Intrapleural Use of Tissue Plasminogen Activator and DNase in Pleural Infection

Rahman, Najib M.; Maskell, Nick A; West, Alex; Teoh, Richard; Arnold, Anthony; Mackinlay, Carolyn; Peckham, Daniel; Davies, C. W. H.; Ali, Nabeel; Kinnear, William; Bentley, Andrew; Kahan, Brennan C; Wrightson, John; Davies, Helen; Hooper, Clare; Lee, Y C Gary; Hedley, Emma; Crosthwaite, Nicky; Choo, Louise; Helm, Emma; Gleeson, Fergus; Nunn, Andrew; Davies, Robert J. O.

doi:10.1056/nejmoa1012740

Cited by 675 publications

(826 citation statements)

References 46 publications

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“…Several reviews have concluded that IPFT appears to decrease the requirement for surgical interventions but does not decrease mortality in adults 8, 9. Although early studies in people identified improved survival after IPFT,10, 11, 12 2 of the largest randomized, placebo‐controlled studies in adults failed to show a positive effect with IPFT without concurrent intrapleural administration of DNase 13, 14. This discrepancy has been attributed to wide variation in patient selection, dosage regimens, and type of fibrinolytic agent used (including urokinase, streptokinase, alphadornase, and rTPA).…”

Section: Discussionmentioning

confidence: 99%

“…In humans, doses from 2–100 mg of alteplase have been used with variable success 11. Dwell times have varied from 1 to 24 hours and frequency of administration from 1 to 3 times daily 10, 11, 14, 19. For rTPA to be effective, endogenous plasminogen must be available for conversion into plasmin.…”

Section: Discussionmentioning

confidence: 99%

“…It is unknown whether or not larger or more frequent doses are futile because the natural supply of plasminogen is exhausted. In human and preclinical rodent studies, 1 of the few consistent aspects of dosing is the use of repeated administrations, with once or twice daily administration for 3 days being the most common approach 9, 10, 11, 14, 19, 20. If a standard 3 day dosing regimen were adopted for horses, results might be better, but several contributing clinicians reported that their ability to use a higher dose or to repeat dosing was limited by the owner's financial commitment to treatment.…”

Section: Discussionmentioning

confidence: 99%

“…There is some evidence to suggest that rTPA is only beneficial in the subset of human patients that did not have resolution of pleural effusion after 24 h of conventional tube drainage. In a series of prospective trials in people, all patients with purulent or septic pleural fluid were treated beginning on the day of admission and no difference in outcome was seen with IPFT versus placebo 14. Conversely, in studies in which IPFT was limited to patients that still had pleural effusion after 24 h of chest drainage, a positive effect was observed 10, 11.…”

Section: Discussionmentioning

confidence: 99%

“…Coagulation profiles were not performed and subclinical prolongations could have been present. In humans, bleeding complications occur in approximately 7% of patients treated with IPFT, but patients who had bleeding complications more often were receiving concurrent anticoagulation treatment or intrapleural DNase treatment 11, 14, 20…”

Section: Discussionmentioning

confidence: 99%

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The Use of Recombinant Tissue Plasminogen Activator (rTPA) in The Treatment of Fibrinous Pleuropneumonia in Horses: 25 Cases (2007–2012)

Tomlinson

Byrne

Pusterla

et al. 2015

Veterinary Internal Medicne

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BackgroundInformation about treatment protocols, adverse effects and outcomes with intrapleural recombinant tissue plasminogen activator (rTPA) use in horses with fibrinous pleuropneumonia is limited.Hypothesis/ObjectivesDescribe factors that contribute to clinical response and survival of horses treated with rTPA intrapleurally.AnimalsHorses with bacterial pneumonia and fibrinous pleural effusion diagnosed by ultrasonography, that were treated with rTPA intrapleurally.MethodsRetrospective multicenter case series from 2007–2012. Signalment, history, clinical and laboratory evaluation, treatment, and outcome obtained from medical records. Regression analysis used to identify associations between treatments and outcomes.ResultsThirty three hemithoraces were treated in 25 horses, with 55 separate treatments. Recombinant tissue plasminogen activator (375–20,000 μg/hemithorax) was administered 1–4 times. Sonographically visible reduction in fibrin mat thickness, loculations, fluid depth, or some combination of these was seen in 32/49 (65%) treatments. Response to at least 1 treatment was seen in 17/20 (85%) horses with sonographic follow‐up evaluation after every treatment. Earlier onset of rTPA treatment associated with increased survival odds. No association was found between cumulative rTPA dose or number of rTPA doses and survival, development of complications, duration of hospitalization or total charges. Clinical evidence of hypocoagulability or bleeding was not observed. Eighteen horses (72%) survived to discharge.Conclusions and clinical importanceTreatment with rTPA appeared safe and resulted in variable changes in fibrin quantity and organization within the pleural space. Recombinant tissue plasminogen activator could be a useful adjunct to standard treatment of fibrinous pleuropneumonia, but optimal case selection and dosing regimen remain to be elucidated.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

