Mg Of Alteplase Research Articles

Abstract 19175: Anaphylaxis After Alteplase During Treatment of Pulmonary Embolism

Introduction: Anaphylaxis is a rare complication to alteplase, a recombinant tissue plasminogen activator (tPA), during administration for pulmonary embolism (PE). Case Presentation: A 72-year-old male with a history of necrotizing fasciitis, recent below the knee amputation, and concern for metastatic melanoma had been undergoing treatment for an acute DVT with apixaban when he presented with an extensive saddle pulmonary embolism. He was evaluated by a Pulmonary Embolism Response Team (PERT) and classified as high risk (sPESI 2, new right ventricular dysfunction, and hypoxemia) and treated with 50 mg alteplase over two hours. At the end of his infusion, he experienced worsening hypoxemia and sudden hypotension treated with fluid resuscitation and an epinephrine infusion. Hemodynamic instability was thought to be secondary to obstructive shock so an additional 50 mg of alteplase was ordered. After the initial bolus of 10 mg alteplase, the patient demonstrated signs of anaphylaxis. He was initially treated with epinephrine, diphenhydramine, famotidine, methylprednisolone, and lactated ringers for the anaphylactic shock. The patient eventually required the addition of norepinephrine, vasopressin, and methylene blue for resolution of the shock. No additional alteplase was administered and a heparin infusion was resumed for treatment of the pulmonary embolism. He was ultimately successfully weaned off vasopressors and oxygen support with resolution of the pulmonary embolism. Discussion: Cardiac critical care providers should monitor for signs of anaphylaxis when using tPA in the management of PE. The main intervention of anaphylactic shock is administration of epinephrine. Updated guidelines recommend use of intramuscular epinephrine in the setting of anaphylaxis.

#5245 SUCCESSFUL THROMBOLYSIS OF AN ATRIAL TUNNELED DIALYSIS CATHETER AS A LAST RESORT VASCULAR ACCESS

Abstract Background and Aims The prolonged survival of patients on dialysis has resulted in a higher frequency of complications and failure related to vascular access. As a result, the situation of depleted vasculature in hemodialysis is becoming increasingly prevalent. The use of an atrial tunneled dialysis catheter (ATDC) has been reported as an effective solution for vascular access in these patients, but limited data is available on the associated complications, particularly thrombosis. Method This study reports the experience of a single nephrology center in Tunis with thrombosis of an ATDC as a last resort vascular access for dialysis. Results A 32-year-old patient with undetermined tubulo-interstitial nephropathy receiving dialysis presented in November 2022 with depleted vasculature. An ATDC was inserted as a final solution for vascular access, with an initial complication of a catheter-related bloodstream infection, which was resolved with broad-spectrum antibiotics with favorable results. One month later, dialysis could not be initiated through the ATDC. Catheter thrombosis was diagnosed as a guidewire was unable to pass through the catheter's lumen. The patient was successfully treated with thrombolysis using 50 mg of Alteplase, allowing dialysis to be resumed with a blood flow of 300 mL/min. Conclusion ATDC is a lifesaving and safe option for patients with depleted vasculature, with only 51 cases reported since 1999 [1]. The treatment of catheter thrombosis is not well defined, and to the best of our knowledge, no thrombolysis protocol has been established. This successful case may contribute to filling the knowledge gap in this field.

EKOS™ Jena Experience: Safety, Feasibility, and Midterm Outcomes of Percutaneous Ultrasound-Assisted Catheter-Directed Thrombolysis in Patients with Intermediate-High-Risk or High-Risk Pulmonary Embolism.

Background Percutaneous catheter-based ultrasound-assisted thrombolysis (UACDT) is recommended for patients with intermediate-high-risk or high-risk pulmonary embolism (PE) in whom systemic thrombolysis has failed or is contraindicated. Aim To evaluate the safety and efficiency of UACDT in patients with intermediate-high-risk or high-risk PE. Methods Between October 2017 and January 2020, we performed UACDT using the EkoSonic™ Endovascular System (EKOS™) in 51 patients (21 males, age 63 ± 18 years) with a sPESI of 1.3 ± 0.7. The EKOS™-catheter was implanted within 24 h after admission. Over 15 hours, 11.5 mg of alteplase was administered per catheter. We evaluated right ventricular stress and cardiac biomarkers before and after UACDT. Results 24 h post-UACDT, median RV/LV ratio decreased from 1.13 to 0.96 (p < 0.001) and the mean sPAP decreased from 47 ± 3 to 32 ± 2 mmHg + CVP (p < 0.0002). There were 6 major bleeding events resulting in transfusion. No stroke, myocardial infarction, right heart decompensation, or recurrent PE occurred. 31 patients (63%) were discharged without any signs of right ventricular stress. After at least 3 months, 73% of our patients did not show any signs of right ventricular dysfunction. The mean RV/LV ratio decreased to 0.75 ± 0.03 (p < 0.0001) in comparison with pre-UACDT, sPAP to 23 mmHg + CVP (p < 0.0001), and BNP to 40 pg/ml (p < 0.0001). Conclusions The treatment with UACDT reduced right heart stress during the first 24 hours and midterm in patients with intermediate-high-risk or high-risk PE at an acceptable rate of severe complications.

