What is the mechanism of action of TPA/DNase?
The mechanistic actions of tPA/DNase have not yet been clearly established. Intense pleural inflammation is thought to create an imbalance between fibrinolytic (e.g., tPA) and profibrotic (e.g., plasminogen activator inhibitor 1) mediators in the pleural space, favoring fibrin deposition and loculation of pleural effusions ( 18 ).
Can TPA and DNase be administered through intrapleural catheters?
Combination Tissue Plasminogen Activator (Tpa) and Dornase Alfa (Dnase) Administration Through Intrapleural Catheters for the Treatment of Loculated or Non-Draining Malignant Pleural Effusions. The safety and scientific validity of this study is the responsibility of the study sponsor and investigators.
What is the role of TPA/DNase in the treatment algorithm for pleural infection?
The optimal role of tPA/DNase in the treatment algorithm for pleural infection remains to be determined. VATS remains the preferred treatment for pleural infection in many centers, and direct comparison of VATS with intrapleural tPA/DNase is a current topic of interest.
What is the efficacy of TPA/DNase in the treatment of tracheostomy?
Treatment with tPA/DNase was effective, and 92.3% of patients were successfully treated without surgery. Eight patients required surgery despite intrapleural therapy. Three patients died between 20 and 30 days after intrapleural therapy.
What is tPA instillation?
Rationale: Treatment of pleural infection with instillation of intrapleural tissue plasminogen activator (tPA) and human recombinant DNase (DNase) has been proven to decrease the length of hospital stay, decrease surgical referral, and improve drainage.
How do you administer tPA Dornase?
Instil diluted alteplase first into the chest drain, clamp the drain for 1 hour and then unclamp and allow drainage for 1 hour. After 1 hour drainage repeat with dornase alfa (2x2. 5mg ampoules diluted with 30mL water for injection).
What is tPA and Dornase?
Combination Tissue Plasminogen Activator (Tpa) and Dornase Alfa (Dnase) Administration Through Intrapleural Catheters for the Treatment of Loculated or Non-Draining Malignant Pleural Effusions.
Can tPA and Dornase be given together?
Intrapleural fibrinolysis with a combination of alteplase (tPA) and dornase alfa (DNase) has been shown in a randomised controlled trial (MIST2) to reduce rate of referral for surgery and the duration of hospital stay for patients with pleural infection treated with antibiotics and chest drain insertion.
How do you give a tPA in a chest tube?
The protocol is: 6 mg of alteplase in 50 mL of normal saline instilled via a pleural chest tube. The chest tube is clamped for 4 hours (dwell time); then, unclamped and allowed to drain. One dose was given per 24 hour period, for a total of three doses.
Can an RN administer alteplase?
Abstract 97: Cerebrovascular Trained Advance Practice Nurse Practitioners Can Safely and Accurately Administer Alteplase as Well as Their Neurology Physician Colleagues via Telemedicine.
What does dornase alfa do?
Descriptions. Dornase alfa inhalation solution is used together with other medicines (eg, antibiotics, bronchodilators, and steroids) to control symptoms of cystic fibrosis. Cystic fibrosis is a condition in which a thick mucus is formed in the lungs and breathing passages.
Is alteplase an antiplatelet?
In patients treated with tissue plasminogen activator (alteplase), initiation of antiplatelet agents should be delayed until after the 24-hour post-thrombolysis scan has excluded intracranial hemorrhage [Evidence Level B].
How is dornase alfa made?
Dornase alfa is a biosynthetic form of human deoxyribunuclease I (DNase I) enzyme. It is produced in genetically modified Chinese hamster ovary (CHO) cells using recombinant DNA technology. The 260-amino acid sequence of dornase alfa is identical to the endogenous human enzyme.
What is fibrinolytic therapy used for?
Thrombolytic treatment is also known as fibrinolytic or thrombolysis to dissolve dangerous intravascular clots to prevent ischemic damage by improving blood flow. Thrombosis is a significant physiological response that limits hemorrhage caused by large or tiny vascular injury.
How do you reconstitute alteplase?
Reconstitution should be carried out using the transfer device provided and by adding the contents of the 100‑mL vial of preservative free SWFI to the 100-mg vial of Activase powder. Reconstitute Activase immediately before administration, using aseptic technique at all times.
How is intrapleural alteplase administered?
