East Multicenter Study Proposal

EAST MULTICENTER STUDY PROPOSAL

GENERAL INFORMATION

Study Title: Hemothorax Management and Outcomes in Blunt and Penetrating Trauma

Primary investigator / Senior researcher: Jeremy Cannon, MD, SM, FACS

Co-primary investigator: Mark Seamon, MD, FACS

BACKGROUND AND SIGNIFICANCE

Use this area to briefly (1-2 paragraphs only) outline the burden of the problem to be examined: The true incidence and outcomes of traumatic hemothorax remains unknown. The landmark study by the AAST Retained Hemothorax Study Group described the management course in these patients once a retained hemothorax has been identified. However, management during the index presentation with a hemothorax remains poorly quantified. In addition, interventions which might mitigate the progression of a hemothorax to either a retained hemothorax or empyema have not been fully characterized. Presently, the non-perative management options for primary traumatic hemothorax include observation, open tube thoracostomy, percutaneous/small-bore tube thoracostomy, or Yankauer-assisted evacuation (i.e. “YATS”). To fully characterize the ideal management strategy for hemothorax following blunt or penetrating trauma, the natural history of this disease needs to be captured from initial presentation through to post-discharge follow-up.

The specific aims of this multicenter study are: Primary aim: We aim to fully characterize the incidence and outcomes of hemothorax management in blunt and penetrating trauma. Hypothesis: YATS results in fewer moderate to large retained hemothorax as compared to all other non-operative techniques

Secondary aims: Any secondary aims should be stated here:

EXPERIMENTAL DESIGN/METHODS

Inclusion Criteria: Any age, blunt or penetrating trauma resulting in a hemothorax of any size on initial Chest CT on the day of admission for trauma.

Exclusion Criteria: Hemothorax requiring initial operative evacuation.

Therapeutic Interventions: Prospective observational study managed at the surgeon’s discretion with observation through the 1st follow-up visit post-discharge.

Outcomes Measures: Primary Outcome:

Retained hemothorax ≥ 300 mL on chest CT (moderate-large) obtained at any time after initial chest CT

Secondary Outcomes:

Death Hospital length of stay Ventilator-free days in 1st 30 days of admission Glasgow Outcomes Scale-Extended SF-36 Empyema/pleural infection Number of interventions including tube thoracostomy, VATS, thoracotomy or other procedures

Variables:

DEMOGRAPHICS Age Gender COPD/Home O2 Antiplatelets/Anticoagulants Obesity (BMI) Interval from trauma to hemothorax diagnosis (hours)

ADMISSION PHYSIOLOGY HR Blood Pressure HCT Cr INR Base Excess Lactate TEG/TEM

INJURY CHARACTERISTICS Mechanism of injury (blunt, penetrating, both, other) Hemothorax Side Hemothorax Size (mL--measured on CT) Diaphragmatic injury Rib fractures (number, location) Flail chest ISS AIS head AIS chest AIS abdomen Pulmonary contusion

MANAGEMENT Initial Management-Injury Day 1 Observation Open tube thoracostomy Percutaneous tube thoracostomy (“pigtail”) “YATS” Estimated hemothorax evacuated (mL) Antibiotics used

Follow-up CT Imaging Indication (abnormality on CXR, respiratory symptoms, other) Day of follow-up imaging Size of retained hemothorax or effusion, if present (mL) Other findings (pneumothorax, pulmonary embolism, consolidation, pneumatocele)

Management—Admission Day 2 to Discharge Successful initial management Subsequent tube (injury day) Subsequent thrombolytics (injury day) Subsequent VATS (injury day) Subsequent thoracotomy (injury day)

OUTCOMES Retained hemothorax (describe management) Persistent/loculated pneumothorax (describe management) Hemo-pneumothorax (describe management) Death Discharge (LTAC, SNF, Rehab, or Home) Hospital LOS Ventilator-free days in the first 30 Post-discharge visit x1 Post-injury day at follow-up

CXR findings on post-discharge visit (if obtained) CT findings on post-discharge visit (if obtained) Empyema/Pleural Infection (describe management and cultures) Glasgow Outcomes Scale-Extended (at discharge, at 1st follow-up and at 6 months) SF-36 (at 1st follow-up and at 6 months) Need for additional interventions after initial discharge

Data Collection and Statistical Analysis: The above data will be collected on each patient starting within 24 hours of admission and continuing through their hospital course. Follow-up data will be collected within 24 hours of their post-discharge visit. Data will be entered into a de-identified online data repository. Target enrollment is 640 patients over 2 years. Risk factors for retained hemothorax or empyema development will be assessed using univariate and multivariate analysis. Continuous variables will be compared using Student’s t-test and the Mann Whitney U test. The Chi-squared tests or Fisher’s exact test will be used to compare categorical variables. ANOVA will be used to identify differences among management techniques. All variables with a p value <0.2 on univariate analysis will be entered into a multivariable logistic regression analysis to identify independent risk factors for retained hemothorax or empyema development. Data will be reported as adjusted odds ratios with 95 % confidence intervals. Statistical significance will be set at a p<0.05.