The Use of Recombinant Tissue Plasminogen Activator (rTPA) in The Treatment of Fibrinous Pleuropneumonia in Horses: 25 Cases (2007–2012)

Tomlinson

Byrne

Pusterla

et al. 2015

Veterinary Internal Medicne

View full text Add to dashboard Cite

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Effect of Opioids vs NSAIDs and Larger vs Smaller Chest Tube Size on Pain Control and Pleurodesis Efficacy Among Patients With Malignant Pleural Effusion

Rahman

Pepperell

Rehal

et al. 2015

JAMA

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179

138

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Effect of Thoracoscopic Talc Poudrage vs Talc Slurry via Chest Tube on Pleurodesis Failure Rate Among Patients With Malignant Pleural Effusions

Bhatnagar

Piotrowska

Laskawiec-Szkonter

et al. 2020

JAMA

Self Cite

106

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IMPORTANCE Malignant pleural effusion (MPE) is challenging to manage. Talc pleurodesis is a common and effective treatment. There are no reliable data, however, regarding the optimal method for talc delivery, leading to differences in practice and recommendations. OBJECTIVE To test the hypothesis that administration of talc poudrage during thoracoscopy with local anesthesia is more effective than talc slurry delivered via chest tube in successfully inducing pleurodesis. DESIGN, SETTING, AND PARTICIPANTS Open-label, randomized clinical trial conducted at 17 UK hospitals. A total of 330 participants were enrolled from August 2012 to April 2018 and followed up until October 2018. Patients were eligible if they were older than 18 years, had a confirmed diagnosis of MPE, and could undergo thoracoscopy with local anesthesia. Patients were excluded if they required a thoracoscopy for diagnostic purposes or had evidence of nonexpandable lung. INTERVENTIONS Patients randomized to the talc poudrage group (n = 166) received 4 g of talc poudrage during thoracoscopy while under moderate sedation, while patients randomized to the control group (n = 164) underwent bedside chest tube insertion with local anesthesia followed by administration of 4 g of sterile talc slurry. MAIN OUTCOMES AND MEASURES The primary outcome was pleurodesis failure up to 90 days after randomization. Secondary outcomes included pleurodesis failure at 30 and 180 days; time to pleurodesis failure; number of nights spent in the hospital over 90 days; patient-reported thoracic pain and dyspnea at 7, 30, 90, and 180 days; health-related quality of life at 30, 90, and 180 days; all-cause mortality; and percentage of opacification on chest radiograph at drain removal and at 30, 90, and 180 days. RESULTS Among 330 patients who were randomized (mean age, 68 years; 181 [55%] women), 320 (97%) were included in the primary outcome analysis. At 90 days, the pleurodesis failure rate was 36 of 161 patients (22%) in the talc poudrage group and 38 of 159 (24%) in the talc slurry group (adjusted odds ratio, 0.91 [95% CI, 0.54-1.55]; P = .74; difference,-1.8% [95% CI,-10.7% to 7.2%]). No statistically significant differences were noted in any of the 24 prespecified secondary outcomes. CONCLUSIONS AND RELEVANCE Among patients with malignant pleural effusion, thoracoscopic talc poudrage, compared with talc slurry delivered via chest tube, resulted in no significant difference in the rate of pleurodesis failure at 90 days. However, the study may have been underpowered to detect small but potentially important differences.

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Intrapleural Use of Tissue Plasminogen Activator and DNase in Pleural Infection

Cited by 675 publications

References 46 publications

The Use of Recombinant Tissue Plasminogen Activator (rTPA) in The Treatment of Fibrinous Pleuropneumonia in Horses: 25 Cases (2007–2012)

The Use of Recombinant Tissue Plasminogen Activator (rTPA) in The Treatment of Fibrinous Pleuropneumonia in Horses: 25 Cases (2007–2012)

Effect of Opioids vs NSAIDs and Larger vs Smaller Chest Tube Size on Pain Control and Pleurodesis Efficacy Among Patients With Malignant Pleural Effusion

Effect of Thoracoscopic Talc Poudrage vs Talc Slurry via Chest Tube on Pleurodesis Failure Rate Among Patients With Malignant Pleural Effusions

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