Correlation Between Serum and CSF Concentrations of Midazolam and 1-Hydroxy-Midazolam in Critically Ill Neurosurgical Patients.

BACKGROUND: Midazolam (MZ) is commonly used in critically ill neurosurgical patients. Neuro-penetration of MZ and its metabolite, 1-hydroxy-midazolam (1-OH-MZ), is not well characterized. OBJECTIVE: This study evaluated correlations between serum and cerebrospinal fluid (CSF) concentrations of MZ and 1-OH-MZ and assessed implications on patient sedation. METHODS: Adults in the neurosurgical intensive care unit (ICU) with external ventricular drains receiving MZ via continuous infusion were prospectively studied. Serum and CSF samples were obtained 12-24 h and 72-96 h after initiation, and concentrations were determined in duplicate by high-performance liquid chromatography with tandem mass spectrometry. Bivariate correlation analyses used Pearson coefficient. RESULTS: A total of 31 serum and CSF samples were obtained from 18 subjects. At sampling, mean MZ infusion rate was 3.9 ± 4.4 mg/h, and previous 12-h cumulative dose was 51.4 ± 78.2 mg. Mean concentrations of MZ and 1-OH-MZ in serum and CSF were similar between timepoints. Similarly, ratios of 1-OH-MZ to MZ in serum and CSF remained stable over time. Serum MZ (126.2 ± 89.3 ng/mL) showed moderate correlation (r2 = 0.68, P < 0.001) with serum 1-OH-MZ (17.7 ± 17.6 ng/mL) but not CSF MZ (3.9 ± 2.5 ng/mL; r2 = 0.24, P = 0.005) or CSF 1-OH-MZ (2.5 ± 0.6 ng/mL; r2 = 0.47, P = 0.30). CSF MZ did not correlate with CSF 1-OH-MZ (r2 = 0.003, P < 0.001). Mean serum ratio of 1-OH-MZ to MZ (0.14 ± 0.2 ng/mL) did not correlate with CSF ratio (1.06 ± 0.83 ng/mL; r2 = 0.06, P = 0.19). Concentrations and ratios were unrelated to MZ infusion rate or 12-h cumulative dose. Sedation was weakly correlated with CSF 1-OH-MZ, but not with serum MZ, serum 1-OH-MZ, or CSF MZ. CONCLUSION AND RELEVANCE: Continuous infusions of MZ result in measurable concentrations of MZ and 1-OH-MZ in CSF; however, CSF concentrations of MZ and 1-OH-MZ poorly represent serum concentrations or dosages. Accumulation of MZ and 1-OH-MZ in serum or CSF over time was not evident. Concentrations of MZ and 1-OH-MZ do not predict sedation levels, reinforcing that pharmacodynamic assessments are warranted.

Periprocedural management of ruptured blister aneurysms treated with pipeline flow diversion.

Background: Blister aneurysms are high-risk intracranial vascular lesions. Definitive treatment of these lesions has been challenging. Severe disability or mortality rates are as high as 55% when these lesions are treated with open surgery. Recent data show that flow diversion is a safe and effective alternative treatment for blister aneurysms. Rerupture of the functionally unsecured lesion remains a concern as flow diversion does not immediately exclude the aneurysm from the circulation. Methods: A retrospective review was performed of any patients with ruptured blister aneurysms treated with a pipeline embolization device between 2010 and 2020 at the University of Colorado. Results: In this paper, we present the results of the intensive care management of ruptured intracranial blister aneurysms after flow-diverting stent placement. Conclusion: Despite the need for dual antiplatelet therapy and the delayed occlusion of blister aneurysms treated with flow diversion, we did not find an increase in periprocedural complications.

Anti-neutrophil cytoplasmic antibody associated central nervous system vasculitis with brain and spinal cord subarachnoid hemorrhage: A rare case report and review of the literature.

