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1.
JAMA ; 327(9): 826-835, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1750256

ABSTRACT

Importance: It is estimated that only 27% of patients with acute ischemic stroke and large vessel occlusion who undergo successful reperfusion after mechanical thrombectomy are disability free at 90 days. An incomplete microcirculatory reperfusion might contribute to these suboptimal clinical benefits. Objective: To investigate whether treatment with adjunct intra-arterial alteplase after thrombectomy improves outcomes following reperfusion. Design, Setting, and Participants: Phase 2b randomized, double-blind, placebo-controlled trial performed from December 2018 through May 2021 in 7 stroke centers in Catalonia, Spain. The study included 121 patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and with an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3. Interventions: Participants were randomized to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes (n = 61) or placebo (n = 52). Main Outcomes and Measures: The primary outcome was the difference in proportion of patients achieving a score of 0 or 1 on the 90-day modified Rankin Scale (range, 0 [no symptoms] to 6 [death]) in all patients treated as randomized. Safety outcomes included rate of symptomatic intracranial hemorrhage and death. Results: The study was terminated early for inability to maintain placebo availability and enrollment rate because of the COVID-19 pandemic. Of 1825 patients with acute ischemic stroke treated with thrombectomy at the 7 study sites, 748 (41%) patients fulfilled the angiographic criteria, 121 (7%) patients were randomized (mean age, 70.6 [SD, 13.7] years; 57 women [47%]), and 113 (6%) were treated as randomized. The proportion of participants with a modified Rankin Scale score of 0 or 1 at 90 days was 59.0% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% CI, 0.3%-36.4%; P = .047). The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, -3.8%; 95% CI, -13.2% to 2.5%). Ninety-day mortality was 8% with alteplase and 15% with placebo (risk difference, -7.2%; 95% CI, -19.2% to 4.8%). Conclusions and Relevance: Among patients with large vessel occlusion acute ischemic stroke and successful reperfusion following thrombectomy, the use of adjunct intra-arterial alteplase compared with placebo resulted in a greater likelihood of excellent neurological outcome at 90 days. However, because of study limitations, these findings should be interpreted as preliminary and require replication. Trial Registration: ClinicalTrials.gov Identifier: NCT03876119; EudraCT Number: 2018-002195-40.


Subject(s)
Cerebral Arteries , Fibrinolytic Agents/administration & dosage , Ischemic Stroke/drug therapy , Ischemic Stroke/surgery , Thrombectomy , Tissue Plasminogen Activator/administration & dosage , Aged , Aged, 80 and over , Arterial Occlusive Diseases/complications , Combined Modality Therapy , Double-Blind Method , Female , Humans , Ischemic Stroke/complications , Male , Middle Aged , Treatment Outcome
2.
J Stroke Cerebrovasc Dis ; 31(1): 106179, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1525870

ABSTRACT

OBJECTIVES: This study aims to evaluate shortening door-to-needle time of intravenous recombinant tissue plasminogen activator of acute ischemic stroke patients by multidisciplinary collaboration and workflow optimization based on our hospital resources. MATERIALS AND METHODS: We included patients undergoing thrombolysis with intravenous recombinant tissue plasminogen activator from January 1, 2018, to September 30, 2020. Patients were divided into pre- (January 1, 2018, to December 31, 2019) and post-intervention groups (January 1, 2020, to September 31, 2020). We conducted multi-department collaboration and process optimization by implementing 16 different measures in prehospital, in-hospital, and post-acute feedback stages for acute ischemic stroke patients treated with intravenous thrombolysis. A comparison of outcomes between both groups was analyzed. RESULTS: Two hundred and sixty-three patients received intravenous recombinant tissue plasminogen activator in our hospital during the study period, with 128 and 135 patients receiving treatment in the pre-intervention and post-intervention groups, respectively. The median (interquartile range) door-to-needle time decreased significantly from 57.0 (45.3-77.8) min to 37.0 (29.0-49.0) min. Door-to-needle time was shortened to 32 min in the post-intervention period in the 3rd quarter of 2020. The door-to-needle times at the metrics of ≤ 30 min, ≤ 45 min, ≤ 60 min improved considerably, and the DNT> 60 min metric exhibited a significant reduction. CONCLUSIONS: A multidisciplinary collaboration and continuous process optimization can result in overall shortened door-to-needle despite the challenges incurred by the COVID-19 pandemic.


