Fever after subarachnoid hemorrhage: risk factors and impact on outcome.

OBJECTIVE: To identify risk factors for refractory fever after subarachnoid hemorrhage (SAH), and to determine the impact of temperature elevation on outcome. METHODS: We studied a consecutive cohort of 353 patients with SAH with a maximum daily temperature (T(max)) recorded on at least 7 days between SAH days 0 and 10. Fever (>38.3 degrees C) was routinely treated with acetaminophen and conventional water-circulating cooling blankets. We calculated daily T(max) above 37.0 degrees C, and defined extreme T(max) as daily excess above 38.3 degrees C. Global outcome at 90 days was evaluated with the modified Rankin Scale (mRS), instrumental activities of daily living (IADLs) with the Lawton scale, and cognitive functioning with the Telephone Interview of Cognitive Status. Mixed-effects models were used to identify predictors of T(max), and logistic regression models to evaluate the impact of T(max) on outcome. RESULTS: Average daily T(max) was 1.15 degrees C (range 0.04 to 2.74 degrees C). The strongest predictors of fever were poor Hunt-Hess grade and intraventricular hemorrhage (IVH) (both p < 0.001). After controlling for baseline outcome predictors, daily T(max) was associated with an increased risk of death or severe disability (mRS > or = 4, adjusted OR 3.0 per degrees C, 95% CI 1.6 to 5.8), loss of independence in IADLs (OR 2.6, 95% CI 1.2 to 5.6), and cognitive impairment (OR 2.5, 95% CI 1.2 to 5.1, all p < or = 0.02). These associations were even stronger when extreme T(max) was analyzed. CONCLUSION: Treatment-refractory fever during the first 10 days after subarachnoid hemorrhage (SAH) is predicted by poor clinical grade and intraventricular hemorrhage, and is associated with increased mortality and more functional disability and cognitive impairment among survivors. Clinical trials are needed to evaluate the impact of prophylactic fever control on outcome after SAH.

Recovery of brain function during induced cerebral hypoperfusion.

We used the setting of clinically indicated internal carotid artery balloon test occlusions in 44 patients with inoperable carotid cavernous aneurysms or head and neck tumours to examine real-time changes in higher cerebral function that correlate with specific levels of cerebral blood flow. By making detailed haemodynamic and neurobehavioural measurements during the 30 min the carotid artery was occluded, we were able to quantify higher cerebral function patterns in relation to absolute cerebral blood flow (CBF) levels. We found that once the carotid artery was occluded, patients whose CBF averaged 47 ml/100 g/min (no different from baseline) maintained consistent performance on a sustained attention task; those whose CBF dropped to an average 37 ml/100 g/min had a reversible deterioration of sustained attention, and those whose CBF fell to 27 ml/100 g/min had impaired sustained attention that persisted until the carotid occlusion was reversed. The relevance of these results to the pathological state of clinical stroke is discussed with respect to the haemodynamic and physiological mechanisms that may determine how brain function is lost and regained in the setting of acute cerebral hypoperfusion.

Effect of intracarotid papaverine on human cerebral blood flow and vascular resistance during acute hemispheric arterial hypotension.