Modified lyse and wait technique for the treatment of dialysis fistula thrombosis: Percutaneous thrombolytic therapy with a 27-G dental needle.

The lyse and wait technique is a percutaneous endovascular technique in the treatment of thrombosed dialysis fistulas. In this study, our aim was to introduce a more easily applicable modification of the lyse and wait technique and present our results. A total of 84 patients (56 male; 66.6%), with a mean age of 61 years, were included in the study. The treatment was performed in patients presenting with dialysis fistula thrombosis no more than 1 week before the procedure, whose thrombosed segment length was less than 10cm. A 27-G dental needle was inserted into the thrombosed segment under ultrasonography guidance, and 5mg of alteplase was injected in a controlled manner. After about 6 to 12 h, the patients were taken to the angiography unit, and balloon angioplasty was performed. The technical and clinical success of the procedure was 98.8%. Technical and clinical failure occurred in only one patient. The median primary patency duration was 13.5months. None of the patients had major complications. At the end of 12 months, the primary patency rate was 66.6%, and the secondary patency rate was 80%. Our technique has shown to have high technical and clinical success and patency.

Low-dose intracoronary alteplase during primary percutaneous coronary intervention in patients with acute myocardial infarction: the T-TIME three-arm RCT

Background Microvascular obstruction commonly affects patients with acute ST-segment elevation myocardial infarction and is independently associated with adverse outcomes. Objective To determine whether or not a strategy involving low-dose intracoronary fibrinolytic therapy infused early after coronary reperfusion will reduce microvascular obstruction. Design This was a multicentre, randomised, double-blind, parallel-group, placebo-controlled, dose-ranging trial. Setting The trial took place at 11 hospitals in the UK between 17 March 2016 and 21 December 2017. Participants Patients with acute ST-segment elevation myocardial infarction and a symptom onset to reperfusion time of ≤ 6 hours were eligible for randomisation. Radial artery access was a requirement, and further angiographic criteria included a proximal-to-middle coronary artery occlusion or impaired coronary flow in the presence of a definite thrombus in the culprit coronary artery. Exclusion criteria included a functional coronary collateral supply to the infarct-related artery, any contraindication to fibrinolysis and lack of informed consent. Additional exclusion criteria for safety were (1) requirement for immunosuppressive drug therapy for ≤ 3 months and (2) treatment with an antimicrobial agent. Intervention A total of 440 participants were randomly assigned 1 : 1 : 1 to treatment with placebo (n = 151), 10 mg of alteplase (n = 144) or 20 mg of alteplase (n = 145) administered by manual infusion directly into the infarct-related coronary artery over 5–10 minutes. The intervention was scheduled to happen after reperfusion and before stent implantation. Outcomes The primary outcome was the amount of microvascular obstruction (percentage of left ventricular mass) demonstrated by contrast-enhanced cardiac magnetic resonance imaging at 2–7 days after enrolment. The primary analysis was the comparison between the 20 mg of alteplase group and the placebo group; if this comparison was not significant, the comparison of the 10 mg of alteplase group with the placebo group was considered as a secondary analysis. Sample size A total of 618 patients (minimum of 558 patients). Recruitment was halted on 21 December 2017 given that conditional power for the primary outcome based on a prespecified analysis of the first 267 randomised participants was &lt; 30% in both treatment groups (futility criterion). Methods The primary outcome was compared between groups using a stratified Wilcoxon rank-sum test (van Elteren test), stratified by the location of the myocardial infarction. Results Among the 440 patients (mean age of 60.5 years; 15% women), the primary end point was measured in 396 (90%) patients, 17 (3.9%) withdrew, seven died and all other patients were followed up to 3 months. The amount (mean percentage of left ventricular mass) of microvascular obstruction was 2.3% versus 2.6% versus 3.5% in the placebo, 10 mg of alteplase and 20 mg of alteplase groups, respectively. In the primary analysis, microvascular obstruction did not differ between the 20 mg of alteplase group and the placebo group: 3.5% versus 2.3%, estimated difference 1.16% (95% confidence interval –0.08% to 2.41%; p = 0.32). In the secondary analysis, microvascular obstruction did not differ between the 10 mg of alteplase group and the placebo group: 2.6% versus 2.3%, estimated difference 0.29% (95% confidence interval –0.76% to 1.35%; p = 0.74). By 3 months, major adverse cardiac events (cardiac death, non-fatal myocardial infarction and unplanned hospitalisation for heart failure) had occurred in 15 (10.1%) patients in the placebo group, 18 (12.9%) in the 10 mg of alteplase group and 12 (8.2%) in the 20 mg of alteplase group. Conclusions Adjunctive low-dose intracoronary alteplase given during the primary percutaneous intervention did not reduce microvascular obstruction compared with placebo. Limitations Premature discontinuation of enrolment limited the power of the secondary and safety analyses. Future work Low-dose intracoronary alteplase or tenecteplase could be compared with placebo at the end of primary percutaneous coronary intervention in patients with an ischaemic time of &lt; 4 hours. Trial registration This trial is registered as ClinicalTrials.gov NCT02257294. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 7, No. 5. See the NIHR Journals Library website for further project information.

