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Background: During cardiopulmonary bypass (CPB), global hypoperfusion of the brain has been shown to result in ischemic insult and subsequent neurologic injury., Methods: We measured cerebral blood flow during independent manipulations of arterial blood pressure and pump flow rate to determine which of these hemodynamic parameters regulates cerebral perfusion during CPB. Seven adolescent baboons were placed on CPB and cooled to 28 degrees C. Pump flow rate and arterial blood pressure were altered in varied sequence to each of four conditions: (1) full flow (2.23 +/- 0.06 L.min-1.m-2, mean +/- standard deviation) at high pressure (61 +/- 2 mm Hg), (2) full flow (2.23 +/- 0.06 L.min-1.m-2) at low pressure (24 +/- 3 mm Hg), (3) low flow (0.75 L.min-1.m-2) at high pressure (62 +/- 2 mm Hg), and (4) low flow (0.75 L.min-1.m-2) at low pressure (23 +/- 3 mm Hg). During each of these hemodynamic conditions cerebral blood flow was measured by washout of intracarotid xenon 133., Results: Cerebral blood flow was greater at high blood pressure than at low pressure during CPB both at low flow (34 +/- 8.3 versus 14.1 +/- 3.7 mL.min-1.100 g-1) and full flow (27.6 +/- 9.9 versus 16.8 +/- 3.7 mL.min-1.100 g-1) (p < 0.01). At comparable mean arterial blood pressure, alteration of pump flow rate produced no significant change in cerebral blood flow., Conclusions: These results indicate that during low-flow CPB, mean arterial pressure should be maintained within the brain's autoregulatory range to maximize cerebral blood flow.

Purpose: To evaluate the relationship among feeding arterial pressure, lesion size, and perfusion in cerebral cortex adjacent to cerebral arteriovenous malformations (AVMs)., Methods: Eleven patients with hemispheric AVMs underwent 99mTc hexamethyl-propyleneamine oxime single-photon emission CT before and after 1 g of acetazolamide was administered intravenously. AVM volume was estimated from MR dimensions and measured according to the method described by Pasqualin. Pressure measurements were obtained in arteries feeding the cortex adjacent to AVMs. Single-photon emission CT regions of interest were defined in cortex adjacent to the AVM and compared with contralateral regions using the Mountz method to estimate a baseline and dynamic (acetazolamide-challenged) perfusion defect volume., Results: Eight of 11 patients had baseline perfusion defects, but these defects were unrelated to feeding artery pressures (y = -.06x + 9.92, r2 = .04) or the dynamic change in defect volume after acetazolamide administration (y = .01x + .02, r2 = .002). However, there was a correlation between AVM volume and the baseline defect volume (y = .75x - 1.9, r2 = .76). Five patients had increased defect volume after acetazolamide administration; 5 patients had either no change in or improvement of perfusion. Dynamic changes in defect volume were related to feeding artery pressures., Conclusion: Perilesional baseline perfusion defects appear to be related to lesion size and not to local arterial pressure. Cerebrovascular reserve generally was preserved, and perfusion defects appeared to be more pronounced with lower arterial pressures in feeding vessels. Although vasodilatory testing can unmask hemodynamic failure with severe local hypotension, baseline perfusion defects near the lesion and distant perfusion changes are more likely attributable to other causes such as mass-related or neurogenic changes.

Transcranial Doppler sonography of the middle cerebral artery was used to determine whether cerebral perfusion was detectable in low flow states during operations with cardiopulmonary bypass in pediatric patients. Quantitative and qualitative differences in cerebral blood flow velocity after rewarming in patients treated with continuous low-flow bypass or deep hypothermic circulatory arrest were assessed. To determine whether the alterations in cerebrovascular resistance pattern observed in our patients undergoing profound hypothermia was more a function of perfusion technique than of minimum temperature during operation, a third group of patients treated with moderate hypothermia was studied. The three patient groups were the arrest group (N = 16), comprised of patients undergoing circulatory arrest at 18 degrees to 20 degrees C; the low-flow group (N = 16), patients treated with continuous low-flow (cardiac index 0.5 L/min per square meter) bypass at 18 degrees to 20 degrees C; and the moderate group (N = 5), patients treated with moderate hypothermia at 24 degrees to 28 degrees C. Flow velocity was detectable in all patients in the low-flow group, with mean arterial pressures as low as 15 mm Hg. Mean flow velocity was reduced after bypass as compared with prebypass values in both the arrest and low-flow groups (p = 0.0001). Mean flow velocity increased after bypass in the moderate group (p = 0.0001). A Doppler waveform pattern consistent with high cerebrovascular resistance was found in 67% of patients in the arrest group and 44% of those in the low-flow group. None of the patients in the moderate group exhibited such a pattern. Patients treated with profound hypothermia who underwent a period of cold full-flow reperfusion before rewarming did not exhibit this high resistance pattern after rewarming. The present findings indicate that profound hypothermia may evoke changes in the cerebral vasculature that result in decreased mean cerebral blood flow velocity after cardiopulmonary bypass rewarming. A period of cold full-flow reperfusion before rewarming may prevent these alterations and improve cerebral perfusion during rewarming.

Purpose: To determine the influence of preoperative N-butyl cyanoacrylate embolization on outcome in the treatment of cerebral arteriovenous malformations., Methods: Two groups were compared: 30 patients who underwent surgery and embolization versus 41 patients who underwent surgery only. Both groups were categorized by Spetzler-Martin grade and evaluated with the Glasgow Outcome Scale at various intervals. The long-term follow-up in months was, for surgery only, mean of 35 and range of 4 to 59, and for surgery and embolization, mean of 10 and range of 1 to 19)., Results: The arteriovenous malformations in the surgery and embolization group had a larger average greatest diameter (4.2 +/- 1.5 cm versus 3.4 +/- 1.8 cm) and were of higher Spetzler-Martin grade (89% versus 68% grade III-V). No significant difference in the preoperative or immediate postoperative (less than 24 hours) Glasgow Outcome Scale was identified between the two groups. At I week after surgery, the surgery and embolization group displayed a significantly better outcome evaluation (70% versus 41% with Glasgow Outcome Scale score of 5). The long-term evaluation continued to favor the surgery and embolization patients (86% versus 66% with Glasgow Outcome Scale score of 5)., Conclusion: Preoperative N-butyl cyanoacrylate embolization improves postsurgical outcome.

The purpose of this study was to compare the time course of the bradycardic and hypotensive effects of esmolol. Ten patients undergoing craniotomy requiring hypotension were anesthetized with nitrous oxide and isoflurane. During steady state anesthesia, the response to an infusion of esmolol 500 micrograms.kg-1.min-1 for 90 s followed by 300 micrograms.kg-1.min-1 was measured over 60 min. Heart rate (HR), mean arterial pressure (MAP), and plasma renin activity (PRA) responses did not occur with equal rapidity. The half-time for the 14% decrease in HR (81 +/- 13 bpm to 70 +/- 9 bpm) was 1.2 min. MAP decreased by 26% (85 +/- 7 mm Hg to 63 +/- 6 mm Hg) with a 17.8 min half-time. This delay in MAP response may, in part, be related to the gradual 44% decline in PRA (9.5 +/- 4.5 ng.mL-1.h-1 to 5.3 +/- 2.5 ng.mL-1.h-1) occurring with a half-time of 11.9 min. The times to attainment of 90% maximum decreases were 4.8 +/- 3.0 min for HR, 42.5 +/- 8.9 min for MAP, and 32.1 +/- 15.0 min for PRA. Thus although esmolol has an ultrashort kinetic half-life, only the HR effect can be considered to have an ultrashort onset.