This study assessed the feasibility of augmenting cerebral blood flow (CBF) and decreasing hemispheric cerebrovascular resistance (CVR) by intracarotid papaverine during acute cerebral hypotension. Awake patients (n = 10) undergoing transfemoral balloon occlusion of an internal carotid artery (ICA) with nitroprusside (SNP)-induced systemic hypotension (10% reduction of mean arterial pressure) were studied. We measured mean femoral artery pressure (MAP), mean distal ICA pressure (P(ica)), and CBF (intracarotid 133Xe) at two time points: before and after intracarotid papaverine infusion (1 or 7 mg/min). Two patients became symptomatic immediately after ICA occlusion and were excluded. One patient developed a focal seizure during papaverine infusion. In another, the occlusion balloon deflated prematurely. Of the remaining six patients, two of the three patients who received high-dose papaverine (7 mg/min) developed transient obtundation. The remaining three patients, who received low-dose papaverine (1 mg/min), did not develop any neurologic symptoms. There was a trend for intracarotid papaverine to increase hemispheric CBF by 36% (33 +/- 10 versus 45 +/- 22 ml x 100 g(-1) x min(-1), P = .084, n = 6); papaverine decreased CVR from 1.3 +/- 0.4 to 1.0 +/- 0.3 mm Hg x ml(-1) x 100 g(-1) x min(-1) (P = .049). There was no significant change in heart rate, MAP, or P(ica) during experimental protocol. Manipulation of CVR by intracarotid papaverine during acute hemispheric arterial hypotension appears to be feasible. Further studies are needed to establish safety and efficacy.

Adenosine-induced ventricular asystole to induce transient profound systemic hypotension in patients undergoing endovascular therapy. Dose-response characteristics.

BACKGROUND: Adenosine-induced asystole has been used to induce transient systemic hypotension for various vascular procedures. Dose-response characteristics of adenosine-induced ventricular asystole have not been determined. METHODS: During endovascular embolization of cerebral arteriovenous malformations, the authors performed a series of adenosine test injections to establish a dose-response relation in each patient. After an interval of 3-10 min, the dose was escalated by 10-20 mg for each injection to achieve an end point of 20-30 s of stable mean arterial pressure (MAP) reduction to 25-30 mmHg. All patients received constant infusion of nitroprusside (approximately 1 microgram. kg-1. min-1) throughout the procedure. RESULTS: The authors studied four adult patients (age, 22-44 yr; two patients had two separate procedures) and one pediatric patient (age, 4 yr). Twenty-three adenosine injections resulted in measurable asystole. The adenosine dose was 0. 98 +/- 0.40 mg/kg (mean +/- SD), and the dose range was 0.24-1.76 mg/kg (6-90 mg). The duration of asystole, MAP < 30 mmHg, and MAP < 50 mmHg, were 8 +/- 3 s, 18 +/- 12 s, and 50 +/- 29 s, respectively. The minimum MAP and the MAP for the first 20 s were 16 +/- 3 mmHg and 30 +/- 9 mmHg, respectively. There was a linear relation between adenosine dose and the duration of hypotension with MAP < 30 mmHg and MAP < 50 mmHg. CONCLUSIONS: In the dose range studied, a series of adenosine test injections can be used to determine optimal adenosine dose for induction of transient profound hypotension.

Intracarotid infusion of the nitric oxide synthase inhibitor, L-NMMA, modestly decreases cerebral blood flow in human subjects.

BACKGROUND: The authors hypothesized that if nitric oxide (NO) was a determinant of background cerebrovascular tone, intracarotid infusion of NG-monomethyl-L-arginine (L-NMMA), a NO synthase (NOS) inhibitor, would decrease cerebral blood flow (CBF) and intracarotid L-arginine would reverse its effect. METHODS: In angiographically normal cerebral hemispheres, after the initial dose-escalation studies (protocol 1), the authors determined the effect of intracarotid L-NMMA (50 mg/min for 5 min) on CBF and mean arterial pressure (MAP) over time (protocol 2). Changes in CBF and MAP were then determined at baseline, during L-NMMA infusion, and after L-NMMA during L-arginine infusion (protocol 3). To investigate effects of higher arterial blood concentrations of L-NMMA, changes in CBF and MAP were assessed at baseline and after a bolus dose of L-NMMA (250 mg/1 min), and vascular reactivity was tested by intracarotid verapamil (1 mg/min, protocol 4). CBF changes were also assessed during induced hypertension with intravenous phenylephrine (protocol 5). RESULTS: Infusion of L-NMMA (50 mg/min for 5 min, n = 7, protocol 2) increased MAP by 17% (86 +/- 8 to 100 +/- 11 mmHg; P < 0.0001) and decreased CBF by 20% (45 +/- 8 to 36 +/- 6 ml. 100 g-1. min-1; P < 0.005) for 10 min. Intracarotid l-arginine infusion after L-NMMA (protocol 3) reversed the effect of L-NMMA. Bolus L-NMMA (protocol 4) increased MAP by 20% (80 +/- 11 to 96+/-13 mmHg; P< 0.005), but there was no significant decrease in CBF. Intracarotid verapamil increased CBF by 41% (44+/- 8 to 62 +/- 9 ml. 100 g-1. min-1; P< 0.005). Phenylephrine-induced hypertension increased MAP by 20% (79 +/- 9 to 95 +/- 6 mmHg; P = 0.001) but did not affect CBF. CONCLUSIONS: The results suggest that intracarotid L-NMMA modestly decreases CBF, and the background tone of cerebral resistance vessels may be relatively insensitive to NOS inhibition by the intraarterial route.

