Retrospective Evaluation of Intrapleural Tissue Plasminogen Activator With or Without Dornase Alfa for the Treatment of Traumatic Retained Hemothorax: A 6-Year Experience

Abstract

Background:

Intrapleural fibrinolytic instillation is second-line treatment for retained hemothorax. Dornase alfa (DNase) has demonstrated efficacy in parapneumonic effusion, but the lack of deoxyribonucleoproteins limits direct extrapolation to traumatic retained hemothorax treatment.

Objective:

This study evaluated the effectiveness of intrapleural tissue plasminogen activator (tPA) with and without DNase in the treatment of retained traumatic hemothorax.

Methods:

This retrospective cohort study included patients aged 16 years and older admitted to a level 1 trauma center from January 2013 through July 2019 with retained hemothorax and one or more intrapleural tPA instillations. Exclusion criteria were tPA for other indications or concomitant empyema. The primary endpoint was treatment failure defined as the need for operative intervention.

Results:

Fifty patients were included (tPA alone: 28; tPA with DNase: 22). Baseline characteristics were similar between groups, including time to diagnosis (6.5 [interquartile range (IQR), 4-15.5] days vs 6 [IQR, 6.3-10.8] days, P = 0.52). Median tPA dose per treatment (6 [IQR, 6-6.4] mg vs 10 [IQR, 8.4-10] mg, P < 0.001) and cumulative tPA (18 [IQR, 6.5-24] mg vs 30 [IQR, 29.5-40], P < 0.001) dose were significantly lower in the tPA alone group. Treatment failure was similar between groups. Chest tube output, retained hemothorax reduction, and bleeding incidences were similar between groups. Multivariate logistic regression demonstrated no significant risk factors for treatment failure.

Conclusions and Relevance:

Dornase alfa added to tPA may not reduce the need for operation to treat retained hemothorax. Further studies should be directed at optimal tPA dose determination and economic impact of inappropriate DNase use.

Keywords

tissue plasminogen activator dornase alfa retained hemothorax trauma fibrinolytic

Introduction

Hemothorax is the presence of blood in the pleural space and considered a surgical emergency. Incidence following blunt chest trauma is up to 38% with intrapleural catheter placement for fluid drainage as first-line treatment.^1,2 Retained hemothoraces occur when clotted blood in the intrapleural space cannot be adequately drained with an incidence of 10% to 35%.^1,3 Clinically, a retained hemothorax increases the risk for empyema development, contributes to acute respiratory compromise, and may progress to fibrothorax.⁴

First-line treatment of retained hemothorax is early video-assisted thoracoscopic surgery (VATS) during the first 3 to 7 days of hospitalization. Intrapleural fibrinolytic administration, such as tissue plasminogen activator (tPA), is recommended second line in patients at high risk of surgical complications.^2,5 Intrapleural fibrinolytics (eg, urokinase, streptokinase, alteplase) work by activating plasminogen to plasmin that degrades thrombin facilitating hemothorax drainage.^1,3 However, current data are either retrospective or heterogeneous, leading to the need to find optimal dose, frequency, dwell time, and duration of therapy.^1,3,6-19

Dornase alfa (DNase) has been successfully used in conjunction with tPA in parapneumonic effusions to break down extracellular deoxyribonucleic acid (DNA) and bacterial components; yet, patients with recent traumatic injury were excluded.²⁰ One case report demonstrated hemothorax resolution when DNase was used in conjunction with tPA 3 days after thoracotomy and decortication.²¹ This has led to expanded DNase use in retained hemothoraces despite the different nature of intrathoracic blood compared with pleural space disease in sepsis wherein extracellular deoxyribonucleic acid and bacterial components in infection contribute to biofilm formation and increased fluid viscosity.^20-22 Moreover, borrowed use of DNase from pleural space disease ignores the pathophysiologic difference in traumatic systemic inflammatory response, coagulopathy, and lack of deoxyribonucleoproteins in hemothorax without empyema.^1,3,20,22

The lack of definitive data driving retained hemothorax management in complex trauma patients merits further exploration. The purpose of this study was to evaluate the treatment failure and success rates for intrapleural tPA alone versus tPA with DNase in traumatic retained hemothorax.