This case report describes a 48-year old female who presented with altered mental status, lower extremity weakness, low back pain and a recent history of subjective fevers and night sweats found to have posterior parieto-occipital and spinal subarachnoid hemorrhage on imaging. Further work-up revealed vasculitic changes in the intracranial vasculature and the external carotid artery on angiography. She also demonstrated positivity for perinuclear anti-neutrophil cytoplasmic (p-ANCA) antibodies overall consistent with ANCA associated central nervous system vasculitis (AAV). The present case describes a rare and new presentation of AAV that caused both a cerebral and spinal subarachnoid hemorrhage. There has been no documentation of spinal subarachnoid hemorrhage associated with primary or secondary vasculitis in the literature. Ultimately, this case demonstrates the important finding that AAV can have spinal cord manifestations and cervical vasculature involvement along with the more classic intra-cranial vasculitis findings.

Divergent humoral responses to 23-valent pneumococcal polysaccharide vaccine in critically-ill burn and neurosurgical patients.

INTRODUCTION: Critically ill hospitalized patients are at increased risk of infection so we assessed the immunogenicity of 23-valent pneumococcal polysaccharide vaccine (PPSV23) administered within six days of injury. METHODS: This prospective observational study compared the immunogenicity of PPSV23 among critically ill burn and neurosurgical patients at a tertiary, academic medical center. Patients received PPSV23 vaccination within six days of ICU admission per standard of care. Consent was obtained to measure concentrations of vaccine-specific IgG to 14 of 23 serotype capsule-specific IgG in serum prior to and 14-35 days following PPSV23. A successful immunologic response was defined as both a ≥2-fold rise in capsule-specific IgG from baseline and concentrations of >1 mcg/mL to 10 of 14 measured vaccine serotypes. Immunologic response was compared between burn and neurosurgical patients. Multiple variable regression methods were used to explore associations of clinical and laboratory parameters to immunologic responses. RESULTS: Among the 16 burn and 27 neurosurgical patients enrolled, 87.5% and 40.7% generated a successful response to the vaccine, respectively (p = 0.004). Both median post-PPSV23 IgG concentrations (7.79 [4.56-18.1] versus 2.93 [1.49-8.01] mcg/mL; p = 0.006) and fold rises (10.66 [7.44-14.56] versus 3.48 [1.13-6.59]; p<0.001) were significantly greater in burn compared with neurosurgical patients. Presence of burn injury was directly and days from injury to immunization were inversely correlated with successful immunologic response (both p<0.03). Burn injury was associated with both increased median antibody levels post-PPSV23 and fold rise to 14 vaccine serotypes (p<0.03), whereas absolute lymphocyte count was inversely correlated with median antibody concentrations (p = 0.034). CONCLUSION: Critically ill burn patients can generate successful responses to PPSV23 during acute injury whereas responses among neurosurgical patients is comparatively blunted. Further study is needed to elucidate the mechanisms of differential antigen responsiveness in these populations, including the role of acute stress responses, as well as the durability of these antibody responses.

Levetiracetam Pharmacokinetics in a Patient with Intracranial Hemorrhage Undergoing Continuous Veno-Venous Hemofiltration.

BACKGROUND Levetiracetam is an antiepileptic drug frequently used in critically ill patients. Levetiracetam is primarily eliminated as a parent compound via glomerular filtration and requires dose adjustment in renal insufficiency, but the literature on patients receiving continuous veno-venous hemofiltration (CVVH) is scant. CASE REPORT We report the levetiracetam pharmacokinetic profile of a patient being treated with levetiracetam 1000 mg intravenously every 12 h who required continuous veno-venous hemofiltration (CVVH). The patient underwent CVVH utilizing a high-flux polyethersulfone membrane filter. The blood flow rate was 250 ml/min, and the predilution replacement therapy fluid flow rate was 2000 ml/h. After achieving presumed steady-state on levetiracetam 1000 mg q12h, serial plasma samples (pre- and post-filter) and effluent samples were drawn at 2, 4, 6, 8, and 10 h. Levetiracetam concentrations were determined utilizing LC-MS/MS. The levetiracetam maximum concentration (Cmax), minimum concentration (Cmin), half-life, area under the concentration-time curve (AUC0-12), clearance (CL), and volume of distribution (Vd) were 30.7 µg/ml, 16.1 µg/ml, 12.9 h, 272 mg·hr/L, 3.68 L/h, and 0.73 L/kg, respectively. The sieving coefficient was 1.03±0.08. CVVH represented 61.3% of the total levetiracetam clearance. The patient was maintained on CVVH for 24 consecutive days and then transitioned to intermittent hemodialysis and remained seizure-free. CONCLUSIONS CVVH is highly effective in removing levetiracetam from circulating plasma. Due to the effective removal, standard doses of levetiracetam are required to maintain adequate plasma concentrations. Dose reductions utilizing HD or estimated creatinine clearance recommendations will likely lead to subtherapeutic levels, especially if higher CVVH flow rates are used.

