Neuroprotective effect of curcumin in an experimental rat model of subarachnoid hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) causes a high mortality rate and morbidity. It was suggested that oxidant stress plays an important role in neuronal injury after SAH. Therefore, we assessed the effect of curcumin on reducing cerebral vasospasm and neurologic injury in a SAH model in rat. METHODS: A double-hemorrhage model was used to induce SAH in rats. Groups of animals were treated with intraperitoneal injection of 20 mg/kg curcumin (curcumin group, n = 24) or dimethyl sulfoxide (vehicle group, n = 33), normal saline (SAH group, n = 34) or normal saline (sham group, n = 22), 3 h after SAH induction and daily for 6 days. Glutamate was measured before SAH induction and once daily for 7 days. Glutamate transporter-1, wall thickness and the perimeter of the basilar artery, neurologic scores, neuronal degeneration, malondialdehyde, superoxide dismutase, and catalase activities were assessed. RESULTS: Changes of glutamate levels were lower in the curcumin group versus the SAH and vehicle groups, especially on day 1 (56 folds attenuation vs. vehicle). Correspondingly, glutamate transporter-1 was preserved after SAH in curcumin-treated rats. In the hippocampus and the cortex, malondialdehyde was attenuated (30% and 50%, respectively). Superoxide dismutase (35% and 64%) and catalase (34% and 38%) activities were increased in the curcumin rats compared with the SAH rats. Mortality rate (relative risk: 0.59), wall thickness (30%) and perimeter (31%) of the basilar artery, neuron degeneration scores (39%), and neurologic scores (31%) were improved in curcumin-treated rats. CONCLUSIONS: Curcumin in multiple doses is effective against glutamate neurotoxicity and oxidative stress and improves the mortality rate in rats with SAH.

A comparison of the combination of aprepitant and dexamethasone versus the combination of ondansetron and dexamethasone for the prevention of postoperative nausea and vomiting in patients undergoing craniotomy.

BACKGROUND: Postoperative nausea and vomiting (PONV) occur commonly after craniotomy. In patients receiving prophylaxis with ondansetron and dexamethasone, vomiting occurred in 45% of patients at 48 hours. In addition to causing patient discomfort, the physical act of vomiting may increase intracranial pressure or cerebral intravascular pressure, jeopardizing hemostasis and cerebral perfusion. Aprepitant is a neurokin-1 receptor antagonist with a long duration of action and no sedative side effect. In a large multicenter study in patients undergoing abdominal surgery, aprepitant was significantly more effective than was ondansetron in preventing vomiting at 24 and 48 hours postoperatively. We hypothesized that the combination of aprepitant with dexamethasone will decrease the incidence of postoperative vomiting when compared with the combination of ondansetron and dexamethasone in patients undergoing craniotomy under general anesthesia. METHODS: Patients scheduled to undergo craniotomy under general anesthesia were enrolled in this prospective, double-blind, randomized study. Patients were randomized to receive oral aprepitant 40 mg (or matching placebo) 1 to 3 hours before induction of anesthesia or ondansetron 4 mg IV (or placebo) within 30 minutes of the end of surgery. All patients received dexamethasone 10 mg after induction of anesthesia. The anesthetic technique was standardized. Data were collected at regular intervals by blinded personnel for 48 hours after surgery. Statistical analysis was performed using Wilcoxon's ranked sum test and χ(2) test. P < 0.05 was considered statistically significant. RESULTS: One hundred four patients completed the study. The cumulative incidence of vomiting at 48 hours was 16% in the aprepitant group and 38% in the ondansetron group (P = 0.0149). The incidence of vomiting was also decreased in the aprepitant group at 2 hours (6% vs. 21%, P = 0.0419) and 24 hours (14% vs. 36%, P = 0.0124). From 0 to 48 hours, there was no difference between the aprepitant and ondansetron groups in the incidence of nausea (69% vs. 60%), nausea scores, need for rescue antiemetics (65% vs. 60%), complete response (no PONV and no rescue, 22% vs. 36%), or patient satisfaction with the management of PONV. CONCLUSION: The combination of aprepitant and dexamethasone was more effective than was the combination of ondansetron and dexamethasone for prophylaxis against postoperative vomiting in adult patients undergoing craniotomy under general anesthesia. However, there was no difference between the groups in the incidence or severity of nausea, need for rescue antiemetics, or in complete response between the groups.

