Relationship between angiographic vasospasm and regional hypoperfusion in aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Angiographic vasospasm frequently complicates subarachnoid hemorrhage and has been implicated in the development of delayed cerebral ischemia. Whether large-vessel narrowing adequately accounts for the critical reductions in regional cerebral blood flow underlying ischemia is unclear. We sought to clarify the relationship between angiographic vasospasm and regional hypoperfusion. METHODS: Twenty-five patients with aneurysmal subarachnoid hemorrhage underwent cerebral catheter angiography and 15O-positron emission tomographic imaging within 1 day of each other (median of 7 days after subarachnoid hemorrhage). Severity of vasospasm was assessed in each intracranial artery, whereas cerebral blood flow and oxygen extraction fraction were measured in 28 brain regions distributed across these vascular territories. We analyzed the association between vasospasm and perfusion and compared frequency of hypoperfusion (cerebral blood flow<25 mL/100 g/min) and oligemia (low oxygen delivery with oxygen extraction fraction≥0.5) in territories with versus without significant vasospasm. RESULTS: Twenty-four percent of 652 brain regions were supplied by vessels with significant vasospasm. Cerebral blood flow was lower in such regions (38.6±12 versus 48.7±16 mL/100 g/min), whereas oxygen extraction fraction was higher (0.48±0.19 versus 0.37±0.14, both P<0.001). Hypoperfusion was seen in 46 regions (7%), but 66% of these were supplied by vessels with no significant vasospasm; 24% occurred in patients without angiographic vasospasm. Similarly, oligemia occurred more frequently outside territories with vasospasm. CONCLUSIONS: Angiographic vasospasm is associated with reductions in cerebral perfusion. However, regional hypoperfusion and oligemia frequently occurred in territories and patients without vasospasm. Other factors in addition to large-vessel narrowing must contribute to critical reductions in perfusion.

Comparison of induced hypertension, fluid bolus, and blood transfusion to augment cerebral oxygen delivery after subarachnoid hemorrhage.

OBJECT: Critical reductions in oxygen delivery (DO(2)) underlie the development of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). If DO(2) is not promptly restored, then irreversible injury (that is, cerebral infarction) may result. Hemodynamic therapies for DCI (that is, induced hypertension [IH] and hypervolemia) aim to improve DO(2) by raising cerebral blood flow (CBF). Red blood cell (RBC) transfusion may be an alternate strategy that augments DO(2) by improving arterial O(2) content. The authors compared the relative ability of these 3 interventions to improve cerebral DO(2), specifically their ability to restore DO(2) to regions where it is impaired. METHODS: The authors compared 3 prospective physiological studies in which PET imaging was used to measure global and regional CBF and DO(2) before and after the following treatments: 1) fluid bolus of 15 ml/kg normal saline (9 patients); 2) raising mean arterial pressure 25% (12 patients); and 3) transfusing 1 U of RBCs (17 patients) in 38 individuals with aneurysmal SAH at risk for DCI. Response between groups in regions with low DO(2) (< 4.5 ml/100 g/min) was compared using repeated-measures ANOVA. RESULTS: Groups were similar except that the fluid bolus cohort had more patients with symptoms of DCI and lower baseline CBF. Global CBF or DO(2) did not rise significantly after any of the interventions, except after transfusion in patients with hemoglobin levels < 9 g/dl. All 3 treatments improved CBF and DO(2) to regions with impaired baseline DO(2), with a greater improvement after transfusion (23%) than hypertension (14%) or volume loading (10%); p < 0.001. Transfusion also resulted in a nonsignificantly greater (47%) reduction in the number of brain regions with low DO(2) when compared with fluid bolus (7%) and hypertension (12%) (p = 0.33). CONCLUSIONS: The IH, fluid bolus, and blood transfusion interventions all improve DO(2) to vulnerable brain regions at risk for ischemia after SAH. Transfusion appeared to provide a physiological benefit at least comparable to IH, especially among patients with anemia, but transfusion is associated with risks. The clinical significance of these findings remains to be established in controlled clinical trials.

Effect of mannitol on cerebral blood volume in patients with head injury.

