A. David Mendelow, Benjamin H. Eidelman and Thomas A. McCalden
✓ The effect of intracarotid infusion of dexamethasone on cerebral blood flow and cerebral oxygen utilization was measured in baboons using the xenon-133 clearance technique. The cerebrovascular response to intracarotid infusion of 5-hydroxytryptamine (5-HT) was then determined during simultaneous infusion of the steroid. Infusion of dexamethasone alone and infusion with 5-HT produced no significant change in cerebral blood flow or cerebral oxygen utilization when compared to baseline values. The study indicates that neither dexamethasone nor 5-HT with dexamethasone modify cerebral blood flow when infused via the internal carotid artery.
Iain Robert Chambers, Lynne Treadwell and A. David Mendelow
Object. Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) are frequently monitored in severely head injured patients. To establish which one (ICP or CPP) is more predictive of outcome and to examine whether there are significant threshold levels in the determination of outcome, receiver—operating characteristic (ROC) curves were used to analyze data in a large series of head-injured patients.
Methods. Data were obtained from a total of 291 severely head injured patients (207 adults and 84 children). Outcome was categorized as either independent (good recovery or moderate disability) or poor (severely disabled, vegetative, or dead) by using the Glasgow Outcome Scale; patients were also grouped according to the Marshall computerized tomography scan classification.
Conclusions. The maximum value of a 2-minute rolling average of ICP readings (defined as ICPmax) and the minimum value of the CPP readings (CPPmin) were then used to calculate the sensitivity and specificity of the ROC curves over a range of values. Using ROC curves, a threshold value for CPPmin of 55 mm Hg and for ICPmax of 35 mm Hg appear to be the best predictors in adults. For children the levels appear to be 43 to 45 mm Hg for CPPmin and 35 mm Hg for ICPmax. Higher levels of CPPmin seem important in adults with mass lesions. These CPP thresholds (45 mm Hg for children and 55 mm Hg for adults) are lower than previously predicted and may be clinically important, especially in children, in whom a lower blood pressure level is normal. Also, CPP management at higher levels may be more important in adults with mass lesions. A larger observational series would improve the accuracy of these predictions.
Patrick Mitchell, Richard Kerr, A. David Mendelow and Andy Molyneux
The present purpose is to define the sensitivity of the superiority of coil embolization observed in the International Subarachnoid Aneurysm Trial (ISAT) according to the rate of late rebleeding over a reasonable range, and to find the range of rebleeding rates for which it may be overturned. In the ISAT, coil embolization appears to be safer than clip ligation at 1 year, and clip occlusion has better long-term efficacy at preventing rebleeding. This leaves open the question of which is better in the longer term.
The authors calculate the life expectancy of patients following a subarachnoid hemorrhage (SAH) and compare the life expectancy of those who underwent coil embolization with those who underwent clip ligation in the ISAT cohort.
The 1-year poor outcome rate following treatment climbs rapidly with advancing age. A consequence is that the absolute difference between the poor outcome rates after coil embolization and clip occlusion is lower in those < 50 years of age (3.3%) than it is for those > 50 years of age (10.1%). This difference may be enough to give clip application the advantage in the < 40-year-old group despite the small size of the difference in 1-year rebleeding rates thus far observed (0.152%).
When treating ruptured cerebral aneurysms, the advantage of coil embolization over clip ligation cannot be assumed for patients < 40 years old. In this age range the difference in the safety of the 2 procedures is small, and the better long-term protection from SAH afforded by clip placement may give this treatment an advantage in life expectancy for patients < 40 years of age.
Thomas A. Kingman, A. David Mendelow, David I. Graham and Graham M. Teasdale
✓ Cerebral blood flow (CBF) was measured at different times during the first 150 minutes following an experimental space-occupying lesion produced with a 50-µl microballoon in rats. Local CBF was measured with the carbon-14-labeled iodoantipyrine quantitative autoradiographic technique. A region of local ischemia developed around the mass, while the remote effects of the mass were minimal. The focal ischemic lesion enlarged with time, and simulated removal of the lesion within this design did not alleviate the ischemia.
A. David Mendelow, David I. Graham, Ursula I. Tuor and William Fitch
✓ The purpose of this study was to determine in subhuman primates whether hemodynamic mechanisms (as compared with embolic mechanisms) contribute to cerebral ischemia following carotid artery occlusion or stenosis. Following carotid artery occlusion there was loss of cerebral autoregulation: cerebral blood flow (CBF) measured with the xenon-133 technique became passively dependent upon the mean arterial blood pressure (MABP) over an MABP range of 30 to 110 mm Hg. By contrast, autoregulation was preserved in normal animals and in animals with a 90% carotid artery stenosis. Regional CBF was measured with carbon-14-labeled iodoantipyrine autoradiography in normotensive baboons, in hypotensive animals, and in hypotensive animals with carotid artery occlusion or stenosis. With carotid artery occlusion and hypotension, reduced levels of local CBF were seen ipsilaterally in the boundary zones between the anterior and middle cerebral arteries with 35% of the area of an anterior section through the hemisphere displaying a CBF value of less than 20 ml/100 gm/min. Comparable values with hypotension were 21% with carotid artery stenosis, 20% with no proximal vascular lesion, and 1% in normotensive animals. These areas of reduced CBF corresponded with areas of boundary-zone ischemia seen with light microscopy. The study suggests that while hemodynamic ischemia develops with carotid artery occlusion, it does not occur with even a 90% carotid artery stenosis or in normal animals.