Materials and Methods

Study Design

This retrospective, single-center, cohort study was conducted at an urban, academic, quaternary referral, American College of Surgeons–verified level 1 trauma center with 724 licensed beds and 4176 trauma encounters in fiscal year 2019. The study was approved by the local institutional review board.

Patients were identified via a report from the electronic medical record for intrapleural tPA administration. Patients aged 16 years and older admitted to the trauma service between January 2013 and July 2019 were eligible for inclusion if they were diagnosed with retained hemothorax treated with intrapleural tPA with or without DNase. Retained hemothorax was defined as the presence of heterogeneous intrapleural fluid on cross-sectional imaging following drainage with intrapleural catheter.^2,4,5 Diagnosis was confirmed through progress note documentation during medical record review. Patients were excluded if they were diagnosed with concomitant empyema or infected parapneumonic effusion prior to or during intrapleural therapy, received tPA for any indication besides retained hemothorax (eg, intravenous catheter clearance; intra-abdominal catheter instillation), or were prisoners or pregnant.

Study Definitions and Outcomes

Study groups were classified as tPA alone or tPA with DNase. Patients in the tPA group received intrapleural tPA at any dose without DNase. The tPA with DNase group received intrapleural tPA at any dose with receipt of one or more coordinated DNase instillation(s). Of note, the trauma service protocol for retained hemothorax was early VATS with the alternative of intrapleural tPA if surgery was contraindicated: tPA 6 mg in 50 mL of 0.9% sodium chloride instilled via intrapleural catheter, which is clamped for a 3-hour dwell time followed by opening to suction or gravity every 12 hours for 4 doses. Guidance on the use of DNase for traumatic retained hemothorax was not protocolized. Institutional guidance existed for the use of tPA with DNase for parapneumonic effusion treatment: tPA 10 mg in 30 mL of 0.9% sodium chloride instilled, flushed, and followed by DNase 5 mg in 30 mL of sterile water, which is clamped for a 2-hour dwell time and allowed to drain freely for 1 hour every 12 hours for 6 doses.²⁰ Protocols for both indications and doses were not modified over the study period. All treatments were selected and modified at the discretion of the treatment team attending. Standardized orders were available in the electronic medical record during the study period. All doses were administered by the prescriber and not nursing staff. Treatment days were those in which tPA with or without DNase was administered.

The primary outcome was treatment failure of instilled intrapleural therapy for retained hemothorax. Treatment failure was defined as the need for surgical intervention after intrapleural therapy to clear the pleural space such as VATS or thoracotomy with decortication. Treatment success was defined as clinical resolution of the retained hemothorax leading to removal of the intrapleural catheter without further surgical intervention.

Secondary outcomes included comparisons of bleeding complications, placement of additional intrapleural drain-age catheter(s), intrapleural catheter drainage volume, and change in size of hemothorax on subsequent radiographic imaging. Bleeding complications were defined by International Society on Thrombosis and Haemostasis (ISTH) criteria, including fatal bleeding, symptomatic bleeding, extrasurgical site bleeding leading to a drop in hemoglobin of 2 g per deciliter or more or requiring transfusion of 2 or more units of packed red blood cells within 24 to 48 hours, surgical site bleeding that requires intervention, surgical site bleeding that causes hemodynamic instability, or any bleeding that required medical intervention by a health care professional.^23,24 Hemoglobin and hematocrit values across treatment days were evaluated. Transfusions of packed red blood cells during treatment days and the immediate 48 hours after intrapleural therapy completion were compared. Hemothorax size was estimated in milliliters on available preintervention and postintervention cross-sectional imaging as previously described.²⁵ Pleural fluid volume was quantified as small (< 300 mL), moderate (300-900 mL), or large (> 900 mL).^4,19,25 Risk factors for therapy failure were evaluated as a secondary outcome. A post hoc analysis was performed estimating the cumulative cost per patient of administered therapies in each group. Estimated cost was calculated based on institutional average wholesale price per milligram of drug for both tPA and DNase.