Temporal changes in glutamate, glutamate transporters, basilar arteries wall thickness, and neuronal variability in an experimental rat model of subarachnoid hemorrhage.

BACKGROUND: Glutamate and glutamate transporters (GTs) (including glutamate/aspartate transporter, glutamate transporter-1, and excitatory amino acid carrier 1) have important roles in the pathogenesis of ischemic neurological injury. The changes in glutamate, GTs, and neuronal injury after subarachnoid hemorrhage (SAH) have not been widely investigated. In this study, we examined the changes in extracellular glutamate concentration, GTs, wall thickness of basilar arteries (BAs), and neuronal degeneration in experimental SAH rats. METHODS: An intrathecal microdialysis probe was inserted into male Sprague Dawley rats. SAH was induced using a double-hemorrhage model. To measure glutamate concentrations, extracellular dialysates were collected for 30 minutes before, and daily for 7 days after SAH. Changes in neurological scores, body weight, and BA wall thickness were measured. The neuron degeneration in the hippocampus and the changes of GTs in the cerebral cortex and hippocampus were measured. RESULTS: Glutamate concentrations were significantly higher in SAH rats from day (D)1 to D7 after SAH compared with the sham rats, especially at D1. A significant body weight reduction and neurological defects were observed at D3 after SAH. The walls of BAs in SAH rats were significantly thicker compared with those of sham rats; the maximum change was observed at D7. Hippocampal neuronal degeneration was observed after SAH and the highest severity was at D7. The expression of GTs was downregulated after SAH and persisted for 7 days. CONCLUSIONS: SAH induced in the double-hemorrhage rat model may produce an excessive and prolonged increase of extracellular glutamate concentrations and downregulation of GTs, which are accompanied by BA wall thickness, and hippocampal neuronal degeneration.

A comparison of 3% hypertonic saline and mannitol for brain relaxation during elective supratentorial brain tumor surgery.

BACKGROUND: In this study, we compared the effects of 3% hypertonic saline (HTS) and 20% mannitol on brain relaxation during supratentorial brain tumor surgery, intensive care unit (ICU) stays, and hospital days. METHODS: This prospective, randomized, and double-blind study included patients who were selected for elective craniotomy for supratentorial brain tumors. Patients received either 160 mL of 3% HTS (HTS group, n = 122) or 150 mL of 20% mannitol infusion (M group, n = 116) for 5 minutes at the start of scalp incision. The PCO(2) in arterial blood was maintained within 35 to 40 mm Hg, arterial blood pressure was controlled within baseline values +/-20%, and positive fluid balance was maintained intraoperatively at a rate of 2 mL/kg/h. Outcome measures included fluid input, urine output, arterial blood gases, serum sodium concentration, ICU stays, and hospital days. Surgeons assessed the condition of the brain as "tight," "adequate," or "soft" immediately after opening the dura. RESULTS: Brain relaxation conditions in the HTS group (soft/adequate/tight, n = 58/43/21) were better than those observed in the M group (soft/adequate/tight, n = 39/42/35; P = 0.02). The levels of serum sodium were higher in the HTS group compared with the M group over time (P < 0.001). The average urine output in the M group (707 mL) was higher than it was in the HTS group (596 mL) (P < 0.001). There were no significant differences in fluid input, ICU stays, and hospital days between the 2 groups. CONCLUSIONS: Our results suggest that HTS provided better brain relaxation than did mannitol during elective supratentorial brain tumor surgery, whereas it did not affect ICU stays or hospital days.

