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BRAIN ISCHAEMIA—ITS PREVENTION AND TREATMENT
" / would have everie man write what he knowes and no more."—
BRITISH
JOURNAL
OF
MONTAIGNE
ANAESTHESIA
VOLUME 57, No. 1
JANUARY 1985 EDITORIAL BRAIN ISCHAEMIA—ITS PREVENTION AND TREATMENT Downloaded from http://bja.oxfordjournals.org/ at Pennsylvania State University on June 26, 2015
Anaesthetists are involved regularly in the manage- tissue fluid pressure will result in further ischaemia ment of patients who have suffered brain ischaemia, and he therefore advocates the careful maintenance for example following circulatory arrest, head injury of normotension. However, in some patients with or hypoxia secondary to pulmonary dysfunction. developing focal ischaemia, for example a progresFurthermore, the anaesthetic use of induced sing monoparesis following aneurysm clipping, hypotension, deliberate circulatory arrest in cardiac deliberate hypertension is known to produce clinical surgery and local cerebral circulatory arrest in improvement. The situation is complex, but all are neurosurgery require an understanding of the toler- agreed that hypotension is bad and most accept that able limits of such brain "insults". There has been normotension is usually wise, but that in individual considerable progress in elucidating the cases the clinical response to induced hypertension pathophysiology of brain ischaemia and some should be assessed in focal ischaemia. Symon advances in therapy. Undoubtedly, however, the emphasized in the Workshop that, before inducing best treatment is still prevention and, to that extent, hypertension he would exclude actual infarction the anaesthetist needs to keep abreast of develop- indicated as brain shift on the CT scan, which is an absolute contraindication to increasing the arterial ments in the monitoring of brain function. The British Journal of Anaesthesia promoted a pressure. Graham stressed that, after total circulatWorkshop attended by the authors of the papers in ory arrest, brain swelling is only moderate and does this issue, together with additional invited experts at not induce shift or impaction. Furthermore, major which each review paper was discussed with particu- increases in ICP are uncommon after circulatory lar emphasis on the anaesthetic relevance of the arrest, although it must be admitted that the amount points raised. In this Editorial, major points made in of ICP data in this circumstance is small. Brain swelthat discussion and not covered within the papers ling and oedema with increased ICP are commonly seen in focal or regional brain ischaemia, for examare included. ple strokes and head injury. Graham opens this issue with an account of the Symon, and Heuser and Guggenheimer describe pathophysiology of brain ischaemia in which he describes the development of the histological the flow thresholds in brain ischaemia for electrical changes over hours and days, a time-scale which failure (EEG and evoked potentials) for ionic shifts encourages hopes of therapeutic intervention in the resulting from membrane dysfunction and for water process. One component of the post-insult condition accumulation within the brain. Of particular which the anaesthetist attempts to treat is brain interest to anaesthetists is the possibility of lowering swelling, part of which results from cerebral these thresholds with drugs, for example reducing oedema. Klatzo classifies the types of brain oedema the blood flow at which electrical or ionic failure, or and explains the mechanisms of each, and the reader both, occurs and the effects of barbiturates, prostawill gain an understanding of the temporal sequence glandin inhibitors and calcium entry blockers of events in post-ischaemic brain swelling on which amongst others, are considered in these papers. In to build a logical strategy of treatment. Klatzo the discussion at the Workshop it was clear that emphasizes that hypertension at times when the there is a re-awakening of interest in the role of blood-brain barrier is open will worsen vasogenic "mild" hypothermia with central temperatures of oedema, while hypotension in the presence of high 33-36 °C on the ischaemic process, since there are
BRITISH JOURNAL OF ANAESTHESIA than for electrical depression. However, in her paper Prior concludes "(decrease in EEG power) is a warning . . . and the patient is at risk of ischaemia and time is limited". The recent increase in clinical interest in evoked potential monitoring is put in the overall context of electrical monitoring in Prior's paper and the value of these techniques in the deeply sedated patient emphasized. In the Workshop discussion, the importance of maintaining a steady level of anaesthesia during intraoperative EEG or CFM monitoring was stressed. Now that so much is known regarding brain ischaemia, can we effectively intervene therapeutically? Shapiro reviews the barbiturate situation and Gisvold and Steen survey other possible therapies. The Workshop discussed the general circulatory problems of high dose barbiturates and of calcium entry blockers, and the point was made that the maintenance of satisfactory systemic arterial pressure is probably at least as valuable as most forms of drug therapy. In a discussion of the choice of individual drugs, Shapiro recommended pentobarbitone for its pharmacokinetic profile and its lower fat solubility than thiopentone. Finally two clinical areas in which brain ischaemia may be encountered—head injury and induced hypotension—were reviewed by Miller and McDowall, respectively. N. Branston, PH.D. (Gough-Cooper Department of Neurological Surgery, Institute of Neurology, The National Hospital, London WC1E 3BG) pointed out that subcortical changes may also be important in induced hypotension, for example in regional cortical ischaemia there is a loss of autoregulation in the thalamus. Siesjo agreed, and pointed to differences in responses to carbon dioxide and hypoglycaemia in the cerebellum and in the deep nuclei. In the discussion of head injury, the influence of barbiturate therapy on the incidence of pulmonary infection and ARDS was raised, and Shapiro stated that his survey of the literature revealed no statistically significant increase in pulmonary infection in any one series, but that in most reports there was a non-statistically significant excess of pulmonary infections in barbiturate-treated patients. D. G. McDowall