Background: During cardiopulmonary bypass, global hypoperfusion of the brain has been shown to result in ischemic insult and subsequent neurologic injury. Furthermore, outcome after focal cerebral ischemia depends on collateral circulation, which is determined by the parameters of global perfusion. We therefore measured cerebral blood flow during independent manipulations of arterial blood pressure and pump flow rate to determine which of these hemodynamic parameters regulates cerebral perfusion during cardiopulmonary bypass., Methods: Seven anesthesized baboons were placed on cardiopulmonary bypass and cooled to 28 degrees C. Pump flow rate and arterial blood pressure were altered in varied sequence to each of four conditions: (1) full flow (2.23 +/- 0.06 L.min-1.m-2, mean +/- standard deviation) at high pressure (61 +/- 2 mm Hg), (2) full flow (2.23 +/- 0.06 L.min-1.m-2) at low pressure (24 +/- 3 mm Hg), (3) low flow (0.75 L.min-1.m-2) at high pressure (62 +/- 2 mm Hg), and (4) low flow (0.75 L.min-1.m-2 at low pressure (23 +/- 3 mm Hg). During each of these hemodynamic conditions cerebral blood flow was measured by washout of intracarotid xenon., Results: Cerebral blood flow was greater at high blood pressure than at low pressure during cardiopulmonary bypass both at low flow (34 +/- 8.3 versus 14.1 +/- 3.7 mL.min-1 x 100 g-1) and full flow (27.6 +/- 9.9 versus 16.8 +/- 3.7 mL.min-1 x 100 g-1) (p < 0.01). At comparable mean arterial blood pressures alteration of pump flow rate produced no changes in cerebral blood flow., Conclusions: These results indicate that cerebral blood flow during moderately hypothermic cardiopulmonary bypass is regulated by arterial blood pressure and not pump flow rate.

Background: Brain temperature is closely approximated by most body temperature measurements under normal anesthetic conditions. However, when thermal autoregulation is overridden, large temperature gradients may prevail. This study sought to determine which of the standard temperature monitoring sites best approximates brain temperature when deep hypothermia is rapidly induced and reversed during cardiopulmonary bypass., Methods: Twenty-seven patients underwent cardiopulmonary bypass and deep hypothermic circulatory arrest in order for each to have a giant cerebral aneurysm surgically clipped. Brain temperatures were measured directly with a thermocouple embedded in the cerebral cortex. Eight other body temperatures were monitored simultaneously with less invasive sensors at standard sites., Results: Brain temperature decreased from 32.6 +/- 1.4 degrees C (mean +/- SD) to 16.7 +/- 1.7 degrees C in 28 +/- 7 min, for an average cerebral cooling rate of 0.59 +/- 0.15 degrees C/min. Circulatory arrest lasted 24 +/- 15 min and was followed by 63 +/- 17 min of rewarming at 0.31 +/- 0.09 degrees C/min. None of the monitored sites tracked cerebral temperature well throughout the entire hypothermic period. During rapid temperature change, nasopharyngeal, esophageal, and pulmonary artery temperatures corresponded to brain temperature with smaller mean differences than did those of the tympanic membrane, bladder, rectum, axilla, and sole of the foot. At circulatory arrest, nasopharyngeal, esophageal, and pulmonary artery mean temperatures were within 1 degree C of brain temperature, even though individual patients frequently exhibited disparate values at those sites., Conclusions: When profound hypothermia is rapidly induced and reversed, temperature measurements made at standard monitoring sites may not reflect cerebral temperature. Measurements from the nasopharynx, esophagus, and pulmonary artery tend to match brain temperature best but only with an array of data can one feel comfortable disregarding discordant readings.

Deliberate hypocapnia during the anaesthetic management of the patient undergoing craniotomy has become an accepted standard of care. However there has been a resurgence of interest, in how hypocapnia should be applied in intra- and extra-operative settings. There are three possible therapeutic effects of hypocapnia, namely, (a) reduction of brain bulk through a reduction in cerebral blood volume, with a decrease cerebral blood flow; (b) developing an "inverse steal" by redistribution of blood from normal to ischaemic regions and (c) acting to offset cerebral acidosis by increasing pH in the extracellular space. In anaesthetic intraoperative practice, hypocapnia is used as a specific treatment of, or prophylaxis against, intracranial hypertension during induction of anaesthesia and the period before dural exposure. More commonly, hypocapnia is used for intraoperative brain relaxation (intracranial pressure = 0). Severe hypocapnia (< 20 mmHg) may result in cerebral production of lactate; however no studies have shown that a Paco2 in the range of 23-28 mmHg has deleterious effects. Recent studies in head-injured patients suggest that routine long-term hyperventilation, without an objective index of cerebral flow/metabolism coupling, may place the brain at risk for adverse outcome. The few data available for intraoperative management suggest that Paco2 figures of 30-35 mmHg result in acceptable operating conditions. Unless otherwise specifically indicated by surgical conditions or cerebral flow/metabolism coupling (e.g. jugular O2 saturation), routine application of profound (Paco2 < 28-30 mmHg) hyperventilation should probably be avoided and its use needs reevaluation.

To study the effect of AVM occlusion on cerebrovascular haemodynamics, a simplified model was simulated consisting of a feeding artery supplying a capillary bed in parallel with a fistula-like malformation, both emptying into a draining vein. An electrical circuit analogue of the physiologic system was developed using lumped proximal and distal pressure dependent resistances, and capacitors representing vascular compliance. Autoregulation was introduced as a pressure varying precapillary arteriolar resistance. Equations derived from the circuit model were simulated using a graphical modeling program. The model successfully simulates phenomena angiographically observed during embolization procedures. Fistula pressure is shown to rapidly fall following proximal AVM occlusion, in contrast to a marked rise seen with distal occlusion, which is associated with biphasic flow into and out of the fistula and the arterial feeder. The model predicts an increase in capillary pressure and capillary flow which, depending on the magnitude of the flow increase and the state of autoregulation, may result either in reversal of ischaemia or hyperperfusion injury. Vascular overload is predicted in the absence of autoregulation. There is, however, little potential for vascular overload when autoregulation is intact. The model represents a first step in the mathematical characterization of the phenomenon of hyperperfusion following AVM occlusion.

Background: Neurologic injury after cardiopulmonary bypass (CPB) is a frequent and devastating complication of cardiothoracic surgery. Disordered cerebral hemodynamics during CPB has been implicated as an important factor in the etiology of these injuries. Evidence of disordered cerebral hemodynamics includes reports of a progressive time-dependent decrease in cerebral blood flow (CBF) during stable full-flow CPB. Low-flow hypothermic CPB has become a preferred technique for the management of pediatric patients undergoing surgical repair of complex cardiac lesions. Because CBF is already substantially reduced with the onset of low-flow CPB, we determined if a similar progressive decline in CBF occurs during the low-flow state., Methods: After induction of general anesthesia in seven baboons, CPB was instituted. alpha-Stat management of arterial blood gases was used. Animals were cooled at a pump flow rate of 2.5 l.min-1.m-2 until tympanic membrane temperature decreased to 18 degrees C. CPB flow was then reduced to 0.5 l.min-1.m-2 and maintained constant for at least 77 min. Thereafter, CPB flow was increased to 2.5 l.min-1.m-2 and baboons rewarmed to normal temperature. CPB was discontinued after return of cardiac function. CBF was measured before, during and after CPB by washout of intraarterial xenon 133., Results: Low-flow CPB resulted in a decrease in CBF to about 50% of the prebypass rate and about 30% of the value measured during full-flow CPB. Sequential measurements of CBF at 30-min intervals during low-flow CPB showed no time-dependent change in cerebral perfusion., Conclusions: Although systemic flow is reduced to 20% of full-flow during low-flow CPB, CBF reduced by half is disproportionately preserved relative to systemic flow. Furthermore, there is no time-dependent change in CBF under these low-flow conditions.