Preoperative cotreatment with dextromethorphan and ketorolac provides an enhancement of pain relief after laparoscopic-assisted vaginal hysterectomy.

OBJECTIVES: Both N-methyl-D-aspartate receptor antagonists and nonsteroidal anti-inflammatory drugs have been demonstrated to produce better postoperative pain relief. The concept of multimodal analgesia has also been used for clinical pain management. The aim of the present study was to examine the analgesic effect of preoperative cotreatment with dextromethorphan (DM) and ketorolac on postoperative pain management after laparoscopic-assisted vaginal hysterectomy (LAVH). METHODS: Eighty ASA physical status I or II patients scheduled for LAVH were included and randomly assigned to 1 of 4 groups. Patients received intramuscular (IM) chorpheniramine 20 mg+ intravenous (IV) 2 mL of normal saline, IM DM 40 mg+IV 2 mL of normal saline, IM chorpheniramine 20 mg+IV 60 mg (2 mL) of ketorolac, and IM DM 40 mg+IV ketorolac 60 mg as the groups C, DM, Keto, and DM+Keto, respectively. All patients were given a patient-controlled analgesia (PCA) with morphine for pain relief postoperatively. Analgesic effects were evaluated using Visual Analog Scale pain scores at rest and during coughing, time to first PCA request for pain relief, total morphine consumption, bed rest time, and the time to first passage of flatus for 48 hours after surgery. RESULTS: Patients in DM and Keto groups had significantly better pain relief than patients in group C. Patients in DM+Keto group exhibited the best postoperative pain relief among groups in the following several categories: time to first trigger of PCA, total morphine consumption, the worst Visual Analog Scale, bed rest time, and the time to first passage of flatus, demonstrating an enhanced effect between DM and ketorolac. Neither synergistic nor antagonistic interaction was observed between DM and ketorolac. DISCUSSION: Preoperative treatment with both DM and ketorolac diminish postoperative pain. Our results suggest that the N-methyl-D-aspartate antagonist-DM and the nonsteroidal anti-inflammatory drugs-ketorolac cotreatment provide an enhancement of analgesia for postoperative pain management in patients after LAVH surgery.

Dissociation between vasospasm and functional improvement in a murine model of subarachnoid hemorrhage.

OBJECT: The efficacy of nimodipine was examined in a murine model of subarachnoid hemorrhage (SAH). End points included the diameter of the lumen of the middle cerebral artery (MCA) and behavioral outcome. An apolipoprotein E (apoE)-mimetic peptide, acetyl-AS-Aib-LRKL-Aib-KRLL-amide, previously shown to have promise in this model was tested both alone and in combination with nimodipine. The effects of carboxyamidotriazole (CAI), a non-voltage-gated calcium channel blocker, were explored using the same animal paradigm. METHODS: Experimental SAH was induced in male C57B1/6J mice. For 3 days postoperatively, behavioral analyses were performed. In the first experiment, the mice were treated with vehicle or with low- or high-dose CAI for 3 days. In the second experiment, the mice were treated with vehicle, high- and low-dose nimodipine, and/or the apoE-mimetic peptide. On postoperative Day 3 each mouse was killed and perfused. Following this, the right MCA was removed and its lumen measured. Mice that received nimodipine demonstrated significant behavioral improvements when compared with vehicle-treated mice, but there was no clear dose-dependent effect on MCA diameter. Administration of the apoE-mimetic peptide was associated with improved functional performance and a significant reduction in vasospasm. Mice that received high-dose CAI performed worse on functional tests, despite a significant increase in the diameters of their MCA lumina. CONCLUSIONS: These results demonstrate a dissociation between vasospasm and neurological outcomes that is consistent with findings of previous clinical trials.

Correlation between changes in regional cerebral blood flow and pain relief in complex regional pain syndrome type 1.