Intrapleural tPA was administered as 4 mg/30 to 50 mL normal saline instilled through a chest tube, which was clamped for 1 hour. Early and late administration was defined as the first dose administered at or sooner than 24 hours after diagnosis and more than 24 hours after diagnosis, respectively.
How do you administer a tPA bolus?
Administer the IV bolus directly through the Y site injection port of the vented IV tubing or program the infusion pump to deliver the bolus dose. Immediately following the bolus dose, infuse the remaining 90% of the 0.9 milligrams per kilogram dose over 60 minutes.
How do you give a tPA to nursing?
Administer within 30 minutes of hospital arrival.Adults greater than or equal to 67 kg get 100 mg total dosage administered as a 15 mg IV bolus, followed by 50 mg IV infused over 30 minutes, and then 35 mg IV infused over the next 60 minutes.More items...•
How do you administer actilyse?
Treatment with Actilyse must be started as early as possible within 4.5 hours of the onset of symptoms (see section 4.4)....Hide table of contents.Volume to be administered according to alteplase concentration15 mg as an intravenous bolus, immediately followed by15 ml7.5 ml3 more rows
How do you give a tenecteplase in MI?
A single bolus dose should be administered over 5 seconds based on patient weight. Treatment should be initiated as soon as possible after the onset of AMI symptoms (see Clinical Studies). *From one vial of TNKase reconstituted with 10 mL SWFI.
Abstract
A recent randomized controlled trial showed 12 serial doses of tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) is safe and effective in managing complicated parapneumonic pleural effusions and empyema (CPEE). However, this regimen is laborious, requiring trained personnel to open/close the chest tube 8 times daily for 3 days.
MATERIALS AND METHODS
This is a retrospective observational study of patients who were treated with coadministered intrapleural tPA (Alteplase) and DNase for complicated parapneumonic effusion from January 1, 2012 to April 30, 2015 at the University of Texas Medical Branch. This practice is standard of care at our institution.
RESULTS
From January 1, 2012 to April 30, 2015, 39 patients received at least 1 coadministered tPA and DNase dose for CPEE ( Table 1 ). Baseline characteristics of the study cohort are summarized in Table 2. Patients were relatively young and were admitted to general hospital beds. Half had at least 1 major comorbidity.
DISCUSSION
Our experience shows that the majority (85%) of patients with CPEE treated by a coadministration regimen of intrapleural tPA 10 mg and DNase 5 mg were successfully discharged home alive without need for surgery. This method seems to be safe and effective but warrants further study.
CONCLUSIONS
In our single-center study, intrapleural coadministration of tPA/DNase seems to be effective and safe in patients with complicated parapneumonic effusions and empyema. This case series supports the use of a simplified regimen which should be investigated in future prospective studies.
REFERENCES
1. Corcoran JP, Wrightson JM, Belcher E, et al. Pleural infection: past, present, and future directions. Lancet Respir Med. 2015;3:563–577.
What is DNase therapy?
Rationale: Intrapleural tissue plasminogen activator (tPA)/deoxyribonuclease (DNase) therapy for pleural infection given at the time of diagnosis has been shown to significantly improve radiological outcomes. Published cases are limited to only a single randomized controlled trial and a few case reports.
Is tPA/DNase effective?
Our baseline data confirmed that the study group had significant pleural infection, as evidenced by the low pH and high LDH, and a high percentage had frank pus and presence of loculations. tPA/DNase was effective despite significant pleural infection, and the predefined cure was achieved in 89.7% without the need for thoracic surgery. This result is particularly important, as 76.6% of the patients had at least one comorbidity and up to 15% had major life-limiting diseases (e.g., cancer or end-stage renal failure)—patients who were otherwise not suitable for surgery.
Does tPA/DNase cause drainage?
The clinical outcome data were also associated with improvements in other parameters. Intrapleural tPA/DNase promoted a significant volume of drainage (up to 2.5 L). Despite increasing recognition that fibrinolytics can potentially stimulate excess reactive pleural fluid, increased drain output in our patients was paralleled by improved radiographic appearances. This suggests that the combination treatment was able to break down loculations and allow free drainage of otherwise noncontiguous fluid pockets. It is also possible that this consistent production of large volumes of fluid serves to lavage the infected cavity and clear infection. Importantly, treatment with tPA/DNase was also associated with reduction of systemic infection markers.
Is VATS a DNase?