Data Collection

Data were extracted from the electronic medical record (EPIC, Madison, Wisconsin) and an institutional trauma registry. The trauma registry is a site-specific database containing administrative, pharmacy, laboratory, clinical, and demographic data for patients presenting with traumatic injuries. Registry data can be reported into regional and national repositories such as the Ohio Trauma Registry and National Trauma Data Bank, respectively. This study collected basic demographic information (age, sex, ethnicity, height, weight, body mass index [BMI]), injury characteristics (mechanism of injury, Injury Severity Score [ISS], chest Abbreviated Injury Scale [AIS]), and hospitalization characteristics (hospital length of stay, intensive care unit [ICU] length of stay) from the trauma registry. Data not included in the registry were collected from the electronic medical record, including diagnosis of retained hemothorax, surgical interventions for retained hemothorax, duration of mechanical ventilation, dates of diagnoses and interventions, bleeding characteristics (hemoglobin, hematocrit, transfusions), respiratory parameters (oxygen saturation and incentive spirometry immediately before and after or on the day of intrapleural therapy administration, as applicable), chest tube size, daily intrapleural tube output, and intrapleural therapy characteristics (drug [dose, frequency, duration]). Relevant thoracic imaging studies were reviewed by a trauma surgeon (C.F.J.).

Statistical Analysis

Descriptive statistics were used to summarize baseline demographic data and clinical outcomes. Categorical data were analyzed using χ² or Fisher exact tests and reported as number (percent), as appropriate. Continuous data were analyzed using Student t test or Wilcoxon Rank Sum and reported as mean (standard deviation [SD]) or median (interquartile range [IQR]), respectively, as appropriate. A P value ≤ 0.05 was used to define statistically significant differences between groups. A multivariate logistic regression for therapy failure risk factor determination was performed including characteristics with a P value < 0.2 on univariate analysis. DNase use and tPA dose were included a priori into the model. Statistical analyses were performed using SigmaPlot 14.0 (Systat Software, Inc, San Jose, California).

A convenience sample over the 6-year study period was used to capture the required population within the specified inclusion and exclusion criteria. An exploratory a priori power analysis was performed to determine treatment superiority of tPA with DNase over tPA alone. This indicated that 86 patients were required to achieve 80% power at an α of 0.05 to find a 25% difference in treatment failure assuming the tPA plus DNase group had a 10% failure rate.³

Results

Demographics

A total of 1140 patients presented with traumatic hemothoraces, of which 638 patients (56.0%) had intrapleural drainage catheters placed. Of these, 101 patients had intrapleural tPA ordered for instillation. Fifty patients met inclusion criteria with 19 patients receiving tPA for non-chest catheter clearance (Figure 1). The study population had the following characteristics: 40 (80%) men, mean age of 53.6 (SD, 18.3) years, 36 (72%) blunt trauma mechanism, median ISS of 17.5 (IQR, 12.3-26.3), ICU length of stay of 5 (IQR, 2-8) days, and hospital length of stay of 10 (IQR, 8-16.3) days. Median tPA dose per administration was 7 (IQR, 6-10) mg for 3 (IQR, 2-4) doses resulting in a cumulative dose of 26 (IQR, 10-30) mg.

A total of 28 (56%) patients received tPA alone while 22 (44%) patients received tPA with DNase 5 mg. Median number of DNase administrations was 3 (IQR, 2-3) doses. Other baseline demographics of each group can be found in Table 1. Baseline demographics and injury characteristics were similar between groups including median hemothorax size and classification. The cumulative tPA dose and dose per treatment were lower in the tPA alone group (Table 1). No differences were observed in hospital and ICU length of stay and mechanical ventilation days between groups.