Assessing and Restoring Patency in Midline Catheters.

Maintaining and restoring patency in midline catheters has been a significant issue in the hospitalized patient requiring a multitude of infusates and frequent blood specimen collection. Currently, clinicians may not use this device as often as clinically indicated because they lack an approved intervention to treat thrombotic occlusions. The purpose of this research was to show evidence that alteplase, a US Food and Drug Administration-approved thrombolytic for central vascular access devices, is a safe and effective thrombolytic for midline catheters. A prospective open label study of 497 midline catheters was conducted from July 2018 to December 2018. Of those studied, 112 devices were treated with 1 mg of alteplase, and 109 had patency restored with 1 dose. None of the 112 patients had a major adverse event, and only 1 minor event was recorded and was resolved without removal of the midline catheter. Treating occluded central vascular access devices with 2 mg of alteplase has been safe and effective since 2001. With this research, safety and efficacy appears to be established for 1 mg of alteplase, repeat times 1 mg if necessary, in midline catheters. With the option to treat patients with occluded midline catheters rather than replace, clinicians can reduce cost, increase patient satisfaction, and preserve vein health.

Thrombolysis with Low-Dose Versus Standard-Dose Alteplase in 4.5 Hours After Acute Ischemic Stroke; A Four-Months Prospective Study.

Abstract Background: In Japan, Pakistan and Vietnam, 0.6 mg of Alteplase per kilogram body weight within 3 hours was approved for standard guideline, although the safety and efficacy in acute ischemic stroke within 4.5 hours has not been established. We conducted four-month prospective study to compare the safety and efficacy of 0.6 mg, 0.75 mg and 0.9 mg of Alteplase per kilogram body weight. Methods: In cohort A, the patients were randomly assigned to receive intravenous 0.6 mg or 0.75 mg or 0.9 mg of Alteplase per kilogram body weight in a 1:1:1. Interim analysis was performed after complete cohort A. In cohort B, patients were assigned to receive 0.9 mg of Alteplase per kilogram body weight (standard-dose). The primary end points were death, favorable outcome at discharge and 90-day and intra-cerebral hemorrhage. The secondary end points were good outcomes, Improved mRS at discharged and 90-day, number of patients with length of hospital stay &lt;7 days and overall complications. Results: In Cohort A, 78 were randomly assigned to receive 0.6 mg or 0.75 mg (low-dose) or 0.9 mg of intravenous Alteplase per kilogram body weight. Less patients had favorable outcomes in 0.6 mg and 7.5 mg than 0.9 mg of Alteplase per kilogram body weight at discharge (P=0.0004) and at 90-day (P=0.05). In Cohort B, 330 were assigned to receive standard-dose Alteplase. Finally, 408 patients were enrolled with median time of Alteplase administration by 2 hours 49 min. There was no different onset to needle and death between low-dose and standard-dose Alteplase (P=0.82 and P=0.85). Less patients had favorable outcome and intra-cerebral hemorrhage with low-dose than standard-dose Alteplase (favorable outcomes: Relative risk (RR), 1.18; 95% confidence interval (CI), 1.09 to 1.27; P &lt;0.001 at discharge and RR, 1.25; 95%CI, 1.07 to 1.46; P=0.003 at 90 day, intra-cerebral hemorrhage: RR, 0.05; 95%CI, 0.00 to 0.95; P=0.04. Less patients had improved modified Rankin Scale [mRS] at 90-day with low-dose than standard-dose Alteplase (RR, 1.66; 95%CI, 1.22 to 2.25; P=0.001; especially in the patients with initial systolic blood pressure &lt;180 mmHg ; RR, 1.86; 95%CI, 1.35 to 2.56; P=0.0001). In patients with initial systolic blood pressure &gt;180 mmHg, low-dose Alteplase group had more patients with mRS of 0-3 at 90-day and less patients with of mRS 4-6 at 90-day than standard-dose Alteplase (P=0.002). There was no significant different in length of stay and overall complications with low-dose than standard-dose Alteplase (P=0.15). Conclusion: As compared with standard-dose, intravenous low-dose Alteplase administered within 4.5 hours after the onset of stroke significant less favorable outcome, intra-cerebral hemorrhage, but not different in death, especially in the patients with initial systolic blood pressure &lt;180 mmHg. However, patients with initial systolic blood pressure &gt;180 mmHg, intravenous low-dose Alteplase had less patients with disability and death and more patient’s recovery with mRS of 0-3 at 90-day. (ClinicalTrial.gov Number, NCT03847883).