Adenosine-induced cardiac pause for endovascular embolization of cerebral arteriovenous malformations: technical case report.

OBJECTIVE: Extremely high flow through arteriovenous malformations (AVMs) may limit the safety and effectiveness of endovascular glue therapy. To achieve a more controlled deposition of glue, we used transient but profound systemic hypotension afforded by an intravenously administered bolus of adenosine to induce rapidly reversible high-degree atrioventricular block. METHODS AND CASE REPORT: A patient with a large high-flow occipital AVM fed primarily by the posterior cerebral artery underwent n-butyl cyanoacrylate glue embolization. Nitroprusside-induced systemic hypotension did not adequately reduce flow through the nidus, as determined by contrast injection in the feeding artery. In a dose-escalation fashion, boluses of adenosine were administered to optimize the dose and verify that there was no flow reversal in the AVM and no other unexpected hemodynamic abnormalities by arterial pressure measurements and transcranial Doppler monitoring of the posterior cerebral artery feeding the AVM. Thereafter, 64 mg of adenosine was rapidly injected as a bolus to provide 10 to 15 seconds of systemic hypotension (approximately 20 mm Hg). Although there were conducted beats and some residual forward flow through the AVM during this time, the mean systemic and feeding artery pressures were roughly similar and remained relatively constant. A slow controlled injection of n-butyl cyanoacrylate glue was then performed, with excellent filling of the nidus. CONCLUSION: Adenosine-induced cardiac pause may be a viable method of partial flow arrest in the treatment of cerebral AVMs. Safe, deep, and complete embolization with a permanent agent may increase the likelihood of endovascular therapy's being curative or may further improve the safety of microsurgical resection.

The feasibility of intracarotid adenosine for the manipulation of human cerebrovascular resistance.

UNLABELLED: To assess the feasibility of manipulating human cerebrovascular resistance with adenosine, we measured cerebral blood flow (CBF) by determining the initial slope (IS) of tracer washout 20-80 s after intracarotid 133Xe injection (standard IS) during sequential 3-min intracarotid infusions of (a) saline; (b) adenosine 1.2-mg bolus followed by an infusion of 1 mg/min (bolus + infusion); (c) saline; and (d) nicardipine (0.1 mg/min). During 133Xe washout, adenosine caused a rapidly clearing compartment. Therefore, tracer washout was also analyzed 5-25 s after injection (early IS). Nicardipine (n = 8) increased both standard IS (from 39+/-12 to 53+/-16 mL 100g.min(-1); P < 0.005) and early IS (from 40+/-9 to 55+/-20 arbitrary units; P < 0.02) to a similar degree. Adenosine bolus + infusion increased early IS (from 33+/-6 to 82+/-43 arbitrary units; P < 0.02) but did not increase standard IS (from 41+/-12 to 43 +/-16 mL 100g(-1) min(-1)). Standard and early IS values were then determined before and after adenosine delivered either by infusion alone (2 mg/min for 3 min, n = 5) or bolus alone (2 mg in 1 s, n = 3). Neither standard nor early IS changed after adenosine infusion alone. Early IS increased after adenosine bolus alone. Increase in early IS, but not standard IS, suggests a transient (<30 s) increase in CBF. IMPLICATIONS: Intracarotid adenosine, in the 1- to 2-mg dose range, may cause a transient, but not a sustained, increase in cerebral blood flow. Intracarotid adenosine in such a dose range does not seem to be an appropriate drug for sustained manipulation of cerebrovascular resistance.

