Therapeutic hypothermia in acute liver failure: a multicenter retrospective cohort analysis.

The benefit of therapeutic hypothermia (TH) in acute liver failure (ALF) has not been previously demonstrated in a controlled fashion. This study sought to determine the impact of TH on 21-day survival and complications in ALF patients at high risk for cerebral edema. This was a retrospective cohort study of ALF patients in the US Acute Liver Failure Study Group with grade III or IV hepatic encephalopathy. TH (32°C-35°C) was used in 97 patients (8%); 1135 (92%) who were not cooled were controls. Intracranial pressure was monitored in 38 TH ALF patients (39.2% versus 22% of controls, P < 0.001). Rates of bleeding (12% for both) and bloodstream (17% versus 18%) and tracheal infections (21% versus 23%, P > 0.5 for all) were similar. Unadjusted 21-day overall (62% versus 60%) and transplant-free survival rates (45% versus 39%, P > 0.4 for both) were similar. Multivariate models were created for acetaminophen (APAP) patients (n = 582) and non-APAP patients (n = 613). For APAP patients, the Model for End-Stage Liver Disease [MELD; odds ratio (OR) = 0.91 per increment, 95% confidence interval (CI) = 0.89-0.94, P < 0.001] and vasopressors (OR = 0.16, 95% CI = 0.11-0.24, P < 0.001) were associated with decreased 21-day spontaneous survival. Survival was improved with TH in APAP patients who were <25 years old (age of 25 years: OR = 2.735, 95% CI = 1.001-7.467) but worsened for APAP patients who were 64 years old or older (age of 64 years: OR = 0.167, 95% CI = 0.028-0.999). For non-APAP patients, MELD (OR = 0.93 per increment, 95% CI = 0.91-0.95, P < 0.001) and vasopressors (OR = 0.60, 95% CI = 0.40-0.90, P = 0.01) were associated with worse outcomes, whereas TH had no impact (P = 0.93). In conclusion, TH in ALF was not associated with increased bleeding or infections. Although young APAP ALF patients may benefit, TH did not consistently affect 21-day survival. A prospective trial is required to clarify the utility of TH in ALF patients.

Effects of antimicrobial prophylaxis and blood stream infections in patients with acute liver failure: a retrospective cohort study.

BACKGROUND & AIMS: We investigated whether antimicrobial prophylaxis alters the incidence of bloodstream infection in patients with acute liver failure (ALF), and whether bloodstream infections affect overall mortality within 21 days after development of ALF. METHODS: We performed a retrospective cohort analysis of 1551 patients with ALF enrolled by the US Acute Liver Failure Study Group from January 1998 through November 2009. We analyzed data on infections in the first 7 days after admission and the effects of prophylaxis with antimicrobial drugs on the development of bloodstream infections and 21-day mortality. RESULTS: In our study population, 600 patients (39%) received antimicrobial prophylaxis and 226 patients (14.6%) developed at least 1 bloodstream infection. Exposure to antimicrobial drugs did not affect the proportion of patients who developed bloodstream infections (12.8% in patients with prophylaxis vs 15.7% in nonprophylaxed patients; P = .12), but a greater percentage of patients who received prophylaxis received liver transplants (28% vs 22%; P = .01). After adjusting for confounding factors, overall mortality within 21 days was associated independently with age (odds ratio [OR], 1.014), Model for End-stage Liver Disease score at admission (OR, 1.078), and vasopressor administration at admission (OR, 2.499). Low grade of coma (OR, 0.47) and liver transplantation (OR, 0.101) reduced mortality. Although bloodstream infection was associated significantly with 21-day mortality (P = .004), an interaction between bloodstream infection and etiology was detected: blood stream infection affected mortality to a greater extent in nonacetaminophen ALF patients (OR, 2.03) than in acetaminophen ALF patients (OR, 1.14). CONCLUSIONS: Based on a large, observational study, antimicrobial prophylaxis does not reduce the incidence of bloodstream infection or mortality within 21 days of ALF. However, bloodstream infections were associated with increased 21-day mortality in patients with ALF-to a greater extent in patients without than with acetaminophen-associated ALF. Our findings do not support the routine use of antimicrobial prophylaxis in patients with ALF.

Outcomes and complications of intracranial pressure monitoring in acute liver failure: a retrospective cohort study.