Table 1.

Baseline Patient Demographics and Clinical Features.

	tPA alone(n = 28)	tPA with DNase(n = 22)	P value
Age (years)^a	49.8 ± 18	58.5 ± 18	0.10
Male sex	21 (75)	19 (86.4)	0.48
Race			0.48
Black	7 (25)	3 (13.6)
White	21 (75)	19 (86.4)
Weight (kg)	80.1 (68.9-98.8)	86.5 (71.1-100.2)	0.65
Body mass index (kg/m²)^a	28.2 ± 5.8	28.5 ± 7.1	0.87
Injury mechanism			0.68
Blunt	19 (67.9)	17 (77.3)
Penetrating	9 (32.1)	5 (22.7)
Injury Severity Score	17 (11-26)	20 (13-28)	0.63
Abbreviated Injury Score: Chest	3 (3-3)	3 (3-4)	0.28
Time to rHTX (days)	6.5 (4-15.5)	6 (6.3-10.8)	0.52
Time to tPA from rHTX diagnosis (days)	1 (0-2)	1 (0-2.8)	0.51
tPA dosing (mg)
Cumulative dose	18 (6.5-24)	30 (29.5-40)	<0.001
Dose per treatment	6 (6-6.4)	10 (8.4-10)	<0.001
Cumulative number of doses	3 (1-4)	3 (3-4)	0.10
Number of doses administered			0.25
1	10 (35.7)	2 (9.1)
2	3 (10.7)	1 (4.5)
3	6 (21.4)	10 (45.5)
4	4 (14.3)	5 (22.7)
5	3 (10.7)	2 (9.1)
Hemothorax size pretreatment
Small^b	13 (46.4)	10 (47.6)
Moderate^b	9 (32.1)	5 (23.8)
Large^b	6 (21.4)	6 (28.6)
Size (mL)	315.3 (140.8-867.2)	306.3 (74.9-979.6)	0.71
Chest tube size			0.46
12 French	1 (3.6)	0 (0)
14 French	3 (10.7)	2 (9.1)
16 French	6 (21.4)	4 (18.2)
18 French	1 (3.6)	2 (9.1)
20 French	0 (0)	1 (4.5)
24 French	3 (10.7)	0 (0)
28 French	5 (17.9)	8 (36.4)
32 French	8 (28.6)	5 (22.7)
36 French	1 (3.6)	0 (0)
Mechanical ventilator	9 (40.9)	9 (32.1)	0.73
Mechanical ventilator days^a,c	3.8 ± 2.5	7.2 ± 5.7	0.13
Length of stay
Hospital (days)	10 (6-14.5)	11.5 (9-21.3)	0.063
ICU (days)	5 (2.3-8)	6 (2-10)	0.56

Continuous data report results as median (interquartile range) unless otherwise noted. Categorical data reported as number (percent), unless otherwise noted.

Abbreviations: DNase, dornase alfa; ICU, intensive care unit; rHTX, retained hemothorax; tPA, tissue plasminogen activator.

Data presented as mean ± standard deviation.

Proportion of patients with pleural fluid volume was quantified as small (< 300 mL), moderate (300-900 mL), or large (> 900 mL).

Mechanical ventilator days exclude patients who did not require it.

Outcomes

Among all patients, successful treatment of retained hemothorax with intrapleural tPA-based therapy occurred in 43 (86%) patients with only 7 (14%) requiring surgical intervention. The incidence of treatment failure was similar between groups (4 [14.3%] vs 3 [13.6%], P > 0.99) (Table 2). Oxygen saturation was not different before or after treatment in either group. The average pretreatment incentive spirometry volume was higher in the tPA alone group (P = 0.01). However, the change in incentive spirometry volume across all treatments was not different. Posttreatment hemothorax volume was larger in the tPA with DNase group, but both treatments resulted in decreased residual intrapleural volume on follow-up imaging with similar daily chest tube output.

