Perfusion-weighted MRI as a marker of response to treatment in acute and subacute stroke.

We carried out baseline and short-term follow-up MRI, including perfusion-weighted imaging (PWI) and tests of neurologic and cognitive function on 15 consecutive patients with large-vessel ischemic stroke who showed a persistent large perfusion-diffusion mismatch at enrollment up to seven days after the onset of symptoms. Of these, ten underwent induced blood pressure elevation with phenylephrine and oral medications (in eight) or intravenous fluids (in two) with the goal of improving perfusion; five had no such treatment. Significant functional improvement was defined by a reduction of 3 or more points on the NIH stroke scale (NIHSS). Significant improvement in perfusion was defined by a reduction in the volume of hypoperfused brain by 30 cc on PWI using time-to-peak (TTP) maps, without enlargement of the infarct. There was a strong, statistically significant association between improved function and improved perfusion: six (75%) of eight patients who improved in function, but none of the seven who did not, showed a reduction in volume of hypoperfused brain. All six patients who met the perfusion goal, and only two (22%) of nine who did not showed significant functional improvement (Fisher's exact: P < 0.01). There were no differences between patients who improved functionally and those who did not with respect to age, initial volume of abnormality on DWI or PWI, initial NIHSS, or changes on DWI. These findings indicate that reduction in volume of hypoperfused brain on PWI is a marker of response to treatment to improve perfusion even in subacute stroke and that partial reperfusion of regions of salvageable but dysfunctional tissue is a mechanism of improved function associated with induced blood pressure elevation.

A pilot randomized trial of induced blood pressure elevation: effects on function and focal perfusion in acute and subacute stroke.

BACKGROUND: Small, unrandomized studies have indicated that pharmacologically induced blood pressure elevation may improve function in ischemic stroke, presumably by improving blood flow to ischemic, but noninfarcted tissue (which may be indicated by diffusion-perfusion mismatch on MRI). We conducted a pilot, randomized trial to evaluate effects of pharmacologically induced blood pressure elevation on function and perfusion in acute stroke. METHODS: Consecutive series of patients with large diffusion-perfusion mismatch were randomly assigned to induced blood pressure elevation ('treated' patients, n = 9) or conventional management ('untreated' patients, n = 6). RESULTS: There were no significant differences between groups at baseline. NIH Stroke Scale (NIHSS) scores were lower (better) in treated versus untreated patients at day 3 (mean 5.6 vs. 12.3; p = 0.01) and week 6-8 (mean 2.8 vs. 9.7; p < 0.04). Treated (but not untreated) patients showed significant improvement from day 1 to day 3 in NIHSS score (from mean 10.2 to 5.6; p < 0.002), cognitive score (from mean 58.7 to 27.9% errors; p < 0.002), and volume of hypoperfused tissue (mean 132 to 58 ml; p < 0.02). High Pearson correlations between the mean arterial pressure (MAP) and accuracy on daily cognitive tests indicated that functional changes were due to changes in MAP. CONCLUSION: Results warrant a full-scale, double-blind clinical trial to evaluate the efficacy and risk of induced blood pressure elevation in selective patients with acute/subacute stroke.

Effect of age on cerebral blood flow velocity and incidence of vasospasm after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Current transcranial Doppler criteria for vasospasm after aneurysmal subarachnoid hemorrhage are not age specific. We analyzed the effect of age on cerebral blood flow velocity changes after subarachnoid hemorrhage and constructed an age-adjusted predictive model of cerebral blood flow velocity in subarachnoid hemorrhage patients. METHODS: We identified patients with aneurysmal subarachnoid hemorrhage admitted between 1991 and 1999 with a prospective transcranial Doppler database. Eighty-one patients, with complete medical records and transcranial Doppler examinations of the vessels of interest, were included. Patients were subdivided into 2 groups by age: younger, <68 years of age (n=47) and older, >/=68 years of age (n=34). Maximum mean flow velocity and incidence of symptomatic vasospasm were reported. Linear and nonlinear regression analyses were performed. RESULTS: Middle cerebral artery and internal carotid artery mean flow velocity were lower in older patients (median 76 versus 114 cm/s and 76 versus 126 cm/s, respectively; P<0.003). Incidence of symptomatic vasospasm was lower in older patients (44% versus 66%; P=0.05). Older patients developed symptomatic vasospasm at lower middle cerebral artery (median 57 versus 103 cm/s; P=0.04) and internal carotid artery (median 54 versus 81 cm/s, P=0.02) mean flow velocity. Relationship between middle cerebral artery and internal carotid artery mean flow velocity and age was quadratic (ANOVA, P<0.0001). CONCLUSIONS: Older patients have a lower incidence of symptomatic vasospasm, and such vasospasm develops at lower cerebral blood flow velocity than younger patients. A quadratic relationship was found between age and cerebral blood flow velocity. This model could be used to create an age-adjusted nomogram that might improve diagnostic capabilities of transcranial Doppler.