Ruptured Distal Posterior Inferior Cerebellar Artery (PICA) Aneurysms Associated with Cerebellar Arterial Venous Malformations (AVMs): A Case Series and Review of the Literature Demonstrating the Need for Angiographic Evaluation and Feasibility of Endovascular Treatment.

OBJECTIVE: The characteristics, diagnosis, and preferred management strategies for distal posterior inferior cerebellar artery (PICA) aneurysms associated with cerebellar arteriovenous malformation (AVMs) are poorly understood. We present a case series with attention to aneurysm angioarchitecture, diagnostic imaging, treatment approaches, and a thorough review of the literature. With this information, we demonstrate a specific anatomical pattern for these aneurysms, an underreported need for conventional digital subtraction angiography (DSA) during evaluation, along with the utility of endovascular treatment with liquid embolic agents. METHODS: Neurosurgical patients from 2005 to 2016 were reviewed to identify PICA aneurysms along with distal PICA aneurysms. Details of their presentation, imaging studies, associated AVMs and treatment were recorded. A thorough literature search of previous case series and case reports of distal PICA aneurysms with and without associated small cerebellar AVMs was performed with PubMed and Google Scholar. RESULTS: Thirty-four patients with PICA aneurysms were identified at our institution, 12 of which were in a distal segment. All 12 of these patients underwent DSA as a part of their evaluation. Of the 12 patients with distal PICA aneurysms, 9 presented with subarachnoid hemorrhage and intraventricular hemorrhage. Five of these patients had a small occult cerebellar AVM. All nine patients presenting with a ruptured distal PICA aneurysm had a Fischer grade 4 subarachnoid hemorrhage. Of the five patients with a small occult cerebellar AVM, the AVM nidus was missed on computed tomography angiogram (CTA) interpretation but easily visualized with DSA. CTA followed by DSA with concurrent endovascular treatment was performed in 9 of the 12 patients with distal PICA aneurysms. Two of the 12 patients were treated with microsurgical clip ligation, and one mycotic aneurysm was identified and treated with antibiotics. Parent vessel sacrifice was used distal to the aneurysm in all 5 associated AVM cases with liquid embolic agents as well as AVM embolization in 3 of the 5 cases. Fifty-one well-described case reports of distal PICA aneurysms associated with small cerebellar AVMs have been reported in the literature. A total of 12 well-described case series of distal PICA aneurysms that comment on associated AVMs describe an associated small cerebellar AVM incidence of 4%-50%. In our case series, the incidence of an associated small cerebellar AVM with a distal PICA aneurysm was 42%. CONCLUSIONS: In cases of distal PICA aneurysms, there is a frequent association of a small cerebellar AVM. In our series, CTA was an inadequate diagnostic study to identify the associated AVM, and DSA was necessary to definitely visualize the AVM nidus. Endovascular treatment of the aneurysm and AVM with the use of liquid embolic agents was a feasible and useful management strategy.

Continuous infusion vs intermittent vancomycin in neurosurgical intensive care unit patients.