Subject(s)
Brain Ischemia/drug therapy , COVID-19/complications , Cooperative Behavior , Ischemic Stroke/drug therapy , Patient Care Team , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/administration & dosage , Administration, Intravenous , Early Medical Intervention , Emergency Medical Services , Female , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/therapeutic use , Humans , Male , Pandemics , SARS-CoV-2 , Time Management , Time-to-Treatment , Tissue Plasminogen Activator/therapeutic use , Treatment Outcome , Workflow
3.
Chest ; 161(3): 710-727, 2022 03.
Article in English | MEDLINE | ID: covidwho-1491838

ABSTRACT

BACKGROUND: Pulmonary vascular microthrombi are a proposed mechanism of COVID-19 respiratory failure. We hypothesized that early administration of tissue plasminogen activator (tPA) followed by therapeutic heparin would improve pulmonary function in these patients. RESEARCH QUESTION: Does tPA improve pulmonary function in severe COVID-19 respiratory failure, and is it safe? STUDY DESIGN AND METHODS: Adults with COVID-19-induced respiratory failure were randomized from May14, 2020 through March 3, 2021, in two phases. Phase 1 (n = 36) comprised a control group (standard-of-care treatment) vs a tPA bolus (50-mg tPA IV bolus followed by 7 days of heparin; goal activated partial thromboplastin time [aPTT], 60-80 s) group. Phase 2 (n = 14) comprised a control group vs a tPA drip (50-mg tPA IV bolus, followed by tPA drip 2 mg/h plus heparin 500 units/h over 24 h, then heparin to maintain aPTT of 60-80 s for 7 days) group. Patients were excluded from enrollment if they had not undergone a neurologic examination or cross-sectional brain imaging within the previous 4.5 h to rule out stroke and potential for hemorrhagic conversion. The primary outcome was Pao2 to Fio2 ratio improvement from baseline at 48 h after randomization. Secondary outcomes included Pao2 to Fio2 ratio improvement of > 50% or Pao2 to Fio2 ratio of ≥ 200 at 48 h (composite outcome), ventilator-free days (VFD), and mortality. RESULTS: Fifty patients were randomized: 17 in the control group and 19 in the tPA bolus group in phase 1 and eight in the control group and six in the tPA drip group in phase 2. No severe bleeding events occurred. In the tPA bolus group, the Pao2 to Fio2 ratio values were significantly (P < .017) higher than baseline at 6 through 168 h after randomization; the control group showed no significant improvements. Among patients receiving a tPA bolus, the percent change of Pao2 to Fio2 ratio at 48 h (16.9% control [interquartile range (IQR), -8.3% to 36.8%] vs 29.8% tPA bolus [IQR, 4.5%-88.7%]; P = .11), the composite outcome (11.8% vs 47.4%; P = .03), VFD (0.0 [IQR, 0.0-9.0] vs 12.0 [IQR, 0.0-19.0]; P = .11), and in-hospital mortality (41.2% vs 21.1%; P = .19) did not reach statistically significant differences when compared with those of control participants. The patients who received a tPA drip did not experience benefit. INTERPRETATION: The combination of tPA bolus plus heparin is safe in severe COVID-19 respiratory failure. A phase 3 study is warranted given the improvements in oxygenation and promising observations in VFD and mortality. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04357730; URL: www. CLINICALTRIALS: gov.