Table 2.

Primary and Secondary Clinical Endpoints.

	tPA alone(n = 28)	tPA with DNase(n = 22)	P value
Primary outcome			>0.99
Failure	4 (14.3)	3 (13.6)
Secondary outcomes
Second chest tube placed	13 (46.4)	7 (31.8)	0.45
Chest tube upsized	5 (17.9)	2 (9.1)	0.44
SpO₂ (%)
Baseline on first treatment day^a	95.2 ± 3.3	94.8 ± 3.2	0.63
After first administration^a	95.2 ± 2.3	96 ± 2.4	0.28
Change from baseline	0 (−2 to 2)	2 (−1 to 3)	0.086
Daily during all treatment days^a	95.2 ± 2.2	94.9 ± 1.6	0.5
Change across all treatments days^a	0.066 ± 2.5	1.1 ± 1.6	0.085
Incentive spirometry volume (mL)
First treatment day
Pretreatment	1000 (750-1500)	750 (575-1000)	0.01
Posttreatment	1000 (725-1375)	1000 (750-1250)	0.68
Response	0 (−190 to 100)	0 (−37.5 to 625)	0.17
During treatment days
Pretreatment	1163 (800-1500)	788 (675-1000)	0.004
Posttreatment	1125 (807-1250)	1025 (663-1213)	0.27
Response	−50 (−200 to 150)	100 (−19 to 321)	0.081
Hemothorax size posttreatment
Small	20 (90.1)	14 (73.7)	0.22
Moderate	2 (9.1)	5 (26.3)
Large	0 (0)	0 (0)
Size (mL)	50 (50-84.5)	181 (52-318.5)	0.025
Decrease in size (mL)^b	447 (116-806)	306 (48.1-717.5)	0.53
Daily chest tube output (mL)
First treatment day	627.5 (191-1030)	682 (299-1265)	0.35
Average daily output during all treatment days^a	539 (328-667)	697 (473-996)	0.099

Continuous data report results as median (interquartile range) unless otherwise noted. Categorical data reported as number (percent), unless otherwise noted.

Abbreviations: DNase, dornase alfa; SpO₂, oxygen saturation; tPA, tissue plasminogen activator.

Data presented as mean ± standard deviation.

Change in size represents the comparison on chest imaging before and after tPA-based therapy.

The overall incidence of any bleeding event was similar in the tPA alone group and tPA with DNase group despite the higher baseline tPA dose in the latter (Table 3). Hemoglobin, hematocrit, and transfusion requirements during treatment were no different between groups. Change in hemoglobin and hematocrit from the first to last intrapleural therapy treatment day was similar between groups. Only one major bleeding event occurred in the tPA alone group, with a patient experiencing an increase in chest tube output after tPA administration with coincident tachycardia and a 2 g/dL drop in hemoglobin that stabilized without further intervention.

Table 3.

Bleeding Outcomes.

	tPA alone(n = 28)	tPA with DNase(n = 22)	P value
Hemoglobin (g/dL)
First day of treatment^a	9.9 ± 2	9.5 ± 1.7	0.42
Last day of treatment	9 (7.8-10.9)	9 (8.3-9.6)	0.78
Decrease from first to last	−0.15 (−1 to 0.4)	−0.2 (−1.6 to 0.63)	0.81
Average during treatment days	9.1 (8.2-11.1)	9.1 (8.5-10)	0.62
Hematocrit (%)
First day of treatment^a	30.1 ± 6	28.2 ± 4.9	0.24
Last day of treatment	26.8 (24-33.2)	26.2 (23.9-28.5)	0.48
Decrease from first to last	−0.95 (−4.7 to 1.4)	−0.75 (−5.3 to 1.4)	0.91
Average during treatment days^a	29.1 ± 5.5	27.5 ± 3.9	0.24
Transfusions	0 (0-0)	0 (0-0)	0.11
Bleeding
Any major or minor	2 (7.1)	2 (9.1)	>0.99
Major	1 (3.6)	0 (0)	>0.99
Minor	1 (3.6)	2 (9.1)	0.58

Continuous data report results as median (interquartile range) unless otherwise noted. Categorical data reported as number (percent), unless otherwise noted.

