7.2% NaCl/10% dextran 60 versus 20% mannitol for treatment of intracranial hypertension.

Severe head injury is frequently associated with extracranial injuries causing hemorrhagic hypotension. Volume replacement with isotonic fluids not only is therapeutically of limited efficacy but may aggravate posttraumatic brain edema. On the other side, hypertonic/hyperoncotic saline/dextran solution (HHS) shown to restore cardiovascular function in hemorrhagic shock instantaneously, was found to decrease intracranial pressure in experimental head injury. Currently the therapeutic efficacy of HHS and mannitol on ICP was compared at 24 hrs after a focal cerebral lesion and inflation of an epidural balloon in rabbits. Both solutions given at an equimolar dose rapidly lowered the ICP. After the first injection, ICP reduction was longer maintained with mannitol (189 +/- 27 min) as compared to HHS (98 +/- 14 min), while no difference in duration of lowering ICP was found after the second injection. Due to its blood pressure effects, HHS afforded a higher cerebral perfusion pressure than mannitol. In animals with HHS, the water content of the traumatized hemisphere was increased while the contralateral hemisphere was dehydrated. With mannitol, no differences in water content were found between the injured and uninjured hemisphere. The efficiency of HHS in hemorrhagic shock and intracranial hypertension render the fluid mixture particularly promising in patients with polytrauma in combination with head injury.

[Hypertonic solutions in treatment of intracranial pressure]. / Hypertone Lösungen zur Behandlung des intrakraniellen Drucks.

Administration of hypertonic solutions is the method of choice for acute treatment of intracranial hypertension. Recording of the intracranial pressure during treatment facilitates adjustment of the dosis to the actual ICP-response, avoiding thereby administration of an excessive osmotic load as a basis to prolong therapeutical efficacy. The mechanisms underlying reduction of the intracranial pressure by hypertonic solutions are still controversially discussed. Dehydration of normal probably also of edematous brain parenchyma and constriction of cerebral resistance vessels as an autoregulatory response causing reduction of the intracranial blood volume are the most likely options. Administration of hypertonic/hyperoncotic solutions has regained attention on account of its unmatched therapeutical efficacy to reestablish normal conditions in severe hemorrhagic shock. Administration of, e.g. 7.2% NaCl/10% Dextran 60 in an amount equivalent of only 10% of the shed blood volume is immediately normalizing cardiac output and improving the microcirculation in peripheral organs. These therapeutical properties are relevant in head injury, since inflicted patients quite often are suffering from peripheral trauma and consequently from hemorrhagic shock. No evidence has been obtained in a variety of experimental studies that hypertonic/hyperoncotic solutions have adverse effects on the brain in the presence of a cerebral lesion. To the contrary, the fluid mixture has been found to lower the increased intracranial pressure. Administration of hypertonic/hyperoncotic solutions appears therefore appropriate in acute cerebral insults from head injury and impending circulatory failure from shock in order to inhibit development of secondary brain damage.

[Therapy of hemorrhagic shock using small volumes of hypertonic-hyperoncotic NaCl-dextran solution--effects on the brain]. / Therapie des hämorrhagischen Schocks mit kleinen Volumina hyperton-hyperonkotischer NaCl-Dextranlösung--Auswirkungen auf das Gehirn.

Infusion of small volumes of hypertonic/hyperoncotic solution (HHL: 7.2% NaCl/10% dextran 60) is highly effective in haemorrhagic shock. Cardiovascular function is restored in a matter of minutes by rapid mobilisation of extravasal fluid. However, little experience has been collected to date on the side effects on the brain by this new form of shock therapy. The present studies on HHL were conducted with particular reference to cerebral blood flow, cerebral oxygen supply, and intracranial pressure. Haemorrhagic shock with a drop in arterial blood pressure to 40 mmHg over a period of 30 min was induced in rabbits under alpha-chloralose anaesthesia by means of bloodletting. Subsequently, the hypertonic/hyperoncotic solution (HHL) was infused into the experimental animals within two minutes. The regional cerebral blood flow (H2-clearance) and the cerebral O2 supply were studied by determining the pO2 of the cerebral cortex in experimental animals without haemorrhagic shock but with infusion of HHL. Finally, separate single tests were conducted to analyse the effect of the infusion of HHL on the intracranial pressure after induction of a focal cold lesion of the brain in combination with the implantation of a rubber balloon in the epidural space as an intracranial space-occupying growth. Infusion of HHL during shock produced rapid normalisation of cardiac output, whereas in normovolaemic animals without shock it produced a temporary increase of this parameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of hemorrhagic hypotension with hypertonic/hyperoncotic solutions: effects on regional cerebral blood flow and brain surface oxygen tension.