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.

Manipulation of cerebrovascular resistance during internal carotid artery occlusion by intraarterial verapamil.

UNLABELLED: Occlusion of the internal carotid artery (ICA) results in acute cerebral hypotension. We hypothesized that during acute cerebral hypotension, in addition to physiological autoregulation, further arteriolar relaxation is possible by pharmacological means. We tested the feasibility of using intracarotid verapamil, a calcium channel blocker, to decrease the cerebrovascular resistance (CVR) and augment cerebral blood flow (CBF) at low postocclusion distal ICA pressures (PICA). Eleven patients undergoing trial occlusion of ICA were enrolled. Distal ICA or stump pressure, hemispheric CBF, and CVR were determined before and after carotid occlusion. During ICA occlusion, CBF and other physiological variables were determined before and after intracarotid verapamil. Two patients were excluded from the study. Carotid occlusion (n = 9) significantly decreased PICA (mean +/- SD, from 82 +/- 22 to 46 +/- 11 mm Hg, P = 0.001) and CBF (from 42 +/- 11 to 33 +/- 11 mL.100 g-1.min-1, P < 0.05). During occlusion, after intracarotid verapamil (3.9 +/- 1.6 mg), hemispheric CBF tended to increase from 31 +/- 11 to 35 +/- 14 mL.100 g-1.min-1 (P = 0.067). However, the percent increase in CBF after verapamil was a linear function of PICA (y = 1.01 x -32, n = 9, r2 = 0.84, P = 0.006). The decrease in CBF during carotid occlusion suggests that near maximal cerebral autoregulatory vasodilation had occurred, although our results indicate that it may be feasible to further augment CBF by pharmacological means during acute cerebral hypotension. IMPLICATIONS: When the internal carotid artery is occluded during neurosurgical procedures, there may be a significant reduction in cerebral perfusion. The authors have demonstrated that the intraarterial administration of verapamil increases cerebral blood flow as a linear function of cerebral artery pressure. Intracarotid injection of vasodilators may augment cerebral blood flow during acute cerebral hypotension.

Intra-arterial nitrovasodilators do not increase cerebral blood flow in angiographically normal territories of arteriovenous malformation patients.

BACKGROUND AND PURPOSE: The mechanism of adaptation to chronic cerebral hypotension in normal brain adjacent to cerebral arteriovenous malformations (AVMs) is unknown. To clarify these mechanisms, we performed cerebral blood flow (CBF) studies in structurally and functionally normal vascular territories during 53 distal cerebral angiographic procedures in 37 patients with AVMs. METHODS: CBF was measured using the superselective intra-arterial 133Xe method before and after a 3-minute infusion of either verapamil (1 mg.min-1, n = 23), acetylcholine (1.33 micrograms.kg-1.min-1, n = 7), nitroprusside (0.5 microgram.kg-1.min-1, n = 16) or nitroglycerin (0.5 microgram.kg-1.min-1, n = 7). RESULTS: Mean +/- SD systemic (76 +/- 13 mm Hg) and distal cerebral arterial (55 +/- 16 mm Hg; range, 20 to 97 mm Hg) pressures were not different among groups. Verapamil increased CBF (45 +/- 12 to 65 +/- 21 mL.100 g-1.min-1, P < .001). There was no effect of acetylcholine (no change [46 +/- 9 to 46 +/- 9 mL.100 g-1.min-1], NS) or nitroglycerin (36 +/- 14 to 36 +/- 13 mL.100 g-1.min-1, NS). Nitroprusside decreased CBF (40 +/- 12 to 31 +/- 11 mL.100 g-1.min-1, P < .001). The percent change in CBF after drug administration was proportional to cerebral arterial pressure for verapamil only (r = .57, P = .0051). CONCLUSIONS: When infused intra-arterially in clinically relevant doses in both hypotensive and normotensive normal vascular territories remote from an AVM nidus, calcium channel blockade caused vasodilation, but there was an absence of response to nitric oxide-mediated vasodilators. These data suggest that (1) the nitric oxide pathway probably is not involved in the adaptation to chronic cerebral hypotension in AVM patients and (2) if our findings in vessels remote from or contralateral to the AVM are applicable to vessels of patients with other forms of cerebrovascular disease, clinically relevant doses of intra-arterial nitrovasodilators may not be useful in the manipulation of cerebrovascular resistance.