Cerebral vasculitis: diagnosis and follow-up with transcranial Doppler ultrasonography.

The authors report a patient with postpartum intracerebral hemorrhage associated with cerebral vasculitis. Cerebral circulation was assessed with transcranial Doppler (TCD) ultrasonography, magnetic resonance angiography, and conventional cerebral angiography. Initial TCD studies demonstrated bilateral patchy increased cerebral blood flow velocity (CBFV) in the anterior circulation with complete normalization during remission. This case report provides evidence that cerebral vasculitis leads to relevant CBFV changes and that the TCD technique may assist in diagnosis and follow-up of these patients.

Diagnostic impact of early transcranial Doppler ultrasonography on the TOAST classification subtype in acute cerebral ischemia.

OBJECTIVE: The impact of early transcranial Doppler ultrasonography (TCD) upon stroke subtype diagnosis is unknown and may affect therapeutic strategies. In this study, the diagnostic usefulness of TCD in stroke subtype diagnosis according to the criteria of the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) study was investigated in patients with acute cerebral ischemia. METHODS: TCD examination within 24 h of symptom onset was performed in 50 consecutive patients with acute cerebral ischemia. Of these 54% were female. Sixty percent of patients were black, 36% white, and 4% Asian. Initial TOAST stroke subtype diagnosis (ITSSD) was based upon clinical presentation and initial brain imaging studies. Modified TOAST stroke subtype diagnosis was determined subsequently after additional review of the TCD examination. Final TOAST stroke subtype diagnosis was determined at hospital discharge, incorporating all diagnostic studies. Using final TOAST stroke subtype diagnosis as the 'gold standard' ITSSD and modified TOAST stroke subtype diagnosis were compared in order to determine additional benefit from the information obtained by TCD. Data were collected retrospectively by a single investigator. RESULTS: ITSSD classified 23 of 50 (46%) patients correctly. After TCD, 30 of 50 (60%) patients were classified correctly, for an absolute benefit of 14% and a relative benefit of 30% (p = 0.018). Most benefit from TCD was observed in the TOAST stroke subtype category large-artery atherosclerosis, in particular in patients with intracranial vascular disease. In this category, ITSSD had a sensitivity of 27% which increased to 64% after TCD (p = 0.002). CONCLUSION: TCD within 24 h of symptom onset improves the accuracy of early stroke subtype diagnosis in patients with acute cerebral ischemia due to large-artery atherosclerosis. This may have clinical implications for early therapeutic interventions.

Two-compartment exchange model for perfusion quantification using arterial spin tagging.

The original well-mixed tissue model for the arterial spin tagging techniques is extended to a two-compartment model of restricted water exchange between microvascular (blood) and extravascular (tissue) space in the parenchyma. The microvascular compartment consists of arterioles, capillaries, and venules, with the blood/tissue water exchange taking place in the capillaries. It is shown that, in the case of limited water exchange, the individual FAIR (Flow-sensitive Alternating Inversion Recovery) signal intensities of the two compartments are comparable in magnitude, but are not overlapped in time. It is shown that when the limited water exchange is assumed to be fast, flows quantified from the signal-intensity difference are underestimated, an effect that becomes more significant for larger flows and higher magnetic field strengths. Experimental results on cat brain at 4.7 T comparing flow data from the FAIR signal-intensity difference with those from microspheres over a cerebral blood flow range from 15 to 150 mL 100 g(-1) min(-1) confirm these theoretic predictions. FAIR flow values with correction for restricted exchange, however, correlate well with the radioactive microsphere flow values. The limitations of the approach in terms of choice of the intercompartmental exchange rates are discussed.