Comparison of Ultrasound-Accelerated Versus Multi-hole Infusion Catheter-Directed Thrombolysis for the Treatment of Acute Limb Ischemia

Retrospective single-center review between 2006 and 2008 Thrombolysis of thrombosed native arteries and arterial bypasses was performed with Uni-Fuse multihole catheters (AngioDynamics, Latham, NY) in 69 cases and EKOS ultrasound-accelerated catheters (EKOS Corporation, Bothell, Wash) in 22 cases. All patients were initially treated with the power-pulse feature of an AngioJet catheter (Boston Scientific, Marlborough, Mass) administering 10 mg of alteplase (tissue plasminogen activator [tPA]) followed 20 minutes later by rheolytic catheter-directed thrombectomy. Residual thrombus was treated with either Uni-Fuse or EKOS catheters with tPA infused at 0.5 to 2.0 mg/h overnight. The mean duration of thrombolysis, mean volume of tPA, technical success, and complications were similar in both groups. The standard multihole infusion catheter demonstrates similar clinical safety and efficacy as the ultrasound-accelerated EKOS system to treat acute arterial limb ischemia.

1115 Ultra-slow low-dose thrombolytic therapy as an option of treatment in intracardiac thrombus: a case report

Abstract We present a case of a 57-year-old male with previously known primary severe mitral regurgitation, who was admitted to the ICU due to massive venous thromboembolism with associated right ventricle dysfunction and with two large mobile right atrial thrombi (2.4 x 1.5 cm and 3.6 x 3.7 cm). Despite of five days with a therapeutic aPTT achieved with unfractionated heparin (UFH), a TTE showed deterioration of the right ventricle systolic function, persistence of the right atrial masses with similar dimensions together with new mobile thrombi on the coronary sinus and on the right pulmonary artery. Due to deterioration of his clinical condition and given the refractoriness to the classical treatment with UFH, it was decided to administer an ultra-slow low-dose thrombolysis protocol, which consisted in a 24-hour infusion of 24 mg of alteplase at a rate of 1 mg per hour, without bolus. The treatment was continued by 48 consecutive hours, with clinical improvement and important reduction of the right atrial masses with resolution of the coronary sinus and right pulmonary artery thrombi. The patient started hypocoagulation with warfarin bridging with low molecular weight heparin (LMWH). Seven days after alteplase discontinuation there was complete resolution of the intracardiac thrombi. One month after ICU admission a successful mitral valve replacement surgery was conducted. Three months after discharge, the patient is in functional New York Heart Association (NYHA) class I with no cardiovascular events or hospitalizations. This case demonstrates that ultra-slow low-dose thrombolysis is a valid bailout treatment option in patients with large intracardiac thrombi refractory to anticoagulation. Abstract 1115 Figure. TTE showing right atrial masses