OBJECTIVE: Analyzing changes in regional cerebral blood flow (rCBF) with SPECT in complex regional pain syndrome type 1 (CRPS 1), formerly known as reflex sympathetic dystrophy, is an optimal method for evaluating effective pain relief. We attempted to investigate the correlation of changes in rCBF with pain relief during treatments of sympathetic blockade and multimodal epidural pain control. CASE REPORT: We describe a patient with severe CRPS 1 in whom conventional treatment failed to relieve the pain. Combined repeated lumbar sympathetic blocks and long-term epidural morphine, bupivacaine, and ketamine administration provided satisfactory pain relief and functional activity recovery. Six normal control subjects having one Tc-99m HMPAO scan each and the patient with CRPS having 3 Tc-99m HMPAO scans (once before treatment and twice at 4 months and 6 months after treatment, respectively). The patient with CRPS showed lower rCBF than normal controls in the left thalamus and higher rCBF than normal controls in the right parietal lobe and left frontal lobe. After subsequent treatment, the subtraction images showed increased rCBF in the left thalamus and decreased rCBF in the right parietal and left frontal lobes. CONCLUSIONS: Tc-99m HMPAO SPECT showed a relationship of rCBF in the thalamus, parietal lobe, and frontal lobe with pain relief. rCBF alterations may provide an indicator for the quality of pain management for neuropathic pains. Subtraction analysis between pre- and posttreatment, by using statistical parametric mapping (version 2), can be used as an objective indicator for the effectiveness of therapy.

Anesthetic management of an AAI pacemaker patient with paroxysmal atrial fibrillation during colorectal surgery.

Perioperative management of patients with cardiac pacemakers may be challenging because of the increasing sophistication of these devices. We report a case of a patient with paroxysmal atrial fibrillation (PAF) and with a permanent AAIR (bipolar atrial-inhibited adaptive rate) pacemaker who suffered life-threatening episodes of arrhythmias during operation. The first episode was vagally induced PAF during bowel manipulation; the second, induced by the increased pacing threshold from the external electric cardioversion and hyperkalemia. Transcutaneous pacing provided cardiac pacing and stabilized the patient during the second episode. Thorough preoperative evaluation and prophylactic placement of temporary pacing or at least transcutaneous pacing are important for the avoidance and minimization of intraoperative complications in patients with sick sinus syndrome and with an AAI (atrial inhibited) pacemaker.

Possible role for vascular cell proliferation in cerebral vasospasm after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: During vasospasm after subarachnoid hemorrhage (SAH), cerebral blood vessels show structural changes consistent with the actions of vascular mitogens. We measured platelet-derived vascular growth factors (PDGFs) in the cerebrospinal fluid (CSF) of patients after SAH and tested the effect of these factors on cerebral arteries in vivo and in vitro. METHODS: CSF was sampled from 14 patients after SAH, 6 patients not suffering SAH, and 8 normal controls. ELISA was performed for PDGF-AB, transforming growth factor-beta1, and vascular endothelial growth factor. A mouse model was used to compare cerebral vascular cell proliferation and PDGF staining in SAH compared with sham-operated controls. Normal human pial arteries were incubated for 7 days in vitro, 2 groups with human blood clot and 1 with and 1 without PDGF antibodies. RESULTS: PDGF-AB concentrations in CSF from SAH patients were significantly higher than those from non-SAH patients and normal controls, both during the first week after SAH and for all time points measured. Smooth muscle and fibroblast proliferation was observed after SAH in the mouse model, and this cellular replication was observed in conjunction with PDGF protein at the sites of thrombus. In human pial arteries, localized thrombus stimulated vessel wall proliferation, and proliferation was blocked by neutralizing antibodies directed against PDGFs. CONCLUSIONS: Vascular mitogens are increased in the CSF of patients after SAH. Proliferation of cells in the vascular wall is associated with perivascular thrombus. Cellular proliferation and subsequent vessel wall thickening may contribute to the syndrome of delayed cerebral vasospasm.

A randomized, double-blind comparison of ondansetron versus placebo for prevention of nausea and vomiting after infratentorial craniotomy.