OBJECTIVE: To determine if intracranial pressure monitor placement in patients with acute liver failure is associated with significant clinical outcomes. DESIGN: Retrospective multicenter cohort study. SETTING: Academic liver transplant centers comprising the U.S. Acute Liver Failure Study Group. PATIENTS: Adult critically ill patients with acute liver failure presenting with grade III/IV hepatic encephalopathy (n = 629) prospectively enrolled between March 2004 and August 2011. INTERVENTION: Intracranial pressure monitored (n = 140) versus nonmonitored controls (n = 489). MEASUREMENTS AND MAIN RESULTS: Intracranial pressure monitored patients were younger than controls (35 vs 43 yr, p < 0.001) and more likely to be on renal replacement therapy (52% vs 38%, p = 0.003). Of 87 intracranial pressure monitored patients with detailed information, 44 (51%) had evidence of intracranial hypertension (intracranial pressure > 25 mm Hg) and overall 21-day mortality was higher in patients with intracranial hypertension (43% vs 23%, p = 0.05). During the first 7 days, intracranial pressure monitored patients received more intracranial hypertension-directed therapies (mannitol, 56% vs 21%; hypertonic saline, 14% vs 7%; hypothermia, 24% vs 10%; p < 0.03 for each). Forty-one percent of intracranial pressure monitored patients received liver transplant (vs 18% controls; p < 0.001). Overall 21-day mortality was similar (intracranial pressure monitored 33% vs controls 38%, p = 0.24). Where data were available, hemorrhagic complications were rare in intracranial pressure monitored patients (4 of 56 [7%]; three died). When stratifying by acetaminophen status and adjusting for confounders, intracranial pressure monitor placement did not impact 21-day mortality in acetaminophen patients (p = 0.89). However, intracranial pressure monitor was associated with increased 21-day mortality in nonacetaminophen patients (odds ratio, ~ 3.04; p = 0.014). CONCLUSIONS: In intracranial pressure monitored patients with acute liver failure, intracranial hypertension is commonly observed. The use of intracranial pressure monitor in acetaminophen acute liver failure did not confer a significant 21-day mortality benefit, whereas in nonacetaminophen acute liver failure, it may be associated with worse outcomes. Hemorrhagic complications from intracranial pressure monitor placement were uncommon and cannot account for mortality trends. Although our results cannot conclusively confirm or refute the utility of intracranial pressure monitoring in patients with acute liver failure, patient selection and ancillary assessments of cerebral blood flow likely have a significant role. Prospective studies would be required to conclusively account for confounding by illness severity and transplant.

Screen failure data in clinical trials: Are screening logs worth it?

BACKGROUND: Clinical trials frequently spend considerable effort to collect data on patients who were assessed for eligibility but not enrolled. The Consolidated Standards of Reporting Trials (CONSORT) guidelines' recommended flow diagram for randomized clinical trials reinforces the belief that the collection of screening data is a necessary and worthwhile endeavor. The rationale for collecting screening data includes scientific, trial management, and ethno-socio-cultural reasons. PURPOSE: We posit that the cost of collecting screening data is not justified, in part due to inability to centrally monitor and verify the screening data in the same manner as other clinical trial data. METHODS: To illustrate the effort and site-to-site variability, we analyzed the screening data from a multicenter, randomized clinical trial of patients with transient ischemic attack or minor ischemic stroke (Platelet-Oriented Inhibition in New Transient Ischemic Attack and Minor Ischemic Stroke (POINT)). RESULTS: Data were collected on over 27,000 patients screened across 172 enrolling sites, 95% of whom were not enrolled. Although the rate of return of screen failure logs was high overall (95%), there were a considerable number of logs that were returned with 'no data to report' (23%), often due to administrative reasons rather than no patients screened. CONCLUSION: In spite of attempts to standardize the collection of screening data, due to differences in site processes, multicenter clinical trials face challenges in collecting those data completely and uniformly. The efforts required to centrally collect high-quality data on an extensive number of screened patients may outweigh the scientific value of the data. Moreover, the lack of a standardized definition of 'screened' and the challenges of collecting meaningful characteristics for patients who have not signed consent limits the ability to compare across studies and to assess generalizability and selection bias as intended.

ADAPT FAST study: a direct aspiration first pass technique for acute stroke thrombectomy.