VATS remains the preferred treatment for pleural infection in many center s, and direct comparison of VATS with intrapleural tPA/DNase is a current topic of interest. Likewise, identifying predictors of tPA/DNase therapy failure may aid in early selection of patients for surgical intervention.
Is DNase a synergistic agent?
The combined use of fibrinolytics and DNase has been shown to have synergistic actions in an animal model of empyema ( 13 ), as well as subsequently in the MIST2 study ( 9 ), whereas individual agents alone appear to be ineffective or worse than placebo. In MIST2, 196 patients were randomized to combined intrapleural treatment with tPA and DNase, tPA alone, DNase alone, or neither. Combined intrapleural tPA/DNase therapy significantly improved radiographic clearance compared to all other groups and reduced surgical referrals and hospital stays. The results from the 48 patients treated with tPA and DNase showed that 96% were successfully treated without surgery.
How much DNase is given?
The dose of DNase (Pulmozyme, Roche) was 5 mg, and the dose of t-PA (Actilyse, Boehringer Ingelheim) was 10 mg. Intrapleural medications were each given twice daily for 3 days, and each administration was followed by clamping of the drain to permit the study drug to remain in the pleural space for 1 hour.
How long did a DNase patient stay in the hospital?
The hospital-stay data included two outlying results: one patient in the DNase group had a hospital stay of 386 days, and one in the placebo group had a stay of 391 days. A post hoc analysis excluding these observations showed that the mean hospital stay was significantly reduced in the t-PA–DNase group (11.8 days, vs. 17.0 days in the placebo group; difference, −6.7 days; 95% CI, −12.0 to −1.9; P=0.006). The mean hospital stay in the other two treatment groups remained similar to the value in the placebo group (19.3 days in the DNase group; difference, 1.9 days; 95% CI, −5.1 to 10.8; P=0.61; and 16.5 days in the t-PA group; difference, −0.6 days; 95% CI, −6.9 to 10.5; P=0.93).
Is DNase monotherapy effective?
DNase monotherapy was ineffective in improving pleural drainage and was associated with an increase in surgical referrals by a factor of 3. Independent review of the indications for surgery indicated that this was due to clinical evidence of worsening infection. We hypothesize that this deterioration may be due to systemic absorption of bacterial or inflammatory components after DNase-mediated biofilm disruption in a pleural space with ineffective drainage due to undisrupted fibrinous septations. Whatever the mechanism, our study shows that DNase monotherapy provides no fluid-drainage benefit and significantly increases the need for surgery, and it should therefore be avoided.
Does t-PA help with drainage?
No drainage benefit was seen with either t-PA alone or DNase alone ( Figure 2 ). This result supports data from the MIST1 trial, 9 which remain a source of clinical debate. 44-48 It is unclear why fibrinolytic agents do not appear to be helpful in patients with extensive deposition of fibrin in the pleural space. 49-51 This lack of efficacy suggests that free DNA cleavage is necessary to reduce fluid viscosity and permit pleural clearance by fibrinolytic drugs. A similar treatment combination has been shown to be helpful in other diseases. 52-54 The current trial somewhat clarifies this debate by showing that the use of a different fibrinolytic agent (i.e., t-PA rather than streptokinase) and the additional cleavage of uncoiled DNA by DNase may have allowed fibrinolytic treatment to work. This observation is consistent with in vitro studies 33,34 and an animal model 35 of pleural infection, which show that free DNA cleavage is necessary to reduce fluid viscosity and permit pleural clearance by fibrinolytic drugs. Thus, our results are consistent with the MIST1 results and suggest a new therapeutic strategy for this disease.
Does T-PA help with pleural infection?
Our trial shows that as compared with placebo, combined treatment with t-PA and DNase improved the drainage of infected fluid in patients with pleural infection. Each of the agents alone was ineffective. The reduction in the infected pleural fluid collection was approximately doubled with the use of the combination therapy (with clearing of approximately 30% of the ipsilateral hemithorax volume and approximately a 60% reduction in the baseline pleural collection). This new treatment effect was not associated with an excess of adverse events.
Is white cell count higher with t-PA or DNase?
By day 7, the average white-cell count in the systemic circulation was nonsignificantly higher with t-PA and nonsignificantly lower with DNase than with placebo. The average count was significantly lower in the t-PA–DNase group than in the placebo group (difference, −3.4×10 9 per liter; 95% CI, −6.4 to −0.3; P=0.03).