Consent Procedures: This is a prospective observational stud intended to record data on patients who are managed according to institutional patient management protocols. Waiver of informed consent will be requested; however, we appreciate that some institutional IRBs may request formal consent from the patient or a legally authorized representative. Data will be recorded on a data sheet and transferred to a secured database that is devoid of patient identifiers.

Risk/ Benefit Analysis: The incidence and natural history of traumatic hemothorax is unknown. If the optimal timing for and type of intervention can be identified to optimize outcomes in these patients, then significant benefit will be realized by future patients.

Instructions for submitting data collection tools: All data submissions should be entered through the EAST Multicenter Trial Taskforce website portal. Instructions can be found on the EAST website. The data collection sheet located under the Multicenter Trial Taskforce heading for this study can be utilized to record the data, and then the information transferred to the portal entry system. For any questions regarding this study, please contact the PI.

References:

1. Stiles PJ, Drake RM, Helmer SD, Bjordahl PM, Haan JM. Evaluation of chest tube administration of tissue plasminogen activator to treat retained hemothorax. Am J Surg. 2014 Jun;207(6):960-3. PubMed PMID: 24495319.

2. Kulvatunyou N, Erickson L, Vijayasekaran A, Gries L, Joseph B, Friese RF, O'Keeffe T, Tang AL, Wynne JL, Rhee P. Randomized clinical trial of pigtail catheter versus chest tube in injured patients with uncomplicated traumatic pneumothorax. Br J Surg. 2014 Jan;101(2):17-22. PMID: 24375295.

3. Kulvatunyou N, Joseph B, Friese RS, Green D, Gries L, O'Keeffe T, Tang AL, Wynne JL, Rhee P. 14 French pigtail catheters placed by surgeons to drain blood on trauma patients: is 14-Fr too small? J Trauma Acute Care Surg. 2012 Dec;73(6):1423-7. PubMed PMID: 23188235.

4. Moore FO, Duane TM, Hu CK, Fox AD, McQuay N Jr, Lieber ML, Como JJ, Haut ER, Kerwin AJ, Guillamondegui OD, Burns JB; Eastern Association for the Surgery of Trauma. Presumptive antibiotic use in tube thoracostomy for traumatic hemopneumothorax: an Eastern Association for the Surgery of Trauma practice management guideline. J Trauma Acute Care Surg. 2012 Nov;73(5 Suppl 4):S341-4. PubMed PMID: 23114491.

5. DuBose J, Inaba K, Okoye O, Demetriades D, Scalea T, O'Connor J, Menaker J, Morales C, Shiflett T, Brown C, Copwood B; AAST Retained Hemothorax Study Group. Development of posttraumatic empyema in patients with retained hemothorax: results of a prospective, observational AAST study. J Trauma Acute Care Surg. 2012 Sep;73(3):752-7. PubMed PMID: 22929504.

6. Inaba K, Lustenberger T, Recinos G, Georgiou C, Velmahos GC, Brown C, Salim A, Demetriades D, Rhee P. Does size matter? A prospective analysis of 28-32 versus 36-40 French chest tube size in trauma. J Trauma Acute Care Surg. 2012 Feb;72(2):422-7. PubMed PMID: 22327984.

7. DuBose J, Inaba K, Demetriades D, Scalea TM, O'Connor J, Menaker J, Morales C, Konstantinidis A, Shiflett A, Copwood B; AAST Retained Hemothorax Study Group. Management of post-traumatic retained hemothorax: a prospective, observational, multicenter AAST study. J Trauma Acute Care Surg. 2012 Jan;72(1):11-22; discussion 22-4; quiz 316. PubMed PMID: 22310111.

8. Smith JW, Franklin GA, Harbrecht BG, Richardson JD. Early VATS for blunt chest trauma: a management technique underutilized by acute care surgeons. J Trauma. 2011 Jul;71(1):102-5; discussion 105-7. PubMed PMID: 21818019.

9. Mahmood I, Abdelrahman H, Al-Hassani A, Nabir S, Sebastian M, Maull K. Clinical management of occult hemothorax: a prospective study of 81 patients. Am J Surg. 2011 Jun;201(6):766-9. PubMed PMID: 21741510.

10: Mowery NT, Gunter OL, Collier BR, Diaz JJ Jr, Haut E, Hildreth A, Holevar M, Mayberry J, Streib E. Practice management guidelines for management of hemothorax and occult pneumothorax. J Trauma. 2011 Feb;70(2):510-8. PubMed PMID: 21307755.