2173 Successful Endoscopic Drainage of Intraperitoneal Hematoma Using Lumen Opposing Fully Covered Metal Stent and Intracavitatory Thrombolytics

INTRODUCTION: Incompletely drained intraperitoneal collections represent a therapeutic challenge. Interventional radiologists and surgeons have employed adjunctive intracavitary fibrinolytic agents to break down collections, however it has not been employed endoscopically to the best of our knowledge. We present a case of an intraperitoneal hematoma in a patient which was successfully drained endoscopically using thrombolytics. CASE DESCRIPTION/METHODS: A 16 year old male with past medical history of idiopathic thrombocytopenic purpura presented to our hospital with complains of left upper quadrant abdominal pain, radiating to the back for four days prior to the presentation. He also reported a blunt trauma to the upper abdomen two months prior to the presentation. Abdominal examination revealed tenderness to palpation in LUQ, with no guarding or rigidity and normal bowel sounds. Laboratory values at the time of presentation were within normal limits. Upper endoscopy and Colonoscopy were performed. Upper endoscopy revealed mild erosive gastritis. Colonoscopy was normal. He underwent Computed Tomography (CT) of abdomen and pelvis with contrast, revealing a 5 × 6 × 6.7 cm mass likely a hematoma abutting the spleen, pancreas and left kidneys. Hospital course complicated by fever and leukocytosis. Transgastric drainage of hematoma was performed by Endoscopic Ultrasound (EUS) using fully covered lumen opposing 1.5 cm wide and 1 cm long stent placement with initial drainage of purulent material. Two additional EGDs needed over subsequent two weeks to address one episode of fever with unchanged collection size and thick internal debris. First washout was done with 2000cc of Normal Saline, 500cc of Gentamicin, and 4 mg of Alteplase. During the second washout, we instilled 4 mg of Alteplase and 5 mg DNAse in 60 ml saline with occlusion technique for 10 minutes and subsequent drainage. Patient was discharged and was symptom free. CT scan performed at 8 weeks post placement showed complete drainage of hematoma and stent was removed. Patient is pain free and doing well after that. DISCUSSION: The use of fibrinolytics in endoscopic drainage of intraabdominal effusions has not been explored. In our case the use of fibrinolytics facilitated the dissolution of thick internal debris resulting in complete resolution of the collection. In conclusion, adjunctive use of tPA and DNAse along with EUS guided drainage appears to be safe and effective to dissolve thick internal debris avoiding the need for surgical intervention.

6030Effects of adjunctive treatment with low-dose alteplase during primary percutaneous coronary intervention according to ischaemic time

Abstract Background Microvascular obstruction affects half of patients with acute ST-segment elevation myocardial infarction and confers an adverse prognosis. Purpose We aimed to determine whether the efficacy and safety of a therapeutic strategy involving low-dose intra-coronary alteplase infused early after coronary reperfusion associates with ischaemic time. Methods We conducted a prospective, multicentre, parallel group, 1:1:1 randomised, dose-ranging trial in patients undergoing primary percutaneous coronary intervention. Ischaemic time, defined as the time from symptom onset to coronary reperfusion, was a pre-specified sub-group of interest. Between March 17, 2016, and December 21, 2017, 440 patients presenting at 11 hospitals in the UK were enrolled with follow up to 3 months. Patients with acute myocardial infarction due to occlusion of a major coronary artery presenting ≤6 hours from symptom onset were randomly assigned to treatment with placebo, alteplase 10mg or alteplase 20mg. The primary outcome was the amount of microvascular obstruction disclosed by cardiac magnetic resonance imaging at 2–7 days. Secondary outcomes included infarct size, myocardial haemorrhage, left ventricular ejection fraction, and troponin T area-under-the curve. Results 440 patients were randomized (figure), the primary endpoint was achieved in 396 (90%), seventeen (3.9%) withdrew and all other patients were followed up to 3 months. In the primary analysis, the amount of microvascular obstruction did not differ between the groups. Their ischaemic times were: ≤2 hours, n=98; ≥2–&lt;4 hours, n=215; and ≥4–6 hours, n=83. In patients with an ischaemic time ≥4 hours, treatment with alteplase (10 mg, n=26; 20 mg, n=30) was associated with a dose dependent increase in the amount (mean) of microvascular obstruction (% left ventricular mass) compared to placebo (n=27) 1.14 vs. 3.11 vs. 5.20; mean difference on square root scale 0.81 (95% CI 0.21, 1.42), p=0.009. The interaction test between ischaemic time and treatment (active vs. placebo) was not statistically significant p=0.06, however when the interaction was assessed for a trend across treatment groups this did reach statistical significance, p=0.018. Furthermore, a higher proportion of patients presenting ≥4–6 hours treated with 20 mg of alteplase had myocardial haemorrhage (59.3%) compared to the placebo group (28.0%), odds ratio 3.81 (95% CI 1.19, 12.25), p=0.025. The amount of haemorrhage was also greater; estimated mean difference 3.49 (95% CI 1.22, 5.75), p=0.0026. No between-treatment group differences for myocardial haemorrhage were observed in patients presenting with shorter ischaemic times. Study flow diagram Conclusions In patients presenting with an ischaemic time ≥4 hours, adjunctive treatment with low-dose intra-coronary alteplase during primary PCI was associated with increases in microvascular obstruction and myocardial haemorrhage. The mechanism may involve haemorrhagic transformation within the infarct core. Acknowledgement/Funding NIHR EME programme (reference: 12/170/45); British Heart Foundation (BHF reference FS/16/74/32573)

