UNOS Region 5 Meeting March 18, 2015 DMG Web Portal Update UNOS Region 5 Meeting March 18, 2015 Darren Malinoski, MD Mitch Sally, MD Megan Crutchfield, MPH

INTRODUCTION Shortage of organs available for transplantation Efforts needed to increase number and quality of organs from donors after neurologic determination of death (DNDDs)

INTRODUCTION Donor Management Goals (DMGs) Checklist of critical care endpoints Standardize care of potential organ donors Normal cardiovascular, respiratory, endocrine, renal, and acid-base parameters

INTRODUCTION

DMG Web Portal Update SCD DCD ECD Total Number of Donors n=2,714 66%   66% DCD n=553   14% ECD n=827 20% From March 15, 2012 to March 11, 2015

DMG Web Portal Update Number of Donors by Region and OPO n=351 9%  Region 4 (n=351) (since January 2014) Life Gift of Texas (TXGC)  n=351 9%  Region 5 (n=3,644) Donor Network of Arizona (AZOB)  n=409 10% California Transplant Donor Network (CADN)  n=891 22% Golden State Donor Services (CAGS)  n=180 4% One Legacy (CAOP)  n=1234 30% Lifesharing (CASD)  n=293 7% New Mexico Donor Services (NMOP)  n=118 3% Nevada Donor Network (NVLV)  n=245 6% Intermountain Donor Services (UTOP)  n=274  Region 6 (n=99) (since November 2013) Pacific Northwest Transplant Bank (ORUO)  n=99 2%

Organs Transplanted per Donor (OTPD) DMG Web Portal Update Organs Transplanted per Donor (OTPD) OTPD Overall 3.18 + 3.00  SCD 3.76 + 4.00  DCD 1.95 + 2.00  ECD 2.08 + 2.00  Mean + SD

Individual Organs Transplanted by Donor Type DMG Web Portal Update Individual Organs Transplanted by Donor Type   Heart Left Lung Right Lung Left Kidney Right Kidney Liver Pancreas Intestines All Donors (n=4094) 1380, (34%) 914, (22%) 891 3248 (79%) 3177 (78%) 2870 (70%) 433 (11%) 32 (<1%) SCD (n=2714) 1338 (51%)  792 (29%) 769 (28%) 2339 (86%) 2302 (85%) 2147 (79%) 427 (16%) (1%) DCD (n=553) 8 469 (85%) 451 (82%) 138 (25%) 6 ECD (n=827) 42 (5%) 114 (14%) 114 (14%) 440 (53%) 425 (51%) 585 (71%)

Number of Donors That Met the DMG Bundle DMG Web Portal Update Number of Donors That Met the DMG Bundle   Referral Authorization 12-18 Hours Prior to OR  All DNDDs (n=3541) 588 (17%) 804 (23%) 1657 (47%) 2279 (64%) SCD (n=2714) 444 (16%) 641 (24%) 1371 (51%) 1863 (69%) ECD (n=827) 144 (17%) 163 (20%) 286 (35%) 416 (50%)

Percent DMGs Met at Each Time Point DMG Web Portal Update Percent DMGs Met at Each Time Point   Referral Authorization 12-18 Hours Prior to OR MAP (60-110 mmHg) 84% 91% CVP (4-12mmHg) 10% 28% 49% 50% EF (>50%) 15% 43% 62% pH (7.3-7.5) 65% 78% 87% 90% PF Ratio (>300) 39% 46% 56% Sodium (<155) 92% 71% 79% 86% Glucose (<180 mg/dL) 55% 76% 68% 81% Urine (0.5 cc/kg/h over 4 hours) 83% Pressors (<1 and low dose) 75% 66%

DMG Web Portal Update Met DMG Bundle 15% 26% 59% 68% 21% 27% 56% 79%   Referral Authorization 12-18 Hours Prior to the OR OPO 1 15% 26% 59% 68% OPO 2 21% 27% 56% 79% OPO 3 13% 31% 55% 58% OPO 4 24% 29% 57% OPO 5 20% 25% 46% OPO 6 22% 42% OPO 7 16% 32% OPO 8 37% OPO 9 11% 17% 61% OPO 10 18% 66% Average 19% 53% 64%