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.

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.

Superselective intraarterial papaverine administration: effect on regional cerebral blood flow in patients with arteriovenous malformations.

In this study the authors determined the effect of papaverine on regional cerebral blood flow (rCBF) in the angiographically normal arteriolar beds of patients with arteriovenous malformations (AVMs) who underwent transfemoral superselective angiography. Middle cerebral artery (MCA) branch vessels were catheterized during 10 procedures performed in nine patients. The mean (+/- standard deviation) largest AVM diameter was 4.4 +/- 1 cm. Regional CBF was measured by recording the washout of a bolus of xenon-133 injected through the microcatheter. In a dose-ranging study. rCBF and MCA pressure in two patients were repeatedly measured after 3-minute infusions of papaverine at 0.07, 0.7, and 7 mg/minute. In a single-dose study, an additional eight patients received only the highest dose of papaverine administered over a 3-minute period. In the dose-ranging study, CBF increased from baseline in a dose-dependent fashion. In the single-dose study, papaverine increased in rCBF 103%, from 48 +/- 11 to 95 +/- 23 ml/100 g/minute at an MCA pressure of 55 +/- 23 mm Hg. Increase in rCBF was linearly related (y = 2.2x - 17, r2 = 0.84; p = 0.001) to baseline MCA pressure (range 22-84 mm Hg). Papaverine increases rCBF in a direct proportion to baseline MCA pressure, even at low baseline pressures. Selective infusion of vasodilators should be investigated in acute cerebral hypotension to facilitate either primary or collateral recruitment of CBF by aiding spontaneous autoregulatory vasodilation. In addition, rCBF monitoring may be useful in determining the most effective intraarterial dose of papaverine while minimizing complications due to hyperemia.

Consequences of electroencephalographic-suppressive doses of propofol in conjunction with deep hypothermic circulatory arrest.

BACKGROUND: Some patients who undergo cerebral aneurysm surgery require cardiopulmonary bypass and deep hypothermic circulatory arrest. During bypass, these patients often are given large doses of a supplemental anesthetic agent in the hope that additional cerebral protection will be provided. Pharmacologic brain protection, however, has been associated with undesirable side effects. These side effects were evaluated in patients who received large doses of propofol. METHODS: Thirteen neurosurgical patients underwent cardiopulmonary bypass and deep hypothermic circulatory arrest to facilitate clip application to a giant or otherwise high-risk cerebral aneurysm. Electroencephalographic burst suppression was established before bypass with an infusion of propofol, and the infusion was continued until the end of surgery. Hemodynamic and echocardiographic measurements were made before and during the prebypass propofol infusion and again after bypass. Emergence time also was determined. RESULTS: Prebypass propofol at 243 +/- 57 micrograms.kg-1.min-1 decreased vascular resistance from 34 +/- 8 to 27 +/- 8 units without changing heart rate, arterial or filling pressures, cardiac index, stroke volume, or ejection fraction. Propofol blood concentration was 8 +/- 2 micrograms/ml. Myocardial wall motion appeared hyperdynamic at the end of cardiopulmonary bypass, and all patients were weaned therefrom without inotropic support. After bypass, vascular resistance decreased further, and cardiovascular performance was improved compared to baseline values. Nine of the 13 patients emerged from anesthesia and were able to follow commands at 3.1 +/- 1.4 h. Three others had strokes and a fourth had cerebral swelling. CONCLUSIONS: Propofol infused at a rate sufficient to suppress the electroencephalogram does not depress the heart or excessively prolong emergence from anesthesia after cardiopulmonary bypass and deep hypothermic circulatory arrest.