Pharmacoeconomic impact of an alternative workflow process for stroke

ObjectiveThe objective of this study was to evaluate a new multidisciplinary process in which intravenous alteplase (tPA) waste, used for acute ischemic stroke (AIS), was salvaged in an attempt to maximize cost effectiveness without impacting door-to-needle (DTN) administration times. DesignThis was a retrospective cohort between May 2017 and February 2018. The primary endpoint evaluated for this study was the total tPA salvaged and total cost savings in U.S. dollars. Secondary endpoints evaluated included overall DTN time in minutes. SettingEmergency department of a primary stroke center. PatientsA convenience sample of sequential adult (>18 years) patients who received tPA in the ED for AIS were included for analysis. InterventionsNew stroke process which involved bedside mixing of tPA and salvaging of excess waste in the main central pharmacy. Measurements and main resultsA total of 50 patients were included in the final analysis. There were 25 patients included in the new process and old process groups respectively. A total of 605 mg of alteplase was salvaged from 25 patients in the new process group which was associated with an estimated cost savings of over $120,000 annually. Patients in the new process group had statistically faster average (52 min vs. 60 min; p = 0.01) and median (50 min vs. 58 min; p = 0.03) DTN administration times. ConclusionPreliminary data, in this pilot study, utilizing a multidisciplinary model for tPA administration led to significant cost savings of tPA and decreases in overall DTN administration times.

4:12 PM Abstract No. 359 Single-session flow restoration in May-Thurner syndrome with secondary acute iliofemoral deep venous thrombosis

Catheter-directed thrombolysis (CDT) for iliofemoral deep venous thrombosis (DVT) associated with May-Thurner syndrome (MTS) traditionally requires lytic infusion in an intensive care unit (ICU) and multi-day procedures. The advent of venous-specific thrombolytic devices has improved procedural efficiency. We aim to evaluate the efficacy of single-session therapy utilizing rheolytic pharmacomechanical thrombectomy (PMT) followed by stent placement for MTS with secondary acute DVT. MTS patients treated in a single-session were retrospectively analyzed. All procedures were performed utilizing 8Fr rheolytic PMT with power-pulse administration of 10 mg of alteplase into thrombosed segments, 30-minute dwell time, followed by thrombectomy mode. Additional balloon angioplasty/suction thrombectomy was employed as necessary; 14 mm iliac vein self-expanding stents were placed in all patients. Pre- and postprocedure venous clinical severity scores (VCSS) were calculated and paired t-test was performed; significance was determined at p<0.05. From 7/2016 to present, 6 patients (4M:2F, mean age 51) with acute left iliofemoral DVT secondary to MTS were identified; initial diagnosis was via venous duplex exam. All patients presented with lower extremity edema/pain; mean symptom duration was 3 (range, 1-7) days. Rheolytic PMT with total run time confined to less than 240 seconds, followed by suction thrombectomy (4/6 patients), balloon angioplasty (2/6 patients), and stent placement was performed. Single-session flow restoration with symptomatic relief was achieved in all patients; VCSS decreased from a mean of 6 ± 0.8 (SEM) to 1.8 ± 0.8 (p = 0.002) postprocedure. Patients were followed up by computed tomographic venography (CTV) at approximately 1 month, all patients demonstrated stent patency. Single-session treatment appears effective for MTS with secondary acute DVT when 8Fr rheolytic PMT is used with local lytic administration, potentially improving DVT thrombolysis safety profile by limiting prolonged lytic exposure and avoiding ICU observation. Further study is necessary to confirm the long-term efficacy of this protocol.