Arteriovenous malformation (AVM) draining vein pressure (DVP) may have an influence on both the natural history of the disease and treatment outcome. The purposes of this study were to assess the relationship between DVP and other clinical and physiological variables and to characterize the transmission of arterial pressure across the AVM nidus. DVP measurements were carried out during elective AVM resection with isoflurane/nitrous oxide anesthesia with arterial carbon dioxide pressure of approximately 30 mm Hg. The gradient between the right atrium and operative measurement site was noted. Pre-excision feeding mean arterial pressure and DVP were measured with a 26-gauge needle simultaneously with systemic mean arterial pressure and central venous pressure (CVP). DVP was tested with systemic mean arterial pressure increased to approximately 20 mm Hg with phenylephrine or CVP increased with a Valsalva maneuver. Finally, preresection and postresection DVP values were compared. Relative to the site of measurement, DVP was 7 +/- 5 mm Hg at a CVP of -4 +/- 5 mm Hg (n = 45). There was no influence of presentation, presence of deep venous drainage, size, location, or prior embolization on DVP. In 19 patients, DVP decreased (8 +/- 4 to 5 +/- 3; P < 0.05) whereas CVP increased from pre- to postresection (-4 +/- 5 to -2 +/- 5; P < 0.05). For the phenylephrine challenge (n = 11), there was no difference (P = 0.84) between the delta DVP (2 +/- 1 mm Hg) and the delta CVP (2 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Despite enthusiasm for the use of mild hypothermia during neurosurgical procedures, this therapy has not been evaluated systematically. This study examined the feasibility and safety of deliberate mild hypothermia and rewarming., Methods: Thirty patients scheduled for craniotomy were assigned to either a normothermic or mildly hypothermic group. Tympanic membrane temperature was monitored at anesthetic induction, throughout the isoflurane-fentanyl-N2O-O2 anesthetic, and for 18 h postoperatively. Normothermic patients were warmed to 36.5-37.0 degrees C after an initial temperature decrease, and hypothermic patients were cooled to 35 degrees C. In the hypothermic group temperatures were allowed to drift to 34.5 degrees C before rewarming was initiated. Water blankets and convective heating devices were used to cool and rewarm., Results: The minimum temperature achieved by the hypothermic group was 34.3 +/- 0.4 degrees C. Cooling occurred at a rate of 1.0 +/- 0.4 degrees C/h. Rewarming took place at a rate of 0.7 +/- 0.6 degrees C/h (range 0.1-1.8) in the hypothermic group. Hypothermia did not delay emergence from anesthesia (20 +/- 15 min) compared with normothermia (15 +/- 15 min, P = .45). Mean temperature upon intensive care unit admission was 35.8 +/- 1.0 degrees C for the hypothermic group and 37.1 +/- 0.5 degrees C for the normothermic group (P < 0.0001). The hypothermic patients had more postoperative shivering. From 8 to 18 h postoperatively the temperatures of the two groups were similar except for a slightly greater temperature in the hypothermic patients at 12 h (37.6 +/- 0.5 vs. 37.3 +/- 0.4 degrees C, P = .029)., Conclusions: Although deliberate mild hypothermia is easily achieved intraoperatively, complete rewarming may be difficult to attain during craniotomy with current methods. In addition to the need for determining whether deliberate mild hypothermia confers cerebral protection in humans, the potential risks of the therapy need to be further characterized.

The physiological and anatomical aberrations that result in hemorrhage from cerebral arteriovenous malformations (AVMs) remain unclear. In an attempt to clarify which conditions may predispose to hemorrhage, we examined clinical and physiological indices on presentation groups of either hemorrhage or nonhemorrhage in a large cohort of patients (n = 449). Variables examined included AVM size, type of venous drainage, transcranial Doppler (TCD) velocities, feeding mean arterial pressure (FMAP), and draining vein pressure. TCD and pressure data were obtained before any treatment. Age (mean +/- standard deviation) at the time of presentation was 33 +/- 13 years and did not differ between groups. Patients with small (< or = 2.5 cm) AVMs presented more frequently with hemorrhage (90%) than did patients with medium (> 2.5 and < or = 5.0 cm; 52%) or large (> 5.0 cm; 50%) AVMs (P = 0.0001). The 48 of 94 AVMs (51%) with deep venous drainage were more likely to have hemorrhage (P = 0.0219) than were those with superficial drainage (24 of 73 [33%]). Deep drainage was a predictor of hemorrhage even in the subgroup of medium and large supratentorial AVMs (P = 0.005). There was no difference in draining vein pressure (n = 18) between groups (21 +/- 10 and 19 +/- 11 mm Hg, respectively; P = 0.7812). FMAP (n = 52) was higher in the hemorrhage than in the nonhemorrhage group (44 +/- 13 versus 34 +/- 10 mm Hg; P = 0.0007) but was only weakly related to the size of the lesion (largest dimension) (y = -0.74x + 40; r = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

We hypothesized that chronic hypotension in normal vascular territories fed by arteriovenous malformation pedicles may reset the lower limit of autoregulation and allow flow to remain constant over a lower pressure range. We studied the effect of increasing systemic mean arterial pressure (SMAP) with phenylephrine on cerebral blood flow using a novel technique. Fourteen patients undergoing 15 procedures were studied before endovascular embolization of arteriovenous malformations under neuroleptic conscious sedation. Mean pressures were transduced via a 1.5-F intracranial microcatheter, which was passed under fluoroscopic guidance into the target feeding artery. The microcatheter was positioned (unwedged) at a point that was relatively hypotensive to systemic pressure but that irrigated normal cortex on angiography; feeding mean arterial pressure (FMAP) and SMAP were recorded. A bolus of 133Xe in saline was injected into the microcatheter, and washout was recorded for 3 minutes by a scintillation detector placed over the vascular territory of the injected pedicle. SMAP was then increased approximately 25 mm Hg by phenylephrine infusion, a second bolus was given, and washout was recorded. After exclusion of the shunt spike, initial slope was calculated. The SMAP (mean +/- standard error) increased from 65 +/- 3 to 89 +/- 2 mm Hg (P < 0.0001), and FMAP increased from 46 +/- 3 to 63 +/- 3 mm Hg (P < 0.0001); cerebral blood flow did not change (40 +/- 2 to 40 +/- 2 ml/100 g per min, P = 0.9199). Dividing the cases on the basis of the baseline FMAP into a "severe" hypotensive group (FMAP = 38 +/- 2; n = 7) and a "moderate" hypotensive group (FMAP = 54 +/- 3; n = 8), cerebral blood flow did not change in either group during phenylephrine challenge. Chronic hypotension does not necessarily result in "vasomotor paralysis" with loss of the ability to vasoconstrict to acute increases in perfusion pressure. Instead, it appears to displace adaptively the lower limit of autoregulation in affected vascular territories by a shift of the autoregulatory curve to the left, conceptually analogous to the adaptive displacement seen with chronic hypertension and its treatment.

Purpose: To characterize cerebral hemodynamics in patients immediately before microsurgical resection of moderate to large arteriovenous malformations during isoflurane anesthesia., Methods: In angiographically defined arteriovenous malformation feeding and nonfeeding arteries, transcranial Doppler studies were performed in 25 surgeries on 22 patients. The mean blood flow velocity and pulsatility index were recorded in the middle, anterior, and posterior cerebral arteries. Transcranial Doppler velocities were measured at end-tidal carbon dioxide tensions (PetCO2) of about 25 and 35 mm Hg. Carbon dioxide reactivity was calculated as percentage mean blood flow velocity change per mm Hg PetCO2 change., Results: Patient demographic and clinical data for the arteriovenous malformation group followed the expected strata of a large arteriovenous malformation population. All patients were neurologically stable before surgery. A total of 43 feeding arteries and 55 nonfeeding arteries were studied. Compared with nonfeeders, feeders exhibited higher mean blood flow velocity (68 +/- 5 vs 31 +/- 3 cm/sec, P < 0.0001) and lower pulsatility index (0.64 +/- 0.03 vs 0.88 +/- 0.04, P < 0.001); anterior and middle cerebral artery velocities at normo- and hypocapnia were significantly higher than posterior cerebral arteries for both feeders and nonfeeders (P < 0.001). Carbon dioxide reactivity was 0.2 +/- 0.2%/mm Hg in feeders and 2.1 +/- 0.2%/mm Hg in nonfeeders, with no significant difference between arteries. In four of eight patients with lesions fed by the anterior circulation (middle cerebral artery with or without anterior cerebral artery feeders), posterior cerebral artery nonfeeders exhibited low reactivity. In 2 of 5 patients with ipsilateral posterior cerebral artery feeders, contralateral posterior cerebral artery nonfeeders exhibited impaired reactivity., Conclusions: Quantitative transcranial Doppler studies are technically feasible in the operating room or interventional suite during anesthesia. Hemodynamic assessment using physiologic challenges of arteriovenous malformation feeders as well as angiographically uninvolved vessels may be useful as criteria in the assessment of malformations and arteriovenous malformation patients may exhibit abnormal vasoreactivity in distant uninvolved perfusion territories, suggesting a deranged neural control mechanism.