BACKGROUND: The development of new revascularization devices has improved recanalization rates and time, but not clinical outcomes. We report a prospectively collected clinical experience with a new technique utilizing a direct aspiration first pass technique with large bore aspiration catheter as the primary method for vessel recanalization. METHODS: 98 prospectively identified acute ischemic stroke patients with 100 occluded large cerebral vessels at six institutions were included in the study. The ADAPT technique was utilized in all patients. Procedural and clinical data were captured for analysis. RESULTS: The aspiration component of the ADAPT technique alone was successful in achieving Thrombolysis in Cerebral Infarction (TICI) 2b or 3 revascularization in 78% of cases. The additional use of stent retrievers improved the TICI 2b/3 revascularization rate to 95%. The average time from groin puncture to at least TICI 2b recanalization was 37 min. A 5MAX demonstrated similar success to a 5MAX ACE in achieving TICI 2b/3 revascularization alone (75% vs 82%, p=0.43). Patients presented with an admitting median National Institutes of Health Stroke Scale (NIHSS) score of 17.0 (12.0-21.0) and improved to a median NIHSS score at discharge of 7.3 (1.0-11.0). Ninety day functional outcomes were 40% (modified Rankin Scale (mRS) 0-2) and 20% (mRS 6). There were two procedural complications and no symptomatic intracerebral hemorrhages. DISCUSSION: The ADAPT technique is a fast, safe, simple, and effective method that has facilitated our approach to acute ischemic stroke thrombectomy by utilizing the latest generation of large bore aspiration catheters to achieve previously unparalleled angiographic outcomes.

Impact of the ASPECT scores and distribution on outcome among patients undergoing thrombectomy for acute ischemic stroke.

INTRODUCTION: This study investigates whether the Alberta Stroke Program Early CT Score (ASPECTS) quantification is associated with outcome following mechanical thrombectomy. OBJECTIVE: To determine whether preintervention non-perfect ASPECT scores involving cortical or subcortical regions and the side of the non-perfect ASPECT score affects outcomes. METHODS: A retrospective review of a prospectively maintained database of patients with acute ischemic stroke involving the anterior circulation who underwent thrombectomy between May 2008 and August 2012 at a single tertiary care center. The device for mechanical thrombectomy used was the penumbra aspiration system (Penumbra Inc, Alameda, California, USA) and the Solitaire stent retriever (ev3, Irvine, California, USA). A 'blinded' neuroradiologist obtained ASPECTS quantification and noted each region demonstrating early changes. RESULTS: 149 patients (51.7% female, mean age 66.1±15.1 years) were included with an average National Institutes of Health Stroke Scale of 16.2±6.7. Patients with non-perfect ASPECT scores on pretreatment imaging were more likely to have a hemorrhagic conversion (p=0.04) evident on post-procedure CT. However, functional outcomes were the same. Patients with both cortical and basal ganglia non-perfect ASPECT scores were more likely to be in a persistent vegetative state or expire. No differences were identified in outcome among patients with left- versus right-sided infarcts affecting the basal ganglia or cortical regions. CONCLUSIONS: These findings support a strategy of selecting candidacy for thrombectomy that does not exclude patients with non-perfect ASPECT scores involving either the basal ganglia or cortical regions. Outcomes were identical among patients with no non-perfect ASPECT scores and those with cortical or subcortical infarcts, despite a higher incidence of hemorrhagic conversion found among those with non-perfect ASPECT scores.

Comparison of endovascular treatment approaches for acute ischemic stroke: cost effectiveness, technical success, and clinical outcomes.

INTRODUCTION: The use of mechanical thrombectomy for the treatment of acute ischemic stroke has significantly advanced over the last 5 years. Few data are available comparing the cost and clinical and angiographic outcomes associated with available techniques. The aim of this study is to compare the cost and efficacy of current endovascular stroke therapies. METHODS: A single-center retrospective review was performed of the medical record and hospital financial database of all ischemic stroke cases admitted from 2009 to 2013. Three discrete treatment methodologies used during this time were compared: traditional Penumbra System (PS), stent retriever with local aspiration (SRLA) and A Direct Aspiration first Pass Technique (ADAPT). Statistical analyses of clinical and angiographic outcomes and costs for each group were performed. RESULTS: 222 patients (45% men) underwent mechanical thrombectomy. Successful revascularization was defined as Thrombolysis In Cerebral Infarction (TICI) 2b/3 flow, which was achieved in 79% of cases with PS, 83% of cases with SRLA, and 95% of cases with ADAPT. The average total cost of hospitalization for patients was $51,599 with PS, $54,700 with SRLA, and $33 ,11 with ADAPT (p<0.0001). Average times to recanalization were 88 min with PS, 47 min with SRLA, and 37 min with ADAPT (p<0.0001). Similar rates of good functional outcomes were seen in the three groups (PS 36% vs SRLA 43% vs ADAPT 47%; p=0.4). CONCLUSIONS: The ADAPT technique represents the most technically successful yet cost-effective approach to revascularization of large vessel intracranial occlusions.

