Treatment of acute hydrocephalus and cerebral ischemia after subarachnoid hemorrhage

Only recently has acute hydrocephalus after subarachnoid hemorrhage been recognized as a clinical important problem. The mortality rate in patients with acute hydrocephalus after subarachnoid hemorrhage is higher than in those without, which is mainly caused by cerebral ischemia. An explanation for the role of acute hydrocephalus in producing fatal cerebral ischemia is offered by the significant correlation between acute hydroceghalus and hyponatremia and between hyponatremia and death from cerebral ischemia, whereas cerebral ischemia is relatively rare in patients with acute hydrocephalus who do not develop hyponatremia. The relation between hydrocephalus and hyponatremia is possibly explained by enlargement of the third ventricle which could interfere with hypothalamic function. Dysfunction of the hypothalamus may result in the release of a natriuretic factor which in turn causes salt wasting and hypovolemia. This hypovolemia may contribute to the development of cerebral ischemia after subarachnoid hemorrhage. Therefore, treatment of acute hydrocephalus should not be aimed only at the reduction of cerebro-spinal fluid pressure, but also at the prevention of a negative sodium- and fluidbalance. This strategy is the subject of this thesis

Detection of 'best' positive end-expiratory pressure derived from electrical impedance tomography parameters during a decremental positive end-expiratory pressure trial

Introduction: This study compares different parameters derived from electrical impedance tomography (EIT) data to define 'best' positive end-expiratory pressure (PEEP) during a decremental PEEP trial in mechanically-ventilated patients. 'Best' PEEP is regarded as minimal lung collapse and overdistention in order to prevent ventilator-induced lung injury.Methods: A decremental PEEP trial (from 15 to 0 cm H2O PEEP in 4 steps) was performed in 12 post-cardiac surgery patients on the ICU. At each PEEP step, EIT measurements were performed and from this data the following were calculated: tidal impedance variation (TIV), regional compliance, ventilation surface area (VSA), center of ventilation (COV), regional ventilation delay (RVD index), global inhomogeneity (GI index), and intratidal gas distribution. From the latter parameter we developed the ITV index as a new homogeneity parameter. The EIT parameters were compared with dynamic compliance and the PaO2/FiO2 ratio.Results: Dynamic compliance and the PaO2/FiO2 ratio had the highest value at 10 and 15 cm H2O PEEP, respectively. TIV, regional compliance and VSA had a maximum value at 5 cm H2O PEEP for the non-dependent lung region and a maximal value at 15 cm H2O PEEP for the dependent lung regio

Lung stress and strain calculations in mechanically ventilated patients in the intensive care unit

Background Stress and strain are parameters to describe respiratory mechanics during mechanical ventilation. Calculations of stress require invasive and difficult to perform esophageal pressure measurements. The hypothesis of the present study was: Can lung stress be reliably calculated based on non-invasive lung volume measurements, during a decremental Positive end-expiratory pressure (PEEP) trial in mechanically ventilated patients with different diseases? Methods Data of 26 pressure-controlled ventila

Impact of medical treatment on the outcome of patients after aneurysmal subarachnoid hemorrhage

BACKGROUND AND PURPOSE: The rationale behind early aneurysm surgery in patients with subarachnoid hemorrhage (SAH) is the prevention of rebleeding as early as possible after SAH. In addition, by clipping the aneurysm as early as possible, one can apply treatment for cerebral ischemia more vigorously (induced hypertension) without the risk of rebleeding. Hypervolemic hemodilution is now a well-accepted treatment for delayed cerebral ischemia. We compared the prospectively collected clinical data and outcome of patients admitted to the intensive care unit in the period 1977 to 1982 with those of patients admitted in the period 1989 to 1992 to measure the effect of the change in medical management procedures on patients admitted in our hospital with SAH. METHODS: We studied 348 patients admitted within 72 hours after aneurysmal SAH. Patients with negative angiography results and those in whom death appeared imminent on admission were excluded. The first group (group A) consisted of 176 consecutive patients admitted from 1977 through 1982. Maximum daily fluid intake was 1.5 to 2 L. Hyponatremia was treated with fluid restriction (<1 L/24 h). Antihypertensive treatment with diuretic agents was given if diastolic blood pressure was >110 mm Hg. Patients in the second group (172 consecutive patients; group B) were admitted from 1989 through 1992. Daily fluid intake was at least 3 L, unless cardiac failure occurred. Diuretic agents and antihypertensive medications were avoided. Cerebral ischemia was treated with vigorous plasma volume expansion under intermittent monitoring of pulmonary wedge pressure, cardiac output, and arterial blood pressure, aiming for a hematocrit of 0.29 to 0.33. Aneurysm surgery was planned for day 12. RESULTS: Patients admitted in group B had less favorable characteristics for the development of cerebral ischemia and for good outcome when compared with patients in group A. Despite this, we found a significant decrease in the frequency of delayed cerebral ischemia in patients of group B treated with tranexamic acid (P=0.00005 by log rank test) and significantly improved outcomes among patients with delayed cerebral ischemia (P=0.006 by chi2 test) and among patients with deterioration from hydrocephalus (P=0.001 by chi2 test). This resulted in a significant improvement of the overall outcome of patients in group B when compared with those in group A (P=0.006 by chi2 test). The major cause of death in group B was rebleeding (P=0.011 by chi2 test). CONCLUSIONS: We conclude that the outcome in our patients with aneurysmal SAH was improved but that rebleeding remains a major cause o

