A2ALL - Safe and Effective Postoperative Pain Management in Living Liver Donors

1. A2ALL - Safe and Effective Postoperative Pain Management in Living Liver Donors • D Woods, E Pomfret, MA Simpson, J Guarrera,  R Fisher, A Skaro, T Curtis, • E Reyes, A Daud, E Wymore, and B Platt, DP Ladner • American Public Health Association Annual Meeting, 2015 • November 2, 2015 – Chicago, IL

2. Donna Woods, EdM, PhD No relationships to disclose A2ALL-Patient Safety System Improvement in Living Donor Liver Transplantation an ancillary study of the Adult to Adult Living Donor Liver Transplantation Cohort Study NIH/NIDDK – R01DK090129: PI: Woods/Ladner PRESENTER DISCLOSURE

3. Living Donor Liver Transplantation (LDLT) • Living donor liver transplantation has emerged as an important, life saving option for many patients. • In living donor liver transplantation, a healthy donor altruistically undergoes a major procedure to save the life of another. • The live donor procedures are considerably more complex than decreased donor transplantation. Donor safety is imperative!

4. Living liver donors experience pain post liver donation Holtzman, et al, Liver transpl, 2014 Nov; Pomfret, et al, ATC, 2013; BACKGROUND

5. The Adult-to-Adult Living Donor Liver Transplant Cohort study (A2ALL) involves 9 living donor liver transplant centers (2002-2015) with A2ALL ‘Deux’ focusing on donor outcomes Four A2ALL centers participated in an ancillary R01 study to the A2ALL to study and improve patient safety Living liver donors experience pain post liver donation Living liver donors experience surprisingly high rate of complications related to opioid pain medication 97 medical records of living donors were reviewed entirely by trained RN  100% (n=97) had complications associated with opioid use  73%(n=71) had respiratory or cardiovascular events Ladner, et al. AASLD, 2013; Ladner, et al WTC, 2014; Platt/Ladner, et al. ATC, 2015 BACKGROUND

6. Ladner, et al. AASLD, 2013; Ladner, et al WTC, 2014; Platt/Ladner, et al. ATC, 2015 PRE - FINDINGS • 73% living donors at 4 centers • transfer to the ICU • Intubation • Naloxone N: # Subjects PRE: Prior to Opioid Sparing Protocol POST: After Opioid Sparing Protocol •  FINDINGS CONFIRMED BY INDEPENDENT MONITOR

7. The high complication rates related to opioid use were surprising to all participating centers and primarily associated with opioid use Pharmacokinetics of opioids after extensive liver resection undescribed – but constant worry of surgeons We engaged pain management experts Conducted a Breakthrough Series Learning Collaborative including four-center, multi-disciplinary teams and developed a opioid sparing postoperative donor pain protocolfor LDLT Transplant anesthesiologists, Transplant surgeons, Acute pain experts, and Patient safety experts Multi-modal Opioid-Sparing Donor Pain Protocol BACKGROUND

8. Preoperative Assessment and Management: • Assessment of Patient Risk factors for Respiratory Depression (OSA Assessment: STOP BANG Questionnaire) • Bowel preparation (e.g. Colace or Golytely) • Patient Postoperative Pain Education - educational handout on postoperative pain • During Surgery: • *Local Anesthetic (TAP block, OnQ device, intrathecal, local infiltration) • *IV Ketorolac (adequate hemostasis is determined by surgeon and urine output is >500cc) • *IV Steroids (Dexamethasone or Solumedrol) • After Surgery During Hospitalization: • *NSAIDS x 72 hours followed by PO Cox2-inhibitor until discharge (e.g. Celecoxib) • Opioids (Dilaudid PCA followed by oral opioids [e.g., Tylenol #3]) *Pharmacological components of opioid sparing protocol MULTI-MODAL OPIOID-SPARING DONOR PAIN PROTOCOL

9. METHODS • Participating centers: • Northwestern University • Columbia University Medical Center • Lahey Clinic Medical Center • Virginia Commonwealth University • Prospective study with PRE/POST analysis: • Pre-implementation data (PRE): January 2008-July 2010 • Post-implementation data (POST): March 2013 – May 2015 (enrollment just closed) • Entire medical record (all elements) from donor hospitalization were copied, de-identified, then fully reviewed by trained RN • All complications were reviewed by MD • Validation of findings through external monitor (Dr. E. Pretto, University of Miami) • This study was approved by the Northwestern University IRB and the IRBs at each of the participating sites

10. RESULTS • 97 living donors prior to Opioid-sparing Donor Pain Protocol (PRE) • 77 living donors were assessed after implementation of the Opioid-sparing Donor Pain Protocol (POST)

11. DONOR CHARACTERISTICS N: # Subjects PRE: Prior to Opioid Sparing Protocol POST: After Opioid Sparing Protocol 4 A2ALL living donor liver transplant centers

12. DONOR PAIN MANAGEMENT - RESULTS N: # Subjects PRE: Prior to Opioid Sparing Protocol POST: After Opioid Sparing Protocol

13. RESULTS • Pain scores showed a largely non-significant trend toward reduced post-operative pain PRE and POST

14. CONCLUSIONS • Opioid related complications are far more frequent than previously reported in living liver donors • This is particularly concerning in view of past donor deaths • A multi-modal approach to donor pain management can reduce the complication rate related to opioids • This approach did not lead to higher pain perception of the living donors • No complications associated with the new opioid sparing approach were identified (e.g. hyperglycemia)

15. Co-PI: Daniela Ladner, MD, MPH • Co-Investigators: • E. Pomfret • J Guarrera • R. Fisher • MA Simpson • A Skaro • Collaborators: • Michael Abecassis • Jane Holl ACKNOWLEDGEMENTS • Team: • A. Daud • E. Reyes • T. Curtis • R. Khorzad • E. Wymore • B. Platt

16. Thank You