Serum elastase and alpha-1-antitrypsin levels in patients with ruptured and unruptured cerebral aneurysms.

Despite advances in surgical treatment and postoperative care, subarachnoid hemorrhage from ruptured cerebral aneurysms remains a devastating event. Excellent surgical results in treating unruptured aneurysms suggest the utility of screening tests to identify high-risk individuals. Unfortunately, none of the known risk factors for subarachnoid hemorrhage correlates strongly enough with the illness to warrant widespread screening for occult aneurysms. Other disease entities suggest that protease-antiprotease imbalances contribute to somatic vessel wall degradation and aneurysm formation. Detection of similar imbalances in selected patients may identify a predisposition to cerebral aneurysm formation. Serum concentrations of elastase and alpha-1-antitrypsin (AAT), important proteolytic and antiproteolytic enzymes, were measured in a series of 19 patients with unruptured aneurysms, 41 patients with ruptured aneurysms, and 27 age-matched operative and nonoperative controls. The elastase:AAT ratio was nearly twice as high in patients with unruptured aneurysms as in operative controls (0.527 +/- 0.1 versus 0.285 +/- 0.06; P < 0.04). Elastase:AAT ratios in patients with ruptured aneurysms (subarachnoid hemorrhage < 48 h) were roughly twice those of controls (0.582 +/- 0.095; P < 0.01). There was no statistical difference between elastase:AAT ratios for patients with ruptured and unruptured aneurysms. Likewise, elastase-AAT values for operative controls and nonoperative volunteers were not significantly different. Differences in serum elastase:AAT ratios between patients with aneurysms and controls reflected differences in elastase concentration (99 +/- 56 micrograms/ml versus 67 +/- 56 micrograms/ml; P < 0.03), not in AAT levels (147 +/- 56 micrograms/ml versus 141 +/- 56 micrograms/ml; P < 0.72).(ABSTRACT TRUNCATED AT 250 WORDS)

Direct intraoperative measurement of human brain temperature.

OBJECTIVE: Because hypothermia enhances human tolerance for cerebral ischemia, profound hypothermia is induced in many centers so that the circulation can be arrested while clips are applied to high-risk giant cerebral aneurysms. Brain temperature is measured directly with an intracerebral probe that avoids the uncertainty of surrogate monitoring. However, when there is a large thermal gradient between brain temperature and that of the operating room, even direct measurements can sometimes be misleading. This study was undertaken to determine how deeply a thermal sensor must be embedded in the cerebral parenchyma to ensure that the ambient environment does not distort the measurement of brain temperature. METHODS: Each of 39 normothermic patients had a thermocouple sensor inserted into a temporal lobe seizure focus just before its resection. Brain temperature was measured as the sensor was withdrawn in stages. RESULTS: At both 3 and 2 cm beneath the cortical surface, the temperature of the brain was essentially the same. However, when the sensor was withdrawn to 1 cm, recorded temperature decreased from 35.7 +/- 0.9 to 34.3 +/- 1.4 degrees C (P < 0.001) and irrigation in the vicinity caused major thermal change. At shallower depths, even lower brain temperatures were recorded. No morbidity was attributable to the temperature measurements. CONCLUSION: Direct intraoperative measurement of human brain temperature is feasible and safe, but accuracy requires that the temperature sensor be inserted at least 2 cm into the cerebral cortex.

Cerebral hyperemia after arteriovenous malformation resection is related to "breakthrough" complications but not to feeding artery pressure. The Columbia University Arteriovenous Malformation Study Project.

To study the pathophysiology of idiopathic postoperative brain swelling or hemorrhage after arteriovenous malformation resection, termed normal perfusion pressure breakthrough (NPPB), we performed cerebral blood flow (CBF) studies during 152 operations in 143 patients, using the xenon-133 intravenous injection method. In the first part of the study, CBF was intraoperatively measured (isoflurane/N2O anesthesia) during relative hypocapnia in 95 patients before and after resection. The NPPB group had a greater increase (P < 0.0001) in mean +/- standard deviation global CBF (28 +/- 6 to 47 +/- 16 ml/100 g/min, n = 5) than did the non-NPPB group (25 +/- 7 to 29 +/- 10 ml/100 g/min, n = 90); both arteriovenous malformation groups showed greater increase (P < 0.05) than did controls undergoing craniotomy for tumor (23 +/- 6 to 23 +/- 6 ml/100 g/min, n = 22). Ipsilateral and contralateral CBF changes were similar. In a second cohort of patients with arteriovenous malformations, CBF was measured at relative normocapnia and it increased (P < 0.002) from pre- to postresection (40 +/- 13 to 49 +/- 15 ml/100 g/min, n = 57). There were no NPPB patients in this latter cohort. The feeding mean arterial pressure was measured intraoperatively before resection or at the last embolization before surgery (n = 64). The feeding mean arterial pressure (44 +/- 16 mm Hg) was 56% of the systemic arterial pressure (78 +/- 12 mm Hg, P < 0.0001) and was not related to changes in CBF from pre- to postresection. There was an association between increases in global CBF from pre- to postresection and NPPB-type complications, but there was no relationship of these CBF changes to preoperative regional arterial hypotension. These data do not support a uniquely hemodynamic mechanism that explains cerebral hyperemia as a consequence of repressurization in hypotensive vascular beds.