E. J. Sinar, A. David Mendelow, David I. Graham and Graham M. Teasdale
✓ Late pathophysiological events after the production and subsequent removal of an intracerebral mass were investigated using a mechanical microballoon model to simulate intracerebral hemorrhage. Immediately following balloon inflation in the caudate nucleus of rats, there was a significant increase in intracranial pressure to 14 ± 1 mm Hg (mean ± standard error of the mean), accompanied by a reduction in cerebral blood flow (CBF) in the ipsilateral frontal cortex, as measured by the hydrogen-clearance technique. Carbon-14-iodoantipyrine autoradiography revealed a significant reduction in the CBF of the ipsilateral caudate nucleus 4 hours after balloon inflation: 31% of the caudate nucleus had a CBF of less than 20 ml ⋅ 100 gm−1 ⋅ min−1 compared to only 1% in the sham-treated control group (balloon insertion without inflation). The rats with an intracerebral mass exhibited a significant increase in the volume of ischemic damage in the ipsilateral caudate nucleus (17.1% of total volume) compared to only 1.7% in the sham-treated group; however, there was no evidence of cerebral edema. Ischemic damage and reduced CBF persisted for 4 hours after transient inflation of a microballoon in the caudate nucleus. This suggests that ischemic damage occurs at the time of formation of the lesion and is not prevented by its early removal.
Fredrik P. Nath, Alistair Jenkins, A. David Mendelow, David I. Graham and Graham M. Teasdale
✓ A model of experimental intracerebral hemorrhage is described in which carefully controlled volumes of autologous blood were injected at arterial pressure into the caudate nucleus of the rat. A comparison of intracranial pressure changes and local cerebral blood flow (CBF) was made between three groups of rats, each receiving different injection volumes, and sham-operated control rats by monitoring intraventricular pressure and by obtaining quantitative autoradiographic measurements of CBF within 1 minute of the experimental hemorrhage. Cerebral blood flow was reduced both around the hematoma and in the surrounding brain. This change was strongly volume-dependent and was not accompanied by significant alterations in cerebral perfusion pressure. This finding suggests that the degree of ischemia at the time of an intracerebral bleed depends on the size of the lesion, and implicates local squeezing of the microcirculation by the hematoma, rather than a generalized alteration in perfusion pressure, as the cause of ischemia.
Philip Barlow, A. David Mendelow, Audrey E. Lawrence, Marion Barlow and John O. Rowan
✓ Recordings from two different types of subdural pressure monitor with simultaneous intraventricular pressure (IVP) tracings are compared in 20 head-injured patients. In the first 10 patients a fluid-filled catheter was placed subdurally and connected to an external transducer, and in the second 10 the Gaeltec model ICT/b solid state miniature transducer was used. The latter system has the advantage that both zero and calibration checks can be carried out after insertion. Only 44% of the fluid-filled catheter readings corresponded with IVP in series of 10-mm Hg ranges, while 53% of readings were lower; this tendency was more marked at higher pressures. With the Gaeltec transducer, 72% of subdural pressure readings corresponded with IVP, while only 9% were lower and 19% were higher than IVP. The differences may have been due to technical causes or to true pressure differentials. The subdural catheter appears too unreliable for routine clinical use, but the Gaeltec transducer may be a satisfactory alternative to ventricular pressure monitoring.
A. David Mendelow, Graham M. Teasdale, Thomas Russell, John Flood, James Patterson and Gordon D. Murray
✓ Patients with severe head injury frequently have evidence of elevated intracranial pressure (ICP) and ischemic neuronal damage at autopsy. Mannitol has been used clinically to reduce ICP with varying success, and it is possible that it is more effective in some types of head injury than in others. The aim of the present study was to determine the effect of mannitol on ICP, cerebral perfusion pressure (CPP), and cerebral blood flow (CBF) in patients with severe head injury, and to discover if these effects differed in different types of injury. Measurements of CPP, ICP, and CBF were made in 55 patients with severe head injury. In general, the resting level of CBF was higher in patients with diffuse injury (mean 50.2 ml/100 gm/min) than in those with focal injury (mean 39.8 ml/100 gm/min). Mannitol consistently reduced ICP and increased CPP and CBF by 10 to 20 minutes after infusion. The lowest flows (31.8 ml/100 gm/min) were recorded from the most damaged hemispheres of patients with focal injuries and elevated ICP. The baseline levels of flow did not correlate with ICP, CPP, Glasgow Coma Scale score, or outcome. Only four of the 55 patients had a CBF of less than 20 ml/100 gm/min in either or both hemispheres. The few low CBF's in this and other studies may reflect the steady-state conditions under which measurements are made in intensive care units, and that these patients have entered a phase of reperfusion.