Subject(s)
COVID-19/complications , Pandemics , Respiratory Insufficiency/drug therapy , SARS-CoV-2 , Thrombosis/complications , Tissue Plasminogen Activator/administration & dosage , Adolescent , Adult , Aged , COVID-19/blood , COVID-19/epidemiology , Cross-Sectional Studies , Female , Fibrinolytic Agents/administration & dosage , Follow-Up Studies , Humans , Male , Middle Aged , Partial Thromboplastin Time , Respiratory Insufficiency/blood , Respiratory Insufficiency/etiology , Retrospective Studies , Thrombosis/blood , Thrombosis/drug therapy , Treatment Outcome , Young Adult
4.
J Stroke Cerebrovasc Dis ; 30(10): 106035, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1347731

ABSTRACT

OBJECTIVES: Most data on telestroke utilization come from single academic hub-and-spoke telestroke networks. Our objective was to describe characteristics of telestroke consultations among a national sample of telestroke sites on one of the most commonly used common vendor platforms, prior to the COVID-19 public health emergency. MATERIALS AND METHODS: A commercial telestroke vendor provided data on all telestroke consultations by two specialist provider groups from 2013-2019. Kendall's τ ß nonparametric test was utilized to assess time trends. Generalized linear models were used to assess the association between hospital consult utilization and alteplase use adjusting for hospital characteristics. RESULTS: Among 67,736 telestroke consultations to 132 spoke sites over the study period, most occurred in the emergency department (90%) and for stroke indications (final clinical diagnoses: TIA 13%, ischemic stroke 39%, hemorrhagic stroke 2%, stroke mimics 46%). Stroke severity was low (median NIHSS 2, IQR 0-6). Alteplase was recommended for 23% of ischemic stroke patients. From 2013 to 2019, times from ED arrival to NIHSS, CT scan, imaging review, consult, and alteplase administration all decreased (p<0.05 for all), while times from consult start to alteplase recommendation and bolus increased (p<0.01 for both). Transfer was recommended for 8% of ischemic stroke patients. Number of patients treated with alteplase per hospital increased with increasing number of consults and hospital size and was also associated with US region in unadjusted and adjusted analyses. Longer duration of hospital participation in the network was associated with shorter hospital median door-to-needle time for alteplase delivery (39 min shorter per year, p=0.04). CONCLUSIONS: Among spoke sites using a commercial telestroke platform over a seven-year time horizon, times to consult start and alteplase bolus decreased over time. Similar to academic networks, duration of telestroke participation in this commercial network was associated with faster alteplase delivery, suggesting practice improves performance.


Subject(s)
COVID-19 , Fibrinolytic Agents/administration & dosage , Practice Patterns, Physicians'/trends , Remote Consultation/trends , Stroke/surgery , Thrombolytic Therapy/trends , Time-to-Treatment/trends , Tissue Plasminogen Activator/administration & dosage , Aged , Aged, 80 and over , Databases, Factual , Female , Humans , Male , Middle Aged , Quality Improvement/trends , Quality Indicators, Health Care/trends , Stroke/diagnosis , Time Factors , Treatment Outcome , United States
5.
J Thromb Haemost ; 18(7): 1752-1755, 2020 07.
Article in English | MEDLINE | ID: covidwho-1317980

ABSTRACT

A prothrombotic coagulopathy is commonly found in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS). A unique feature of COVID-19 respiratory failure is a relatively preserved lung compliance and high Alveolar-arterial oxygen gradient, with pathology reports consistently demonstrating diffuse pulmonary microthrombi on autopsy, all consistent with a vascular occlusive etiology of respiratory failure rather than the more classic findings of low-compliance in ARDS. The COVID-19 pandemic is overwhelming the world's medical care capacity with unprecedented needs for mechanical ventilators and high rates of mortality once patients progress to needing mechanical ventilation, and in many environments including in parts of the United States the medical capacity is being exhausted. Fibrinolytic therapy has previously been used in a Phase 1 clinical trial that led to reduced mortality and marked improvements in oxygenation. Here we report a series of three patients with severe COVID-19 respiratory failure who were treated with tissue plasminogen activator. All three patients had a temporally related improvement in their respiratory status, with one of them being a durable response.