Intact cerebral blood flow reactivity during remifentanil/nitrous oxide anesthesia.

Remifentanil hydrochloride is a new opioid rapidly metabolized by blood and tissue esterases. The swift degradation accounts for the elimination half-life (t1/2 beta) of < 10 min. An anesthetic agent allowing more rapid postoperative assessment of the neurosurgical patient would be beneficial. This study examined the effect of remifentanil on cerebral blood flow (CBF) reactivity to changes in the arterial pressure of carbon dioxide (PaCO2). Cerebral blood flow was measured with intravenous 133-Xenon during remifentanil/ nitrous oxide (N2O) anesthesia in 10 patients undergoing craniotomy. Cerebrovascular reactivity was determined by repeating CBF measurements after the addition of carbon dioxide (CO2) to the inspired gas mixture. The CBF increased from 21 +/- 6 to 31 +/- 7 ml/100 g/min as the PaCO2 increased from 27 +/- 4 to 36 +/- 3 mm Hg. The relative CBF reactivity was 3.6 +/- 1.2%/mm Hg CO2. During the CBF determinations, the doses of remifentanil administered were not significantly different (0.38 +/- 0.18 microgram/kg/min at hypocapnia vs. 0.34 +/- 0.16 microgram/kg/min at normocapnia). Electroencephalographic monitoring showed a spectral edge frequency of 26 +/- 1 Hz before induction, 25 +/- 1 Hz during maintenance of the remifentanil/N2O anesthetic (0.32 +/- 0.15 microgram/kg/ min), 24 +/- 1 Hz during hypocapnic CBF determination, and 24 +/- 2 Hz during normocapnic CBF determination. At the completion of the procedure, the patients responded to commands within 3.6 +/- 2.5 min and were extubated 7.2 +/- 4.5 min after the remifentanil/N2O was discontinued. In conclusion, absolute CBF values during remifentanil/N2O are similar to previously reported CBF values during fentanyl/N2O and isoflurane/N2O anesthesia, and cerebrovascular reactivity to CO2 remains intact.

The equivalence of anesthetic regimens with respect to plasma glucose elevation during cerebrovascular surgery.

Hyperglycemia, even if mild, is known to aggravate neuronal damage from cerebral ischemia. In order better to define the influence of currently used anesthetic techniques on plasma glucose levels during cerebrovascular surgery, we examined serial plasma glucose values during 43 carotid endarterectomies (CEA) and 19 intracranial arteriovenous malformation (AVM) resections. CEA patients (aged 67.6 +/- 1.4 years and weighing 76.4 +/- 2.3 kg, mean +/- SEM) received N2O in O2 and either isoflurane (ISO) (n = 14), halothane (n = 8), fentanyl (n = 10), or sufentanil (n = 11). Plasma glucose was compared at 1.12 +/- 0.05 h (stage 1), 2.08 +/- 0.07 h (stage 2), and 3.12 +/- 0.1 h (stage 3) after induction of anesthesia. AVM patients received ISO and N2O in O2. Plasma glucose was compared 2.32 +/- 0.14 h (stage 1) and 6.25 +/- 0.34 h (stage 2) after induction of anesthesia (surgical stage). Glucose was determined by the hexokinase method. In the CEA cases, progressively elevated plasma glucose levels were associated with successive surgical stage (114 +/- 6, 122 +/- 6, and 138 +/- 6 mg/dl). The seven CEA patients that carried the diagnosis of diabetes mellitus tended to have higher glucose levels but they did not differ significantly from nondiabetic patients. The AVM patients (aged 35.7 +/- 2.3 years and weighing 71.1 +/- 2.9 kg) were all nondiabetic. They were significantly younger than the CEA patients and each received dexamethasone intraoperatively. In these patients, there was a significant effect (p <0.04) of surgical stage to increase plasma glucose (115 +/- 10 vs. 126 +/- 10 mg/dl). For CEA, the anesthetic techniques examined do not differ significantly in their influence on plasma glucose levels, but all techniques were associated with a gradual increase in plasma glucose levels intraoperatively, even in nondiabetic patients. Compared to the group of younger AVM patients, glucose elevation was more pronounced in the elderly CEA patients. We conclude that intraoperative monitoring of plasma glucose may be useful in elderly patients during prolonged neurovascular procedures.

Deliberate mild intraoperative hypothermia for craniotomy.

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.

Cerebral blood flow and CO2 reactivity is similar during remifentanil/N2O and fentanyl/N2O anesthesia.

