP. The increase in muscle blood volume, in the presence of a decreased MAP and an adequate CVP, suggests that mannitol may have caused vasodilation in these experiments