Reperfusion of specific brain regions by raising blood pressure restores selective language functions in subacute stroke.

We report a series of six single subject studies examining the effects of pharmacological blood pressure elevation on regional brain perfusion and language function. Previous reports indicate that hypoperfusion of specific brain regions, as delineated by magnetic resonance perfusion weighted imaging (PWI), is associated with disruption of selective lexical functions. On this basis, we hypothesized that reperfusion of the same regions, in the absence of infarct in that region, would restore the associated lexical function. We present five patients with impaired lexical-semantics associated with poor perfusion, but not infarction, of Brodmann's area 22 (BA 22), and one patient with impaired lexical-semantics and a superimposed deficit in retrieving the phonological representations of words, associated with poor perfusion Brodmann's area 37 (BA 37) as well as BA 22. Each patient was treated with induced blood pressure elevation to increase perfusion of the ischemic and dysfunctional tissue. Daily testing of naming and comprehension, with stimulus sets matched for frequency, familiarity, and length, showed improved lexical-semantics in the patients who showed reperfusion of BA 22 and improved oral naming (but not lexical-semantics) in the patient who showed reperfusion of BA 37. These cases illustrate that loss of function with hypoperfusion of a circumscribed area of the brain, and recovery of the same function with improved perfusion of that brain region, can reveal brain/language relationships prior to reorganization after brain injury.

Long-term outcome after medical reversal of transtentorial herniation in patients with supratentorial mass lesions.

OBJECTIVE: To determine the short- and long-term outcomes after successful reversal of transtentorial herniation by medical treatment. Although it has been recognized that aggressive medical management can reverse transtentorial herniation, it is believed that overall outcome in such patients is poor. DESIGN: Prospective cohort study. SETTING: Neurocritical care unit of a university hospital. PATIENTS: A total of 28 consecutive patients who underwent an episode of transtentorial herniation (defined as decrease in level of consciousness accompanied by pupillary dilation) secondary to a supratentorial mass lesion followed by successful reversal. INTERVENTION: Herniation was reversed by using a combination of hyperventilation, mannitol and hypertonic saline. MEASUREMENTS AND MAIN RESULTS: The following outcomes were analyzed: risk of second herniation, radiologic evidence of structural damage or vascular compromise related to herniation on post-herniation computed tomographic scan, in-hospital mortality, and long-term functional outcome using Rankin score and Barthel index. A total of 32 episodes of transtentorial herniations were reversed in 28 patients during a 14-month period. The most common precipitating cause were edema (n = 23) or new/expanding intracerebral hematoma (n = 5). After first reversal of transtentorial herniation in 28 patients, a second herniation episode was observed in 16 patients after a mean interval of 88.2 hrs (range, 23-432 hrs); four were successfully reversed. On follow-up computed tomographic scan, hypodense lesion in midbrain (n = 6), temporal lobe contusion (n = 2), posterior cerebral artery (n = 3), and middle cerebral artery (n = 1) infarction were visualized in a minority of patients. The in-hospital mortality was 60% (n = 15) with brain death being the cause of death in 13 patients; care was withdrawn in eight patients. Second episode of herniation (p = .002) and midbrain involvement during herniation (p = .02) were associated with in-hospital mortality. During a mean follow-up period of 11.4+/-4.2 months, two patients died of cerebral neoplasm and human immunodeficiency virus-related sepsis, respectively. Of the 11 survivors, 7 were functionally independent (Rankin score <3 and Barthel index >60). CONCLUSIONS: Although mortality after transtentorial herniation is high, we found a prominent potential for meaningful recovery with aggressive medical reversal of transtentorial herniation. Our study implies that timely medical intervention for reversing transtentorial herniation can result in preservation of neurologic function.

