Cerebral oedema and increased intracranial pressure in chronic liver disease

BACKGROUND: Cerebral oedema is a cause of morbidity and mortality in fulminant hepatic failure but has not been well documented as a complication of chronic liver diseases. We report here the development of cerebral oedema and increased intracranial pressure in 12 patients with chronic liver disease. METHODS: Between July 1, 1987, and Dec 31, 1993, we studied 12 patients aged 29-67 years with end-stage chronic liver disease. All the patients had cirrhosis, portal hypertension, hypoprothrombinaemia, hepatic encephalopathy, and decreased serum concentrations of albumin (<25 g/L). During the study, the patients developed signs of increased intracranial pressure and had documented intracranial hypertension, cerebral oedema, or both. Intracranial hypertension was suspected on physical examination and confirmed by epidural catheters. We detected cerebral oedema by computed axial tomography of the head and necropsy of the brain when possible. FINDINGS: All the patients had intracranial hypertension and cerebral oedema. Two patients had successful treatment of cerebral hypertension with improvement of intracranial pressure such that orthotopic liver transplantation was undertaken. Both patients became neurologically normal after transplantation. Eight patients had only a transient response to treatment and died of cerebral oedema before a transplant could be done. INTERPRETATION: Cerebral oedema and increased intracranial pressure can occur in chronic liver disease and presents as neurological deterioration. Treatment guided by monitoring of intracranial pressure can lead to the reversal of intracranial hypertension, but in most patients cerebral oedema contributes to death or places them at too high a risk for liver transplantation.     

An evidence-based approach to management of increased intracranial pressure

This article reviews the current understanding of genetic factors involved in the development of intracranial aneurysms. Of the large number of heritable connective tissue disorders that have been associated with intracranial aneurysms, three are discussed in detail: autosomal dominant polycystic kidney disease, Ehlers-Danlos syndrome type IV, and alpha 1-antitrypsin deficiency. The author reviews the familial occurrence of intracranial aneurysms, which is found in about one-fifth of patients with aneurysm subarachnoid hemorrhage. Guidelines are provided for the evaluation of patients with familial intracranial aneurysms and screening of their relatives.     

Temperature of the cerebrovenous blood in a model of increased intracranial pressure

Hypothermia has a considerable protective effect during brain ischemia. On the other hand small increases of brain temperature have a remarkable effect on the exacerbation of neurological damage following an ischemic event. Hyperthermia of the brain tissue after severe head injury is described. The effect of acutely increased intracranial pressure on cerebrovenous blood temperature is not described yet. The aim of this study was to investigate the relationship between temperature in the cerebrovenous compartment (Tcv) and changes of the CPP in an animal model of raised intracranial pressure. METHODS: A thermocouple was inserted in the sagittal sinus in 9 pigs under general anesthesia. By stepwise inflating a supracerebral and infratentorial placed balloon catheter intracranial pressure (ICP) was increased and CPP concomitantly decreased. The central body temperature was measured simultaneously in the abdominal aorta (Ta) with a second thermocouple. RESULTS: In our model th Tcv was lower than Ta at the beginning of the ICP increase. The mean difference between Ta and Tcv, (delta Ta-cv) was 0.86 degree C (+/- 0.44) prior to ICP increase and 1.19 degrees C (0.58) at the maximum ICP increase. Thus, delta Tav increased during CPP reduction. This relation was represented by an adjusted R(square) of r2 = 0.89 (p < 0.001). CONCLUSIONS: The CPP decrease, caused by an increasing ICP, results in changes of the cerebrovenous blood temperature. Interpreting the present results the experimental situation of a relative colder cerebral compartment in comparison to the central body temperature has to be considered. However, the results imply, that simultaneous temperature monitoring of the central body temperature and the cerebrovenous blood temperature is an additional source of information about relative changes of the CBF.     

Hypertonic saline dextran prime reduces increased intracranial pressure during cardiopulmonary bypass in pigs

Children and adults who develop neurologic deficits after cardiac surgery may experience cerebral ischemia during cardiopulmonary bypass. Increased intracranial pressure (ICP) may contribute to cerebral ischemia during bypass. Hypertonic saline dextran (HSD), a hyperosmotic, hyperoncotic resuscitation solution, decreases ICP in trauma resuscitation. We hypothesized that HSD would decrease ICP, reduce brain water, and reduce intravascular fluid requirements during bypass. Twelve swine were divided into two bypass groups: Group 1 (ISO = isotonic) received as prime 1 L of lactated Ringer's solution and 500 mL of 6% hydroxyethyl starch. Group 2 (HSD = hypertonic saline/dextran) received as prime 1 L of lactated Ringer's solution, 500 mL of 6% hydroxyethyl starch, and 1 mL/kg of 24% hypertonic saline/25% dextran. Normothermic bypass was instituted at 100 mL.kg-1.min-1. ICP increased significantly during bypass with ISO prime but not with HSD. Brain water in the cerebrum did not differ between groups but was reduced in the cerebellum to 75.9% +/- 1.4%. We conclude that HSD prevented any significant increase in ICP during normothermic bypass, and substantially improved fluid balance during bypass. In cardiac surgery patients in whom maintaining decreased ICP and reducing isotonic fluid administration is important, HSD may be a useful addition to the bypass prime solution.     