Downloaded from http://bja.oxfordjournals.org/ at Pennsylvania State University on June 26, 2015
suggestions in the literature of a protective effect of such small and easily-achieved reductions in body temperature. Clinically, what matters is neuronal cell death, and the ionic changes are but steps on the road to that event. The nearest ionic change in terms of flow threshold is the movement of calcium ions into the cell and the resultant increase in free calcium may have a causal connection with histological change. The method of Meldrum and colleagues for visualizing abnormal intracellular accumulation of calcium does not relate to the calcium entry at ischaemic thresholds, but probably reflects later calcium entry into the cells in the recovery phase, particularly if seizure activity occurs in the neurones. Meldrum and colleagues conclude that post-ischaemic seizure activity must be suppressed and this is supported by clinical experience. It is particularly important to monitor post-seizure activity in patients being managed by controlled ventilation under muscle paralysis. Siesjo and Wieloch next tackle the fundamental topic of metabolic changes which underlie the features of brain ischaemia, including the oedema and the structural damage. They emphasize the deleterious effect of high blood glucose concentrations during partial brain ischaemia and in the recovery period since this leads to increased formation of brain lactacidosis. The resultant severe intracellular acidosis is thought to be a factor in ischaemic cell death. The accepted preoperative starvation regimen used clinically may therefore have more advantages than realized, and one might also infer that infusions of glucose should not be given before induced hypotension and that anaesthetics which increase blood glucose should be avoided. There has been much progress in correlating changes in electrical function with varying degrees of flow deprivation, and Prior emphasizes the value of monitoring brain electrical function in high risk situations, especially since electrical failure precedes, and therefore forewarns of, structural damage. Indeed, in the Workshop it was argued that decreases in EEG power during induced hypotension can be accepted in the knowledge that the flow threshold for structural change is considerably lower
BRITISH
JOURNAL
OF
MONTAIGNE
ANAESTHESIA
VOLUME 57, No. 1
JANUARY 1985 EDITORIAL BRAIN ISCHAEMIA—ITS PREVENTION AND TREATMENT Downloaded from http://bja.oxfordjournals.org/ at Pennsylvania State University on June 26, 2015
Anaesthetists are involved regularly in the manage- tissue fluid pressure will result in further ischaemia ment of patients who have suffered brain ischaemia, and he therefore advocates the careful maintenance for example following circulatory arrest, head injury of normotension. However, in some patients with or hypoxia secondary to pulmonary dysfunction. developing focal ischaemia, for example a progresFurthermore, the anaesthetic use of induced sing monoparesis following aneurysm clipping, hypotension, deliberate circulatory arrest in cardiac deliberate hypertension is known to produce clinical surgery and local cerebral circulatory arrest in improvement. The situation is complex, but all are neurosurgery require an understanding of the toler- agreed that hypotension is bad and most accept that able limits of such brain "insults". There has been normotension is usually wise, but that in individual considerable progress in elucidating the cases the clinical response to induced hypertension pathophysiology of brain ischaemia and some should be assessed in focal ischaemia. Symon advances in therapy. Undoubtedly, however, the emphasized in the Workshop that, before inducing best treatment is still prevention and, to that extent, hypertension he would exclude actual infarction the anaesthetist needs to keep abreast of develop- indicated as brain shift on the CT scan, which is an absolute contraindication to increasing the arterial ments in the monitoring of brain function. The British Journal of Anaesthesia promoted a pressure. Graham stressed that, after total circulatWorkshop attended by the authors of the papers in ory arrest, brain swelling is only moderate and does this issue, together with additional invited experts at not induce shift or impaction. Furthermore, major which each review paper was discussed with particu- increases in ICP are uncommon after circulatory lar emphasis on the anaesthetic relevance of the arrest, although it must be admitted that the amount points raised. In this Editorial, major points made in of ICP data in this circumstance is small. Brain swelthat discussion and not covered within the papers ling and oedema with increased ICP are commonly seen in focal or regional brain ischaemia, for examare included. ple strokes and head injury. Graham opens this issue with an account of the Symon, and Heuser and Guggenheimer describe pathophysiology of brain ischaemia in which he describes the development of the histological the flow thresholds in brain ischaemia for electrical changes over hours and days, a time-scale which failure (EEG and evoked potentials) for ionic shifts encourages hopes of therapeutic intervention in the resulting from membrane dysfunction and for water process. One component of the post-insult condition accumulation within the brain. Of particular which the anaesthetist attempts to treat is brain interest to anaesthetists is the possibility of lowering swelling, part of which results from cerebral these thresholds with drugs, for example reducing oedema. Klatzo classifies the types of brain oedema the blood flow at which electrical or ionic failure, or and explains the mechanisms of each, and the reader both, occurs and the effects of barbiturates, prostawill gain an understanding of the temporal sequence glandin inhibitors and calcium entry blockers of events in post-ischaemic brain swelling on which amongst others, are considered in these papers. In to build a logical strategy of treatment. Klatzo the discussion at the Workshop it was clear that emphasizes that hypertension at times when the there is a re-awakening of interest in the role of blood-brain barrier is open will worsen vasogenic "mild" hypothermia with central temperatures of oedema, while hypotension in the presence of high 33-36 °C on the ischaemic process, since there are
BRITISH JOURNAL OF ANAESTHESIA than for electrical depression. However, in her paper Prior concludes "(decrease in EEG power) is a warning . . . and the patient is at risk of ischaemia and time is limited". The recent increase in clinical interest in evoked potential monitoring is put in the overall context of electrical monitoring in Prior's paper and the value of these techniques in the deeply sedated patient emphasized. In the Workshop discussion, the importance of maintaining a steady level of anaesthesia during intraoperative EEG or CFM monitoring was stressed. Now that so much is known regarding brain ischaemia, can we effectively intervene therapeutically? Shapiro reviews the barbiturate situation and Gisvold and Steen survey other possible therapies. The Workshop discussed the general circulatory problems of high dose barbiturates and of calcium entry blockers, and the point was made that the maintenance of satisfactory systemic arterial pressure is probably at least as valuable as most forms of drug therapy. In a discussion of the choice of individual drugs, Shapiro recommended pentobarbitone for its pharmacokinetic profile and its lower fat solubility than thiopentone. Finally two clinical areas in which brain ischaemia may be encountered—head injury and induced hypotension—were reviewed by Miller and McDowall, respectively. N. Branston, PH.D. (Gough-Cooper Department of Neurological Surgery, Institute of Neurology, The National Hospital, London WC1E 3BG) pointed out that subcortical changes may also be important in induced hypotension, for example in regional cortical ischaemia there is a loss of autoregulation in the thalamus. Siesjo agreed, and pointed to differences in responses to carbon dioxide and hypoglycaemia in the cerebellum and in the deep nuclei. In the discussion of head injury, the influence of barbiturate therapy on the incidence of pulmonary infection and ARDS was raised, and Shapiro stated that his survey of the literature revealed no statistically significant increase in pulmonary infection in any one series, but that in most reports there was a non-statistically significant excess of pulmonary infections in barbiturate-treated patients. D. G. McDowall
Downloaded from http://bja.oxfordjournals.org/ at Pennsylvania State University on June 26, 2015
suggestions in the literature of a protective effect of such small and easily-achieved reductions in body temperature. Clinically, what matters is neuronal cell death, and the ionic changes are but steps on the road to that event. The nearest ionic change in terms of flow threshold is the movement of calcium ions into the cell and the resultant increase in free calcium may have a causal connection with histological change. The method of Meldrum and colleagues for visualizing abnormal intracellular accumulation of calcium does not relate to the calcium entry at ischaemic thresholds, but probably reflects later calcium entry into the cells in the recovery phase, particularly if seizure activity occurs in the neurones. Meldrum and colleagues conclude that post-ischaemic seizure activity must be suppressed and this is supported by clinical experience. It is particularly important to monitor post-seizure activity in patients being managed by controlled ventilation under muscle paralysis. Siesjo and Wieloch next tackle the fundamental topic of metabolic changes which underlie the features of brain ischaemia, including the oedema and the structural damage. They emphasize the deleterious effect of high blood glucose concentrations during partial brain ischaemia and in the recovery period since this leads to increased formation of brain lactacidosis. The resultant severe intracellular acidosis is thought to be a factor in ischaemic cell death. The accepted preoperative starvation regimen used clinically may therefore have more advantages than realized, and one might also infer that infusions of glucose should not be given before induced hypotension and that anaesthetics which increase blood glucose should be avoided. There has been much progress in correlating changes in electrical function with varying degrees of flow deprivation, and Prior emphasizes the value of monitoring brain electrical function in high risk situations, especially since electrical failure precedes, and therefore forewarns of, structural damage. Indeed, in the Workshop it was argued that decreases in EEG power during induced hypotension can be accepted in the knowledge that the flow threshold for structural change is considerably lower