PURPOSE: Target plasma level achievement has remained a challenge in neurosurgical intensive care unit patients receiving intravenous vancomycin. We evaluated continuous infusion (CI) and intermittent vancomycin dosing strategies in these patients. METHODS: This retrospective cohort compared CI vancomycin (target random levels, 20-30 mg/L) to intermittent vancomycin (target troughs, 15-20 mg/L) in regards to achievement of target plasma levels, nephrotoxicity, pharmacodynamic target attainment, and cost savings in 130 patients. RESULTS: Continuous infusion resulted in greater achievement of goal plasma concentrations at the first steady-state level (40 vs 21.5%, P = .02), more rapid achievement of goal plasma concentrations (2.04 vs 3.76 days, P < .0001), and increased time within therapeutic range (55% vs 34%, P < .0001) but no significant difference in nephrotoxicity (15.4% vs 21.5%, P = .5). Continuous infusion improved pharmacodynamic target attainment (92.3% vs 30.8%, P < .0001) and also reduced levels drawn (3.8 vs 5.7, P = .0007), dose adjustments (1.4 vs 2.4, P = .0006), days of therapy (10.4 vs 14.1, P = .01), and mean total daily dose requirements (33 vs 35.7 mg/kg, P < .0001) per patient. CONCLUSIONS: Continuous infusion appears beneficial for improving attainment of target plasma concentrations, pharmacodynamic goals, and financial burden, without increasing risk of acute kidney injury.

Investigating the utility of previously developed prediction scores in acute ischemic stroke patients in the stroke belt.

BACKGROUND: To assess the utility of previously developed scoring systems, we compared SEDAN, named after the components of the score (baseline blood Sugar, Early infarct signs and (hyper) Dense cerebral artery sign on admission computed tomography scan, Age, and National Institutes of Health Stroke Scale on admission), Totaled Health Risks in Vascular Events (THRIVE), Houston Intra-arterial Therapy (HIAT), and HIAT-2 scoring systems among patients receiving systemic (intravenous [IV] tissue plasminogen activator [tPA]) and endovascular (intra-arterial [IA]) treatments. METHODS: We retrospectively reviewed all IV tPA and IA patients presenting to our center from 2008-2011. The scores were assessed in patients who were treated with IV tPA only, IA only, and a combination of IV tPA and IA (IV-IA). We tested the ability of THRIVE to predict discharge modified Rankin scale (mRS) 3-6, HIAT and HIAT-2 discharge mRS 4-6, and SEDAN symptomatic intracerebral hemorrhage (sICH). RESULTS: Of the 366 patients who were included in this study, 243 had IV tPA only, 89 had IA only, and 34 had IV-IA. THRIVE was predictive of mRS 3-6 in the IV-IA (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.30-2.91) and the IV group (OR, 1.71; 95% CI, 1.43-2.04), but not in the IA group. HIAT was predictive of mRS 4-6 in the IA (OR, 3.55; 95% CI, 1.65-7.25), IV (OR, 3.47; 95% CI, 2.26-5.33), and IV-IA group (OR, 6.48; 95% CI, 1.41-29.71). HIAT-2 was predictive of mRS 4-6 in the IA (OR, 1.39; 95% CI, 1.03-1.87) and IV group (OR, 1.36; 95% CI, 1.18-1.57), but not in the IV-IA group. SEDAN was not predictive of sICH in the IA or the IV-IA group, but was predictive in the IV group (OR, 1.54; 95% CI, 1.01-2.36). CONCLUSIONS: Our study demonstrated that although highly predictive of outcome in the original study design treatment groups, prediction scores may not generalize to all patient samples, highlighting the importance of validating prediction scores in diverse samples.

CLOTBUST-hands free: initial safety testing of a novel operator-independent ultrasound device in stroke-free volunteers.

BACKGROUND AND PURPOSE: We aimed to evaluate safety and tolerability of a novel operator-independent ultrasound device among stroke-free volunteers. METHODS: A headframe containing 18 ultrasound transducers (each operating at 2 MHz, pulsed-wave) was used to expose both temporal windows and the suboccipital window. The transmission characteristics were set to emulate the acoustic characteristics of the exposure levels in the Combined Lysis of Thrombus in Brain Ischemia using Transcranial Ultrasound and Systemic tPA (CLOTBUST) trial and to never exceed Food and Drug Administration mandated diagnostic ultrasound exposure limits. Volunteers underwent 2 hours of insonation with transducer activation one at a time. Safety was captured using serial neurological examinations and pre- and postinsonation MRI for detection of the blood brain barrier permeability. RESULTS: A total of 15 volunteers (40% men; 49 ± 16 years; 27% black; all pre-exposure National Institutes of Health Stroke Scale scores 0) were enrolled. Five volunteers received pulsed-wave ultrasound via the best pair temporal transducers, 5 via sequential activation of the suboccipital transducers, and 5 via sequential activation of all bilateral temporal and suboccipital transducers. All subjects were safely insonated with no adverse effects as indicated by the neurological examinations during, immediately after the exposure, and at 24 hours, and no abnormality of the blood brain barrier was found on any of the MRIs. CONCLUSIONS: Our novel device was well tolerated by stroke-free volunteers and did not cause any neurological dysfunction nor did it affect blood brain barrier integrity. The safety and efficacy of the device are now being tested in stroke patients receiving intravenous tissue-type plasminogen activator in phase II-III clinical trials.