The two major neurological complications of subarachnoid haemorrhage (SAH) due to an intracranial aneurysm are rebleeding and delayed cerebral ischaemia related to cerebral vasospasm. The best way to prevent rebleeding is early surgery. Even when surgery is performed within the first 72 hours posthaemorrhage, the risk of cerebral ischaemia due to vasospasm is high. Conventional medical treatment of cerebral vasospasm includes haemodilution, hypervolaemia and increase of arterial blood pressure. Haemodilution is of limited value as the patients suffering from SAH have usually a low haematocrit. The effectiveness of hypervolaemia is controversial and it may worsen cerebral and pulmonary oedema. Systemic hypertension is an effective therapy of vasospasm, but which can only be used once the aneurysm is controlled. Nimodipine and nicardipine, two calcium antagonists, have a beneficial effect on neurologic outcome following SAH. Today, it is still debated whether the beneficial effect of nimodipine results from the vascular effect of the drug or from a direct cerebral cytoprotective mechanism. Early surgery implies that surgeons operate on brains in acute inflammatory state. Thus, it is mandatory to use peroperative techniques improving cerebral exposure. These techniques include infusion of mannitol, lumbar cerebrospinal fluid (CSF) drainage, administration of anaesthetic agents known to decrease cerebral blood flow (CBF) and hypocapnia. Usually, the effect of CSF drainage is very effective and sufficient by itself. The second objective in the peroperative period is to avoid ischaemia. In areas with decreased flow distal to vasospasm, autoregulation is impaired and CBF is directly dependent on cerebral perfusion pressure. Furthermore, the safe practice of transient clipping of vessels supplying the aneurysm has dramatically reduced the indications of controlled hypotension. During temporary clipping, some authors recommend a pharmacological brain protection using barbiturates, etomidate or propofol, but this practice has not been validated by randomized studies. However, it is generally agreed that the arterial pressure should be increased during temporary clipping to improve collateral blood flow and to maintain it after the aneurysm has been secured. To conclude, together with lumbar CSF drainage and transient clipping, the anaesthetic management of the patients should include: maintenance of the arterial blood pressure close to its preoperative level, maintenance of PaCO2 between 30 and 35 mmHg and of normovolaemia through replacement of fluid and blood losses. After completion of surgery, recovery from anaesthesia should be rapid to allow fast diagnosis of neurological complications. The monitoring of the status of consciousness is the key of the diagnosis of early postoperative complications.

Background and Purpose: Feeding mean arterial pressure immediately proximal to the nidus of arteriovenous malformations may influence the frequency of spontaneous intracerebral hemorrhage. This study assessed the usefulness of transcranial Doppler ultrasound velocities as a noninvasive estimate of feeding mean arterial pressure., Methods: We studied 41 patients undergoing 73 staged treatments of arteriovenous malformations with endovascular embolization, surgery, or both. Before treatment during the awake state, transcranial Doppler mean and peak velocities were recorded in proximal Willisian vessels. During superselective angiography with the patient under conscious sedation or during surgery with the patient under general anesthesia, feeding mean arterial pressure was measured through a 1.5F transfemoral intracranial microcatheter or a 26-g needle by direct puncture. Measurement of insonated artery diameter was possible in 41 embolizations, and a flow velocity index (mL/min) and Reynolds' number were estimated., Results: Mean +/- SEM feeding mean arterial pressure was 38 +/- 2 mm Hg at a systemic mean arterial pressure of 77 +/- 2 mm Hg; mean velocity was 102 +/- 4 cm/s. There was an inverse correlation between feeding mean arterial pressure and parent artery mean velocity (y = -0.74x + 130, r = .35, P = .0025). The best correlation was for the first treatment in each patient (n = 27) using the highest peak velocity obtainable in a Willisian vessel ipsilateral to the arteriovenous malformation (y = -1.61x + 221, r = .62, P = .0005). Flow velocity index (775 +/- 106 mL/min) did not correlate with feeding mean arterial pressure, but there was a weak correlation with Reynolds' number (y = -12x + 1616, r = .27, P = .1283). Mean Reynolds' number was 1257 +/- 119., Conclusions: Transcranial Doppler mean velocity is correlated with feeding mean arterial pressure but only weakly predictive. Considerations influencing the relation of distal feeding mean arterial pressure to proximal mean velocity might include the influence of other fistulae in the circuit between major inflow and outflow channels as well as turbulent flow at vascular branch points between point of insonation and the nidus, as suggested by Reynolds' number values of more than 400.

Objective: Intravascular pressure and cardiac output monitoring are frequently performed in the operating room and intensive care unit. Currently, cardiac output is only measured intermittently, although continuous measurement would be preferable. One method proposed for measuring cardiac output continuously is arterial waveform pulse contour analysis. This study examines the utility of trending cardiac output using pulse contour analysis during manipulations of blood pressure., Methods: Eleven patients were studied while undergoing resection of cerebral arteriovenous malformations. Cardiac output measured by pulse contour analysis was compared with thermodilution cardiac output measurements in patients subjected to induced hypotension with esmolol and restoration of blood pressure with phenylephrine., Results: Esmolol infusion resulted in a decrease in mean arterial pressure from 81 +/- 13 to 62 +/- 7 mm Hg (p < 0.025), a decrease in thermodilution cardiac output from 6.4 +/- 0.9 to 4.4 +/- 1.1 L/min (p < 0.025), and a decrease in pulse contour cardiac output from 6.2 +/- 1.0 to 4.5 +/- 0.9 L/min. Phenylephrine increased mean arterial pressure from 68 +/- 6 to 95 +/- 9 mm Hg with no change in either thermodilution or pulse contour cardiac output., Conclusions: This study demonstrates that during surgery for arteriovenous malformations in the brain, the pulse contour method was able to reflect cardiac output accurately during induced hypotension with esmolol and during restoration of blood pressure with phenylephrine.

Background: Before desflurane is advocated for patients undergoing neurosurgical procedures, it is necessary to determine the effect of desflurane on cerebral blood flow (CBF). In this study, CBF values are compared between desflurane and isoflurane at two doses. In addition, CBF reactivity to CO2 and the effect of prolonged exposure were compared between the two agents., Methods: Cerebral blood flow measurements with intravenous 133Xe were performed in 24 patients undergoing craniotomy for mass lesions, randomized to receive either isoflurane or desflurane in oxygen and air. Cerebral blood flow was determined at 1 and 1.5 MAC concentrations at PaCO2 of 25 mmHg in the absence of surgical stimulation. Intraoperatively, with 1.25 MAC anesthesia, CBF was determined at target PaCO2 of 25 and 35 mmHg. In 15 patients, an additional measurement at 1.25 MAC was made before closure., Results: At 1.0 MAC, mean +/- SD CBF values for the desflurane and isoflurane groups were 18 +/- 2 and 20 +/- 3 ml x 100 g-1 x min-1, respectively. At 1.5 MAC, CBF values were the same for the two anesthetics; 17 +/- 3 ml x 100 g-1 x min-1 for isoflurane and 19 +/- 4 ml.100 g-1 x min-1 for desflurane. During 1.25 MAC anesthesia, there were no differences between groups, with CO2 reactivity 1.3 +/- 1.2 ml x 100 g-1 x min-1 x mmHg-1 for desflurane and 1.6 +/- 0.6 ml.100 g-1 x min-1 x mmHg-1 for isoflurane. There was no demonstrable decrease in CBF with prolonged exposure to either agent., Conclusions: Desflurane and isoflurane are similar in terms of absolute CBF, the response to increasing doses, and the preservation of CO2 reactivity.