BACKGROUND: Mannitol has traditionally been the mainstay of medical therapy for intracranial hypertension in patients with head injury. We previously demonstrated that mannitol reduces brain volume in patients with cerebral edema, although whether this occurs because of a reduction in brain water, blood volume, or both remains poorly understood. OBJECTIVE: To test the hypothesis that mannitol acts by lowering blood viscosity leading to reflex vasoconstriction and a fall in cerebral blood volume (CBV). METHODS: We used O positron emission tomography to study 6 patients with traumatic brain injuries requiring treatment for intracranial hypertension. Cerebral blood flow (CBF), CBV, and cerebral metabolic rate for oxygen (CMRO2) were measured before and 1 hour after administration of 1.0 g/kg 20% mannitol. RESULTS: CBV rose from 4.1 ± 0.4 to 4.2 ± 0.2 mL/100 g (P = .3), while intracranial pressure fell from 21.5 ± 4.9 to 13.7 ± 5.1 mm Hg (P < .003) after mannitol. Blood pressure, PaCO2, oxygen content, CBF, and CMRO2 did not change. CONCLUSION: A single bolus of 1 g/kg of 20% mannitol does not acutely lower CBV. Another mechanism, such as a reduction in brain water, may better explain mannitol's ability to lower intracranial pressure and reduce mass effect.

Effect of osmotic agents on regional cerebral blood flow in traumatic brain injury.

PURPOSE: Cerebral blood flow (CBF) is reduced after severe traumatic brain injury (TBI) with considerable regional variation. Osmotic agents are used to reduce elevated intracranial pressure (ICP), improve cerebral perfusion pressure, and presumably improve CBF. Yet, osmotic agents have other physiologic effects that can influence CBF. We sought to determine the regional effect of osmotic agents on CBF when administered to treat intracranial hypertension. MATERIALS AND METHODS: In 8 patients with acute TBI, we measured regional CBF with positron emission tomography before and 1 hour after administration of equi-osmolar 20% mannitol (1 g/kg) or 23.4% hypertonic saline (0.686 mL/kg) in regions with focal injury and baseline hypoperfusion (CBF <25 mL per 100 g/min). RESULTS: The ICP fell (22.4 ± 5.1 to 15.7 ± 7.2 mm Hg, P = .007), and cerebral perfusion pressure rose (75.7 ± 5.9 to 81.9 ± 10.3 mm Hg, P = .03). Global CBF tended to rise (30.9 ± 3.7 to 33.1 ± 4.2 mL per 100 g/min, P = .07). In regions with focal injury, baseline flow was 25.7 ± 9.1 mL per 100 g/min and was unchanged; in hypoperfused regions (15% of regions), flow rose from 18.6 ± 5.0 to 22.4 ± 6.4 mL per 100 g/min (P < .001). Osmotic therapy reduced the number of hypoperfused brain regions by 40% (P < .001). CONCLUSION: Osmotic agents, in addition to lowering ICP, improve CBF to hypoperfused brain regions in patients with intracranial hypertension after TBI.

Year in review 2010: Critical Care--Neurocritical care.

In 2010 Critical Care published a large number of articles on critical care aspects of neurologic and neurosurgical conditions. These aspects included investigation of diagnostic criteria for bacterial meningitis, critical illness myopathy and their relationship to systemic inflammation. A number of studies investigated the biology of sepsis-related delirium, its biomarkers, its relationship to inflammation and its impact on outcome. Other teams reported on the use of magnetic resonance imaging, biomarkers and electroencephalogram to predict outcome in patients who were comatose following cardiac arrest. Our understanding of the pathophysiology as well as management of subarachnoid hemorrhage was addressed in several papers. Topics included the effect of hemodynamic treatment of delayed cerebral ischemia, pulmonary edema and the impact of subarachnoid hemorrhage on endocrine function. Finally, outcome from neurocritical care and patients' retrospective willingness to consent to the treatment they received were reported.

Cerebral hemodynamic and metabolic effects of equi-osmolar doses mannitol and 23.4% saline in patients with edema following large ischemic stroke.

