A combined intrapleural administration of dornase alfa and tissue plasminogen activator is safe in children with empyema – A pilot study

Slaats, M.; Dooy, Jozef De; Hoorenbeeck, Kim Van; Schil, Paul Van; Verhulst, Stijn; Hendriks, Jeroen

doi:10.1080/00015458.2019.1696516

Cited by 3 publications

(8 citation statements)

References 19 publications

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“…The fundamental difference between the 2 groups is the rarity for underlying lung disease in children in contrast to adult favoring the almost always excellent prognosis in the pediatric group treated for empyema as described by the British Society for Thoracic Surgeons guidelines in 2005. 4 However, the reason behind why some healthy children develop empyema and others not is still not clear; perhaps future studies will show genetic predisposition behind that. 8 The 2 ancient pillars for management of empyema thoracis are antibiotics and tube thoracostomy drainage of the purulent fluid.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the strong advices against standard open thoracotomy as a first-line management, this latter option is only reserved for case of failure of thrombolytic trial and limited expertise in VATS surgery. 8,4,12,13,14 In developing countries, choosing the best treatment modality relies on the existing expertise and common local practices. Currently, we are lacking randomized control trials from developing nations to assess the efficacy of intrapleural thrombolytics versus VATS.…”

Section: Discussionmentioning

confidence: 99%

“…3 Though its well-known that the infection process occurs in a continuum and not distinctly, pediatric thoracic empyema (PTE) has been classified into 3 different stages: (1) exudative or simple parapneumonic effusion, where there is only clear pleural fluid; (2) fibriopurulent stage, where the fibrin starts to deposit forming septations and loculations within which the fluid is still flowing freely; and (3) organizing phase, where the fluid would be infiltrated by fibroblast and the thin intrapleural membranes changes to thick nonelastic peel resulting in impairment of lung function. [1][2][3][4] Currently, management of pediatric empyema is dependent on local practice guidelines and physician preference as there is no standardized treatment regimen for PTE yet. This might be due to a deficiency of pediatric-based and population-based evidence.…”

Section: Introductionmentioning

confidence: 99%

“…This might be due to a deficiency of pediatric-based and population-based evidence. 4,5 Sixty-nine years ago, use of fibrinoltyics was described in the management of complex pleural process by Tillet and Sherry when they introduced streptokinase. Ever since, the use of streptokinase as a thrombolytic agent was taxing because of the possibility of antibodies' development and the occurrence of delayed hypersensitivity reaction.…”

Section: Introductionmentioning

confidence: 99%

“…The use of intrapleural thrombolytics in certain patients has been stated by many authors despite the controversies about many aspects. [4][5][6] In spite of the breakthrough in antibiotics therapy in the latest era, parapneumonic effusion and pleural empyema are still a frequent clinical problem that may cause significant mortality and morbidity. The well-established treatment for parapneumonic effusions is drainage by closed system tube drainage and systemic antibiotics.…”

Section: Introductionmentioning

confidence: 99%

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Pediatric Thoracic Empyema—Outcomes of Intrapleural Thrombolytics: Ten Years of Experience

Baram

Yaldo

2020

Global Pediatric Health

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Introduction. Pediatric thoracic empyema is a special entity with increasing frequency. Consensus regarding the best management strategy is still evolving. We describe our single-center 10-year experience adopting intrapleural thrombolytics using tissue plasminogen activator as first-line treatment following failure of simple thoracostomy drainage techniques. Methods. Observational prospective study included all children from 1 day to 18 years admitted for parapneumonic effusion and treated with intrapleural thrombolytics. Results. From January 2008 to December 2018, 95 patients were treated by intrapleural thrombolytics for different stages of empyema thoracis. Number of thrombolytic doses required is 2.1 (range = 1-3), and mean amount of drainage is 1050 mL (range = 400-2500 mL). Mean total days of hospitalization is 7.3 days. Complete re-expansion was the primary outcome in 94 patients (98.9%). Conclusion. Intrapleural thrombolytics in complicated pediatric thoracic empyema results in excellent outcome and should be encouraged particularly in limited resource countries.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pediatric Thoracic Empyema—Outcomes of Intrapleural Thrombolytics: Ten Years of Experience