Ondansetron was compared with placebo for nausea and vomiting prophylaxis after fentanyl/isoflurane/relaxant anesthesia and infratentorial craniotomy. Eight milligrams intravenous ondansetron or vehicle was administered at skin closure. Nausea, emesis, and antiemetic use were recorded at 0, 0.5, 1, 4, 8, 12, 24, and 48 hours. There were no significant intergroup differences for nausea incidence at any interval, but cumulatively the placebo group was 3.2 times more likely to develop nausea during the first 12 hours (P = .04). Nausea incidence was bimodal in both groups, peaking during the first 1 to 4 hours. A nadir occurred at 8 to 12 hours, but nausea increased during the next 36 hours. By 48 hours, approximately 40% of patients in both groups were still nauseated. Reduced vomiting frequency was seen with ondansetron at 4, 8, 12, and 24 hours (P < .05). Despite rescue antiemetics, emesis occurred in an irregular pattern with episodes still observed in 35% of placebo patients at 48 hours. For ondansetron, emesis was infrequent for the first 12 hours but then a persistent increase was observed (48 hours, 22%). The incidence of rescue antiemetic use was 65% for both groups. There was no effect of gender. Nausea and vomiting are frequent and protracted after infratentorial craniotomy. Administration of single-dose ondansetron (8 mg intravenously) at wound closure was partially effective in reducing acute nausea and vomiting but had little delayed benefit. Scheduled prophylactic administration of antiemetic therapy during the first 48 hours after infratentorial craniotomy should be evaluated for efficacy and safety.

Adenosine-induced transient asystole for intracranial aneurysm surgery: a retrospective review.

UNLABELLED: BRIEF SUMMARY: We describe the use of adenosine-induced cardiac arrest to facilitate intracranial aneurysm clip ligation. BACKGROUND: Cerebral aneurysms are highly variable which may result in difficult surgical exposure for clip ligation in select cases. Secure clip placement is often not feasible without temporarily decompressing the aneurysm. This can be accomplished with temporary clip ligation of proximal vessels, or with deep hypothermic circulatory arrest on cardiopulmonary bypass, although these methods have their own inherent risks. Here we describe an alternate method of decompressing the aneurysm via adenosine-induced transient asystole. METHODS: We examined the records of 27 patients who underwent craniotomy for cerebral aneurysm clipping in which adenosine was used to induce transient asystole to facilitate clip ligation. Duration of adenosine-induced bradycardia (heart rate <40) and hypotension (SBP < 60) recorded on the electronic anesthesia record and outcome data including incidence of successful clipping, intraoperative and postoperative complications, and mortality were recorded. RESULTS: Satisfactory aneurysm decompression was achieved in all cases, and all aneurysms were clipped successfully. The median dose of intravenous adenosine resulting in bradycardia greater than 30 seconds was 30 mg. The median dose of adenosine resulting in hypotension greater than 30 seconds was 15 mg, and greater than 60 seconds was 30 mg. One case of prolonged hypotension after rapid redosing of adenosine required brief closed chest compressions before circulation was spontaneously restored. No other adverse events were observed. CONCLUSIONS: Adenosine cardiac arrest is a relatively novel method for decompression of intracranial aneurysms to facilitate clip application. With appropriate safety precautions, it is a reasonable alternative method when temporary clipping of proximal vessels is not desirable or not possible.

Transient adenosine-induced asystole during the surgical treatment of anterior circulation cerebral aneurysms: technical note.