Early identification of patients at risk for symptomatic vasospasm after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To develop a scheme for early identification of individuals at risk for symptomatic vasospasm after subarachnoid hemorrhage (SAH). DESIGN: Analysis of prospectively collected data from the placebo-treated group in a multicenter clinical trial. SETTINGS: Fifty-four neurosurgical centers in North America. MEASUREMENTS AND MAIN RESULTS: We identified independent predictors of symptomatic vasospasm using stepwise logistic regression analysis from demographic, clinical, laboratory, and neuroimaging characteristics of the participants. We developed a scoring system (symptomatic vasospasm risk index) based on a combination of these predictors. Out of 283 patients in the analysis (all treated with oral nimodipine), 93 (33%) developed symptomatic vasospasm within 14 days after SAH. There were four independent predictors of symptomatic vasospasm: thickness of subarachnoid clot on computed tomographic scan (odds ratio [OR], 4.1; 95% confidence interval [CI], 1.8-10.0); early rise in middle cerebral artery mean flow velocity (MCA-MFV), defined as a value > or =110 cm/sec recorded on or before post-SAH day 5 (OR, 1.9; 95% CI, 1.1-3.3), Glasgow Coma Scale score <14 (OR, 1.8; 95% CI, 1.1-3.1); and rupture of anterior cerebral or internal carotid artery aneurysm (OR, 1.9; 95% CI, 1.0-3.4). The probability of identifying patients who would develop symptomatic vasospasm (percentage of area under receiver operating characteristics curve +/- SEM) was higher with symptomatic vasospasm risk index (68%+/-8%) compared with thickness of clot (62%+/-8%; p = .08) or MCA-MFV (45%+/-7%, p < .05) criteria alone. CONCLUSIONS: Patients at high risk for symptomatic vasospasm can be identified early in the course of SAH using a risk index. A risk index based on a combination of variables may represent a predictive paradigm superior to conventionally used criteria based on clot thickness or MCA-MFV criteria.

Treatment of intraventricular hemorrhage with urokinase : effects on 30-Day survival.

BACKGROUND AND PURPOSE: Intraventricular hemorrhage (IVH) remains associated with high morbidity and mortality. Therapy with external ventricular drainage alone has not modified outcome in these patients. METHODS: Twelve pilot IVH patients who required external ventricular drainage were prospectively treated with intraventricular urokinase followed by the randomized, double-blinded allocation of 8 patients to either treatment or placebo. Observed 30-day mortality was compared with predicted 30-day mortality obtained by use of a previously validated method. RESULTS: Twenty patients were enrolled; admission Glasgow Coma Scale score in 11 patients was

Early predictors of outcome in patients receiving hypervolemic and hypertensive therapy for symptomatic vasospasm after subarachnoid hemorrhage.

OBJECTIVE: Symptomatic vasospasm after subarachnoid hemorrhage (SAH) is associated with a high incidence of permanent disability and death. For early identification of patients who are at risk for poor outcome, we determined the predictors of outcome in patients with symptomatic vasospasm after SAH. DESIGN: We retrospectively determined the prognostic value of clinical characteristics and computed tomographic scan both at admission and at the time of initiation of hypervolemic and hypertensive therapy. SETTINGS: Neurosciences critical care unit at a University hospital. PATIENTS: A total of 70 consecutive patients who developed symptomatic vasospasm after SAH. INTERVENTION: Treatment with oral nimodipine, hypervolemic therapy, and hypertensive therapy. Angioplasty and intra-arterial papaverine were used in patients with vasospasm resistant to standard treatment. MEASUREMENTS AND MAIN RESULTS: Poor outcome, defined as Glasgow Outcome Scale Score of 3-5 at 2 months or discharge, was observed in 32 (46%) patients. In the logistic regression analysis, a Glasgow Coma Scale (GCS) score of < or =11 (odds ratio, 11.0; 95% confidence interval, 3.6-39.3) and hydrocephalus (odds ratio, 4.3; 95% confidence interval, 1.2-18.2) at the time of initiation of hypervolemic and hypertensive therapy were significantly associated with poor outcome. Poor outcome was observed in 91% of the patients who had both a GCS score of < or =11 and hydrocephalus compared with 15% of patients with a GCS score of >11 and no hydrocephalus at the time of initiation of hypervolemic and hypertensive therapy. A GCS score of < or =11 was also independently associated with length of intensive care unit stay (F ratio = 18.0; p = .0011) and hospital stay (F ratio = 9.2; p = .0034) after initiation of hypervolemic and hypertensive therapy. CONCLUSIONS: The results of this study suggest that outcome in patients with symptomatic vasospasm can be effectively predicted by routinely available information, including GCS score at the time of initiation of hypervolemic and hypertensive therapy. This information can be used for selection and stratification of patients in future treatment studies of patients with symptomatic vasospasm.