OTPD when bundle met v. not met DMG Web Portal Update OTPD when bundle met v. not met   Referral Authorization 12-18 Hours Prior to OR Met Not Met All DNDDs 3.44 3.12 3.64 3.04 3.77 2.71 3.75 2.35 SCD (n=2714) 4.09 3.69 4.28 3.60 4.23 3.28 4.16 2.87 ECD (n=827) 2.36 2.02 2.34 2.39 1.92 2.44 1.72

Lactate Levels as Predictors of Organ Transplantation Rates after Neurologic Determination of Death UNOS Region 5 Meeting March 18, 2015 Mitchell Sally, MD Darren Malinoski, MD, FACS VA Portland Healthcare System Oregon Health & Science University Portland, OR

As you have seen, and as I hope to convey here, meeting the DMG bundle is a/w more OTPD and superior graft function in those transplanted organs. Here are examples of three of our recent publications, the first two, in JOT and CCM, that focus on OTPD, and the third, which looks at the DMGs effect on DGF and kidney function. Our group has also looked at predictors of liver graft function with DMG influence.

And I personally have been involved in improvements in DMGs, looking at one particular component of the bundle, the glucose. About two years ago, we were able to show that a glucose level of < 180 in DNDDs was independently associated with 4 or more OTPD, and we recommended raising the DMG glucose threshold from 150 to 180, which is consistent with current critical care recommendations in the ICU.

LACTATE Peripheral biomarker Common use in trauma, burns, critical illness, and sepsis to guide resuscitation SvO2, ScvO2 CVP UOP BP Well, if you’ll indulge me, I’d like to discuss another potential addition and change to the DMG bundle, one that we feel will result in improved organ outcomes. Lactate is a …. And it is commonly used in multiple disease states to guide resuscitation. Other markers of resuscitation include the biomarkers SvO2 and ScvO2, and the clinical parameters such as BP, CVP and UOP.

LACTATE End product of anaerobic metabolism (glycolysis) Usually in skeletal muscle, bowel, brain and RBC Taken up and converted to glucose (gluconeogenesis) by liver Marker for adequacy of resuscitation Normal levels: < 2 mmol/L Lactate is… Curr Opin Crit Care, 2012 Jun; 18 (3): 267-272

GUIDING RESUSCITATION Living Patient DNDD Urine output Normal BP Normal CVP ScvO2 Lactate Diabetes insipidus Vasopressor use Multiple organ issues No brain oxygen extraction Unaffected by exterior pressures DNDDs bring with them a host of complicated physiologic processes, and though they may appear to be “normal” or stable, there may be many issues underlying the actual physiology. In living patients, there may often be normal (or even high) UOP, BP, CVP, and even normal ScvO2. However, there are multiple underlying issues that may contribute to the management of the organ donor. With urine output, a DNDD may be given a diuretic, or may have the condition of diabetes insipidus, common in neurologic death, and which results in high volume urine output. Normal BP may be masked by high or multiple vasopressor use. A CVP within range for the DMGs (4-12) may not tell the entire story, for example if great volumes of fluid are needed to maintain CVP, the likelihood of using the lungs diminishes. ScvO2, a commonly used biomarker in living patients. May misrepresent oxygen utilization, as the brain, which normally extracts a significant portion of the blood oxygen, is unable to do so after neurologic injury and death. In contrast, lactate is unaffected by many of these confounding variables, and may represent the most true status of acid base physiology.

LACTATE Not currently part of the DMG Bundle Recorded only sporadically Utility in guiding donor management has not been examined We would like to propose that lactate be considered to be added to the current DMG bundle, and have a bit of data to support this notion.