Background: Some cerebral artery aneurysms require cardiopulmonary bypass and deep hypothermic circulatory arrest to be clipped safely. During bypass these neurosurgical patients often are given large doses of thiopental in the hope that additional cerebral protection will be provided. However, thiopental loading during bypass has been associated with subsequent cardiac dysfunction in patients with heart disease. This study was undertaken to determine how patients without concomitant heart disease would respond to thiopental loading., Methods: Twenty-four neurosurgical patients with giant cerebral aneurysms and little or no cardiac disease were anesthetized with fentanyl, nitrous oxide, and isoflurane. Thiopental was titrated to achieve electroencephalographic burst-suppression before bypass, and the infusion was continued until after separation. Prebypass hemodynamic and echocardiographic measurements were obtained during a stable baseline and 15 min after thiopental loading began. They were repeated after bypass., Results: Prebypass thiopental loading increased heart rate from 61 +/- 11 to 72 +/- 13 beats/min and decreased stroke volume from 43 +/- 10 to 38 +/- 8 ml.beat-1.m-2, but arterial and filling pressures, vascular resistance, cardiac index, and ejection fraction remained the same. Before bypass, thiopental plasma concentration measured 28 +/- 8 micrograms/ml. Loading continued for 2-3 h until after bypass was terminated, and the overall infusion rate was 18 +/- 5 mg.kg-1.h-1. All patients were easily separated from bypass without inotropic support. Following bypass, vascular resistance was decreased; heart rate, filling pressures, and cardiac index were increased; stroke volume had returned to its baseline; and ejection fraction was unchanged., Conclusions: It was concluded that if preoperative ventricular function is good, thiopental loading to electroencephalographic burst-suppression causes negligible cardiac impairment and does not impede separation from cardiopulmonary bypass.

The loss of autoregulatory control of cerebral perfusion to changes in perfusion pressure in tissue remote from an arteriovenous malformation (AVM) has been proposed as the mechanism underlying "normal perfusion pressure breakthrough." This study is the first direct test of this mechanism. Studies were performed during the resection of moderate to large AVMs in 25 patients undergoing 28 procedures under isoflurane anesthesia. Cerebral blood flow (CBF) was measured (xenon-133 method) in the hemisphere adjacent to the nidus before resection after dural exposure (pre), after AVM removal before dural closure at spontaneous systemic blood pressure (post), and, finally, with the mean arterial pressure increased by 20 mm Hg, using phenylephrine (post-BP). AVM resection resulted in a significant enhancement of perfusion in the adjacent hemisphere (30 +/- 2 vs. 25 +/- 1 ml/100g/min, P < 0.01), but no further increase of CBF occurred during increased perfusion pressure (30 +/- 2 ml/100g/min). One patient suffered a postoperative hemorrhage and another developed intraoperative brain swelling during the course of the resection that necessitated staging the procedure. These two patients had the highest increases in CBF, but intact pressure autoregulation. Preserved autoregulation to increased mean arterial pressure after resection does not support a hemodynamic mechanism for the observed increase in CBF from before the resection to after the resection. Pathological events, however, do appear to be related to increases in hemispheric perfusion.

Desflurane causes dose-dependent decreases in cerebrovascular resistance and cerebral metabolic rate of oxygen consumption (CMRO2), suggesting that desflurane is a cerebral arteriolar dilator with global flow-metabolism coupling similar to halothane and isoflurane. Desflurane is also similar to isoflurane in that cerebrovascular responsivity to carbon dioxide appears to be maintained. In the dog, arterial hypotension to 40 mm Hg induced with 2.4 MAC desflurane resulted in global decreases in cerebral blood flow of 60% and CMRO2 of 20%. Concentrations of cerebral metabolites of high-energy phosphates were not significantly deranged. The intracranial pressure data from humans are controversial. Desflurane and oxygen at 1 MAC caused sustained increases in cerebrospinal fluid pressure (maximum of 19 +/- 6 mm Hg) in patients undergoing craniotomy for mass lesion, despite prior establishment of hypocapnia. In a more recent study, the same investigators reported similar cerebrospinal fluid pressures before and after 0.5 MAC of either isoflurane or desflurane in 50% N2O. The electroencephalographic effects of desflurane are similar to those of isoflurane in humans, and burst suppression is easily achieved. There are no data available concerning possible interactions between desflurane and the outcome of a cerebral ischemic event. Similar to other potent volatile agents, desflurane can cause cerebral vasodilation and may result in intracranial pressure changes in vulnerable patients, but if adequate hyperventilation and depth of anesthesia are maintained, it is probably safe to use desflurane in a manner similar to isoflurane in patients with decreased intracranial compliance.

Descriptors of power and frequency derived from power spectral analysis of the electroencephalogram (EEG) were used to determine the effects of low-dose sufentanil (0.1 micrograms/kg) on brain activity. The effects of hypocarbia alone and of hypocarbia with sufentanil in patients receiving a N2/O2 (70%:30%) anesthetic were also studied. Hypocarbia alone caused changes in most EEG descriptors from both the anterior (F3-C3) and posterior (P3-O1) EEG montages. All EEG descriptors in both hypocarbic and normocarbic patients significantly changed when sufentanil was administered, reflecting a shift of power into the lower frequency ranges. When the anterior EEG montages from the two groups that received sufentanil were compared, the delta power band, spectral edge 50 (median power frequency), and the relative power in the delta power band divided by the alpha plus beta power bands [D/(A + B)] in the hypocarbic group exhibited a significantly greater shift of power into the lower frequency range. It is concluded that (a) power spectral analysis is a sensitive measure of the effects of hypocarbia and small doses of sufentanil on the brain; (b) the power spectral analysis descriptors--delta power band, spectral edge 50, and [D/(A + B)]--are statistically the most sensitive to EEG changes induced by sufentanil; and (c) hypocarbia intensifies patient EEG response to sufentanil, as judged by changes in EEG descriptors.

The authors present two patients with Alzheimer's disease who each received a single intravenous dose of physostigmine. Subjective complaints and mood changes were disproportional with objectively verified physiological side effects. Such observations may contribute to an understanding of affective disorders and should receive more attention in future studies of cholinesterase inhibitors.

The pharmacokinetics of sufentanil were determined in eight obese (94.1 +/- 14 kg, mean +/- SD) and eight control patients (70.1 +/- 13 kg) anesthetized for neurosurgery. After induction of anesthesia, 4 micrograms/kg of sufentanil was administered in a single intravenous bolus. Multiple arterial samples were obtained at timed intervals over 6 h, and plasma concentrations of sufentanil were measured by radioimmunoassay. Calculation of pharmacokinetic variables from the derived compartmental models demonstrated an increased volume of distribution of sufentanil in the obese (9098 +/- 2793 mL/kg ideal body weight, mean +/- SD) when compared with a control group (5073 +/- 1673 mL/kg ideal body weight) (P less than 0.01) and a prolonged elimination half-life (208 +/- 82 min vs 135 +/- 42 min, P less than 0.05). The total volume of distribution correlated linearly with the degree of obesity, as expressed in percent ideal body weight (r = 0.67). In contrast, plasma clearance was similar in both obese and control groups (32.9 +/- 12.5 vs 26.4 +/- 5.7 mL/kg ideal body weight). The high lipid solubility of sufentanil probably explains the altered pharmacokinetics of this opioid in obese patients.

We retrospectively examined arerial and end-tidal estimations of CO2 tension used to calculate cerebrovascular reactivity in 68 anesthetized patients. CBF was measured using the intravenous 133Xe technique at mean +/- SD PaCO2 values of 28.2 +/- 5.2 and 38.8 +/- 4.8 mm Hg. The correlation between all PaCO2 and end-tidal PCO2 (PetCO2) values was y = 0.85x - 0.49 (r = 0.93, p = 0.0001). There was a moderate correlation between age and the difference between PaCO2 and PetCO2 (y = 0.11x + 0.79; r = 0.73, p = 0.0001). Cerebrovascular reactivity to changes in CO2 (ml 100 g-1 min-1 mm Hg-1) was similar (p = 0.358) when calculated by using either PaCO2 (1.9 +/- 0.8) or PetCO2 (1.8 +/- 0.8) and highly correlated (y = 0.86x + 0.23; r = 0.91, p = 0.0001). The CBF response to changes in CO2 tension can be reliably estimated from noninvasive measurement of PetCO2.