Administration of hypertonic (3%) sodium chloride/acetate in hyponatremic patients with symptomatic vasospasm following subarachnoid hemorrhage.

A retrospective study was carried out to evaluate the effect of hypertonic (3%) saline chloride/acetate on various hemodynamic parameters in mildly hyponatremic patients with symptomatic vasospasm following aneurysmal subarachnoid hemorrhage (SAH). We identified 29 hyponatremic (serum sodium < 135 mEq/L) patients who received hypertonic (3%) sodium chloride/acetate as a continuous infusion. Administration of hypertonic (3%) sodium chloride/acetate resulted in higher central venous pressures and positive fluid balance, with a concomitant increase in serum sodium and chloride concentrations without metabolic acidosis. There were no changes in mean cerebral blood flow velocities after infusion of hypertonic (3%) sodium chloride/acetate. We found no reports of congestive heart failure, pulmonary edema, metabolic acidosis, coagulopathy, intracranial hemorrhages, or central pontine myelinolysis in any of these patients. We conclude that hypertonic (3%) sodium chloride/acetate can be administered to patients with mild hyponatremia in the setting of symptomatic vasospasm following SAH without untoward effects. Sample size and limitations of a retrospective analysis preclude conclusions about safety and efficacy of hypertonic (3%) sodium chloride/acetate administration in this patient population. However, our results support justification for a prospective, randomized, double-blind trial of hypertonic (3%) sodium chloride/acetate versus normal saline in patients with symptomatic vasospasm following SAH.

In vivo determination of absolute cerebral blood volume using hemoglobin as a natural contrast agent: an MRI study using altered arterial carbon dioxide tension.

The ability of the magnetic resonance imaging transverse relaxation time, R2 = 1/T2, to quantify cerebral blood volume (CBV) without the need for an exogenous contrast agent was studied in cats (n = 7) under pentobarbital anesthesia. This approach is possible because R2 is directly affected by changes in CBF, CBV, CMRO2, and hematocrit (Hct), a phenomena better known as the blood-oxygenation-level-dependent (BOLD) effect. Changes in CBF and CBV were accomplished by altering the carbon dioxide pressure, PaCO2, over a range from 20 to 140 mm Hg. For each PaCO2 value, R2 in gray and white matter were determined using MRI, and the whole-brain oxygen extraction ratio was obtained from arteriovenous differences (sagittal sinus catheter). Assuming a constant CMRO2, the microvascular CBV was obtained from an exact fit to the BOLD theory for the spin-echo effect. The resulting CBV values at normal PaCO2 and normalized to a common total hemoglobin concentration of 6.88 mmol/L were 42+/-18 microL/g (n = 7) and 29+/-19 microL/g (n = 5) for gray and white matter, respectively, in good agreement with the range of literature values published using independent methodologies. The present study confirms the validity of the spin-echo BOLD theory and, in addition, shows that blood volume can be quantified from the magnetic resonance imaging spin relaxation rate R2 using a regulated carbon dioxide experiment.

Plasma exchange versus intravenous immunoglobulin treatment in myasthenic crisis.

We performed a retrospective multicenter chart review to compare the efficacy and tolerance of plasma exchange (PE) and intravenous immunoglobulin (i.v.Ig) in treatment of 54 episodes of myasthenic crisis. After adjustment for other variables, PE (compared with i.v.Ig) was associated with a superior ventilatory status at 2 weeks (partial F = 6.2, p = 0.02) and 1 month functional outcome (partial F = 4.5, p = 0.04). However, the complication rate was higher with PE compared with i.v.Ig (13 versus 5 episodes, p = 0.07).

Effect of cross-linked hemoglobin transfusion on endothelial-dependent dilation in cat pial arterioles.