A comparison between systolic aortic root pressure and finger blood pressure

Isolation of the rat pup from the nest and dam for one hour per day from PN 2-9 is a useful paradigm for producing stress in the neonate. These previously isolated rats respond to an amphetamine challenge with alterations in activity at the juvenile stage or as adults. Furthermore, when dopamine release is measured in the nucleus accumbens, juveniles release 3 times more dopamine after amphetamine than do controls. This study describes changes in behavior and brain dopamine systems at PN 10. Experiment 1 determined an appropriate amphetamine dose that could be used for behavioral activation at PN 10. Experiment 2 produced significant evidence of enhanced behavioral activation after the isolation paradigm and indicated that brain regions innervated by the mesolimbic dopamine system, septum, and hypothalamus display increased dopamine turnover and that the nigrostriatal pathway is less active. Likewise, in Experiment 3, in vivo microdialysis of the nucleus accumbens indicated that previously isolated pups respond to an amphetamine challenge with a several-fold increase in dopamine release over a 4-hour session.     

Transcranial Doppler and cortical microcirculation at increased intracranial pressure and during the Cushing response: an experimental study on rabbits

The effect of increased intracranial pressure on the flow velocity of the basilar artery was measured with transcranial ultrasonic Doppler in New Zealand White rabbits under alpha-chloralose anesthesia and artificial respiration. Laser Doppler flowmetry served to study changes of the cortical microcirculation. The results confirm a high inverse correlation of the diastolic flow velocity, the pulsatility index, and the resistance index with the cerebral perfusion pressure (CPP). During acute intracranial hypertension, however, these parameters do not show a good correlation with the local cortical blood flow. The absence of a correlation was evident over a wide CPP range down to values of 35 mm Hg. Only at CPP values below this critical threshold is the microcirculation impaired. The threshold is reached at pulsatility index values of more than 2.0 and at resistance index values of more than 0.8. Therefore, transcranial Doppler indices permit the detection of critical reductions of microcirculatory blood flow. The Cushing reaction occurred with a constant time lag of 5.5 +/- 0.7 seconds after the loss of CPP. The Cushing reaction did not establish systolic blood flow, which remained below the functional threshold, as concluded from the temporary loss of somatosensory evoked potentials.     

Huge ossified crust-like subdural hematoma covering the hemisphere and causing acute signs of increased intracranial pressure

We report the successful removal of an ossified crust-like chronic subdural hematoma (SDH) covering the hemisphere in a 16-year-old boy. In this article, the importance of the surgical approach is stressed, and the rarity of this condition in the neurosurgical literature is also outlined.     

Sodium nitroprusside and intracranial pressure

The effects of sodium nitroprusside on intracranial pressure were studied in 10 patients, candidates for surgical treatment, prior to anaesthesia. Blood pressure was lowered to at least 50% of its initial value. In all cases, at the beginning of nitroprusside infusion, both the mean and the pulse intracranial pressures increased (mean increase: 83.2% of the initial value). At a certain moment, however, while the blood pressure continued to fall, the mean intracranial pressure did not increase any more; on the contrary, it decreased. On the other hand, in many cases, the pulse intracranial pressure continued to increase. No neurological or EEG changes were observed. The possible changes of cerebral circulation and CSF dynamics underlying the phenomena observed are discussed.     

Hyperventilation and mannitol administration during surgery in patients with space-occupying intracranial lesions

The aim of this work was to evaluate the effect of hyperventilation and mannitol on brain volume during neurosurgical operations. The material comprises 30 cases of supratentorial tumours. pO2, pCO2, pH and lactate concentration were determined in the arterial blood and in 7 cases also in the CSF. It was established that hyperventilation sometimes fails to decrease ICP; it was observed that hyperventilation was more effective in decreasing brain volume of the pCO2 level decreased by 14,6 mm Hg on the average. The joint use of hyperventilation and hypertonic mannitol was found to be more effective. Neither of the above methods was effective in the case of cystic tumors.     