INTRODUCTION: Cerebral edema after ischemic stroke is frequently treated with mannitol and hypertonic saline (HS); however, their relative cerebrovascular and metabolic effects are incompletely understood, and may operate independent of their ability to lower intracranial pressure. METHODS: We compared the effects of 20% mannitol and 23.4% saline on cerebral blood flow (CBF), blood volume (CBV), oxygen extraction fraction (OEF), and oxygen metabolism (CMRO(2)), in nine ischemic stroke patients who deteriorated and had >2 mm midline shift on imaging. (15)O-PET was performed before and 1 h after administration of randomly assigned equi-osmolar doses of mannitol (1.0 g/kg) or 23.4% saline (0.686 mL/kg). RESULTS: Baseline CBF values (ml/100g/min) in the infarct core, periinfarct region, remaining ipsilateral hemisphere, and contralateral hemisphere in the mannitol group were 5.0 ± 3.9, 25.6 ± 4.4, 35.6 ± 8.6, and 45.5 ± 2.2, respectively, and in the HS group were 8.3 ± 9.8, 35.3 ± 10.9, 38.2 ± 15.1, and 35.2 ± 12.4, respectively. There was a trend for CBF to rise in the contralateral hemisphere after mannitol from 45.5 ± 12.2 to 57.6 ± 21.7, P = 0.098, but not HS. CBV, OEF, and CMRO(2) did not change after administration of either agent. Change in CBF in the contralateral hemisphere after osmotic therapy was strongly correlated with baseline blood pressure (R (2)= 0.879, P = 0.002). CONCLUSIONS: We conclude that at higher perfusion pressures, osmotic agents may raise CBF in non-ischemic tissue. We conclude that at higher perfusion pressures, osmotic agents may raise CBF in non-ischemic tissue.

Metastatic adrenal pheochromocytoma to the thoracic spine / Feocromocitoma adrenal metastático para a coluna torácica / Feocromocitoma adrenal metastásico para la columna torácica

To report on a case of pheochromocytoma metastases to the spine occurring more than 20 years after initial diagnosis. A 34-year-old female with a history of metastatic pheochromocytoma diagnosed at age 12 presented with weakness, heart palpitations, and circumferential back pain of five months duration. The patient had undergone multiple laparatomies for abdominal and hepatic metastases. Work-up revealed a destructive lesion at T9. After two weeks of preoperative phenoxybenzamine to control her hypertension, she underwent decompression, posterior fixation and fusion. Surgical intervention was followed by radiation therapy, zoledronic acid, and only one cycle of chemotherapy due to intolerance of side effects. The patient survived 25 years after original diagnosis, which far exceeds the average survival of less than 15 years. The patient died 26 months postoperatively due to progression of disease. Pheochromocytoma with spine metastases occurring more than 20 years after diagnosis is very uncommon, and should be considered in the differential diagnosis of a patient with a history of pheochromocytoma.

Relato de caso de feocromocitoma adrenal com metástase para a coluna que ocorreu há mais de 20 anos após o diagnóstico inicial. Mulher de 34 anos com história de feocromocitoma metastático diagnosticado na idade de 12 anos, apresentando fraqueza, palpitações do coração e dor nas costas circunferencial há cinco meses. A paciente tinha realizado laparotomia para metástases abdominal e hepática. Durante o procedimento revelou uma lesão destrutiva em T9. Após duas semanas de fenoxibenzamina pré-operatórios para controlar sua hipertensão, submeteu-se a descompressão, fixação e posterior fusão. A intervenção cirúrgica foi seguida por terapia de radiação, ácido zoledrônico e apenas um ciclo de quimioterapia, devido à intolerância e aos efeitos colaterais. A paciente sobreviveu 25 anos após o diagnóstico original, o que excede em muito a sobrevida média de menos de 15 anos. A paciente morreu 26 meses após o pós-operatório, devido à progressão da doença. Feocromocitoma com metástases para coluna ocorrida há mais de 20 anos após o diagnóstico é muito raro, devendo ser considerada no diagnóstico diferencial de um paciente com uma história de feocromocitoma.

Relato de un caso de feocromocitoma adrenal con metástasis para la columna que ocurrió con más de 20 años de diagnóstico inicial. Mujer de 34 años con historia de feocromocitoma metastásico diagnosticado en la edad de 12 años, con presencia de debilidad, palpitaciones del corazón y dolor en la espalda circunferencial, con evolución de cinco meses. A la paciente se le había realizado diversas laparotomías por causa de metástasis abdominales y hepáticas. Durante la inspección, se mostró una lesión destructiva en T9. Después de dos semanas de fenoxibenzamina preoperatoria para controlar la hipertensión, se sometió a descompresión, fijación y posterior fusión. La intervención quirúrgica fue seguida por radioterapia, ácido zoledrónico, y sólo un ciclo de quimioterapia, debido a la intolerancia y a los efectos colaterales.La paciente sobrevivió 25 años después del diagnóstico original, lo que excedió en mucho la sobrevida mediana de menos de 15 años. La paciente murió 26 meses después del postoperatorio debido a la progresión de la enfermedad. El hecho de la metástasis para columna haber ocurrido después de 20 años del diagnóstico es bastante raro y se debe considerar en el diagnóstico diferencial de un paciente con una historia de feocromocitoma.