Timing and mechanism of ischemic stroke due to extracranial blunt traumatic cerebrovascular injury.

OBJECT: Extracranial cerebrovascular injury is believed to be an important cause of neurological injury in patients who have suffered blunt trauma. The authors sought to determine the timing and mechanisms of ischemic stroke in patients who suffered traumatic cerebrovascular injury (TCVI). METHODS: This is a prospective study of all patients with TCVI who were admitted to a Level I trauma center during a 28-month period. All patients who suffered blunt trauma and had risk factors for TCVI underwent screening CT angiography (CTA) of the head and neck on admission. All patients with either an ischemic stroke or CTA suggesting TCVI underwent confirmatory digital subtraction angiography (DSA). Patients with DSA-confirmed TCVI were treated with 325 mg aspirin daily; all patients were observed during their hospitalization for the occurrence of new ischemic stroke. In addition, a subset of patients with TCVI underwent transcranial Doppler ultrasonography monitoring for microembolic signals. RESULTS: A total of 112 patients had CTA findings suggestive of TCVI; 68 cases were confirmed by DSA. Overall, 7 patients had an ischemic stroke in the territory of the affected artery prior to or during admission. Four of the patients had their event prior to diagnosis with CTA and 2 occurred prior to DSA. In 1 patient the ischemic stroke was found to be due to an extracranial atherosclerotic carotid plaque, and this patient was excluded from further analysis. All patients with ischemic stroke had brain CT findings consistent with an embolic mechanism. Two (8.7%) of 23 monitored patients with TCVI had microembolic signals on transcranial Doppler ultrasonography. CONCLUSIONS: Most ischemic strokes due to TCVI are embolic in nature and occur prior to screening CTA and initiation of treatment with aspirin.

Computed tomography perfusion prognostic maps do not predict reversible and irreversible neurological dysfunction following reperfusion therapies.

BACKGROUND: We aimed to evaluate the ability of commercially available computed tomography perfusion (CTP) prognostic maps software to identify reversibly and irreversibly damaged brain functions in the best case scenario: patients who achieved early and complete tissue reperfusion. METHODS: Consecutive ischemic stroke patients who received reperfusion therapies, those with early (less than two-hours from treatment initiation) and complete Thrombolysis in Myocardial Infarction grade III or equivalent reperfusion were included in the analysis. Computed tomography perfusion prognostic maps were assigned as 'red,' or irreversible if cerebral blood volume declined below 2 ml/100 g and 'green,' or recoverable if the affected/unaffected mean transit time ratio was >1.45. Only patients with middle cerebral artery territory affected were included and subcomponents of the National Institutes of Health Stroke Scale scale pre- and posttreatment were analyzed based on anatomical correlation of the affected CTP areas and corresponding neurological functions. RESULTS: Among 109 consecutive patients who had intra-arterial reperfusion procedures, 16 (age 60 ± 17 years, 56% men, median National Institutes of Health Stroke Scale 13 . 5, interquartile range 7-18) had pretreatment CTP and had early complete reperfusion. We identified 44 affected areas on CTP (red 12 (27%), green 32 (73%)) with corresponding measurable neurological deficits including aphasia, arm, face weakness, and inattention. Red areas correctly identified 5/12 (42%) of functions that did not recover despite early reperfusion. Green areas correctly identified 18/32 (56%) of functions that recover after early reperfusion (OR 0.92, 95% CI 0.25-3.39, P = 1.0). CONCLUSIONS: In-patients achieving early and complete reperfusion, pretreatment CTP prognostic maps were not predictive for irreversibly or reversibly lost neurologic functions.