Abbreviations: DNase, dornase alfa; tPA, tissue plasminogen activator.

Data presented as mean ± standard deviation.

On univariate analysis comparing patients with treatment success versus failure, only cumulative number of doses reached the threshold for inclusion in the multivariable model (tPA alone, 3 [IQR, 2-4] vs tPA with DNase, 2 [IQR, 1-3], P = 0.043). Dose of tPA and DNase administration was forced into the model per a priori identification. There were no independent risk factors for treatment failure, including cumulative number of doses, tPA dose, and DNase administration (Table 4).

Table 4.

Multivariable Regression Analysis for Therapy Failure.

Risk factor	Odds ratio	95% confidence interval	P value
Cumulative number of doses	0.51	0.24-1.12	0.094
tPA dose per treatment	1.2	0.65-2.2	0.56
Dornase administration	1.05	0.076-14.52	0.97

Hosmer-Lemeshow 5.976 (P = 0.65).

Abbreviation: tPA, tissue plasminogen activator.

Estimated cost per patient for tPA was significantly higher in the tPA plus DNase group ($1656 [IQR, $598-$2208] vs $2760 [IQR, $2714-$3680], P < 0.001). Median DNase cost was $825 (IQR, $550-$825), resulting in a significantly higher overall therapy price per patient ($3585 [IQR, $3264-$4551]) compared with the tPA alone group (P < 0.001).

Discussion

This study is the largest report of patients receiving intrapleural tPA and the first to include the use of DNase for retained hemothorax. There was no significant difference in operative intervention rates between patients treated with intrapleural tPA alone and those treated with intrapleural tPA with DNase. Moreover, DNase use did not protect against the need for surgery when controlling for tPA dose and administration with equivocal impact on oxygen saturation and incentive spirometry. The addition of DNase to a higher tPA dose was safe given the similar bleeding rates between groups. To our knowledge, this is the first study to report a direct comparison between 2 intrapleural therapeutic regimens in the setting of injury.

The use of tPA in the setting of traumatic hemothorax is generally extrapolated from the use of tPA in heterogeneous populations of patients with empyema, pleural effusion, and postoperative hemothorax. Prior small, retrospective studies reporting tPA experience range from 7 to 24 patients with tPA doses between 6 and 100 mg.^12-19,21 A pooled meta-analysis of 39 patients with traumatic retained hemothorax demonstrated tPA10 to 50 mg avoided operative intervention in 83% (95% confidence interval [CI], 71%-94%) of the population (I² = 0%).³ Our observed treatment success rate was similarly above 80% in a larger, 50 patient sample with lower tPA dosing between 6 and 10 mg. To date, there are no prospective, randomized trials comparing different tPA dosing strategies for retained hemothorax in the setting of trauma. When comparing the 2 treatment regimens, individual and cumulative tPA dose was higher when administered in combination with DNase. This was expected due the differences in the prebuilt electronic medical record dose and duration when tPA was ordered with DNase. Interestingly, tPA dose did not influence the need for surgical intervention, but tPA dose without DNAse was not able to be explored in this investigation. The increased average chest tube output per day in the tPA with DNase group may be clinical artifact rather than precise measure of the therapy effect especially in the context of the larger retained hemothorax size at the end of treatment. Possible explanations include larger instillation volume for tPA with DNase or an independent physiologic pleural response to DNase.