Intrathecal magnesium sulfate administration at the time of experimental ischemia improves neurological functioning by reducing acute and delayed loss of motor neurons in the spinal cord.

BACKGROUND: In this study, the authors determined the effect of magnesium sulfate on intrathecal glutamate concentrations, hindlimb motor function, and histopathology after a transient episode of spinal cord ischemia. METHODS: Fifty-two New Zealand White rabbits underwent spinal cord ischemia for 30 min. Fifteen minutes before ischemia, animals received intrathecal magnesium sulfate (MgSO4) (3 mg/kg) or placebo (artificial cerebrospinal fluid). Intrathecal microdialysis samples were measured for glutamate using high-performance liquid chromatography. Neurologic function and spinal cord histopathology were assessed throughout the recovery period. RESULTS: Intrathecal glutamate levels in placebo-treated animals were higher after spinal cord ischemia compared with sham- and MgSO4-treated animals. MgSO4-treated animals had increased lower extremity motor function compared with the placebo group (64.7% vs 14.3%, P < 0.01). Histologic examination of placebo-treated animals revealed significant motor neuron cell loss at thoracolumbar levels by Day 7 (P < 0.05), whereas lower lumbar regions displayed significant neuron loss on Day 1. Spinal cords from MgSO4-treated animals exhibited less neuronal loss in lumbar regions. Similar effects were present in the thoracolumbar segments on Day 7. A significant correlation existed between diminished neuronal loss and hind leg movement (Tarlov score) and demonstrates that the neurologic outcome after MgSO4 treatment was related to lower lumbar ventral horn cell survival (r2 = 0.812, P < 0.001). CONCLUSIONS: These results demonstrate that MgSO4 affords significant spinal cord motor neuron protection by diminishing acute neuronal loss at the foci of the ischemic injury (L3-L6) with delayed neuronal degeneration in adjacent spinal cord regions (T7-L2).

Acute ethanol exposure combined with burn injury enhances IL-6 levels in the murine ileum.

BACKGROUND: Recent studies suggest that ethanol use imposes a greater risk of trauma-associated intestinal injury than trauma alone. The initiating and regulatory factors for multiple organ dysfunction syndromes are not well defined, yet evidence points to the gut as a possible trigger of the systemic inflammatory cascade as well as a potential source of cytokines. In the current study, we hypothesized that ethanol administration would alter cytokine levels and intestinal infiltration by neutrophils within the ileum of mice exposed to burn injury (15% total body surface of dorsal skin). METHODS: Ileal samples were collected for histological assessment, myeloperoxidase quantitation and the protein presence of tumor necrosis factor alpha (TNFalpha), interleukin (IL-) 6, macrophage inflammatory protein-2 (MIP-2; CXCL2) and the anti-inflammatory cytokine, IL-10. Additional ileal tissue samples were examined for localization of the IL-6 immunoreactivity. RESULTS: We did not detect statistically significant cytokine/chemokine differences (MIP-2 and IL-10) between sham control and treatment conditions at either 2 or 24 hours. However, there was a significant decrease in TNFalpha at 24 hours in both burn injury alone and in combination with ethanol treatment conditions (p < 0.05). In addition, there was an increase in IL-6 levels at 24 hours in intestinal tissue obtained from mice subjected to a combination of acute ethanol and burn injury, compared to the mice receiving burn or sham injury (p < 0.001). Ileal homogenate increases in IL-6 at 24 hours were concurrent with decreased villus height in the ileum, but no discernable changes in neutrophil infiltration (myeloperoxidase activity levels) at either 2 or 24 hours. Additional immunocytochemical localization studies of ileal tissue revealed that there was a substantial increase of IL-6 in intestinal enterocytes subjected to both burn injury alone, or in combination with acute ethanol exposure. CONCLUSIONS: The present study suggests that acute ethanol exposure combined with burn injury enhances levels of IL-6 protein in the ileum. The enhanced levels of ileal IL-6 are likely due to enterocyte production of the cytokine.