Velocity criteria for intracranial stenosis revisited: an international multicenter study of transcranial Doppler and digital subtraction angiography.

BACKGROUND AND PURPOSE: Intracranial atherosclerotic disease is associated with a high risk of stroke recurrence. We aimed to determine accuracy of transcranial Doppler screening at laboratories that share the same standardized scanning protocol. METHODS: Patients with symptoms of cerebral ischemia were prospectively studied. Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) criteria were used for identification of ≥50% stenosis. We determined velocity cutoffs for ≥70% stenosis on digital subtraction angiography by Warfarin-Aspirin Symptomatic Intracranial Disease criteria and evaluated novel stenotic/prestenotic ratio and low-velocity criteria. RESULTS: A total of 102 patients with intracranial atherosclerotic disease (age 57±13 years; 72% men; median National Institutes of Health Stroke Scale 3, interquartile range 6) provided 690 transcranial Doppler/digital subtraction angiography vessel pairs. On digital subtraction angiography, ≥50% stenosis was found in 97 and ≥70% stenosis in 62 arteries. Predictive values for transcranial Doppler SONIA criteria were similar (P>0.9) between middle cerebral artery (sensitivity 78%, specificity 93%, positive predictive value 73%, negative predictive value 94%, and overall accuracy 90%) and vertebral artery/basilar artery (69%, 98%, 88%, 93%, and 92%). As a single velocity criterion, most sensitive mean flow velocity thresholds for ≥70% stenosis were: middle cerebral artery>120 cm/s (71%) and vertebral artery/basilar artery>110 cm/s (55%). Optimal combined criteria for ≥70% stenosis were: middle cerebral artery>120 cm/s, or stenotic/prestenotic ratio≥3, or low velocity (sensitivity 91%, specificity 80%, receiver operating characteristic 0.858), and vertebral artery/basilar artery>110 cm/s or stenotic/prestenotic ratio≥3 (60%, 95%, 0.769, respectively). CONCLUSIONS: At laboratories with a standardized scanning protocol, SONIA mean flow velocity criteria remain reliably predictive of ≥50% stenosis. Novel velocity/ratio criteria for ≥70% stenosis increased sensitivity and showed good agreement with invasive angiography.

Management of blunt extracranial traumatic cerebrovascular injury: a multidisciplinary survey of current practice.

BACKGROUND: Extracranial traumatic cerebrovascular injury (TCVI) is present in 1-3% of all blunt force trauma patients. Although options for the management of patients with these lesions include anticoagulation, antiplatelet agents, and endovascular treatment, the optimal management strategy for patients with these lesions is not yet established. OBJECTIVE: Multidisciplinary survey of clinicians about current management of TCVI. METHODS: A six-item multiple-choice survey was sent by electronic mail to a total of 11,784 neurosurgeons, trauma surgeons, stroke neurologists, and interventional radiologists. The survey included questions about their choice of imaging, medical management, and the use of endovascular techniques. Survey responses were analyzed according to stated specialty. RESULTS: Seven hundred eighty-five (6.7%) responses were received. Overall, a total of 325 (42.8%) respondents favored anticoagulation (heparin and/or warfarin), 247 (32.5%) favored antiplatelet drugs, 130 (17.1%) preferred both anticoagulation and antiplatelet drugs, and 57 (7.5%) preferred stenting and/or embolization. Anticoagulation was the most commonly preferred treatment among vascular surgeons (56.9%), neurologists (50.2%) and neurosurgeons (40.7%), whereas antiplatelet agents were the most common preferred treatment among trauma surgeons (41.5%). Overall, 158 (20.7%) of respondents recommended treatment of asymptomatic dissections and traumatic aneurysms, 211 (27.7%) did not recommend it, and 39.4% recommended endovascular treatment only if there is worsening of the lesion on follow-up imaging. CONCLUSIONS: These data demonstrate the wide variability of physicians' management of traumatic cerebrovascular injury, both on an individual basis, and between specialties. These findings underscore the need for multicenter, randomized trials in this field.

