Unintentional intramuscular administration of tPA / DN ase for pleural infection

Abstract

Intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) therapy has recently been shown to improve outcomes in pleural infection in a randomized trial. Published literature, to date, consists of only ∼50 patients who had received tPA/DNase. Safety data of this regimen remain limited. Pleural contents often track along chest drains, but the effect of tPA/DNase on subcutaneous tissues is unknown. We report a patient treated in another center who was unintentionally administered up to six instillations of tPA (10 mg) and DNase (5 mg) intramuscularly via a malpositioned chest drain. The patient experienced minimal discomfort, and there were no signs of tissue inflammation or necrosis on computed tomography. No complications were detected over a 2-month follow-up. Upon transfer, a new pleural drain was inserted and tPA/DNase administered with clearance of his loculated complicated parapneumonic effusion. This case adds to the safety profile of intrapleural tPA/DNase therapy and highlights the importance of correct tube placement.

Low-dose intrapleural alteplase (without deoxyribonuclease) in complicated parapneumonic effusion: case series and literature reviews

“…Popowicz et al 8 described two courses of intrapleural tPA with DNase administered for two different loculated pleural effusions with good clinical outcome and no adverse effects. The same author illustrated a patient who was unintentionally administered up to six instillations of tPA (10 mg) and DNase (5 mg) intramuscularly via a malpositioned chest drain 9. The patient was reported to have experienced minimal discomfort but no signs of tissue inflammation or necrosis on CT thorax.…”

Evaluation of the need for chest X-rays in the management of asymptomatic, intraluminal vascular access device occlusion in childhood cancer

“…A case report describes a patient exposed to six doses of 10 mg of tPA mixed with 5 mg of DNase in 20 ml of normal saline administered intramuscularly via a malpositioned chest tube. The patient experienced mild discomfort and imaging revealed mild swelling though no hemorrhage and tissue necrosis . The second potentially harmful case would have resulted in tPA being instilled into a line that was internally broken, resulting in systemic dosing of tPA.…”

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

“…Multiple recent clinical trials have demonstrated the efficacy of IPFT in adult patients with empyema ( Thommi et al, 2007 ; Rahman et al, 2011 ; Thommi et al, 2012 ; Popowicz et al, 2014a ; Popowicz et al, 2014b ; Nie et al, 2014 ; Piccolo et al, 2014 ; Piccolo et al, 2015 ; Barthwal et al, 2016 ; Majid et al, 2016 ; Mehta et al, 2016 ; Vial et al, 2016 ; Bishwakarma et al, 2017 ; Popowicz et al, 2017 ; Beckert et al, 2019 ; Godfrey et al, 2019 ). However, the strikingly higher mortality in adults does not allow for extrapolation of treatment strategies used in pediatrics and speaks to the imperative for preclinical studies focused on the mechanisms governing development and resolution of empyema in adults.…”

“…Over the past decade, cost effective ( Asciak et al, 2019 ) IPFT with a combination of tPA and deoxyribonuclease (DNase) (Dornase), as demonstrated in the Multicenter Intrapleural Sepsis Trial 2 (MIST2) ( Rahman et al, 2011 ), has been broadly embraced as IPFT for empyema ( Abu-Daff et al, 2013 ; Popowicz et al, 2014a ; Popowicz et al, 2014b ; Israel and Blackmer, 2014 ; Piccolo et al, 2014 ; Piccolo et al, 2015 ; Majid et al, 2016 ; Bishwakarma et al, 2017 ; Majid et al, 2017 ; Popowicz et al, 2017 ; Innabi et al, 2018 ; Kheir et al, 2018 ; Fitzgerald et al, 2019 ; Fitzgerald et al, 2021 ). A recent expert consensus statement ( Chaddha et al, 2021 ) described the level of severity of empyema that should be treated with tPA/DNase injected concurrently, appropriate dosing (10/5 mg, respectively), dwelling time, dose schedule (twice a day), and an algorithm for IPFT, thus re-establishing a universal “one for all” treatment approach to empyema based on the MIST2 protocol.…”