If the patient underwent recent less than three months ago intracranial or intraspinal surgery or suffered a serious head trauma. If the risk of bleeding is greater than any potential benefit. This risk includes active internal bleeding or patients with a recent history of stroke. If a hypersensitivity reaction occurs in the patient, stop the tPA administration and immediately initiate supportive therapy with antihistamines and corticosteroids.
Order a follow-up CT scan or MRI at least 24 hours before initiating anticoagulants or antiplatelet agents. Continue to monitor for hypersensitivity and signs of orolingual angioedema. Toxicity The drug used to reverse tPA toxicity is aminocaproic acid, an FDA-approved drug for managing acute bleeding caused by increased fibrinolytic activity. Defibrotide: Through pharmacodynamic synergism, defibrotide increases the effects of tPA drugs and is thus contraindicated.
Prothrombin complex concentrate, human: This can cause pharmacodynamic antagonism of the tPA drugs. Apixaban: Apixaban and tPA drugs increase anticoagulation and can lead to an increased bleeding risk. Salicylates: These could enhance the toxic effects of thrombolytic drugs. Monitor therapy, as there is an increased risk of bleeding. Enhancing Healthcare Team Outcomes tPA has a significant risk of causing complications as well as helping the patient.
Review Questions Access free multiple choice questions on this topic. Comment on this article. References 1. Gravanis I, Tsirka SE. Tissue-type plasminogen activator as a therapeutic target in stroke. Expert Opin Ther Targets. J Stroke Cerebrovasc Dis. Tissue plasminogen activator: an evaluation of clinical efficacy in acute myocardial infarction. Indications and therapeutic strategies]. Z Gesamte Inn Med. Catheter-directed thrombolysis with argatroban and tPA for massive iliac and femoropopliteal vein thrombosis.
Cardiovasc Intervent Radiol. Therapeutic effect evaluation of reteplase on acute pulmonary embolism. Pak J Pharm Sci. Indian Heart J. Collen D. Molecular mechanism of action of newer thrombolytic agents. J Am Coll Cardiol. Sci Rep. Neurocrit Care. Tenecteplase versus alteplase for management of acute ischaemic stroke NOR-TEST : a phase 3, randomised, open-label, blinded endpoint trial.
Lancet Neurol. Rosenberg G, Steiner I. And why not thrombolysis in the ambulance at least for some? Off-target effects of thrombolytic drugs: apolipoprotein A-I proteolysis by alteplase and tenecteplase. Biochem Pharmacol. Baldo BA. Enzymes approved for human therapy: indications, mechanisms and adverse effects. Parker S, Ali Y. Curr Cardiol Rep. Case Rep Neurol Med. Int J Telemed Appl. Madden B, Chebl RB.
Hemi orolingual angioedema after tPA administration for acute ischemic stroke. West J Emerg Med. Quality assurance monitoring of a citywide transportation protocol improves clinical indicators of intravenous tissue plasminogen activator therapy: a community-based, longitudinal study. High rate of complete recanalization and dramatic clinical recovery during tPA infusion when continuously monitored with 2-MHz transcranial doppler monitoring.
Studies evaluating the efficacy, safety, and optimal timing of rtPA use are ongoing. Recently, results of new studies led to expansion of the short timeframe from stroke symptom onset in which a patient can receive this treatment. Additionally, more data are available to support the current goals of administration of rtPA to eligible patients as quickly as possible, as earlier treatment has been proven to improve outcomes.
As stroke is the third most frequent cause of death in the USA, killing , people each year, mortality reduction could potentially spare the lives of a large number of patients 5. This article briefly reviews the evidence supporting the use of rtPA for AIS and focuses on important new literature that has impacted practice since the publication of the current AIS guidelines.
The multicenter trial was conducted in 75 European hospitals and included patients. In ECASS, rtPA was not found to be more effective than placebo in improving neurological outcomes at 3 months; however, post hoc analysis showed benefit in patients treated within 3 hours of stroke symptom onset, but not in those treated beyond that timeframe.
Symptomatic intracerebral hemorrhage ICH within 36 hours occurred in 6. Of note, half of the study patients were treated within 90 minutes of stroke symptom onset. A later subgroup analysis of the trial demonstrated that treatment with rtPA within 90 minutes of stroke symptom onset resulted in more favorable outcomes odds ratio [OR], 2.
As mentioned above, the short 3-hour timeframe in which a patient is eligible for treatment with rtPA is a major contributing factor to the relatively small number of patients who receive this medication 4. When the European Medicines Agency approved use of rtPA in Europe in , the agency requested that two follow-up studies be conducted. The second follow-up study evaluated the use of rtPA beyond the 3-hour timeframe.
ECASS III, a double-blind, multicenter, parallel-group trial conducted between July and November 10 , included patients 18 to 80 years of age with a clinical diagnosis of stroke who were able to receive the study drug within 3 to 4 hours of stroke symptom onset. After 2 years, the trial was amended to include patients treated within a 4. A total of patients were randomized to receive either rtPA or placebo, with the primary efficacy endpoint being disability at 90 days dichotomized as a favorable outcome [score 0 or 1] or unfavorable outcome [score 2—6] , as assessed by modified Rankin scale.