Safety and tolerability of early noninvasive ventilatory correction using bilevel positive airway pressure in acute ischemic stroke.

BACKGROUND AND PURPOSE: Hypercapnia can induce intracranial blood-flow steal from ischemic brain tissues, and early initiation of noninvasive ventilator correction (NIVC) may improve cerebral hemodynamics in acute ischemic stroke. We sought to determine safety and tolerability of NIVC initiated on hospital admission without polysomnography study. SUBJECTS AND METHODS: Consecutive acute ischemic stroke patients were evaluated for the presence of a proximal arterial occlusion, daytime sleepiness, or history of obstructive sleep apnea, and acceptable pulse oximetry readings while awake (96%-100% on 2 to 4 L supplemental oxygen delivered by nasal cannula). NIVC was started on hospital admission as standard of care when considered necessary by treating physicians. NIVC was initiated using bilevel positive airway pressure at 10 cmH(2)O inspiratory positive airway pressure and 5 cmH(2)O expiratory positive airway pressure in combination with 40% fraction of inspired oxygen. All potential adverse events were prospectively documented. RESULTS: Among 356 acute ischemic stroke patients (median NIHSS score, 5; interquartile range, 2-13), 64 cases (18%) received NIVC (median NIHSS score, 12; interquartile range, 6-17). Baseline stroke severity was higher and proximal arterial occlusions were more frequent in NIVC patients compared to the rest (P<0.001). NIVC was not tolerated by 4 patients (7%). Adverse events in NIVC included vomiting (n=1), aspiration pneumonia (n=1), respiratory failure/intubation (n=1), hypotension requiring pressors (n=1), and facial skin breakdown (n=3). The in-hospital mortality rate was 13% in NIVC patients and 8% in the rest (P=0.195). Neurological improvement during hospitalization tended to be greater in the NIVC group (median NIHSS score decrease, 2 points; interquartile range, 0-4) compared to the rest (median NIHSS score decrease, 1; interquartile range, 0-2; P=0.078). CONCLUSIONS: In acute ischemic stroke patients with proximal arterial occlusion and excessive sleepiness or obstructive sleep apnea, NIVC can be initiated early with good tolerability and a relatively small risk of serious complications.

Diagnostic criteria and yield of real-time transcranial Doppler monitoring of intra-arterial reperfusion procedures.

BACKGROUND AND PURPOSE: Intra-arterial (IA) rescue procedures are increasingly used to treat acute ischemic stroke. We implemented continuous transcranial Doppler (TCD) monitoring during these procedures to detect any potentially harmful flow changes. Here, we report diagnostic criteria and yield of TCD monitoring. METHODS: We studied consecutive acute stroke patients who underwent IA reperfusion procedures. TCD flow signatures during these procedures were analyzed and any abnormal findings were documented. RESULTS: Patients were included only if there was successful insonation through the skull; of 56 eligible patients, 51 were included. IA procedures included IA tissue plasminogen activator, use of the Merci retriever, the Penumbra system, balloon angioplasty, and stenting. On TCD monitoring, contrast injections produced high-intensity signals and increased the mean flow velocity (MFV). Deployment of the Merci device appeared as high-intensity, short-duration signals with a transient MFV decrease of 11.5%. The Penumbra system produced lower-intensity signals with a greater transient decrease in MFV during aspiration. IA tissue plasminogen activator significantly increased MFV by 7.5% over Merci and Penumbra flow velocity changes. Power motion Doppler-TCD detected reocclusion in 13 patients, artery-to-artery embolization in 2 patients, air embolism in 2 patients, and hyperperfusion in 6 patients. Overall, the yield of TCD monitoring was positive in 23 (49%) patients who received IA reperfusion procedures. CONCLUSIONS: Our velocity, intensity, and flow signatures criteria for TCD monitoring of IA reperfusion procedures detect reocclusion, hyperperfusion, or thromboembolism and air embolism in nearly half of all procedures. This hemodynamic information can be particularly helpful when neurological assessment is limited or delayed.