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.

Pharmacodynamics and pharmacokinetics of cisatracurium in geriatric surgical patients.

BACKGROUND: Cisatracurium, one of ten stereoisomers that comprise atracurium, is more potent than atracurium and has less propensity to release histamine. This study compares the pharmacokinetics and pharmacodynamics of cisatracurium in elderly and young patients. METHODS: Twelve elderly (aged 65-82 yr) and 12 younger patients (aged 30-49 yr) were anesthetized with nitrous oxide, fentanyl, and isoflurane (0.7%, end-tidal). The mechanomyographic response to train-of-four stimulation was assessed every 15 s after the administration of cisatracurium (0.1 mg/kg). Arterial samples were obtained over 6 h. Plasma cisatracurium concentration versus time data were fit to compartmental models. Pharmacokinetic parameters were determined assuming that elimination occurred from the central compartment only. This provides accurate clearance and half-life estimates but underestimates V(ss) (reported herein as V(ss). The pharmacodynamic response was described by the neuromuscular blocking profile. RESULTS: Onset to 90% paralysis (mean +/- SD) was delayed in the elderly (3.4 +/- 1.0 vs. 2.5 +/- 0.6 min). Recovery profiles were the same for both groups. Elimination half-life was minimally prolonged in the elderly (25.5 +/- 3.7 vs. 21.5 +/- 2.4 min). The Vss was larger in the elderly (126 +/- 16 vs. 108 +/- 13 ml/kg), although the clearances were the same for the two groups (5.0 +/- 0.9 vs. 4.6 +/- 0.8 ml.kg(-1).min(-1). CONCLUSIONS: There are minor differences in the pharmacokinetics of cisatracurium between elderly and young patients. These differences are not associated with changes in recovery profile after a single bolus dose, although the mean time to onset was approximately 1 min longer in elderly patients.

Aging alters the pharmacokinetics of pyridostigmine.

The duration of the antagonism to neuromuscular blockade produced by pyridostigmine is prolonged in elderly patients, and a pharmacokinetic explanation was sought. Ten elderly (71-85 yr) and 10 younger (21-51 yr) patients were anesthetized with thiopental, nitrous oxide, and isoflurane and paralyzed with a combination of d-tubocurarine and pancuronium. When twitch height returned to 5% of baseline, pyridostigmine 0.25 mg/kg was administered and blood samples were collected intermittently for 6 h. Pyridostigmine plasma concentrations were determined by radioimmunoassay and after an hour were always greater in the elderly than in the younger patients. In both groups, plasma pyridostigmine decrement curves were best described by triexponential equations. Pharmacokinetic analysis revealed that plasma clearance in the elderly group was significantly decreased compared to that in the younger group (6.7 +/- 2.2 vs 9.5 +/- 2.7 mL.kg-1.min-1, P < 0.05). Elimination half-lives and volumes of distribution were not significantly different between groups. We conclude that a possible explanation for the prolonged duration of action of pyridostigmine in the elderly is its slow plasma clearance.

Are all effects of esmolol equally rapid in onset?

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.

Do standard monitoring sites reflect true brain temperature when profound hypothermia is rapidly induced and reversed?

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.

Characterization of arteriovenous malformation feeding vessels by carbon dioxide reactivity.

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.