BACKGROUND: Transient adenosine-induced asystole is a reliable method for producing a short period of relative hypotension during surgical and endovascular procedures. Although the technique has been described in the endovascular treatment of brain arteriovenous malformations, aortic aneurysms, and posterior circulation cerebral aneurysms, little description of its use in anterior circulation aneurysms is available. OBJECTIVE: To assess the benefits of adenosine-induced transient asystole in complex anterior circulation aneurysms, to describe our experience in selected cases, and to provide the first experience of the use of adenosine in anterior circulation aneurysms. METHODS: The adenosine-induced cardiac arrest protocol allows us to titrate the duration of cardiac arrest on the basis of individual patient responses. The operative setup is the same as with all aneurysm clippings, with the addition of the placement of transcutaneous pacemakers as a precaution for prolonged bradycardia or asystole. Escalating doses of adenosine are given to determine the approximate dose that results in 30 seconds of asystole. When requested by the surgeon, the dose of adenosine is administered for definitive dissection and clipping. We present 6 cases in which this technique was used. RESULTS: The use of transient adenosine-induced asystole provided excellent circumferential visualization of the aneurysm neck and safe clip application. All patients did well neurologically and suffered no evidence of perioperative cerebral ischemia or delayed complication from the use of adenosine itself. CONCLUSION: Transient adenosine-induced asystole is a safe and effective technique in select circumstances that may aid in safe and effective aneurysm clipping. Along with the traditional techniques of brain relaxation, skull base approaches, and temporary clipping, adenosine-induced asystole facilitates circumferential visualization of the aneurysm neck and is another technique available to cerebrovascular surgeons.

Simvastatin treatment duration and cognitive preservation in experimental subarachnoid hemorrhage.

Cognitive dysfunction, a significant complication after subarachnoid hemorrhage (SAH), affects up to 60% of survivors. We hypothesized that oral simvastatin would improve vestibulomotor function and reduce cognitive dysfunction after experimental SAH in the rat, and explored the effects of simvastatin on vasospasm and regional cerebral blood flow (rCBF). In total 160 rats were enrolled. Randomization to simvastatin or vehicle occurred after double intracisternal blood injections. Effects of simvastatin 10 mg/kg/d (SV10), simvastatin 1.5 mg/kg/d, or vehicle on rotarod, Morris water maze, neuronal survival, cerebral arterial diameter, and rCBF were determined by a blinded observer (n=15/group). A dose dependent response to simvastatin was observed, with more rapid improvement in vestibulomotor function, less basilar arterial vasospasm, and improved cortical neuronal survival with SV10. However, rotarod performance in the SV10 group deteriorated after 1 week, which correlated with the increased plasma creatine kinase levels (r=-0.737; P=0.0002). Furthermore, when simvastatin was discontinued after 2 weeks, the usual treatment duration in SAH clinical trials, rotarod performance deteriorated acutely, rCBF returned to control values, and no long-term benefit was observed in terms of visual spatial memory. Continuing simvastatin 1.5 mg/kg/d for 5 weeks resulted in sustained improvement in rotarod performance, reduced escape latency (P=0.001), swimming distance (P=0.002), and swimming speed (P=0.03) versus vehicle (n=12/group). Our results indicate that long-term cognitive dysfunction after experimental SAH in the rat can be reduced by simvastatin. However, treatment had to be extended beyond 2 weeks, the traditional risk period for angiographic vasospasm, to improve long-term outcome.

Long-term cognitive dysfunction following experimental subarachnoid hemorrhage: new perspectives.

Cognitive dysfunction is increasingly recognized as a significant long-term complication following subarachnoid hemorrhage (SAH), affecting up to 60% of survivors. We proposed to determine the incidence and explore potential mechanisms of cognitive dysfunction in a rat model. The effects of intracisternal blood, saline and sham injections were compared. At five weeks, Morris water maze escape latency (P=0.001) and swimming distance (P=0.001) were significantly different between groups, with increased latencies and distances recorded in the blood group in spite of increased swimming speed. The number of morphologically intact cortical (r=-0.75, P=0.0001) and hippocampal CA1 (r=-0.80, P<0.0001) neurons correlated with escape latency. In spite of only slight early reductions in proximal cerebral arterial diameters, pronounced and prolonged reductions in regional cerebral blood flow were observed in SAH rats, suggesting microvascular dysfunction. In concordance, cerebral microangiographic perfusion remained incomplete even after 2 weeks. 8-hydroxydeoxyguanosine immunohistochemistry also revealed microvascular as well as neuronal oxidative DNA damage. These results provide new insights into the pathogenesis of cognitive dysfunction in SAH. They reveal a surprisingly prolonged time course of diffuse cerebrovascular insufficiency, most likely due to reversible microvascular dysfunction. Similar to findings in experimental models of vascular dementia, the data indicate a potentially important role for prolonged cerebrovascular insufficiency, probably due to microvascular dysfunction, and selective cortical and subcortical neuronal loss in cognitive failure following SAH.