Cardioprotection in pigs by exogenous norepinephrine but not by cerebral ischemia-induced release of endogenous norepinephrine

BACKGROUND AND PURPOSE: Endogenous norepinephrine release induced by cerebral ischemia may lead to small areas of necrosis in normal hearts. Conversely, norepinephrine may be one of the mediators that limit myocardial infarct size by ischemic preconditioning. Because brief ischemia in kidneys or skeletal muscle limits infarct size produced by coronary artery occlusion, we investigated whether cardiac norepinephrine release during transient cerebral ischemia also elicits remote myocardial preconditioning. METHODS: Forty-one crossbred pigs of either sex were assigned to 1 of 7 experimental groups, of which in 6 groups myocardial infarct size was determined after a 60-minute coronary occlusion and 12

A feasibility study into adenosine triphosphate measurement in exhaled breath condensate: a potential bedside method to monitor alveolar deformation

Recent research suggested an important role for pulmonary extracellular adenosine triphosphate (ATP) in the development of ventilation-induced lung injury. This injury is induced by mechanical deformation of alveolar epithelial cells, which in turn release ATP to th

Vascular risk factors, atherosclerosis, cerebral white matter lesions and cerebral perfusion in a population-based study

We studied risk factors for cerebral vascular disease (blood pressure and hypertension, factor VIIc, factor VIIIc, fibrinogen), indicators of atherosclerosis (intima-media thickness and plaques in the carotid artery) and cerebral white matter lesions in relation to regional cerebral blood flow (rCBF) in 60 persons (aged 65-85 years) recruited from a population-based study. rCBF was assessed with single-photon emission tomography using technetium-99m d,l-hexamethylpropylene amine oxime (99mTc-HMPAO). Statistical analysis was performed with multiple linear regression with adjustment for age, sex and ventricle-to-brain ratio. A significant positive association was found between systolic and diastolic blood pressure and temporo-parietal rCBF. In analysis with quartiles of the distribution, we found a threshold effect for the relation of low diastolic blood pressure (≤ 60 mmHg) and low temporo-parietal rCBF. Levels of plasma fibrinogen were inversely related to parietal rCBF, with a threshold effect of high fibrinogen levels (> 3.2 g/l) and low rCBF. Increased atherosclerosis was related to low rCBF in all cortical regions, but these associations were not significant. No consistent relation was observed between severity of cerebral white matter lesions and rCBF. Our results may have implications for blood pressure control in the elderly population

Excessive extracellular ATP desensitizes P2Y2 and P2X4 ATP receptors provoking surfactant impairment ending in ventilation-induced lung injury

Stretching the alveolar epithelial type I (AT I) cells controls the intercellular signaling for the exocytosis of surfactant by the AT II cells through the extracellular release of adenosine triphosphate (ATP) (purinergic signaling). Extracellular ATP is cleared by extracellular ATPases, maintaining its homeostasis and enabling the lung to adapt the exocytosis of surfactant to the demand. Vigorous deformation of the AT I cells by high mechanical power ventilation causes a massive release of extracellular ATP beyond the clearance capacity of the extracellular ATPases. When extracellular ATP reaches levels >100 μM, the ATP receptors of the AT II cells become desensitized and surfactant impairment is initiated. The resulting alteration in viscoelastic properties and in alveolar opening and collapse time-constants leads to alveolar collapse and the redistribution of inspired air from the alveoli to the alveolar ducts, which become pathologically dilated. The collapsed alveoli connected to these dilated alveolar ducts are subject to a massive strain, exacerbating the ATP release. After reaching concentrations >300 μM extracellular ATP acts as a danger-associated molecular pattern, causing capillary leakage, alveolar space edema, and further deactivation of surfactant by serum proteins. Decreasing the tidal volume to 6 mL/kg or less at this stage cannot prevent further lung injury

Purinergic signalling links mechanical breath profile and alveolar mechanics with the pro-inflammatory innate immune response causing ventilation-induced lung injury

Severe pulmonary infection or vigorous cyclic deformation of the alveolar epithelial type I (AT I) cells by mechanical ventilation leads to massive extracellular ATP release. High levels of extracellular ATP saturate the ATP hydrolysis enzymes CD39 and CD73 resulting in persistent high ATP levels despite the conversion to adenosine. Above a certain level, extracellular ATP molecules act as danger-associated molecular patterns (DAMPs) and activate the pro-inflammatory response of the innate immunity through purinergic receptors on the surface of the immune cells. This results in lung tissue inflammation, capillary leakage, interstitial and alveolar oedema and lung injury reducing the production of surfactant by the damaged AT II cells and deactivating the surfactant function by the concomitant extravasated serum proteins through capillary leakage followed by a substantial increase in alveolar surface tension and alveolar collapse. The resulting inhomogeneous ventilation of the lungs is an important mechanism in the development of ventilation-induced lung injury. The high levels of extracellular ATP and the upregulation of ecto-enzymes and soluble enzymes that hydrolyse ATP to adenosine (CD39 and CD73) increase the extracellular adenosine levels that inhibit the innate and adaptive immune responses rendering the host susceptible to infection by invading microorganisms. Moreover, high levels of extracellular adenosine increase the expression, the production and the activation of pro-fibrotic proteins (such as TGF-β, α-SMA, etc.) followed by the establishment of lung fibrosis