Subject(s)
Betacoronavirus/pathogenicity , Blood Coagulation Disorders/drug therapy , Coronavirus Infections/drug therapy , Fibrinolysis/drug effects , Fibrinolytic Agents/administration & dosage , Pneumonia, Viral/drug therapy , Thrombolytic Therapy , Tissue Plasminogen Activator/administration & dosage , Aged , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/virology , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Fatal Outcome , Female , Fibrinolytic Agents/adverse effects , Host-Pathogen Interactions , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Recovery of Function , SARS-CoV-2 , Thrombolytic Therapy/adverse effects , Tissue Plasminogen Activator/adverse effects , Treatment Outcome
6.
Clin Neurol Neurosurg ; 201: 106436, 2021 02.
Article in English | MEDLINE | ID: covidwho-1059739

ABSTRACT

BACKGROUND: To evaluate overall ischemic stroke volumes and rates, specific subtypes, and clinical presentation during the COVID-19 pandemic in a multicenter observational study from eight states across US. METHODS: We compared all ischemic strokes admitted between January 2019 and May 2020, grouped as; March-May 2020 (COVID-19 period) and March-May 2019 (seasonal pre-COVID-19 period). Primary outcome was stroke severity at admission measured by NIHSS stratified as mild (0-7), moderate [8-14], and severe (>14). Secondary outcomes were volume of large vessel occlusions (LVOs), stroke etiology, IV-tPA rates, and discharge disposition. RESULTS: Of the 7969 patients diagnosed with acute ischemic stroke during the study period, 933 (12 %) presented in the COVID-19 period while 1319 (17 %) presented in the seasonal pre-COVID-19 period. Significant decline was observed in the mean weekly volumes of newly diagnosed ischemic strokes (98 ± 3 vs 50 ± 20,p = 0.003), LVOs (16.5 ± 3.8 vs 8.3 ± 5.9,p = 0.008), and IV-tPA (10.9 ± 3.4 vs 5.3 ± 2.9,p = 0.0047), whereas the mean weekly proportion of LVOs (18 % ±5 vs 16 % ±7,p = 0.24) and IV-tPA (10.4 % ±4.5 vs. 9.9 % ±2.4,p = 0.66) remained the same, when compared to the seasonal pre-COVID-19 period. Additionally, an increased proportion of patients presented with a severe disease (NIHSS > 14) during the COVID-19 period (29.7 % vs 24.5 %,p < 0.025). The odds of being discharged to home were 26 % greater in the COVID-19 period when compared to seasonal pre-COVID-19 period (OR:1.26, 95 % CI:1.07-1.49,p = 0.016). CONCLUSIONS: During COVID-19 period there was a decrease in volume of newly diagnosed ischemic stroke cases and IV-tPA administration. Patients admitted to the hospital had severe neurological clinical presentation and were more likely to discharge home.


Subject(s)
COVID-19/epidemiology , Neurology/trends , Societies, Medical/trends , Stroke/drug therapy , Stroke/epidemiology , Thrombolytic Therapy/trends , Administration, Intravenous , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , Cohort Studies , Female , Humans , Male , Middle Aged , Pandemics , Retrospective Studies , Stroke/diagnosis , Tissue Plasminogen Activator/administration & dosage , United States/epidemiology , Vascular Diseases/drug therapy , Vascular Diseases/epidemiology
7.
Br J Anaesth ; 126(3): 590-598, 2021 03.
Article in English | MEDLINE | ID: covidwho-965444

ABSTRACT

BACKGROUND: Critically ill coronavirus disease 2019 (COVID-19) patients present with a hypercoagulable state with high rates of macrovascular and microvascular thrombosis, for which hypofibrinolysis might be an important contributing factor. METHODS: We retrospectively analysed 20 critically ill COVID-19 patients at Innsbruck Medical University Hospital whose coagulation function was tested with ClotPro® and compared with that of 60 healthy individuals at Augsburg University Clinic. ClotPro is a viscoelastic whole blood coagulation testing device. It includes the TPA test, which uses tissue factor (TF)-activated whole blood with added recombinant tissue-derived plasminogen activator (r-tPA) to induce fibrinolysis. For this purpose, the lysis time (LT) is measured as the time from when maximum clot firmness (MCF) is reached until MCF falls by 50%. We compared COVID-19 patients with prolonged LT in the TPA test and those with normal LT. RESULTS: Critically ill COVID-19 patients showed hypercoagulability in ClotPro assays. MCF was higher in the EX test (TF-activated assay), IN test (ellagic acid-activated assay), and FIB test (functional fibrinogen assay) with decreased maximum lysis (ML) in the EX test (hypofibrinolysis) and highly prolonged TPA test LT (decreased fibrinolytic response), as compared with healthy persons. COVID-19 patients with decreased fibrinolytic response showed higher fibrinogen levels, higher thrombocyte count, higher C-reactive protein levels, and decreased ML in the EX test and IN test. CONCLUSION: Critically ill COVID-19 patients have impaired fibrinolysis. This hypofibrinolytic state could be at least partially dependent on a decreased fibrinolytic response.