Use of high frequency oscillatory ventilation (HFOV) in neurocritical care patients.

INTRODUCTION: Adult respiratory distress syndrome (ARDS) can be a common problem associated with the treatment of acute brain injury. High frequency oscillatory ventilation (HFOV) is a developing therapy for the treatment of ARDS in adult patients that can be life saving. However, often patients with acute, severe brain injury demonstrate intracranial hypertension (hICP) due to a variety of injuries (e.g., traumatic brain injury, mass lesion, acute hydrocephalus). There is concern over the use of HFOV due to its effects on intracranial pressure in patients with hICP. METHODS: Retrospective case series study. RESULTS: We describe the effects of HFOV on hemodynamics, respiratory function, and intracranial pressure in five patients with acute brain injury being treated for ARDS. CONCLUSIONS: HFOV did not cause unmanageable or sustained increases in ICP in our series of patients. It appears HFOV may be a relatively safe and effective means of oxygenating patients with severe ARDS and concomitant hICP secondary to acute brain injury.

Thromboelastography detects inadequate response to abciximab therapy during stent-assisted cerebral aneurysm coil embolization complicated by stroke.

INTRODUCTION: Thromboembolic stroke is the most common severe complication following coil embolization of intracerebral aneurysms, with a 5% incidence of permanent deficits. Despite heparin anticoagulation, rescue therapy with the platelet glycoprotein IIb/IIIa receptor antagonist abciximab may be required. However, we describe a failure of abciximab rescue therapy and discuss the importance of monitoring the variable individual response to abciximab. CASE REPORTS: Two patients underwent stent-assisted cerebral aneurysm coil embolization complicated by thromboembolic stroke. In one patient, abciximab rescue therapy failed and was associated with a poor neurological outcome. Thromboelastography (TEG model 5000; Haemoscope, Skokie, IL) and platelet aggregometry suggested inadequate platelet inhibition, although other tests of platelet function suggested adequate inhibition. CONCLUSION: We describe a failure of regular-dose abciximab rescue therapy for thromboembolic stroke-complicating stent-assisted cerebral aneurysm coil embolization. The use of TEG to individualize abciximab dosing in this setting may improve patient outcome, as it tracks a pattern of coagulation consistent with the clinical picture.

Role of vascular mitogens in subarachnoid hemorrhage-associated cerebral vasculopathy.

INTRODUCTION: Cerebral vasculopathy may play an important role in the development of delayed cerebral ischemia following subarachnoid hemorrhage (SAH). Platelet-derived growth factor AB (PDGF-AB) and vascular endothelial growth factor (VEGF) released from blood clot may trigger vasculopathy in cerebral arteries. We compared arteriographic and histological response to injection of blood with PDGF-AB and VEGF in basilar artery over 3 days. METHODS: A total of 55 male New Zealand white rabbits were used in this study. SAH was simulated by single injection of 1 ml of autologous blood, while 50 microg PDGF-AB, 100 microg VEGF, and 50 microg PDGF-AB/100 microg VEGF combined were given in autologous cerebrospinal fluid (CSF) into the cisterna magna. Eight rabbits served as controls, receiving arteriograms but no cisternal injections, and 13 rabbits received reinjections of CSF. Basilar artery diameter was measured arteriographically at baseline and 3 days after injection. Immunohistochemistry was performed to assess change in the basilar artery. RESULTS: Control groups showed significantly less (p < 0.0002) basilar artery narrowing than all treatment groups. Proliferating cell nuclear antigen (PCNA) was not significant for treatment groups compared to CSF reinject control. PCNA was significantly different for the no puncture group compared to the CSF reinject control. Von Willebrand Factor staining may indicate endothelial proliferation in the adventitia of SAH, VEGF, and PDGFAB/ VEGF combined groups. PDGF labeling was abundant for SAH, PDGF-AB, and PGDF-AB/VEGF combined. CONCLUSIONS: PDGF-AB/VEGF and VEGF cause narrowing of the basilar artery similar to cisternal blood clot at 3 days, and thus blood clot was not required to cause arteriographic changes consistent with cerebral vasculopathy.