Hypertonic/hyperoncotic solutions (e.g. HHS: 7.2% NaCl/10% dextran-60) are highly effective to normalize cardiovascular function in hemorrhagic shock due to rapid mobilization of fluid from the extravascular compartment. Since experiences are limited with regard to potential side effects of this treatment on the central nervous system, the present studies were carried out under particular consideration of the cerebral blood flow and O2 supply. HHS was administered in albino rabbits subjected to alpha-chloralose anesthesia and artificial ventilation with and without hemorrhagic hypovolemia. Hemorrhagic hypovolemia of 30 min duration was induced by withdrawal of approximately one third of the circulating blood volume resulting in a decrease in arterial blood pressure to 40 mm Hg. HHS was studied in addition to normovolemic animals. Cardiac output was rapidly normalized by infusion of HHS in animals with hypovolemia, while it increased intermittently in normovolemic animals. In animals with hemorrhagic shock arterial blood pressure recovered by treatment to approximately 70% of normal, whereas blood pressure remained unchanged after infusion of HHS in normovolemic controls. Cerebral blood flow, which was assessed by H2 clearance at the brain surface, had a range of 43.0-50.3 ml/100 g/min under control conditions. It remained virtually unchanged during hemorrhagic hypovolemia and also after infusion of HHS in normovolemic animals. Treatment of shock by HHS was followed 90 or 120 min later by a moderate increase in regional cerebral blood flow to 61 ml/100 g/min. Local tissue PO2 at the brain surface was obtained by an O2 multiwire electrode in the vicinity of the H2 clearance measurements using a weightless suspension system to avoid compression of the brain surface. Infusion of HHS in normovolemic animals did not affect the O2 supply of the brain. Hemorrhagic hypovolemia which led to a left shift of the cerebral PO2 histogram was followed by gradual normalization after fluid resuscitation. The current findings taken together do not indicate adverse side effects of this efficient method of fluid resuscitation with regard to the cerebral blood and O2 supply. The results make worthwhile further investigations on HHS in the presence of a focal brain lesion causing brain edema to find out whether the HHS are useful also for the treatment of intracranial hypertension.

The effect of various steroid treatment regimens on cold-induced brain swelling.

The role of steroid therapy in brain oedema following acute cerebral lesions is still unsolved. This study was conducted to compare the efficacy of dexamethasone and triamcinolone, and to analyze the influence of timing and duration of treatment on cold-induced brain swelling. In rabbits, a cryogenic lesion of the left parietal cortex was induced. 24, or 48 hrs after trauma, hemispheric swelling, water- and electrolyte-contents were measured. A first series of animals received dexamethasone, triamcinolone or saline for 24 hrs, starting treatment 10 min after trauma. In a second series, steroid treatment lasted 48 hrs and in a third series the animals were additionally pretreated for 24 hrs. Dexamethasone and triamcinolone slightly decreased posttraumatic hemispheric swelling, from 7.7% in controls to 7.0% in treated animals. There was no significant difference between dexamethasone and triamcinolone. Reduction of swelling was most pronounced in animals with 48 hrs treatment. Pretreatment with steroids was not superior to early posttraumatic treatment. On the other hand, dexamethasone and triamcinolone significantly decreased cerebral water content in the traumatized and contralateral hemisphere, as well as in non-traumatized animals. The unspecific reduction of water content by steroids in rabbits might explain the moderate therapeutical effect on brain swelling. This effect might be beneficial, nevertheless, with respect to an improvement of the intracranial compliance.

The kallikrein-kinin system as mediator in vasogenic brain edema. Part 3: Inhibition of the kallikrein-kinin system in traumatic brain swelling.

Evidence has previously been provided that administration of kinins to the cerebrum causes edema and opening of the blood-brain barrier. It has further been shown that these highly active compounds are formed in the brain under pathophysiological conditions. Their formation was enhanced when cerebral blood flow became compromised by an increase in intracranial pressure. Final evidence, however, was not available as to whether specific inhibition of the kallikrein-kinin (KK) system has a therapeutic function in acute head injury. The authors have demonstrated in rabbits that inhibition of the activating enzyme kallikrein by aprotinin or by aprotinin plus soybean trypsin inhibitor (SBTI), which interfere with plasma and tissue kallikrein, is associated with a decrease in formation of posttraumatic swelling after a standardized cold lesion to the brain. Saline-treated control animals with cerebral cold-induced injury had an increase in hemispheric weight 24 hours later of 13.0% +/- 0.8% (standard error of the mean) in the damaged hemisphere compared to the contralateral nondamaged hemisphere. Administration of aprotinin or aprotinin plus SBTI led to a significant reduction of hemispheric swelling of 10.1% +/- 0.7% or 10.4% +/- 0.7%, respectively. In animals receiving SBTI only, hemispheric swelling evolving from cold injury was not significantly reduced. Therapeutic reduction of brain edema by aprotinin cannot be attributed to a nonspecific effect on the blood pressure, which in the experimental groups remained almost normal as compared to the control animals. Failure of SBTI to influence posttraumatic brain swelling may have resulted from disturbances in intravascular coagulation. Measurements of aprotinin in plasma and tissue demonstrate that the inhibitor doses employed are within an effective therapeutic range. Attenuation of brain edema by specific inhibition of the KK system provides evidence for a mediator role of kinins in vasogenic edema. Clinical trials with inhibitors of the KK system in acute forms of traumatic lesions associated with vasogenic edema appear worthwhile.