As a secondary efficacy endpoint, the study evaluated a combination of global outcome measures. For the intent-to-treat analysis, patients were randomized to receive rtPA and were randomized to receive placebo. Two hundred nineteen These results were also found to be significant in the post hoc intent-to-treat analysis. The safety profile of the treatment also requires validation.
In this cohort of patients who would usually be considered for surgery, except for their comorbidity, No patients died from pleural infection. The median hospital stay from first intrapleural treatment dose was 10 IQR, days. Pleural fluid drainage increased from mL median in the preceding 24 hours to a cumulative amount of 2, mL over the 72 hours following commencement of intrapleural therapy.
Follow-up CXR C showed no significant residual thickening. Chest pain is the most frequent side effect whereas bleeding, though uncommon, remains the biggest concern among clinicians and patients. The pain typically occurs with the administration of the first dose of tPA treatment 17 ; its cause is unclear and may be multifactorial. It is possible that tPA provokes inflammatory changes in an already inflamed pleural cavity.
This sudden expansion of fluid within 60 minutes and the lysis of adhesions may generate pain. Production of a large volume of hemorrhagic pleural fluid is a common observation after intrapleural administration of fibrinolytics, and often provokes anxiety. Significant pleural bleeding, defined as a reduction of haematocrit necessitating blood transfusion, is rare.
In our series significant pleural bleeding occurred in only 2 of 1. There were no episodes of haemoptysis or gastrointestinal bleeding Other studies of single agent intrapleural tPA use also supported its safety. No major bleeding events were reported from patients with pleural effusions of various etiologies who received doses of intrapleural tPA mg daily Another two studies 54 , 55 , with 45 patients combined, also found no major bleeding complications.
Isolated cases of pleural bleeding have been reported in patients treated with intrapleural tPA which were receiving concurrent anticoagulation or had end stage renal diseases 56 - We recommend that response to therapy should be assessed daily.
Lack of clinical improvement should trigger searches for alternative source of infection e. Monitoring the serum haematocrit levels can be helpful in detecting significant blood loss through induced hemorrhagic pleural fluid production. Cessation of therapy and supportive measures e. The MIST-2 data suggested that initiation of treatment significantly shortened hospitalization which argued for its use as a routine.
To date, the regimen has only been used in adults and cannot be recommended in children, and specific patient groups e. Future research should aim to optimize dosing regimes.
Understanding the mechanistic actions of tPA and DNase may allow refinement of treatment and knowledge that may benefit infections of other sites. Cost analysis data will be of interest. National Center for Biotechnology Information , U.
Journal List J Thorac Dis v. J Thorac Dis. Francesco Piccolo 1 Find articles by Francesco Piccolo. Natalia Popowicz 2 Find articles by Natalia Popowicz. Donny Wong 3 Find articles by Donny Wong. Author information Article notes Copyright and License information Disclaimer. Corresponding author. Correspondence to: Prof. Email: ua. Received Dec 29; Accepted Jan Copyright Journal of Thoracic Disease.
All rights reserved. This article has been cited by other articles in PMC. Abstract Pleural infection remains a global health burden associated with significant morbidity. Keywords: Deoxyribonuclease DNase , empyema, fibrinolytics, pleural infection, tissue plasminogen activator tPA. Introduction Pleural infection is increasing worldwide with many reports showing significant rises in the incidence over the last few decades 1 - 6.
DNase therapy Deoxyribonucleoprotein content exerts a major influence in increasing the viscosity of pus in the pleural space. Recombinant tPA Recombinant tPA, or alteplase, is a recognized systemic treatment for myocardial infarction, pulmonary embolism and thromboembolic stroke.
Recombinant human DNase DNase is a naturally occurring nuclease involved in the degradation of extracellular DNA following apoptosis and bacterial lysis in humans. Combined tPA with DNase for pleural infection The combined use of tPA and DNase has been shown to have synergistic actions in an animal model of empyema 29 , and subsequent clinical trials 9.
Open in a separate window. Figure 1. Table 1 Practical approach to managing pleural infection. References 1. Thorax ; 65 Suppl 2 :ii Emergence of parapneumonic empyema in the USA. Thorax ; 66 Management of pleural space infections: a population-based analysis. J Thorac Cardiovasc Surg ; Empyema: an increasing concern in Canada.
Can Respir J ; 15 Epidemiology of pleural infections in Taiwan from through Respirology ; 17 Incidence, length of stay, and prognosis of hospitalized patients with pleural empyema: a year Danish nationwide cohort study. Chest ; Controlled trial of intrapleural streptokinase for pleural infection. N Engl J Med ; Parapneumonic empyema deaths during past century, Utah. Emerg Infect Dis ; 15 Intrapleural use of tissue plasminogen activator and DNase in pleural infection. Birmingham AL.
Aphorism In: Adams LB. The genuine works of Hippocrates: the classics of surgery. Delran: Gryphon Editions, Thoracotomy and thoracoscopy: postoperative pulmonary function, pain and chest wall complaints.
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Intrapleural streptokinase in the management of empyema. Thorax ; 49 Intrapleural streptokinase in experimental empyema. Am Rev Respir Dis ; Treatment of loculated pleural effusions with transcatheter intracavitary urokinase.
Treatment of thoracic multiloculated empyemas with intracavitary urokinase: a prospective study. Radiology ; Lee YC.
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