Giant aneurysm surgery continues to be a technically difficult task with high operative morbidity. Recent advances in cardiac surgery have fueled interest in the technique of deep hypothermic circulatory arrest for the treatment of giant and complex intracranial aneurysms. Fourteen patients with giant intracranial aneurysms operated on with the technique of deep hypothermic circulatory arrest are presented. All 14 aneurysms were successfully treated. There were 2 intraoperative strokes: 1 resulted in severe disability and 1 resulted in mild disability. No significant neurological complications were related to the technique of cardiopulmonary bypass with deep hypothermic circulatory arrest. This initial experience indicates that patients with giant and complex intracranial aneurysms might benefit from a surgical approach that included the use of deep hypothermic circulatory arrest.

The effects of isoflurane or halothane on cerebral blood flow (CBF) reactivity to changes in arterial carbon dioxide tension (PaCO2) during carotid endarterectomy were compared using the intravenous method of 133Xe-CBF determination. Patients, aged 65 +/- 3 yr (mean +/- SE), received O2 and N2O (1:1) and either 0.75% isoflurane (n = 7) or 0.5% halothane (n = 7). Patient demographic and clinical data were similar for both groups and followed the expected strata of patients with ischemic cerebrovascular disease. Measurements were made during the period of temporary bypass shunting. In the isoflurane group, increasing PaCO2 from 33.3 +/- 1.4 to 43.4 +/- 1.3 mm Hg resulted in a significant (P less than 0.05) increase in CBF from 21 +/- 1 to 35 +/- 4 mL.100 g-1.min-1. In the halothane group, increasing PaCO2 from 31.1 +/- 1 to 39.4 +/- 1.6 mm Hg resulted in a significant increase in CBF from 26 +/- 3 to 37 +/- 3 mL.100 g-1.min-1. Mean CBF reactivity to changes in PaCO2 (mL.100 g-1.min-1.mm Hg-1) was 1.74 +/- 0.39 for isoflurane and 1.78 +/- 0.4 for halothane (not significant), corresponding to a relative change of 4.8% +/- 0.8% and 5.2% +/- 1.3% per mm Hg, respectively. There is no significant difference between halothane and isoflurane in their effects on CO2 reactivity in the mildly hypocapnic to normocapnic range.

In order to examine anaesthetic effects on the distribution of cerebral blood flow (CBF) during normo- and hypocapnia, male adult Sprague-Dawley rats were allocated randomly to four groups in a 2 x 2 factorial design, using PaCO2 value and anaesthetic agent as between-group factors. Animals were anesthetized with either 1.38% isoflurane (inspired) or 1.05% halothane (inspired) and the lungs ventilated mechanically at either normocapnia (PaCO2 5.1-5.6 kPa) or hypocapnia (PaCO2 3.1-3.3 kPa) for 1 h. CBF was measured using 14C-iodoantipyrine autoradiography. Local CBF in selected cortical and subcortical regions of interest and area-weighted mean global CBF were calculated. Data were compared by analysis of variance. Normocapnic (mean (SE] CBF for halothane (n = 6) and isoflurane (n = 7) was 120 (8) ml/100 g min-1 (PaCO2 5.6 (0.49) kPa) and 117 (9) ml/100 g min-1 (PaCO2 5.4 (0.5) kPa), respectively. Hypocapnic CBF for halothane (n = 6) and isoflurane (n = 6) was 82 (7) ml/100 g min-1 (PaCO2 3.3 (0.12) kPa) and 82 (6) ml/100 g min-1 (PaCO2 3.2 (0.12) kPa), respectively. Hypocapnia reduced global CBF for both groups by 30% (P less than 0.001), but there was no difference between anaesthetic agents (P greater than 0.8). Hypocapnia decreased CBF in all local structures examined. Although subcortical structures had similar CBF at both normocapnia and hypocapnia, CBF in three cortical samples was greater (P less than 0.05) in both the normocapnic and hypocapnic halothane groups than the corresponding isoflurane groups. The CBF reactivity to changes in PaCO2 was similar for both agents (approximately 2 ml/100 g min-1 mm Hg). (ABSTRACT TRUNCATED AT 250 WORDS)

The effects of single and repeated electroconvulsive shock (ECS) treatment on regional cerebral blood flow (rCBF) and on rates of glucose flow from blood to local brain areas (rCGF), were investigated in pentobarbital-anesthetized rats, using quantitative autoradiographic techniques. Effects of single ECS on rCBF were assessed at two average time points of 15 and 55 sec after the application of the electric current, whereas the effects on rCGF were assessed at 70 and 110 sec. Effects of repeated ECS were assessed 24 hr after the last ECS in a series of eight daily treatments. Single ECS caused marked increases in rCGF in different brain structures, but no significant effects were observed after repeated ECS. Similarly, substantial increases in rCBF were seen during and immediately after the ECS-induced seizure, but not 24 hr after the last treatment of repeated ECS. Single ECS appeared to have differential effects on rCBF in hind-brain structures as compared to more anterior regions. A linear relationship between rCBF and rCGF values was established in control animals, indicating coupling of these two variables with a constant rCBF/rCGF ratio. ECS caused an apparent increase in the CBF/CGF ratio, which might be attributed to the different temporal resolution of the two methods used here to estimate rCGF and rCBF. Analysis of the increments of rCGF and rCBF extrapolated to the same point in time after a single ECS (10 sec), revealed that in many of the examined structures the CBF/CGF ratio was similar to that observed in control animals, indicating that the coupling of CBF and CGF is maintained during the seizure. But in some brain stem structures such as the dorsal raphe, inferior colliculi, superior olivary nucleus, and the vestibular nucleus there were large increases in CGF associated with a marked drop in the CBF/CGF ratio. This observation suggests that high metabolic demands can be met by increased local blood flow up to a given "ceiling" keeping the glucose clearance from blood to brain tissue constant. However, when the metabolic demands exceed this upper limit, the additional demands could be met by an increased clearance of glucose without a change in CBF.

Thirty patients undergoing resection of arteriovenous malformations with deliberate hypotension were randomized to receive 1 of 3 hypotensive agents. Anesthesia was maintained with isoflurane and nitrous oxide in all patients. Mean arterial pressure was reduced 20% to 60-65 mm Hg with use of either isoflurane (less than or equal to 4%), sodium nitroprusside (less than or equal to 8 micrograms.kg-1.min-1), or esmolol (less than or equal to 24 mg/min). Esmolol was associated with a decrease in cardiac output from 6.2 +/- 1.3 to 3.8 +/- 0.8 L/min, which, because of a 22% increase in systemic vascular resistance, far exceeded the reduction in mean arterial pressure. Systemic vascular resistance increased despite a 32% decrease in plasma renin activity. In contrast, with sodium nitroprusside or isoflurane, the decrease in mean arterial pressure was associated with decreases in systemic vascular resistance of similar magnitude, with no change in cardiac output. Plasma renin activity levels increased 48% with sodium nitroprusside and 126% with isoflurane. Heart rate increased 13% with sodium nitroprusside, remained unchanged with isoflurane, and decreased 23% with esmolol. Although esmolol may be used as a primary hypotensive agent, the potential for marked myocardial depression must be recognized. The differences in pharmacologic properties for the different hypotensive agents suggest that combinations of these agents may provide a pharmacologic profile superior to either agent alone.

Nimodipine is a calcium antagonist that binds with high affinity to neuronal membranes. It is a potent cerebrovasodilator and has been demonstrated also to affect neurotransmitter synthesis and release. Because patients undergoing surgery for intracranial aneurysms are frequently receiving nimodipine, the authors determined the MAC of isoflurane in six dogs before and during three infusion doses of nimodipine (0.5, 1.0 and 2.0 micrograms.kg-1.min-1). MAC was also determined in five dogs before and during infusion of the drug vehicle (10 microliters.kg-1.min-1). Nimodipine produced a reduction in MAC from 1.47 +/- 0.33% to 1.19 +/- 0.18, 1.15 +/- 0.18 and 1.15 +/- 0.09% during infusions of nimodipine 0.5, 1.0 and 2.0 micrograms.kg-1.min-1, respectively (P less than 0.05). Infusion of drug vehicle alone produced no change in MAC (1.39 +/- 0.15%). This reduction in anaesthetic requirement by nimodipine may be due to its effect on neurotransmission. Adjustments in anaesthetic dosage may be necessary in patients receiving nimodipine.