Subject(s)
COVID-19/blood , COVID-19/epidemiology , Critical Illness/epidemiology , Fibrinolysis/drug effects , Thrombophilia/blood , Thrombophilia/epidemiology , Adult , Aged , Anticoagulants/administration & dosage , Blood Coagulation Tests/methods , COVID-19/diagnosis , Female , Fibrinolysis/physiology , Humans , Male , Middle Aged , Retrospective Studies , Thrombophilia/diagnosis , Tissue Plasminogen Activator/administration & dosage
11.
Rinsho Shinkeigaku ; 60(10): 706-711, 2020 Oct 24.
Article in Japanese | MEDLINE | ID: covidwho-745654

ABSTRACT

During the COVID-19 pandemic in 2020, an 81-year-old afebrile woman was transported to our institute at 44 minutes after she was found to have global aphasia and weakness of the right extremities. The onset time was unclear. CT showed an occlusion of the left middle cerebral artery without early ischemic changes. MRI revealed a negative fluid-attenuated inversion recovery (FLAIR) pattern, in which several small acute infarcts were seen in diffusion-weighted images with no corresponding hyperintensity lesions on FLAIR. Accordingly, intravenous thrombolysis with alteplase (0.6 mg/kg, the dose approved in Japan) was administered at 1,660 minutes after the last known well and 116 minutes after the symptom recognition. An immediate internal carotid angiogram showed severe stenosis at the distal end of the horizontal portion of the left middle cerebral artery. In the follow-up angiogram at 164 minutes after the symptom recognition, the stenotic lesion almost resolved with the restoration of quick and nearly complete antegrade flow. Her symptoms also resolved promptly. Although the use of MRI is recommended to be minimized in the emergency stroke management during the COVID-19 pandemic, MRI is occasionally mandatory for patient selection, such as cases with unclear onset to perform intravenous thrombolysis. The individualized protected code stroke is essential and must be well considered by each institute for diagnosing patients by selecting appropriate modalities.


Subject(s)
Coronavirus Infections/prevention & control , Diffusion Magnetic Resonance Imaging , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Stroke/diagnostic imaging , Stroke/drug therapy , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/therapeutic use , Aged, 80 and over , COVID-19 , Female , Humans , Infusions, Intravenous , Time Factors , Tissue Plasminogen Activator/administration & dosage
12.
Ann Vasc Surg ; 70: 297-301, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-733967

ABSTRACT

SARS-CoV-2 (COVID-19) patients with associated thromboembolic events have demonstrated poor outcomes despite the use of anticoagulation therapy and surgical intervention. We present a COVID-19 patient with acute limb ischemia, secondary to extensive thrombosis of an aortic aneurysm, iliac arteries, and infrainguinal arteries. Initial treatment with systemic thrombolysis, which restored patency of the aortoiliac occlusion, was followed by open thrombectomies of the infrainguinal occlusions.


Subject(s)
Aortic Aneurysm, Abdominal/complications , Arterial Occlusive Diseases/drug therapy , COVID-19/complications , Fibrinolytic Agents/administration & dosage , Iliac Artery , Thrombolytic Therapy , Thrombosis/drug therapy , Tissue Plasminogen Activator/administration & dosage , Aged , Aortic Aneurysm, Abdominal/diagnostic imaging , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/etiology , Arterial Occlusive Diseases/physiopathology , COVID-19/diagnosis , Humans , Iliac Artery/diagnostic imaging , Iliac Artery/physiopathology , Infusions, Intravenous , Male , Thrombectomy , Thrombosis/diagnostic imaging , Thrombosis/etiology , Thrombosis/physiopathology , Treatment Outcome , Vascular Patency
15.
Neurol Sci ; 41(9): 2325-2329, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-640307

ABSTRACT

The sudden worldwide outbreak of Coronavirus Disease 2019 (COVID-19) has certainly provided new challenges in the management of acute ischaemic stroke, and the risk-benefit ratio of intravenous thrombolysis in COVID-19 positive patients is not well known. We describe four COVID-19 patients treated with intravenous thrombolysis for acute ischaemic stroke. Although rt-PA administration is the main therapeutic strategy, our patients experienced unpredictable complications and showed atypical features: the overall mortality was very high. In conclusion, in this article, we provide information about these cases and discuss the possible explanation behind this trend.