Intracellular calcium and blood pressure: comparison between primary hyperparathyroidism and essential hypertension

Intracellular calcium has been reported to be increased in essential hypertension, and thought to play a role in its genesis through facilitation of vascular smooth muscle contraction. Since hypertension is more prevalent in primary hyperparathyroidism, intracellular calcium may also be increased in this condition. To investigate whether the hyperparathyroid condition, i.e., hypercalcemia and increased PTH per se, could be associated with high intracellular calcium, we measured intracellular calcium in platelets with the Quin-2 AM fluorometric method in 11 normotensive patients with primary hyperparathyroidism, 15 patients with essential hypertension, and 18 normal controls, all matched for age and sex. We repeated the measurements in 9 of the hyperparathyroid patients after successful surgery. We found that intracellular calcium was higher in normotensive patients with primary hyperparathyroidism than in normal controls (198 +/- 24 vs 113 +/- 11 nM, p < 0.05), but lower than in patients with essential hypertension (198 +/- 24 vs 286 +/- 38 nM, p < 0.05). Successful removal of a parathyroid adenoma decreased intracellular calcium from 215 +/- 22 to 116 +/- 19 nM, (p < 0.01). In the patients with primary hyperparathyroidism, intracellular calcium was strongly correlated with the levels of PTH (r = 0.87, p < 0.01), but not with the total serum calcium levels (r = 0.04, NS). The decrease in intracellular calcium after parathyroidectomy was also strongly correlated with the decrease in PTH (r = 0.84, P < 0.01), but not with the decrease in total serum calcium (r = 0.16, NS). In the patients with essential hypertension, intracellular calcium correlated well with systolic (r = 0.69, p < 0.01), diastolic (r = 0.76, p < 0.01) and especially mean arterial pressure (r = 0.86, P < 0.01). There was no correlation between blood pressure and intracellular calcium in the patients with primary hyperparathyroidism. We conclude that normotensive patients with primary hyperparathyroidism, as well as patients with essential hypertension, can have increased concentrations of intracellular calcium in platelets. The correction of the hyperparathyroid condition normalizes intracellular calcium concentration. The close correlation between PTH and intracellular calcium suggests that PTH may act as a ionophore for calcium entry into cells. Whether the increased levels of intracellular calcium may reflect a pre-hypertensive condition in normotensive patients with primary hyperparathyroidism remains to be determined.     

Relationship between intracranial pressure and the development of vasospasm after aneurysmal subarachnoid hemorrhage

The relationship between intracranial pressure (ICP) and the development of vasospasm after subarachnoid hemorrhage caused by the rupture of an intracranial aneurysm was investigated. Eleven patients were divided into high (6 cases) and low (5 cases) ICP groups based on ICP data obtained during the perioperative period by continuous ICP monitoring. Transcranial Doppler ultrasonography was performed every 24 hours for 7 days and the severity, distribution, and duration of vasospasm were assessed. The high ICP group tended to have severe, prolonged, and diffuse vasospasm compared with the low ICP group. However, only duration of vasospasm was statistically different. The relationship between cerebral perfusion pressure (CPP) and the development of vasospasm was also examined. CPP had a less significant effect than ICP although similar tendencies for high ICP and low CPP were observed. High ICP worsens vasospasm and treatment for decreasing ICP with perioperative ICP monitoring has potential for avoiding the development of vasospasm.     

Opioids, cerebral circulation and intracranial pressure

The effects of the opioids alfentanil (A), fentanyl (F), and sufentanil (S) on cerebral blood flow (CBF) and intracranial pressure (ICP) have been discussed in several recent publications. The purpose of this review is to describe the results of studies in animals, healthy volunteers, and patients with and without intracranial diseases. Clinical relevance and mechanisms of the reported ICP and CBF increases are analysed. METHODS. Approximately 70 original articles and abstracts were retrieved by a systematic literature search using the key word list at the end of this abstract. The cited studies came from computerised database systems like Silver Platter and DIMDI, the SNACC reference list, and the bibliographies of pertinent articles and books. These studies were classified into three groups: significant increase of ICP and/or CBF; no significant or clinically relevant alterations; and significant decreases of ICP and/or CBF. RESULTS. The numerical relationship was 6:7:3 for A, 7:16:9 for F, and 5:11:8 for S. Increases of previously normal or only slightly elevated ICP were registered in some studies in connection with a decrease in mean arterial pressure (MAP). On the other hand, in patients with brain injury and elevated ICP opioids did not further increase ICP despite MAP decreases. In studies monitoring ICP and/or CBF continuously, transient and moderate increases of questionable clinical relevance became apparent a few minutes after bolus injection of opioids. Alterations of systemic and cerebral haemodynamics observed after bolus application were not registered during continuous infusion of A and S. DISCUSSION AND CONCLUSIONS. The cerebral effects of opioids are dependent on several factors, e.g., age, species, ventilation, anaesthesia before and during measurements, systemic haemodynamics, and underlying diseases. The probable mechanism of ICP increase during decreasing MAP is cerebral vasodilatation due to maintained autoregulation. With increasing severity of the cerebral lesion autoregulation is often disturbed. Therefore, ICP often remains unaltered despite MAP decreases. However, the resulting decrease in cerebral perfusion pressure makes such patients more susceptible to develop ischaemic neurological deficits. Induction of somatic rigidity or (with high doses) convulsions, exceeding the upper limit of autoregulation, histamine release, cerebral vasodilatation, increased cerebral oxygen consumption, or carbon dioxide accumulation during spontaneous breathing were discussed as mechanisms for transient ICP/CBF increases. It is concluded that opioids are often beneficial and not generally contraindicated for patients with cerebral diseases and compromised intracranial compliance. However, since negative side effects cannot be excluded, opioid effects and side effects should be monitored (MAP, ICP, cerebrovenous oxygen saturation, transcranial Doppler sonography) in patients at risk. It has to be stressed that opioids should be administered only to patients with stable haemodynamic situations and preferably in well-titrated, continuous infusions.     