BACKGROUND: Remifentanil, a rapidly metabolized mu-opioid agonist, may offer advantages for neurosurgical procedures in which prolonged anesthetic effects can delay assessment of the patient. This study compared the effects of remifentanilnitrous oxide on cerebral blood flow (CBF) and carbon dioxide reactivity with those of fentanyl-nitrous oxide anesthesia during craniotomy. METHODS: After institutional approval and informed patient consent were obtained, 23 patients scheduled to undergo supratentorial tumor surgery were randomly assigned to remifentanil or fentanyl infusion groups in a double-blinded manner. Midazolam, thiopental, and pancuronium induction was followed by equipotent narcotic loading infusions of remifentanil (1 microg x kg(-1) x min(-1)) or fentanyl (2 microg x kg(-1) x min(-1)) for 5-10 min. Patients were ventilated with 2:1 nitrous oxideoxygen, and opioid rates were reduced and then titrated to a stable hemodynamic effect. After dural exposure, CBF was measured by the intravenous 133xenon technique at normocapnia and hypocapnia. Reactivity of CBF to carbon dioxide was calculated as the absolute increase in CBF per millimeters of mercury increase in the partial pressure of carbon dioxide (PaCO2). Data were analyzed by repeated-measures analysis of variance, unpaired Student's t-tests, or contingency analysis. RESULTS: In the remifentanil group (n = 10), CBF decreased from 36+/-11 to 27+/-8 ml x 100 g(-1) x min(-1) as PaCO2 decreased from 33+/-5 to 25+/-2 mmHg. In the fentanyl group (n = 8), CBF decreased from 37+/-11 to 25+/-6 ml x 100 g(-1) x min(-1) as PaCO2 decreased from 34+/-3 to 25+/-3 mmHg. Absolute carbon dioxide reactivity was preserved with both agents: 1+/-1.2 ml x 100 g(-1) x min(-1) x mmHg(-1) for remifentanil and 1.5+/-0.5 ml x 100 g(-1) x min(-1) x mmHg(-1) for fentanyl (P = 0.318). CONCLUSION: Remifentanil and fentanyl have similar effects on absolute CBF, and cerebrovascular carbon dioxide reactivity is maintained.

A comparison of the cerebral hemodynamic effects of sufentanil and isoflurane in humans undergoing carotid endarterectomy.

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)

Comparison of remifentanil and fentanyl in patients undergoing craniotomy for supratentorial space-occupying lesions.

BACKGROUND: Remifentanil hydrochloride is an ultra-short-acting, esterase-metabolized mu-opioid receptor agonist. This study compared the use of remifentanil or fentanyl during elective supratentorial craniotomy for space-occupying lesions. METHODS: Sixty-three adults gave written informed consent for this prospective, randomized, double-blind, multiple-center trial. Anesthesia was induced with thiopental, pancuronium, nitrous oxide/oxygen, and fentanyl (n = 32; 2 micrograms.kg.-1. min-1) or remifentanil (n = 31; 1 mu.kg-1.min-1). After tracheal intubation, infusion rates were reduced to 0.03 microgram.kg-1.min-1 (fentanyl) or 0.2 microgram.kg-1.min-1 (remifentanil) and then adjusted to maintain anesthesia and stable hemodynamics. Isoflurane was given only after specified infusion rate increases had occurred. At the time of the first burr hole, intracranial pressure was measured in a subset of patients. At bone flap replacement either saline (fentanyl group) or remifentanil (approximately 0.2 microgram.kg-1.min-1) were infused until dressing completion. Hemodynamics and time to recovery were monitored for 60 min. Analgesic requirements and nausea and vomiting were observed for 24 h. Neurological examinations were performed before operation and on postoperative days 1 and 7. RESULTS: Induction hemodynamics were similar. Systolic blood pressure was greater in the patients receiving fentanyl after tracheal intubation (fentanyl = 127 +/- 18 mmHg; remifentanil = 113 +/- 18 mmHg; P = 0.004). Intracranial pressure (fentanyl = 14 +/- 13 mmHg; remifentanil = 13 +/- 10 mmHg) and cerebral perfusion pressure (fentanyl = 76 +/- 19 mmHg; remifentanil = 78 +/- 14 mmHg) were similar. Isoflurane use was greater in the patients who received fentanyl. Median time to tracheal extubation was similar (fentanyl = 4 min: range = -1 to 40 min; remifentanil = 5 min: range = 1 to 15 min). Seven patients receiving fentanyl and none receiving remifentanil required naloxone. Postoperative systolic blood pressure was greater (fentanyl = 134 +/- 16 mmHg; remifentanil = 147 +/- 15 mmHg; P = 0.001) and analgesics were required earlier in patients receiving remifentanil. Incidences of nausea and vomiting were similar. CONCLUSIONS: Remifentanil appears to be a reasonable alternative to fentanyl during elective supratentorial craniotomy.