The use of thrombolytics in the management of complex pleural fluid collections.

To determine the efficacy of thrombolytics for the management of complex pleural fluid collections. We reviewed patients that received alteplase for persistent loculated pleural fluid collections after simple tube drainage between July 01, 2007 and November 01, 2012. Our alteplase protocol is 6 mg of alteplase in 50 mL of normal saline injected into the pleural chest tube. The chest tube is clamped for four hours and then opened. Normally this is repeated daily for 2 to 3 days (d). One hundred and three [103] patients were identified with 110 interventions. Sixty-eight (66%) of the patients were male, with ages ranging from 20-91 years (y), mean 57.2 y. Twenty (18.2%) patients were trauma patients, 60 (55%) had hypertension and 32 (35%) were smokers. Most patients had one of the following diagnoses: 79.6% (82/110) loculated pleural fluid collection as a result of an empyema or 20.4% (21/110) retained hemothorax. The mean time from diagnosis to alteplase treatment for a hemothorax was 12.8 days (range, 1-32 days) and 16.2 days (range, 4-48 days) for an empyema. The mean duration of therapy was 2.2±1.4 days (1-11 days). The time from alteplase to chest tube removal was 4.5 days (1-21 days). Eleven of 103 (10.7%) patients required surgery including 3 video assisted decortications. The others had adequate radiographic resolution. Seventeen patients (16.5%) died, in the hospital of: sepsis, respiratory failure, aortic injury, and cardiac arrest. Alteplase therapy is an effective alternative to surgery in most complex pleural fluid collections.

Impact of Tissue Plasminogen Activator Dosing on Patients Weighing More Than 100 kg on 3-Month Outcomes in Acute Ischemic Stroke

The landmark National Institute of Neurological Disorders and Stroke (NINDS) tissue plasminogen activator (tPA) trial established the effectiveness and dosing of intravenous tPA for acute ischemic stroke (AIS) at .9 mg/kg with a maximum dose of 90 mg. Since the publication of the NINDS trial in 1995, there has been a drastic increase in the amount of obesity and the average weight of adults in the United States, which has caused an increase in the number of patients receiving 90 mg of alteplase for AIS. This retrospective trial was an attempt to see if reduced-dose tPA is as effective as full .9 mg/kg dosing. We performed a single-center retrospective analysis to assess the dosing rate and 90-day outcomes comparing maximum dosage (90 mg) and standard dosage (.9 mg/kg) of tPA. A total of 301 patients were included in the analysis with 64 (21%) receiving less than .9 mg/kg dosing. The adjusted binary logistic regression model showed a statistically significant association toward a good outcome for increases in tPA dose rate (odds ratio = 1.7, P = .027) when compared against a poor outcome. Our analysis showed that patients receiving doses of alteplase closer to .9 mg/kg had a higher likelihood of a modified Rankin Scale score of 0-1 at 90 days. With the growth of obesity in the United States and the lack of data supporting dose capping of alteplase, it remains unclear if this dosing practice should continue to be accepted without question. Further studies are needed to assess optimum dosing practices particularly given the obesity epidemic.

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial

Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88-1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90-1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41-0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22-3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31-0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64-0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37-3·91], p=0·771) was similar. In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status. National Institute of Neurological Disorders and Stroke.

A Series of Cerebral Venous Sinus Thromboses Treated with Intra-Arterial tPA infused over Ten Hours with a 0.027-inch Catheter and Literature Review.

Cerebral venous sinus thrombosis (CVST) can have devastating results, with mortality reported in 44% of cases. No randomized trials exist in order to define what qualifies as failure of conservative therapy, and there is no specific intervention to date which is considered safe and effective. Case series suggest that thrombolysis infusion is safer than thrombectomy, but methods of administration, dose, and duration of therapy tend to vary widely. We present three consecutive CVST patients treated with heparin who suffered both clinical and radiographic deterioration, and went on to have endovascular therapy. Each patient was successfully recanalized by placing a 0.027-inch microcatheter at the proximal portion of the thrombus and infusing 20 mg of alteplase dissolved in 1 liter of normal saline infused at 100 ml per hour for an infusion of 2 mg of alteplase per hour for ten hours.

Safety and Efficacy of Fibrinolytic Therapy in Restoring Function of an Obstructed Tunneled Pleural Catheter.