11. Stafford RE, Linn J, Washington L. Incidence and management of occult hemothoraces. Am J Surg. 2006 Dec;192(6):722-6. PubMed PMID: 17161082.

12. Bilello JF, Davis JW, Lemaster DM. Occult traumatic hemothorax: when can sleeping dogs lie? Am J Surg. 2005 Dec;190(6):841-4. PubMed PMID: 16307931.

13. Molnar TF, Hasse J, Jeyasingham K, Rendeki MS. Changing dogmas: history of development in treatment modalities of traumatic pneumothorax, hemothorax, and posttraumatic empyema thoracis. Ann Thorac Surg. 2004 Jan;77(1):372-8. PubMed PMID: 14726106.

EAST MULTICENTER STUDY PROPOSAL

HEMOTHORAX MANAGEMENT & OUTCOMES IN BLUNT & PENETRATING TRAUMA

DATA DICTIONARY

Term Definition Hemothorax Fluid in the pleural space identified on a CT after trauma to the ipsilateral hemithorax; Hounsfield units of acute blood should be 35-40

Hemothorax Volume Mergo Definition: V=d2*n*s where d is the A-P depth in cm, n is number of C-C slices, and s is the slice thickness in cm

Retained Hemothorax (RH) Blood-density fluid identified on a CT any time after the initial diagnosis of hemothorax

Large RH > 900 mL by CT

Moderate RH 301-900 mL by CT

Small RH ≤ 300 mL by CT

Empyema/Pleural Infection Positive cultures from pleural fluid; positive Gram stain from pleural fluid; pus drained from the pleural space; pleural fluid with pH<7.2 Observation No intervention on the diagnosed hemothorax

Open Tube Thoracostomy Tube thoracostomy placed using a standard open tube technique

Percutaneous Tube Tube thoracostomy using a closed technique with a small bore catheter (10-16 Thoracostomy (i.e. “pigtail”) Fr) which assumes a curled shape on entry or with a drawstring

Yankauer-assisted Use of a suction device during the initial open tube thoracostomy placement to Thoracostomy (i.e. “YATS”) evacuate part or all of the hemothorax prior to insertion of a tube

VATS Evacuation of a hemothorax using Video-assisted Thoracoscopic Surgery

Open Evacuation Evacuation of a hemothorax through a full surgical thoracotomy

HEMOTHORAX

Management and Outcomes in Blunt and Penetrating Trauma

Jeremy W. Cannon, MD, SM, FACS Mark Seamon, MD, FACS Trauma & Critical Care Traumatology, Critical Care, & San Antonio Military Medical Center Emergency Surgery [email protected] University of Pennsylvania [email protected] Background RETAINED Hemothorax Thoroughly Studied • DuBose et al. J Trauma. Jan 2012. 328 patients; 20 centers. 27% (88) empyema; 20% (67) thoracotomy • DuBose et al. J Trauma Sep 2012. 88 empyema patients. Need for additional interventions. Limited Scope & Multiple Management Strategies • Only focused on retained hemothorax • No follow-up • Observation? Pigtail Drainage? “YATS”?

Aim / Hypothesis

• Fully characterize the incidence and outcomes of hemothorax management in blunt and penetrating trauma.

• YATS results in fewer moderate to large retained hemothorax as compared to all other non- operative techniques. Methods • Study Design: Prospective, Observational over 2 years - Inclusion criteria: Hemothorax on admission CT Mergo definition: depth2*slices*slice thickness Volume in mL: 300 mL——900 mL - Exclusion criteria: initial operative evacuation • Groups: Observation, “Open Tube”, “Pigtail”, “YATS” • Outcomes - Primary Outcome: Retained Hemothorax by CT - Secondary Outcomes: Function at 1st follow-up, Empyema/Pleural Infection, Interventions

Methods Analysis Plan

• ANOVA for any differences among groups • MVLR for independent predictors of retained mod to large hemothorax & secondary outcomes • Power analysis indicates a need for 160 patients per group - 10% absolute reduction in retained hemothorax - 640 patients=16 patients/ctr/year Progress / Needs

• Progress - 2 of 20 centers identified (SAMMC & UPenn) - Protocol development • Needs for participating centers - IRBs may require consent - 0.1-0.25 FTE Research Coordinator - Functional assessment in clinic • Funding?

Goals / Timeline Protocol Development July 1, 2015

IRB Submission September 1, 2015

Patient Enrollment January 1, 2016

Study Closure December 31, 2017

EAST submission July 1, 2018 HEMOTHORAX

Management and Outcomes in Blunt and Penetrating Trauma