We determined whether addition of hemoglobin to the plasma would inhibit endothelial-dependent dilation in brain where tight endothelial junctions limit hemoglobin extravasation. Pial arteriolar diameter was measured by intravital microscopy through closed cranial windows in anesthetized cats either without transfusion (hematocrit = 32%) or after exchange transfusion with an albumin or sebacyl-cross-linked human hemoglobin solution (hematocrit = 18%). Dilation of small, medium, and large arterioles to acetylcholine and ADP was not significantly altered by hemoglobin transfusion. The dilatory responses were inhibited by the nitric oxide synthase inhibitor NG-nitro-L-arginine, although significant dilation to 30 microM acetylcholine persisted in small arterioles in the control and albumin-transfused group but not in the hemoglobin-transfused group. The dilatory response to the nitric oxide donor 3-morpholinosydnonimine was unaffected by albumin or hemoglobin transfusion, but the response to nitroprusside was reduced by one-third after hemoglobin transfusion. When cross-linked hemoglobin was superfused through the cranial window, the acetylcholine response became inhibited at a hemoglobin concentration of 0.1 microM and was completely blocked at 10 microM. Because this concentration is substantially less than the 500 microM hemoglobin concentration in plasma after transfusion when there was no inhibition of the acetylcholine response, hemoglobin permeation of the blood-brain barrier was considered negligible. We conclude that exchange of red cell-based hemoglobin with plasma-based hemoglobin does not produce a more effective sink for endothelial-derived nitric oxide evoked by agonist receptor-mediated activation. Furthermore, decreased hematocrit does not affect agonist-evoked endothelial-dependent dilation.

Noninvasive detection of cerebral hypoperfusion and reversible ischemia from reductions in the magnetic resonance imaging relaxation time, T2.

The hypothesis was tested that hypoperfused brain regions, such as the ischemic penumbra, are detectable by reductions in absolute transverse relaxation time constant (T2) using magnetic resonance imaging (MRI). To accomplish this, temporal evolution of T2 was measured in several models of hypoperfusion and focal cerebral ischemia in the rat at 9.4 T. Occurrence of acute ischemia was determined through the absolute diffusion constant D(av) = 1/3 TraceD, while perfusion was assessed by dynamic contrast imaging. Three types of regions at risk of infarction could be distinguished: (1) areas with reduced T2 (4% to 15%, all figures relative to contralateral hemisphere) and normal D(av), corresponding to hypoperfusion without ischemia; (2) areas with both reduced T2 (4% to 12%) and D(av) (22% to 49%), corresponding to early hypoperfusion with ischemia; (3) areas with increased T2 (2% to 9%) and reduced D(av) (28% to 45%), corresponding to irreversible ischemia. In the first two groups, perfusion-deficient regions detected by bolus tracking were similar to those with initially reduced T2. In the third group, bolus tracking showed barely detectable arrival of the tracer in the region where D(av) was reduced. We conclude that T2 reduction in acute ischemia can unambiguously identify regions at risk and potentially discriminate between reversible and irreversible hypoperfusion and ischemia.

Risk factors for multiple intracranial aneurysms.

OBJECTIVE: Risk factors that predispose to the formation of multiple intracranial aneurysms, which are present in up to 34% of patients with intracranial aneurysms, are not well defined. In this study, we examined the association between known risk factors for cerebrovascular disease and presence of multiple intracranial aneurysms. METHODS: We reviewed the medical records and results of conventional angiography in all patients with a diagnosis of intracranial aneurysms admitted to the Johns Hopkins University hospital between January 1990 and June 1997. We determined the independent association between various cerebrovascular risk factors and the presence of multiple aneurysms using logistic regression analysis. RESULTS: Of 419 patients admitted with intracranial aneurysms (298 ruptured and 121 unruptured), 127 (30%) had multiple intracranial aneurysms. In univariate analysis, female gender (odds ratio [OR] = 1.9; 95% confidence interval [CI], 1.1-3.3) and cigarette smoking at any time (OR = 1.8; 95% CI, 1.1-3.0) were significantly associated with presence of multiple aneurysms. In the multivariate analysis, cigarette smoking at any time (OR = 1.7; 95% CI, 1.1-2.8) and female gender (OR = 2.1; 95% CI 1.2-3.5) remained significantly associated with multiple aneurysms. Hypertension, diabetes mellitus, and alcohol and illicit drug use were not significantly associated with presence of multiple aneurysms. CONCLUSION: Cigarette smoking and female gender seem to increase the risk for multiple aneurysms in patients predisposed to intracranial aneurysm formation. Further studies are required to investigate the mechanism underlying the association between cigarette smoking and intracranial aneurysm formation.