Recombinant human DNase with tPA reduced the need for surgery in the MIST II trial evaluating parapneumonic effusion treatments.²⁰ A major difference in the pathophysiology between retained hemothorax and parapneumonic effusion is the presence or absence of deoxyribonucleoproteins. Considering the mechanism of action of DNase, the higher abundance of these proteins and extracellular DNA in parapneumonic effusions provide a site of action not present in retained hemothorax.^20,22 The MIST II trial excluded patient with major and minor trauma, further reducing applicability to traumatic retained hemothorax, and the single case report extrapolating this practice required surgical intervention.^20,21 The findings in our study indicating intrapleural DNase does not confer a treatment benefit in the setting of retained hemothorax over tPA alone should not be unexpected. While the risk for infectious sequelae in the setting of retained hemothorax is significant,²⁵ the empiric addition of DNase to an intrapleural tPA should not be routine practice for non-infectious retained hemothorax. This may suggest a “less is more” approach to traumatic retained hemothoraces and underscore pathophysiology that guides therapeutic regimens. Questions remain about optimal dosing and dwell time of fibrinolytics for pleural clearance and further study using a multi-institutional approach may offer better clarity and smooth variations. In addition, the accrued costs associated with use of DNase along with a higher tPA dose could present an opportunity to for decreased expenditure of health care dollars that deserves further investigation. Removal of DNase from retained hemothorax treatment provides cost savings for unnecessary therapy.

This study is not without limitations. The retrospective study design prevents controlling for variables that could have introduced treatment and selection bias. For example, it is difficult to determine why specific doses were prescribed. Significant provider practice pattern variation with respect to the indication and timing for tPA with or without DNase may exist. This likely explains why patients received 4 doses of DNase and not 6. Controlling for these variables in future study may help further guide practice. Specific tPA doses, dwell times, and number of doses administered between groups were not able to be controlled given the retrospective design. In addition, this was a small single-center study that lacks broad generalizability, especially to non–level 1 centers. Exploration of patient characteristics that resulted in the use of tPA over early VATS was not performed. Although convenience sampling was employed, the small sample size may have affected statistical analyses and limited the ability to observe less coarse outcomes. However, the hypothesized 10% failure rate was numerically similar to the observed 14.3% in the tPA alone group. In addition, patient-reported outcomes surrounding intrapleural tPA and DNase instillation such as chest pain were not evaluated. It is unknown whether the dual instillation technique required with DNase, given the lack of stability and compatibility information in syringe with tPA, induces pain compared with tPA alone.²⁶

Multiple strengths are present in this study. It is the largest, single-center investigation of intrapleural fibrinolytic therapy for traumatic hemothorax and provides more extensive pilot data to guide future prospective investigations. Success and failure outcome incidences were aligned with prior investigations at overall lower tPA doses. Investigation into multiple demographic and clinical endpoints provides a thorough clinical picture to contextualize patient safety and therapeutic efficacy. Evaluation of hemothorax size before and after treatment follows the precent set in previous literature.^20,25 Description of costs associated with each therapy presents another avenue worthy of exploration in future studies.

Conclusions and Relevance

The use of intrapleural DNase an adjunct to tPA in traumatic retained hemothorax may not be associated with a reduced need for surgical intervention beyond tPA alone. No additional clinical benefit or risk was conferred by DNase given clinical endpoints, including hemothorax size reduction and bleeding, were similar regardless of study group. These findings coupled with the absent pathophysiology and the lack of trauma patients enrolled in the MIST II study discourage routine use of adjunctive DNase in the treatment of retained hemothoraces. As a pilot investigation study, these findings open the opportunity for additional research directed at tPA dose and dwell time refinement for optimal nonsurgical management of traumatic retained hemothorax.

Footnotes

Authors’ Note

Preliminary results from this report were presented at the annual American College of Clinical Pharmacy Global Conference in October 2020, Abstract No 55312.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Christopher Francis Janowak

Christopher Allen Droege

Molly Elizabeth Droege

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