Roles for mannitol and mannitol dehydrogenase in active oxygen-mediated plant defense

Reactive oxygen species (ROS) are both signal molecules and direct participants in plant defense against pathogens. Many fungi synthesize mannitol, a potent quencher of ROS, and there is growing evidence that at least some phytopathogenic fungi use mannitol to suppress ROS-mediated plant defenses. Here we show induction of mannitol production and secretion in the phytopathogenic fungus Alternaria alternata in the presence of host-plant extracts. Conversely, we show that the catabolic enzyme mannitol dehydrogenase is induced in a non-mannitol-producing plant in response to both fungal infection and specific inducers of plant defense responses. This provides a mechanism whereby the plant can counteract fungal suppression of ROS-mediated defenses by catabolizing mannitol of fungal origin.     

Osmotic serum pressure in patients treated with furosemide and hypertonic mannitol solution

In patients with expanding intracranial lesion syndrome osmotic pressure of the serum was measured during administration of furosemide or 20% mannitol solution. Mannitol was administered by two methods: a) a dose of 1.5 g/kg during 3--4 hours, b) a dose of 1 g/kg for about 20 min. When mannitol was administered slowly the osmotic pressure of the serum at the end of infusion was 11--15% above the initial one and returned to the initial level 30--60 min. after the end of infusion. With rapid infusion the peak rise of pressure was observed after 30 min. usually after the end of infusion, and after one hour the pressure returned to values approaching the initial ones. Furosemide in a dose of 40 mg intramuscularly or intravenously caused slight changes of osmotic pressure reaching 13 mOsm/l.     

A method for a simulation of continuous intracranial pressure curves

The study introduces a method to simulate continuously an intracranial pressure (ICP) wave form. In a system analysis approach the intracranial compartment was viewed as a black box with arterial blood pressure (ABP) as an input signal and ICP as an output. A weight function was used to transform the ABP curve into the ICP curve. The output ICP waveform was generated using a weight function derived from the transcranial Doppler blood flow velocity (FV) and ABP curves. In order to establish the relationship between TCD characteristics and weight functions simultaneous recordings of FV, ABP, and ICP curves of a defined group of patients were used. A linear function between the TCD characteristics and the weight functions was obtained by calculating a series of multiple regression analyses. Given examples demonstrate the procedure's capabilities in predicting the mean ICP, the pulse and respiratory waveform modulations, and the trends of ICP changes.     

A new method for chronic intraventricular measurement of intracranial pressure

Aspirin caused epithelial hyperplasia, papillary necrosis with calcification and cortical changes in the rat kidney. After unilateral nephrectomy the lesions appeared more rapidly and were more severe. In the electron microscope the earliest changes were observed in the interstitial cells.     

Continuous intracranial pressure monitoring: review of techniques and presentation of method

Continuous monitoring of intracranial pressure has proved to be of value in guiding the treatment of patients with diffuse cerebral trauma or edema. The evolution of monitoring devices is reviewed from simple lumbar puncture through intraventricular, subdural, epidural and external monitoring with progressively more sophisticated equipment. The device reported in detail connects the subarachnoid space to an on-line data reducer that calculates the percentage time the intracranial pressure is in 16 pressure ranges of 5 mmHg each and portrays it on a histogram. The pressure at that moment, the total range of the intracranial pressure, the level of pressure the patient has had for the largest percented of time, and pressure waves, if present, can all be determined by this process.     

Reticular activity and intracranial pressure. Acute and chronic intracranial hypertension (author's transl)

Modifications of mesencephalic and bulbar reticular formation activity were studied with microelectrodes during acute and chronic intracranial hypertension. In both cases, the mesencephalic reticular activity increased progressively until a pressure level of 70 to 90 cm of CSF was reached and then fell irreversibly to less than the base value. The bulbar reticular activity followed the same pattern but more slowly. Different hypotheses are advanced to explain these modifications and their meanings.