Subject(s)
Betacoronavirus , Brain Ischemia/drug therapy , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Stroke/drug therapy , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/administration & dosage , Administration, Intravenous , Aged , Brain Ischemia/complications , Brain Ischemia/diagnostic imaging , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Recombinant Proteins/administration & dosage , SARS-CoV-2 , Stroke/complications , Stroke/diagnostic imaging
16.
J Thromb Thrombolysis ; 51(2): 293-296, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-621521

ABSTRACT

We describe successful usage of low dose Tissue plasminogen activator (tPA) (30-50 mg) in three COVID19 critically ill patients, who were in worsening respiratory failure in-spite of being on therapeutic anticoagulation. All patients had respiratory rate > 40; FiO2 > 0.7(on NIV); PiO2/FiO2 ratio < 100 and D-dimer>1000 ng/ml. C.T. Pulmonary Angiography could not be done in these patients due to poor general condition, but 2D echo was normal and none of the patients was in shock. So there was no conventional indication of thrombolysis in these patients, yet after thrombolysis, we saw dramatic changes in oxygenation. All patients became off oxygen within 3-7 days and were discharged within 2 weeks. The whole idea was to prevent intubation, since mortality rates are very high in intubated COVID19 patients. tPA is associated with <1% risk of fatal bleed. In this unprecedented pandemic with high mortality rates, thrombolysis could be an effective and safe option in carefully selected critically ill patients of COVID19.


Subject(s)
COVID-19/complications , Fibrinolytic Agents/therapeutic use , Respiratory Distress Syndrome/etiology , Tissue Plasminogen Activator/therapeutic use , COVID-19/therapy , Female , Fibrinolytic Agents/administration & dosage , Humans , Male , Middle Aged , Respiratory Distress Syndrome/therapy , Thrombolytic Therapy , Tissue Plasminogen Activator/administration & dosage
17.
J Trauma Acute Care Surg ; 89(3): 448-452, 2020 09.
Article in English | MEDLINE | ID: covidwho-316022

ABSTRACT

BACKGROUND: Coronavirus patients demonstrate varying degrees of respiratory insufficiency; many will progress to respiratory failure with a severe version of acute respiratory distress syndrome refractory to traditional supportive strategies. Providers must consider alternative therapies to deter or prevent the cascade of decompensation to fulminant respiratory failure. METHODS: This is a case-series of five COVID-19 positive patients who demonstrated severe hypoxemia, declining respiratory performance, and escalating oxygen requirements. Patients met the following criteria: COVID-19 positivity, worsening respiratory performance, severe hypoxemia (PaO2 ≤ 80) despite traditional supportive measures, escalating supplemental oxygen requirements, and D-dimer greater than 1.5 µg/mL. All patients received protocol directed thrombolytic therapy with tissue plasminogen activator (tPA). RESULTS: All five patients improved without deleterious effects of thrombolytic therapy. Patient one was on maximum ventilator support, paralytics, and prone positioning without improvement. During tPA administration his PaO2/FIO2 ratio improved from 69 to 127. Ventilator support was weaned immediately on posttreatment day 1, and he was extubated on posttreatment day 12. Our second through fifth patients were not intubated at time of initiation of tPA therapy. These patients each required significant oxygen supplementation trending toward intubation. After tPA therapy, all patients demonstrated a noticeable increase in PaO2 values overtime. Three of these patients avoided intubation due to COVID-19-associated respiratory failure. CONCLUSION: Administration of thrombolytics was followed by overall improvement in patients' oxygen requirements, and in three cases, prevented progression to mechanical ventilation, without deleterious effects. Clinical trials of thrombolytic therapy would further serve to underscore the efficacy and utility of this therapy. LEVEL OF EVIDENCE: Case series of therapeutic effect, Level V.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Pneumonia, Viral/complications , Respiration, Artificial/methods , Tissue Plasminogen Activator/administration & dosage , Aged , Aged, 80 and over , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Female , Fibrinolytic Agents/administration & dosage , Follow-Up Studies , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Retrospective Studies , SARS-CoV-2
18.
J Clin Neurosci ; 77: 234-236, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-272249

