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Haemodinamic compensation: 
the reanimator's opinion

Given that every cerebral ischaemia event , either focal or global is always caused by an altered ratio between the cerebral oxygen carriage (CDO₂) and the brain metabolic oxygen consumption (CMRO₂), the task of the reanimator is to intervene as immediately as he can (Golden hour) in order to affect the haemodynamic parameters and metabolic and respiratory parameters which are able to quickly restore the CDO₂ / CMRO₂ balance.
CDO₂ is the product of the brain blood flow (BHF = 50 ml /100 gr./min) and the oxygen concentration in the arterial blood (CaO₂).
Normally, the brain receives the 15% of the cardiac output, with a O₂ consumption equal to the 20% of the total O₂ consumption. The O₂ extraction is high and consequently the O₂ saturation and tension in the jugular venous blood (SjvO₂ and PjvO₂ respectively) are lower than the systemic ones in the mixed venous blood (SvO₂ and PvO₂ respectively).
For several reasons, the brain is particularly sensitive to the oxygen deprival. The preservation of a valid neurologic function requires an energy cost which exceeds the maximum energy produced by the anaerobic metabolism.
Besides, at a brain level, O₂ reserves are not existing; on the contrary, there are a few and not perfused capillaries that represent a circulatory reserve available when necessary.
Ischaemia starts a cascade of metabolic events which, beginning from a depletion of energetic substrata such as phosphocreatine and ATP, causes an increase of glucose anaerobic metabolism, followed by a lactate increase, a fast decrease of the neuronic pH, with a resulting unbalance of the ionic gradient. The calcium-ion input activates further destructive cascades such as direct vasoconstriction, the release of thromboxanes A2 and the catabolism of the saturated fatty acids and nucleotides (lipoperoxidation) . These events cause the breaking of the neuronal membranes and the irreversible cellular death.
Given that in the area of a cerebral tissue distal to a vascular obstruction the cerebral ischaemia can be irreversible or potentially reversible, the absolute level of perfusion represents a critical element which affects the potential recovery of the cerebral tissue. The tissue portion which receives a flow lower than 10 ml/100gr./min becomes rapidly infarcted. The tissue survival can be achieved, if the flow is re-established in time to the tissue portions whose received flow is higher than 10 ml /100 gr./min (ischaemic penumbra), altough not sufficient to support the functions. Therefore, the reanimator's task will be to restore the BHF in those parenchymal areas located in the ischaemic penumbra, but liable to bioelectric and functional recovery, before a reperfusion may trigger the above mentioned cascade of negative events (tardive reperfusion syndrome).
 

Measures to increase the cerebral oxygen carriage
The approach will be aggressive even in elderly patients. The reason is that there is not an alternative (especially in consistent focal events) besides, the fast onset of the irreversible ischaemic damage needs to be considered. The management of the respiratory tract is the crucial point of the intensive approach to these patients. It aims to optimise the alveolar ventilation and the ratio Ventilation/ Perfusion: the preference will be given to the non-invasive mechanic ventilation methods which consist in a continuous positive ventilation by mask on patients maintaining their own respiratory drive (CPAP-BIPAP). This is done to avoid that an unnecessary tracheal intubation could expose our patients to precocious bronchopneumonic infections. As it is well-known, this is the most common cause of decease during the first three weeks since the ischaemic event occurrence.
If it is not possible to perform the noninvasive ventilation (in case of serious hemispherium infarction with an alteration of the respiratory drive), then it will be necessary to proceed to the artificial mechanical ventilation by tracheal intubation and/or tracheostomy. Regarding these ventilation techniques, in the last five years, more and more often it has emerged the preference of using the precocious tracheostomy that, compared to the extended intubation, has the advantage to accelerate the weaning from the pulmotor and to facilitate the approach to the respiratory duct for diagnosis purpose (bronchoscopy) and for nursing as well. In the same perspective of mini-invasiveness, in the last years, in I.C., percutaneous subcricoid tracheostomies have been performed using anterograde (Ciaglia), and retrograde (Fantoni) translaringeal techniques; they have the advantage of reducing the rate of peristoma infections and precocious or tardive complications.