Tunneled pleural catheters have been established to be safe and effective in the management of recurrent symptomatic pleural effusions. Obstruction of the tunneled pleural catheter is rare; however, when obstructed the catheter fails to achieve its primary goal of symptom palliation. The management of pleural catheter obstruction has not been studied. We aimed to determine if the use of intracatheter fibrinolytic therapy is safe and effective in restoring catheter function. One hundred seventy-two patients with tunneled pleural catheters placed from 2009 to 2014 were reviewed to identify patients who received fibrinolysis for catheter obstruction, defined by a sudden reduction to less than 10 ml in pleural fluid drainage with fluid visualized in the thorax on ultrasound/radiography. The technique involved intracatheter instillation of 2 to 5 mg of alteplase, which was allowed to remain in the catheter for 60 to 120 minutes, after which drainage was performed. Obstruction occurred in 37 pleural catheters at a median of 2 months from insertion. One hundred percent (37/37) of obstructed catheters resumed drainage after fibrinolytic instillation, from a median of 4 ml before to 300 ml after fibrinolysis (P < 0.001). Twenty-four (65%) were performed in an outpatient setting, and no complications were encountered during or after fibrinolytic therapy. There were 18 episodes of reobstruction, all of which were successfully treated with intracatheter fibrinolytic therapy without complication. Fibrinolytic instillation through a tunneled pleural catheter is safe and effective in restoring function of an obstructed catheter, as evidenced by the lack of complications and success in achieving catheter patency. The procedure can also be performed safely in an outpatient setting. Patients who experience catheter obstruction may be prone to reobstruction; however, fibrinolysis was safe and effective in reestablishing patency of the reobstructed catheter.

Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection

BackgroundTrials of endovascular therapy for ischemic stroke have produced variable results. We conducted this study to test whether more advanced imaging selection, recently developed devices, and earlier intervention improve outcomes.MethodsWe randomly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR (Flow Restoration) stent retriever or to continue receiving alteplase alone. All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic (CT) perfusion imaging. The coprimary outcomes were reperfusion at 24 hours and early neurologic improvement (≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3). Secondary outcomes included the functional score on the modified Rankin scale at 90 days.ResultsThe trial was stopped early because of efficacy after 70 patients had undergone randomization (35 patients in each group). The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group (median, 100% vs. 37%; P<0.001). Endovascular therapy, initiated at a median of 210 minutes after the onset of stroke, increased early neurologic improvement at 3 days (80% vs. 37%, P=0.002) and improved the functional outcome at 90 days, with more patients achieving functional independence (score of 0 to 2 on the modified Rankin scale, 71% vs. 40%; P=0.01). There were no significant differences in rates of death or symptomatic intracerebral hemorrhage.ConclusionsIn patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging, early thrombectomy with the Solitaire FR stent retriever, as compared with alteplase alone, improved reperfusion, early neurologic recovery, and functional outcome. (Funded by the Australian National Health and Medical Research Council and others; EXTEND-IA ClinicalTrials.gov number, NCT01492725, and Australian New Zealand Clinical Trials Registry number, ACTRN12611000969965.)

Usefulness and Safety of Ultrasound-Assisted Catheter-Directed Thrombolysis for Submassive Pulmonary Emboli

The optimal treatment for intermediate-risk pulmonary embolism (PE) remains unclear. Our goal was to describe the safety and efficacy of the EkoSonic ultrasound-assisted catheter-directed thrombolysis system (EKOS Corporation, Bothell, Washington) in a real-world registry of patients with intermediate-risk PE. Fifty-three consecutive patients with intermediate-risk PE treated with ultrasound-assisted catheter-directed thrombolysis at Brigham and Women's Hospital from 2010 to 2014 were analyzed. The primary outcome was a change in directly measured pulmonary artery pressures as assessed using logistic regression with generalized estimating equations to account for serial measurements. Patients received an average of 24.6 ± 9 mg of alteplase using the EKOS catheter with an average treatment time of 15.9 ± 3 hours. After treatment, there was a 7.2- and a 11.4-mm Hg reduction in mean and systolic pulmonary artery pressure (95% confidence interval 4.7 to 9.7 mm Hg, p <0.001, and 95% confidence interval 7.8 to 15.0 mm Hg, p <0.001), respectively. In this cohort, 9.4% had any bleeding complication noted during their hospital stay. One patient's alteplase was prematurely discontinued for access site bleeding although no other interventions were required related to bleeding complications.