Study Objective: To determine whether a drug interaction exists between doxacurium and anticonvulsants., Design: Open-label controlled study., Setting: Inpatient neuroanesthesiology service at a university medical center., Patients: Three groups of nine patients each, consisting of those chronically receiving carbamazepine, phenytoin, or no anticonvulsant therapy., Intervention: Intravenous administration of doxacurium 60 micrograms/kg during anesthesia with nitrous oxide (N2O), fentanyl, and droperidol., Measurements and Main Results: The adductor pollicis mechanical response to single 0.2-millisecond supramaximal pulses delivered to the ulnar nerve at 0.15 Hz was recorded. Patients receiving phenytoin or carbamazepine recovered neuromuscular function more quickly than did the control group. The times from doxacurium injection to 50% recovery of mechanomyographic response, for example, were as follows: control group, 161 +/- 55 minutes (mean +/- SD); phenytoin group, 76 +/- 31 minutes; and carbamazepine group, 66 +/- 27 minutes (p less than 0.05). The time for recovery from 75% to 25% blockade (recovery index) was decreased by 53% in the phenytoin group and by 67% in the carbamazepine group as compared with the control group (41.0 +/- 18.0 minutes and 28.6 +/- 8.6 minutes vs 86.4 +/- 45.2 minutes, respectively)., Conclusion: Chronic treatment with anticonvulsants results in more rapid recovery from neuromuscular blockade produced by doxacurium.

The effect of age on the distribution and elimination of sufentanil was studied in seven elderly (77 +/- 5 yr, mean +/- SD) and seven younger (41 +/- 15 yr) neurosurgical patients. Following a single IV bolus of sufentanil 2 micrograms.kg-1 multiple arterial samples were obtained at timed intervals and plasma concentrations of sufentanil were measured by radioimmunoassay. Pharmacokinetic variables were calculated from the derived compartmental models. The initial volume of distribution was significantly smaller in the elderly patients (310 +/- 109 ml.kg-1 vs 491 +/- 112 ml.kg-1 mean +/- SD). Elimination half-lives, plasma clearances, and total volumes of distribution were similar for elderly and younger subjects. Six of seven elderly patients required administration of naloxone at the termination of surgery to achieve an adequate rate of ventilation (greater than eight breaths.min-1) while only one younger patient required antagonism of ventilatory depression. The authors believe that age-related differences in the action of sufentanil cannot be accounted for by the observed differences in the initial volume of distribution. It is concluded that alterations in pharmacodynamics appear to be of greater importance in the prolonged opioid effect seen in the elderly.

To document the comparability of cerebral blood flow (CBF) values determined by quantification of 133Xe washout after either intravenous or intracarotid administration, 12 patients undergoing elective carotid endarterectomy anesthetized with N2O/O2 and either isoflurane or halothane were studied. Scintillation counters were placed over the middle cerebral artery territory ipsilateral to the operated carotid artery. CBF was measured by the intravenous method during dissection of the carotid sheath and was calculated as the initial slope index from head washout curves collected for 11 min after injection of 10-20 mCi 133Xe in saline into a large vein. Immediately prior to carotid occlusion, CBF was determined by direct injection of 1 mCi 133Xe in saline into either the internal carotid artery or the common carotid artery with the external carotid artery occluded. For the intracarotid injections, the initial slope was calculated from the 1st min of washout. Data were analyzed by linear regression and analysis of variance. Values are expressed as mean +/- SD. The mean CBF for intravenous and intracarotid methods were both 29 +/- 10 ml.100 g-1.min-1. The correlation between CBF measured by intravenous and intracarotid methods was excellent and was described by the line y = x + 0.6, r = 0.92. We conclude that in the flow range studied, the intravenous technique may be applied to measure CBF in physiologically stable situations in which direct intracarotid injection is not feasible.

The effect of age (over 70 yr) on the pharmacokinetics and pharmacodynamics of edrophonium was evaluated in seven patients aged 76-87 yr and in seven patients aged 27-57 yr. When elderly patients were compared with younger controls, the elderly exhibited a statistically significant decreased plasma clearance (5.9 +/- 2 versus 12.1 +/- 4 mL.kg-1.min-1) and a prolonged elimination half-life (84.2 +/- 17 versus 56.6 +/- 16 min). Pharmacodynamically, a higher concentration of edrophonium is required in elderly patients to produce the same effect as in the younger controls. This observation may be explained in part by changes in neuromuscular transmission that are a function of the aging process. In addition, even though plasma concentrations were significantly greater at every sampling point in the elderly than the younger group, there was no difference between either the maximum duration or the total duration of action of edrophonium in the two groups. The maximum duration of action of edrophonium in both groups was very brief (1.3-2.2 min). These results contrast with a previous study of the anticholinesterases neostigmine and pyridostigmine, in which the action of these drugs was significantly prolonged in elderly patients. Explanations for the observed differences between edrophonium and other anticholinesterases may relate to differences in chemical structure and the possibility that edrophonium produces antagonism of neuromuscular blockade by a different mechanism than neostigmine or pyridostigmine.

To investigate the cerebral hemodynamic changes associated with obliteration of arteriovenous malformations (AVMs), we studied 26 patients undergoing total microsurgical AVM resection during isoflurane and N2/O2 anesthesia. Detectors were placed 5 to 6 cm from the margin of the lesion and in a homologous contralateral position. Cerebral blood flow (CBF) was measured using the intravenous xenon-133 technique before and after AVM resection, during both hypocapnia and normocapnia at each stage. Intraoperative changes in CBF were related to a risk score system based on the patient's history and preoperative angiograms. Seven otherwise healthy patients undergoing spinal surgery were studied to control for anesthetic effects. Patient demographic and clinical data for the AVM group conformed to the expected strata of a large AVM population. The CBF increased after excision (22 +/- 1 ml/100 g/min before excision to 30 +/- 2 ml/100 g/min after excision; mean +/- SE, n = 25, P less than 0.002) without a hemispheric difference. CO2 reactivity increased slightly after excision (4.2 +/- 0.3% change/mm Hg before excision to 4.7 +/- 0.3% change/mm Hg after excision; n = 14, P less than 0.02). The baseline CBF and CO2 reactivity were not different from the control group. There was a weak correlation between the risk score and the percentage of change in the ipsilateral CBF, with a trend for the patients with the lowest risk to have the lowest CBF changes after resection. There was no relationship between CO2 reactivity and risk grade. None of the patients awoke from anesthesia with unexpected neurological deficits. The highest CBF increases were associated with postoperative brain swelling in one patient and fatal intracerebral hemorrhage in another. Both patients had normal CO2 reactivity before excision. One patient suffered postoperative intracerebral hemorrhage, attributable to technical problems, and had no increase in CBF. We conclude that, with an acute increase in the arteriovenous pressure gradient (and cerebral perfusion pressure) that results from shunt obliteration, there is an immediate global effect of AVM resection to increase CBF. Cerebrovascular reactivity to CO2 remains intact both before and after excision.

We describe a 63-year-old man with severe bilateral internal carotid artery disease who presented with repeated, brief attacks of left limb shaking precipitated by his standing up. Cerebral blood flow measured by xenon-133 inhalation showed reduced resting flows and a focal perfusion deficit in the right dorsofrontal and upper rolandic regions. Blood flow velocity and pulsatility index of the right middle cerebral artery measured by transcranial Doppler ultrasonography were also reduced. With hypercapnic challenge, both hemispheric tissue perfusion and blood flow velocity showed impaired reactivity. With induced hypotension, the focal perfusion deficit in the right dorsofrontal region was accentuated. Following right internal carotid endartectomy, resting cerebral blood flow and blood flow velocity improved, as did hypercapnic vasoreactivity. These reversible deficits in cerebral blood flow and vasoregulation, which were maximal in the dorsofrontal region, are consistent with low perfusion in the border zone territory or the distal fields and demonstrate that hemodynamic failure is the likely mechanism for limb-shaking transient ischemic attacks from severe carotid artery disease.