Measures to increase the cerebral blood flow (BHF)
1. Hypervolaemic haemodilution: in experiments on animals it has proved to increase the BHF distally to the occluded middle cerebral artery. The clinical effects on human subjects are not well defined yet.
2. Isovolaemic haemodilution: on patients with ictus, it causes an increase of BHF, enhancing the electroencephalographic activity. Multicentric trials on the isovolaemic haemodilution performed during the post-ictus period have given conflicting results. The Scandinavian Stroke Study Group has enphasised the possibility of benefits only when the haemodilution is carried out within 12 hours since the ictus occurrence, when the Ht is reduced at least by 15% and the cardiac output grows at least by 10%. In I.C. both isovolaemic haemodilution and mild iperventilation (PaCO₂ not lower than 30 mm Hg) during the first 24 hours since the stroke occurrence should always be carried out through continuous or intermittent monitoring of the oxygen saturation of the jugular venous blood (SjvO₂) and blood lactates.
SjvO₂ is a direct expression of CDO₂ / CMRO₂ ratio and its value, which is normally about 60%, is a reliable index of the cerebral oxygen extraction. Its sudden reduction indicates either an aggravation of the ischaemic event and/or the cerebral oedema (increased O₂ extraction), or a iatrogenic damage caused by a hyperventilation not well performed and/or haemodilution. In the same way, a reduction of this parameter may occur in case of an unexpected cardiovascular collapse in these patients, for whom a concurrent myocardioischaemic pathology is not rare.
3. Intra-arterial administration of thrombolytic agents: in recent years the close cooperation between the reanimator and the interventional neuroradiologist has allowed to successfully carry out intra-arterial thrombolysis techniques in the first three hours since the ictal event. They have been successfully performed on the anterior cerebral circuit through microcatheterism of the middle cerebral arteries and microinfusion by rTPA pump.
4. Selective Calcium antagonists: they reduce Ca ion input, increase the BHF and have a neuroprotection effect on the cerebral parenchyma distal to the occlusion. In the experimental model, they increase BHF and intracellular pH.
In the patients with a consistent hemispheric infarction, the nimodipine potential benefit must be related to the endocranial pressure increase (ICP), accompanying the cerebral vasodilatation.
5. Pentoxifylline: in patients suffering from chronic cerebrovascular pathology, it causes an increase of the BHF in the areas at low flow. It is useful if administered during the days immediately after the ischaemic event; it has very scarse side effects and it can be considered a valid support to the other treatments in the acute phase.

Measures to reduce the cerebral metabolic oxygen consumption
1. Barbiturates: They are useful only in predictable, imminent or current focal ischaemias, (cardiac and extracranial cerebral vessel surgery, endocranial vascular surgery). Since their specific characteristics are accumulation and slow metabolization, they can be used in I.T. only associated to a haemodynamic systemic support and to the control of the average arterious pressure with vasoactive drugs. Dosage: 0.25-0.5 mg/kg/min, o 15-30 mg/kg/hour.
2. Propofol: hypnonarcotic more recently used in anaesthesia and T.I. (2-6 diisopropylphenol). It allows a better neurosedation with less accumulation compared to barbiturates, if administered in continuous solution controlled by a volumetric pump. Dosage: 3-6 mg/kg/hour.

Measures to fight oxygen free radicals action in the cerebral ischaemia-reperfusion syndrome
Antioxidants: they are the real antimetabolites in the reperfusion syndrome.
Allopurinol: it inhibits the xanthine-oxidase and prevents free radicals formations in physiologic conditions. Superoxide desmutase: it catalyses the transformation of superoxide ion in hydrogenate peroxide. Its limit is a brief half-life.
Albumin: it binds to the ferrous ion preventing the decomposition of hydrogenated peroxide in hydroxylic radical. It binds to the circulating free radicals and prevents their action at tissue level.
Mannitol: it has a well documented activity as a scavenger of the free radicals. Reacting with the hydroxylic radical, it originates a "mannitol-radical", much less reactive compared to the native radical.
Vitamine C: the electrons released by the oxidation of an ascorbic acid molecule are able to reduce two free radicals molecules.
Cortisone in pharmaceutic doses: their strong protective effect against the lipoperoxidation motivates the precocious usage of methylprednisolone, after the aggressive event. The 21-aminosteroids (lazaroides) closely related to the corticosteroids but without endocrino-metabolic effects, will probably bring further advantages in reducing the pathologic effects of the free radicals in the ischaemia- reperfusion conditions.
 

1) Consensus Conference - Treatment of Stroke. BMJ 1988, 297, 126-128.
2) Wechsler L.R., Ropper A.H.: Management of Stroke in Intensive Care Unit - Semin. Neurol. 1986; 324 - 331.
3) Nemoto E.M. Pathogenis of cerebral Ischaemia-Anoxia - Crit. Care Med.; 6, 203, 1978.
4) Wei E.P., Christman C.W., Kontos H.A.: Effects of oxygen radicals on cerebral arterioles. Am. J. Physiol.,H, 157, 1985.
5) Opie L.H.: Proposed Role of Calcium in Riperfusion . Am. J. Physiol., C . 1196, 1985.
6) Kirby RR, Taylor R.W., Civetta J: Handbook of Critical Care - J.B. Lippincott Company, Philadelphia 1994.