The golden hour of stroke intervention: effect of thrombectomy procedural time in acute ischemic stroke on outcome.

INTRODUCTION: Outcome studies in acute ischemic stroke (AIS) have focused on time from symptom onset to treatment. The purpose of this study was to investigate whether time to achieve vessel recanalization from groin puncture affects outcomes. METHODS: We studied all AIS cases that underwent intra-arterial therapy between May 2008 and October 2012 at a high volume center for anterior circulation occlusions. Candidacy for thrombectomy is determined by CT perfusion imaging, irrespective of time of onset. Patients were then dichotomized into two groups: 'Early recan' assigned in which recanalization was achieved in ≤60 min from groin puncture and 'Delayed recan' in which procedures extended beyond 60 min. Time to recanalize was also studied as a continuous variable. RESULTS: 159 patients (53.5% women, mean age 66.4±15.2 years) were identified. The mean National Institutes of Health Stroke Scale (NIHSS) score was similar between 'Early recan' patients (16.8±6.1) compared with 'Delayed recan' patients (15.4±5.8, p=0.149). Among the 'Early recan' patients, recanalization was achieved in 40.7±13.6 min compared with 101.7±32.5 min in the 'Delayed recan' patients (p<0.0001). The likelihood of achieving a good outcome (modified Rankin Scale score 0-2) was higher in the 'Early recan' group (53.6%) compared with the 'Late recan' group (30.8%; p=0.009). On logistic regression analysis, time to recanalization from groin puncture, baseline NIHSS, revascularization, diabetes, and hemorrhages were found to significantly impact on outcome at 90 days, as measured by the modified Rankin Scale. CONCLUSIONS: Our findings suggest that extending mechanical thrombectomy procedure times beyond 60 min increases complications and device cost rates while worsening outcomes. These findings can serve as a time frame of when it is prudent to abort a failed thrombectomy case.

An investigation of the cost and benefit of mechanical thrombectomy for endovascular treatment of acute ischemic stroke.

INTRODUCTION: The use of mechanical thrombectomy for the treatment of acute ischemic stroke has significantly advanced over the past 5 years, with few available data. The aim of this study was to analyze the cost and benefit of mechanical thrombectomy devices utilized during endovascular therapy of ischemic stroke patients. METHODS: A retrospective chart review of patients that underwent intra-arterial stroke interventions was conducted. Clinical, angiographic, all devices used, procedural and postprocedural event and outcome data were collected. Thrombectomy devices were categorized as Penumbra aspiration system thrombectomy (group P) or stent retriever (group S). Statistical analysis of outcomes and costs for each group was performed. RESULTS: 171 patients underwent mechanical thrombectomy. The Penumbra aspiration system was able to primarily achieve recanalization in 41.7% and the stent retriever in 70.4% of the time (p=0.006). The average cost was $11 159 and $16 022 (p=0.0002) in groups P and S, respectively. Average time to recanalization for group P was 85.1 min and for group S, 51.6 min (p<0.0001). Procedural complications were more frequent with the stent retriever (11.1% vs 9.0%; p=0.72) as were periprocedural significant complications (14.8 v 3%; p=0.04). Successful recanalization rates (Thrombolysis in Cerebral Infarction score 2b-3) were the same in groups P and S (78.5 vs. 77.8%). Similar rates of good neurologic outcomes were seen in group P (36.4%) and group S (50.0%) (p=0.19). CONCLUSIONS: For the treatment of acute stroke patients, the use of aspiration appears to be the most cost effective method to achieve acceptable recanalization rates and low complication rates. Stent retriever with local aspiration, despite higher costs and complication rates, yielded better overall outcome.

Hounsfield unit value and clot length in the acutely occluded vessel and time required to achieve thrombectomy, complications and outcome.

