Northwestern University Feinberg School of Medicine

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, 2015November 2, 2015 – Chicago, IL

PRESENTER DISCLOSURE

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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

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!

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BACKGROUND

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• Living liver donors experience pain post liver donation

Holtzman, et al, Liver transpl, 2014 Nov; Pomfret, et al, ATC, 2013;

BACKGROUND

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• 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

PRE - FINDINGS

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CAUSE PRE (N=97)

Hypoxia (< 95% on RA) Opioid 76%Bradypnea (RR < 10) Opioid 53%Hypotension (SBP <100) Opioid 49%Hypoxia (< 90% on RA) Opioid 12%Bradycardia (HR <50) Opioid 9%

Nausea Opioid 80%Constipation Opioid 49%Pruritis Opioid 28%Urinary Retention Opioid 23%Vomiting Opioid 16%Dizziness Opioid 16%Delirium Opioid 12%

Tachycardia (>120) Pain 21%Tachypnea (>20) Pain 68%Hypertension (>160) Pain 39%

N: # Subjects PRE: Prior to Opioid Sparing ProtocolPOST: After Opioid Sparing Protocol

FINDINGS CONFIRMED BY INDEPENDENT MONITOR

Ladner, et al. AASLD, 2013; Ladner, et al WTC, 2014; Platt/Ladner, et al. ATC, 2015

BACKGROUND

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• 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 protocol for LDLT

• Transplant anesthesiologists, Transplant surgeons, Acute pain experts, and Patient safety experts

Multi-modal Opioid-Sparing Donor Pain Protocol

MULTI-MODAL OPIOID-SPARING DONOR PAIN PROTOCOL

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• Preoperative Assessment and Management:1. Assessment of Patient Risk factors for Respiratory Depression (OSA Assessment: STOP BANG

Questionnaire)2. Bowel preparation (e.g. Colace or Golytely)3. Patient Postoperative Pain Education - educational handout on postoperative pain

• During Surgery:4. *Local Anesthetic (TAP block, OnQ device, intrathecal, local infiltration)5. *IV Ketorolac (adequate hemostasis is determined by surgeon and urine output is

>500cc)6. *IV Steroids (Dexamethasone or Solumedrol)

• After Surgery During Hospitalization:• *NSAIDS x 72 hours followed by PO Cox2-inhibitor until discharge (e.g. Celecoxib)1. Opioids (Dilaudid PCA followed by oral opioids [e.g., Tylenol #3])

*Pharmacological components of opioid sparing protocol

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

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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)

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DONOR CHARACTERISTICS

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N: # Subjects PRE: Prior to Opioid Sparing ProtocolPOST: After Opioid Sparing Protocol

PRE (N=97)

POST (N=77) P-value

AGE 0.95

18-34 38% 40%

35-49 41% 39%

50-64 21% 21%

GENDER 0.27

Male 58% 49%

RACE 0.13

White 77% 75%

Black 10% 4%

Hispanic 8% 17%

Asian 2% 4%

LANGUAGE 0.43

English 94% 95%

LIVER LOBE 0.30

Right 90% 84%

Left 10% 16%

BMI > 30 15% 17% 0.80

4 A2ALL living donor liver transplant centers

DONOR PAIN MANAGEMENT - RESULTS

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CAUSE PRE (N=97) POST (N=77) % CHANGE P-value

Delirium Opioid 12% 6% -48% 0.19Dizziness Opioid 16% 9% -45% 0.15Bradypnea Opioid 53% 30% -43% 0.00Pruritis Opioid 28% 17% -39% 0.09Urinary Retention Opioid 23% 14% -37% 0.16Tachypnea (>20) Pain 68% 49% -27% 0.01Hypoxia (< 95% on RA) Opioid 76% 61% -20% 0.03Hypoxia (< 90% on RA) Opioid 12% 10% -16% 0.68Vomiting Opioid 16% 14% -13% 0.69Tachycardia (>120) Pain 21% 18% -12% 0.69Constipation Opioid 49% 44% -11% 0.48Hypotension (<100) Opioid 49% 44% -11% 0.48Hypertension (>160) Pain 39% 36% -7% 0.70Nausea Opioid 80% 78% -3% 0.69Hyperglycemia Steroid 25% 25% 0% 0.99Bradycardia (<50) Opioid 9% 10% 12% 0.81

N: # Subjects PRE: Prior to Opioid Sparing ProtocolPOST: After Opioid Sparing Protocol

RESULTS

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

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Percent of Patients with Highest Pain Score 8 or More

Post-op Day

% Pain Scores 0 1 2 3 4 5 6 7 8 Total

Pre-Intervention

0-7 68.54% 76.29% 79.38% 85.53% 78.13% 81.82% 82.35% 80% 81.8%

8+ 31.46% 23.71% 20.62% 14.47% 21.88% 18.18% 17.65% 20% 18.2%

Total (N) 89 97 97 76 64 55 34 20 11 543

Full Protocol

0-7 86.36% 77.27% 80.49% 77.42% 80% 89.47% 92.86% 100% 75%

8+ 13.64% 22.73% 19.51% 22.58% 20% 10.53% 7.14% 0% 25%

Total (N) 44 44 41 31 25 19 14 5 4 227

P-Value from Chi-Square

0.0266 0.8982 0.8826 0.309 0.8462 0.4351 0.3486 0.28 0.77

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)

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ACKNOWLEDGEMENTS

Co-PI: Daniela Ladner, MD, MPH

Co-Investigators:

-E. Pomfret

-J Guarrera

-R. Fisher

-MA Simpson

-A Skaro

Collaborators:

-Michael Abecassis

-Jane Holl

Team:

-A. Daud

-E. Reyes

-T. Curtis

-R. Khorzad

-E. Wymore

-B. Platt

Thank You

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