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.

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.

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.

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.