Comparing the effects of minimal low-flow desflurane with that of semi-close high flow desflurane on perioperative cytokine response in patients undergoing gastrectomy.

BACKGROUND: Anesthetic techniques may influence the perioperative cytokine response. We investigate two anesthetic techniques: minimal low-flow anesthesia (LFA) and semi-closed high flow anesthesia (HFA) with desflurane on the effect of cytokine response in gastrectomy. METHODS: Forty patients scheduled to undergo elective gastrectomy were randomly allocated to LFA (0.3 mL/min) or HFA (2 L/min) group. Blood was sampled for measurement of tumor necrosis factor (TNF), interleukin (IL)-6, IL-8, and IL-1 receptor antagonist (RA) at scheduled intervals. Hemodynamic responses, desflurane concentrations, numbers of patient using cardiovascular agents, and frequency of vaporizer manipulations were recorded during the operation. RESULTS: For patients in the LFA group, production of IL-8 was significantly less increased at the end of the surgical procedure; however there was no significant difference in total production between groups. There was no significant difference in TNF, IL-6, and IL-1RA production throughout the observed period. The desflurane vaporizer was adjusted more frequently (4 [13-6] versus 2 [1-3] times) for patients in the HFA group, and more patients in this group required the use of cardiovascular agents (10 versus 4) than patients in the LFA group during the operation. CONCLUSIONS: The current study demonstrates that smaller increase in cytokine production in the LFA than HFA with desflurane for the patients receiving gastrectomy.

A retrospective analysis of a remifentanil/propofol general anesthetic for craniotomy before awake functional brain mapping.

UNLABELLED: We performed this study to summarize drug dosing, physiologic responses, and anesthetic complications from an IV general anesthetic technique for patients undergoing craniotomy for awake functional brain mapping. Review of 98 procedures revealed "most rapid" IV infusion rates for remifentanil 0.05, 0.05-0.09 microg x kg(-1) x min(-1) and propofol 115, 100-150 microg x kg(-1) x min(-1). The infusions lasted for 78, 58-98 min. Intraoperative emergence from general anesthesia was 9 (6-13) min after discontinuing IV infusions to allow for brain mapping and was independent of infusion duration and duration of craniotomy before mapping. Spontaneous ventilation was generally satisfactory during drug infusion, as evidenced by Sao(2) = 95% (92%-98%) and Paco(2) = 50 (47-55) mm Hg. However, we recorded at least one 30-s epoch of apnea in 69 of 96 patients. Maximum systolic arterial blood pressure was 150 (139-175) mm Hg and minimal systolic arterial blood pressure was 100 (70-150) mm Hg during drug infusion. Three patients experienced intraoperative seizures. Two patients did not tolerate the awake state and required reinduction of general anesthesia. No patients required endotracheal intubation or discontinuation of surgery. This general anesthetic technique is effective for craniotomy with awake functional brain mapping and offers an alternative to continuous wakefulness or other IV sedation techniques. IMPLICATIONS: An IV general anesthetic technique using remifentanil and propofol is an effective method allowing for reliable emergence for intraoperative awake functional brain mapping during craniotomy.