INTRODUCTION: Intra-arterial therapy for acute ischemic stroke (AIS) now has an established role. We investigated if Hounsfield Units (HU) quantification on non-contrast CT is associated with ease and efficacy of mechanical thrombectomy and outcomes. METHODS: We retrospectively studied a prospectively maintained database of cases of AIS given intra-arterial therapy between May 2008 and August 2012. Functional outcome was assessed by 90-day follow-up modified Rankin Scale (mRS). Patients were dichotomized based on time to recanalization. HU were calculated on head CT and thrombus location and length were determined on CT angiography. Simple linear regression was used to analyze the association between clot length, average HU and other clinical variables. RESULTS: 141 patients were included. There was no difference in clot length or average HU among patients with good recanalization achieved within 1 h and those in which the procedures extended beyond 1 h. There was no relationship between clot length or density and recanalization. The thrombus length and density were not significantly different between patients with procedural complications and those without. Neither the presence of post-procedure intracranial hemorrhage nor the 90-day mRS was associated with thrombus length or density. CONCLUSIONS: We have not found any significant associations between either thrombus length or density and likelihood of recanalization, time to achieve recanalization, intraprocedural complications, postprocedural hemorrhage or functional outcome at 90 days. These results do not support a predictive value for thrombus quantification in the evaluation of AIS.

ADAPT FAST study: a direct aspiration first pass technique for acute stroke thrombectomy.

BACKGROUND: The development of new revascularization devices has improved recanalization rates and time, but not clinical outcomes. We report a prospectively collected clinical experience with a new technique utilizing a direct aspiration first pass technique with large bore aspiration catheter as the primary method for vessel recanalization. METHODS: 98 prospectively identified acute ischemic stroke patients with 100 occluded large cerebral vessels at six institutions were included in the study. The ADAPT technique was utilized in all patients. Procedural and clinical data were captured for analysis. RESULTS: The aspiration component of the ADAPT technique alone was successful in achieving Thrombolysis in Cerebral Infarction (TICI) 2b or 3 revascularization in 78% of cases. The additional use of stent retrievers improved the TICI 2b/3 revascularization rate to 95%. The average time from groin puncture to at least TICI 2b recanalization was 37 min. A 5MAX demonstrated similar success to a 5MAX ACE in achieving TICI 2b/3 revascularization alone (75% vs 82%, p=0.43). Patients presented with an admitting median National Institutes of Health Stroke Scale (NIHSS) score of 17.0 (12.0-21.0) and improved to a median NIHSS score at discharge of 7.3 (1.0-11.0). Ninety day functional outcomes were 40% (modified Rankin Scale (mRS) 0-2) and 20% (mRS 6). There were two procedural complications and no symptomatic intracerebral hemorrhages. DISCUSSION: The ADAPT technique is a fast, safe, simple, and effective method that has facilitated our approach to acute ischemic stroke thrombectomy by utilizing the latest generation of large bore aspiration catheters to achieve previously unparalleled angiographic outcomes.

Platelet-oriented inhibition in new TIA and minor ischemic stroke (POINT) trial: rationale and design.

BACKGROUND: Ischemic stroke and other vascular outcomes occur in 10-20% of patients in the three-months following a transient ischemic attack or minor ischemic stroke, and many are disabling. The highest risk period for these outcomes is the early hours and days immediately following the ischemic event. Aspirin is the most common antithrombotic treatment used for these patients. AIM: The aim of POINT is to determine whether clopidogrel plus aspirin taken <12 h after transient ischemic attack or minor ischemic stroke symptom onset is more effective in preventing major ischemic vascular events at 90 days in the high-risk, and acceptably safe, compared with aspirin alone. DESIGN: POINT is a prospective, randomized, double-blind, multicenter trial in patients with transient ischemic attack or minor ischemic stroke. Subjects are randomized to clopidogrel (600 mg loading dose followed by 75 mg/day) or matching placebo, and all will receive open-label aspirin 50-325 mg/day, with a dose of 162 mg daily for five-days followed by 81 mg daily strongly recommended. STUDY OUTCOMES: The primary efficacy outcome is the composite of new ischemic vascular events - ischemic stroke, myocardial infarction, or ischemic vascular death - by 90 days. The primary safety outcome is major hemorrhage, which includes symptomatic intracranial hemorrhage. DISCUSSION: Aspirin is the most common antithrombotic given to patients with a stroke or transient ischemic attack, as it reduces the risk of subsequent stroke. This trial expects to determine whether more aggressive antithrombotic therapy with clopidogrel plus aspirin, initiated acutely, is more effective than aspirin alone.