ABSTRACT

The 2019 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which was first reported in Wuhan, China last December 2019, has been declared an emergency by the World Health Organization but eventually progressed to become a Pandemic. To date, Coronavirus Disease 2019 (COVID-19) has affected at least 100,000 individuals worldwide, reaching thousands of mortalities (Zhou et al., 2020; World Health Organization, 2020). In the Philippines, the number of COVID-19 confirmed positive cases is over 636 and is expected to rise (Department of Health, 2020). Respiratory infections alongside their comorbidities can induce acute myocardial infarction and acute ischemic stroke (Warren-Gash et al., 2018) [3]. These may further bring challenges in the management and administration of Intravenous (IV) Alteplase in eligible patients. Currently, there are no case reports in the administration IV Altepase in ischemic stroke patients who are COVID-19 positive. We present a case of a 62-year old female who was admitted due to cough, colds and shortness of breath of 2 weeks duration and was tested to be COVD-19 positive. She suffered from an ischemic stroke while in the Medical Intensive Care Unit and was given Intravenous thrombolysis.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/complications , Pneumonia, Viral/complications , Stroke/etiology , Thrombolytic Therapy/methods , Administration, Intravenous , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Female , Humans , Middle Aged , Pandemics , Philippines , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , SARS-CoV-2 , Stroke/drug therapy , Stroke/virology , Tissue Plasminogen Activator/administration & dosage , Tissue Plasminogen Activator/therapeutic use
20.
J Thromb Haemost ; 18(7): 1548-1555, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-116254

ABSTRACT

The global pandemic of coronavirus disease 2019 (COVID-19) is associated with the development of acute respiratory distress syndrome (ARDS), which requires ventilation in critically ill patients. The pathophysiology of ARDS results from acute inflammation within the alveolar space and prevention of normal gas exchange. The increase in proinflammatory cytokines within the lung leads to recruitment of leukocytes, further propagating the local inflammatory response. A consistent finding in ARDS is the deposition of fibrin in the air spaces and lung parenchyma. COVID-19 patients show elevated D-dimers and fibrinogen. Fibrin deposits are found in the lungs of patients due to the dysregulation of the coagulation and fibrinolytic systems. Tissue factor (TF) is exposed on damaged alveolar endothelial cells and on the surface of leukocytes promoting fibrin deposition, while significantly elevated levels of plasminogen activator inhibitor 1 (PAI-1) from lung epithelium and endothelial cells create a hypofibrinolytic state. Prophylaxis treatment of COVID-19 patients with low molecular weight heparin (LMWH) is important to limit coagulopathy. However, to degrade pre-existing fibrin in the lung it is essential to promote local fibrinolysis. In this review, we discuss the repurposing of fibrinolytic drugs, namely tissue-type plasminogen activator (tPA), to treat COVID-19 associated ARDS. tPA is an approved intravenous thrombolytic treatment, and the nebulizer form has been shown to be effective in plastic bronchitis and is currently in Phase II clinical trial. Nebulizer plasminogen activators may provide a targeted approach in COVID-19 patients to degrade fibrin and improving oxygenation in critically ill patients.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/drug therapy , Fibrinolysis/drug effects , Fibrinolytic Agents/administration & dosage , Pneumonia, Viral/drug therapy , Thrombolytic Therapy , Tissue Plasminogen Activator/administration & dosage , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Drug Repositioning , Fibrinolytic Agents/adverse effects , Host-Pathogen Interactions , Humans , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , SARS-CoV-2 , Thrombolytic Therapy/adverse effects , Tissue Plasminogen Activator/adverse effects , Treatment Outcome
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