Baram

Yaldo

2020

Global Pediatric Health

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From Bedside to the Bench—A Call for Novel Approaches to Prognostic Evaluation and Treatment of Empyema

et al. 2022

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Empyema, a severe complication of pneumonia, trauma, and surgery is characterized by fibrinopurulent effusions and loculations that can result in lung restriction and resistance to drainage. For decades, efforts have been focused on finding a universal treatment that could be applied to all patients with practice recommendations varying between intrapleural fibrinolytic therapy (IPFT) and surgical drainage. However, despite medical advances, the incidence of empyema has increased, suggesting a gap in our understanding of the pathophysiology of this disease and insufficient crosstalk between clinical practice and preclinical research, which slows the development of innovative, personalized therapies. The recent trend towards less invasive treatments in advanced stage empyema opens new opportunities for pharmacological interventions. Its remarkable efficacy in pediatric empyema makes IPFT the first line treatment. Unfortunately, treatment approaches used in pediatrics cannot be extrapolated to empyema in adults, where there is a high level of failure in IPFT when treating advanced stage disease. The risk of bleeding complications and lack of effective low dose IPFT for patients with contraindications to surgery (up to 30%) promote a debate regarding the choice of fibrinolysin, its dosage and schedule. These challenges, which together with a lack of point of care diagnostics to personalize treatment of empyema, contribute to high (up to 20%) mortality in empyema in adults and should be addressed preclinically using validated animal models. Modern preclinical studies are delivering innovative solutions for evaluation and treatment of empyema in clinical practice: low dose, targeted treatments, novel biomarkers to predict IPFT success or failure, novel delivery methods such as encapsulating fibrinolysin in echogenic liposomal carriers to increase the half-life of plasminogen activator. Translational research focused on understanding the pathophysiological mechanisms that control 1) the transition from acute to advanced-stage, chronic empyema, and 2) differences in outcomes of IPFT between pediatric and adult patients, will identify new molecular targets in empyema. We believe that seamless bidirectional communication between those working at the bedside and the bench would result in novel personalized approaches to improve pharmacological treatment outcomes, thus widening the window for use of IPFT in adult patients with advanced stage empyema.

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The Efficacy of Intrapleural Fibrinolytic Agents Following Surgical Intervention for Empyema Thoracis: A Prospective Cross-Sectional Study in a Pediatric Population

Sarafi,

Mohajerzadeh,

Ebrahimian

et al. 2023

Iran J Pediatr

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Background: Intrapleural instillation of fibrinolytic agents is novel in treating empyema. Although the efficacy of this method for treating empyema remains a topic of debate among experts, several studies have shown that the results of this technique are almost equivalent to surgical operations in the lower stages of the disease. However, in more advanced stages of empyema, surgery may be required. Despite the worldwide use of fibrinolytic agents instead of surgical procedures, the benefits of using these agents postoperatively still need to be defined. Objectives: In this prospective study, we aimed to compare the effects of streptokinase and alteplase in managing empyema in patients who underwent any surgical operations. Methods: We prospectively compared the outcomes of using alteplase and streptokinase in children who underwent surgical operations for empyema between 2015 and 2022. Following the surgery, fibrinolytic agents were instilled through thoracostomy tubes according to a specific protocol. The length of stay, frequency of complications, need for another surgery, and mortality were measured in each group. Results: Among 53 patients who met the inclusion criteria, 31 (58.5%) patients received streptokinase postoperatively, while the others were treated using alteplase. The length of stay after the surgery, wound infection, and mortality rate did not differ significantly between the groups (P-value = 0.394, 0.080, 0.767, respectively). However, the need for another surgery due to unexpanded lungs was significantly lower in the alteplase group (0% vs. 19.4%, P = 0.028). Conclusions: Alteplase as an intrapleural fibrinolytic is more effective than streptokinase in patients who underwent surgical operations due to empyema. The need for another surgery following the instillation of alteplase through chest tubes postoperatively may be decreased.

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A combined intrapleural administration of dornase alfa and tissue plasminogen activator is safe in children with empyema – A pilot study

Cited by 3 publications

References 19 publications

Pediatric Thoracic Empyema—Outcomes of Intrapleural Thrombolytics: Ten Years of Experience

Pediatric Thoracic Empyema—Outcomes of Intrapleural Thrombolytics: Ten Years of Experience

From Bedside to the Bench—A Call for Novel Approaches to Prognostic Evaluation and Treatment of Empyema

The Efficacy of Intrapleural Fibrinolytic Agents Following Surgical Intervention for Empyema Thoracis: A Prospective Cross-Sectional Study in a Pediatric Population

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