Regional cerebral blood flow studies with xenon-133 are useful in the functional assessment of cerebrovascular diseases. Conventional models for cerebral blood flow calculation employ 11 minutes of data collection. However, in many circumstances it is not possible to maintain steady-state physiologic conditions for 11 minutes. We compared a monocompartmental model that requires only 3 minutes of data collection with the bicompartmental model that requires 11 minutes of data collection. The correlation between the absolute values for global cerebral blood flow (initial slope index, intravenous method) in 72 anesthetized patients was r = 0.88; for 54 awake patients inhaling xenon-133, the correlation was r = 0.77. Cerebral blood flow was determined with intravenous xenon-133 at baseline and during a CO2 challenge in 50 patients during cerebrovascular surgery under general anesthesia. Reactivity to a 10-mm Hg rise in PaCO2 was calculated in absolute terms and as a percentage change from baseline using both the 3-minute and the 11-minute models. The correlation of CO2 reactivity calculated with the two models was r = 0.9 for the absolute values and r = 0.8 for the relative change. Cerebral blood flow calculated with the two models correlated well in both awake and anesthetized patients. In addition, there was a good correlation between CO2 reactivity calculated with the two models. In situations in which physiologic conditions cannot be held stable for 11 minutes, the 3-minute initial slope index may be used to quantitatively assess cerebrovascular reserve with a CO2 challenge.

This study was undertaken to assess differences between young and elderly patients with respect to the duration of antagonism of metocurine neuromuscular blockade by neostigmine (NEO) or pyridostigmine (PYR). Patients were given either NEO (seven elderly and ten young) or PYR (seven elderly and eight young) and received nitrous oxide in oxygen (60:40) and 1 MAC halothane. Neuromuscular transmission was assessed by using evoked compound electromyography. Metocurine 0.1 mg/kg was given, followed by a continuous infusion to achieve 90% reduction in baseline single twitch height. After at least 30 minutes, either NEO (0.07 mg/kg) or PYR (0.14 mg/kg) and atropine (0.02 mg/kg) were given IV. After injection of NEO or PYR, the duration of maximal response (DOMR) was recorded. Mean (+/- SE) ages were 38 +/- 5 and 68 +/- 2 years in the two groups of patients receiving PYR. In the elderly, PYR significantly prolonged DOMR compared to younger patients (35.3 +/- 8.2 vs 14.4 +/- 4.2 minutes, respectively). The mean ages in the two groups of patients receiving NEO were 41.5 +/- 4 and 72 +/- 2 years. The elderly group demonstrated a significant increase in the DOMR compared to younger patients (32 +/- 10 vs 11 +/- 2 minutes, respectively). It is concluded that, compared to younger patients, the duration of action of NEO and PYR in the aged patient is prolonged.

The effects of isoflurane, halothane, and fentanyl on cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) during anesthesia prior to carotid endarterectomy were compared using the intravenous method of 133-Xenon CBF determination. Patients, mean (+/- SE) age 68 +/- 2, received either isoflurane (N = 16), 0.75% in O2 and N2O, 50:50; halothane (N = 11), 0.5% in O2 and N2O, 50:50; or fentanyl (N = 10), 5-6 micrograms/kg bolus and then 1-2 micrograms.kg-1.h-1 infusion in addition to O2 and N2O, 40:60. Measurements were made immediately before carotid occlusion. Mean (+/- SE) CBF (ml.100 g-1.min-1) was 23.9 +/- 2.1 for isoflurane, 33.8 +/- 4.8 for halothane, and 19.3 +/- 2.4 for fentanyl. CMRO2 (ml.100 g-1.min-1) was available from 22 patients and was 1.51 +/- 0.28 for isoflurane (N = 7), 1.45 +/- 0.24 for halothane (N = 6), and 1.49 +/- 0.21 for fentanyl (N = 9). Although CBF was greater during halothane than during isoflurane or fentanyl anesthesia (p less than 0.05), there were no demonstrable differences in CMRO2 among the 3 agents. We conclude that choice of anesthetic agent for cerebrovascular surgery with comparable anesthetic regimens should not be made on the basis of "metabolic suppression." During relatively light levels of anesthesia, vasoactive properties of anesthetics are more important than cerebral metabolic depression with respect to effects on the cerebral circulation.

Prompted by reports of potentially deleterious cerebral vasodilation by the synthetic opioid sufentanil, the authors compared the effects of either isoflurane/N2O and sufentanil/N2O on cerebral blood flow (CBF), arteriovenous difference in oxygen content (AVDO2), and CBF reactivity to changes in PaCO2 during carotid endarterectomy. Cerebral blood flow was measured using the iv method of 133-Xe CBF determination and AVDO2 was measured using systemic arterial-jugular venous oxygen content differences. Patients, age 68 +/- 1 yr (mean +/- SE), received either isoflurane (n = 10), 0.75% in O2 and N2O, 1:1; or sufentanil (n = 10), 1.5-2 micrograms/kg bolus and then 0.2-0.3 micrograms.kg-1.h-1 infusion in addition to O2 and N2O, 2:3. Measurements were made immediately before carotid occlusion, and then at two levels of PaCO2 (approximately 32 and 42 mmHg) after insertion of a temporary in-dwelling bypass shunt. Prior to carotid occlusion, there was no significant difference in CBF (ml.100 g-1.min-1) between patients receiving isoflurane (22 +/- 3) or sufentanil (20 +/- 2). Similarly, there was no difference in AVDO2 (vol-%) between isoflurane (4.5 +/- 0.7) and sufentanil (5.4 +/- 0.8) groups. Using a two-way ANOVA design with anesthetic as the between-group factor and elevation of PaCO2 as the within-group repeated measure, there was a significant effect of hypercarbia to increase CBF (P less than 0.0001) and decrease AVDO2 (P less than 0.001). The product of AVDO2 and CBF, which reflects cerebral metabolic oxygen consumption, remained constant (P = 0.364).(ABSTRACT TRUNCATED AT 250 WORDS)

A new experimental model was employed to investigate alterations of cerebral metabolic activity in rats subjected to extensive subarachnoid hemorrhage (SAH). The hemorrhages were produced in anesthetized animals by inserting 0.37 ml fresh autologous arterial blood into the subarachnoid space. Rats that underwent sham operations received subarachnoid injections of mock CSF to study the effects of sudden raised intracranial pressure (ICP). Forty-eight hours after subarachnoid injection, the unanesthetized rats were given intravenous injections of [14C]2-deoxyglucose. Experiments were terminated 45 min later by decapitation, and the brains were removed and frozen. Regional brain metabolic activity was studied employing quantitative autoradiography. In comparison with control animals, cerebral metabolic activity was diffusely decreased following SAH. Statistically significant decreases in metabolic activity of less than 34% were observed in 17 of 30 brain regions studied. The largest percentage reductions were in regions displaying the highest basal metabolic rates. Subarachnoid injections of mock CSF also produced depression of cerebral metabolic activity, but quantitatively these changes were not as pronounced as in the hemorrhage group. These studies demonstrate regional changes in brain function following SAH. The data relate these changes to both the presence of blood in the subarachnoid space and sudden raised ICP.

The management and evaluation of neurosurgical intracranial catastrophes require a multidisciplinary approach to optimize outcome. Intracranial pathology must be rapidly evaluated. Clinically, the patient's mental status, the degree and extent of focal neurologic deficits, and the dynamic nature of any changes in clinical status are assessed. The CT scan is invaluable for diagnosing and monitoring the progress and extent of intracranial pathology. Medical therapy for the control of intracranial hypertension must be undertaken simultaneously. This begins with provision of an adequate, protected airway and support of cardiopulmonary function. Specific measures to control intracranial hypertension include hyperventilation, osmotherapy, CSF removal, seizure control, autonomic control, sedation (primarily thiopental), muscle relaxation, mild hypothermia, and, if indicated, steroids. The goal of intraoperative management is physiologic support of systemic and cerebral hemodynamics. There should be a smooth transition from the discovery of the patient in extremis through the period of medical stabilization, operative intervention, and ultimate delivery of the patient to the intensive care facility for extended treatment.