Treatment of refractory intracranial hypertension with 23.4% saline.

OBJECTIVE: To evaluate the effect of intravenous bolus administration of 23.4% saline (8008 mOsm/L) on refractory intracranial hypertension (RIH) in patients with diverse intracranial diseases. DESIGN: Retrospective chart review. SETTING: A neurosciences intensive care unit in a university hospital. PATIENTS: We present eight patients and a total of 20 episodes of increased intracranial pressure (ICP) resistant to standard modes of therapy. Five patients had subarachnoid hemorrhage, one patient had traumatic brain injury, one had a brain tumor, and another had spontaneous basal ganglia hemorrhage. Seven patients had intraventricular catheters, and one had a subarachnoid pressure screw placed. We monitored continuously mean ICP, serum sodium concentrations, mean arterial pressure, cerebral perfusion pressure (CPP), central venous pressure, and urine output before and after the administration of hypertonic saline (HS). Post mortem examination of the brain was performed in two patients. INTERVENTION: Intravenous bolus administration of 30 mL of 23.4% saline. MEASUREMENTS AND MAIN RESULTS: There was a significant (p < .05) decrease in ICP from a median of 41.5 mm Hg before HS to 17 mm Hg at 1 hr, 16 mm Hg at 2 hrs, and 14 mm Hg at 3 hrs after HS administration. In 80% of cases, ICP decreased by >50% of the pretreatment value over a duration of 21.2+/-10.3 mins. ICP decreased to <20 mm Hg in 65% of all cases and the mean time for it to again exceed 20 mm Hg was 6.3+/-4.9 hrs. There was a significant improvement in CPP, from 64.7+/-19 (SD) mm Hg before HS to 85.6+/-18 mm Hg (1 hr) and 83+/-18 mm Hg (3 hrs) after HS. There were no significant differences in the other variables measured. The post mortem examinations showed no white matter changes or subdural collections. CONCLUSIONS: This preliminary case series suggests that the intravenous bolus administration of 23.4% saline reduces ICP and augments CPP in patients with resistant increased ICP. This reduction can be maintained for several hours while other therapeutic measures are being considered. The patient population most likely to respond to this therapy needs to be further defined. Although more research is needed, this treatment is promising as a new modality for RIH because of its ICP-lowering effect without intravascular volume depletion.

Cerebral blood flow during hypoxic hypoxia with plasma-based hemoglobin at reduced hematocrit.

We determined whether cerebral blood flow (CBF) remained related to arterial O2 content (CaO2) during hypoxic hypoxia when hematocrit and hemoglobin concentration were independently varied with cell-free, tetramerically stabilized hemoglobin transfusion. Three groups of pentobarbital sodium-anesthetized cats were studied with graded reductions in arterial O2 saturation to 50%: 1) a control group with a hematocrit of 31 +/- 1% (mean +/- SE; n = 7); 2) an anemia group with a hematocrit of 21 +/- 1% that underwent an isovolumic exchange transfusion with an albumin solution (n = 8); and 3) a group transfused with an intramolecularly cross-linked hemoglobin solution to decrease hematocrit to 21 +/- 1% (n = 10). Total arterial hemoglobin concentration (g/dl) after hemoglobin transfusion (8.8 +/- 0.2) was intermediate between that of the control (10.3 +/- 0.3) and albumin (7.2 +/- 0.4) groups. Forebrain CBF increased after albumin and hemoglobin transfusion at normoxic O2 tensions to levels attained at equivalent reductions in CaO2 in the control group during graded hypoxia. Over a wide range of arterial O2 saturation and sagittal sinus PO2, CBF remained greater in the albumin group. When CBF was plotted against CaO2 for all three groups, a single relationship was formed. Cerebral O2 transport, O2 consumption, and fractional O2 extraction were constant during hypoxia and equivalent among groups. We conclude that CBF remains related to CaO2 during hypoxemia when hematocrit is reduced with and without proportional reductions in O2-carrying capacity. Thus O2 transport to the brain is well regulated at a constant level independently of alterations in hematocrit, hemoglobin concentration, and O2 saturation.