Lactate Levels Present at Each Time Point DMG Web Portal Update Lactate Levels Present at Each Time Point   Referral Authorization 12-18 Hours Prior to OR TXGC (n=295) n=19 (6%) n=14 (5%) n=10 (3%) n=7 (2%) AZOB (n=312) n=32 (10%) n=27 (9%) n=15 (5%) CADN (n=828)  n=168 (20%) n=253 (31%) n=363 (44%) n=351 (42%) CAGS (n=156) n=75 (48%) n=71 (45%) n=86 (55%) n=65 (42%) CAOP (n=1105) n=283 (26%) n=708 (64%) n=1007 (91%) n=996 (90%) CASD (n=227)  n=30 (13%) n=27 (12%) n=29 (13%) n=25 (11%) NMOP (n=118)  n=38 (36%) n=14 (13%) n=9 (8%) n=8 (7%) NVLV (n=244)  n=12 (5%) n=4 (2%) n=6 (2%) UTOP (n=209)  n=101 (48%) n=134 (64%) n=110 (53%) n=103 (49%) ORUO (n=68)   n=13 (19%) n=9 (13%) n=5 (7%) n=3 (4%) TOTAL (n=3562) n=771 (22%) n=1261 (35%) n=1640 (46%) n=1571 (44%) A recent pull of data from the web portal supports the idea of lactate being inconsistently recorded, as it is not currently part of the DMG bundle. We can see that these levels are recorded or taken ranging from anywhere from 2 to 90 per cent of the opportunities. Overall, lactate levels appear to be recorded approximately 40% of the time. You will note that these numbers are slightly different than the data the I am going to present, which represent different timing of data downloads from the web portal.

OBJECTIVES/HYPOTHESIS To determine the association between blood lactate levels and organ transplantation rates. We hypothesized that normal lactate levels would be associated with more OTPD.

METHODS Prospective, observational study Three standard time points: All DNDDs 10 OPOs, UNOS Regions 4, 5, and 6 March 2012 - August 2014 Three standard time points: Authorization for donation 12-18 hours after authorization Prior to organ recovery This was a prospective…. The three standard time points that we chose to examine began with authorization for donation… We chose these three time points for two reasons: the first, simply because of the variability and infrequency of recording at referal for donation but perhaps more importantly, because these three time points are truly when donor management occurs.

METHODS Primary outcome: achieving ≥ 4 OTPD Secondary outcomes: individual organ transplantation rates

RESULTS 1351 donors 3.4 ± 1.8 OTPD 45% ≥ 4 OTPD Lactate values recorded: 831/1351 (61.5%) at Authorization 1090/1351 (80.7%) at 12-18 Hours 1045/1351 (77.4%) Prior to recovery

RESULTS – LACTATE Mean lactate levels (mmol/L): 2.5 + 3.1 overall 2.5 + 3.0 at Authorization 2.6 + 3.0 at 12-18 Hours 2.1 + 2.8 Prior to organ recovery 2,008/2,966 (67.7%) levels were < 2 mmol/L.

# Lactates < 2 mmol/L (n=579) RESULTS – UNIVARIATE Continuous OTPD < 4 OTPD > 4 p Overall Mean 3.11 2.88 < 0.01 Authorization Mean 3.01 2.45 12-18 Hrs Mean 2.96 2.58 Terminal Mean 2.78 2.08 Categorical   Authorization Lactate < 2 mmmol/L 60.3% 70.1% 12-18 Hours Lactate < 2 mmol/L 54.3% 66.5% OR Lactate < 2 mmol/L 71.8% 85.0% # Lactates < 2 mmol/L (n=579) 1 measurement (n=116) 18.2% 17.3% 0.76 2 measurements (n=147) 20.5% 24.6% 0.22 3 measurements (n=316) 44.3% 52.7% 0.03

RESULTS - MULTIVARIABLE Continuous OR 95% CI p Overall Mean 0.92 0.86-0.99 0.02 Authorization Mean 0.90 0.83-0.98 0.01 12-18 Hrs Mean 0.94 0.87-1.03 0.06 Terminal Mean 0.88 0.79-0.97 Categorical   Authorization Lactate < 2 mmmol/L 1.37 0.90-2.08 0.14 12-18 Hours Lactate < 2 mmol/L 1.33 0.93-1.89 0.11 OR Lactate < 2 mmol/L 1.93 1.19-3.11 <0.01 # Lactates < 2 mmol/L (n=579) 1 measurement (n=116) 1.35 0.79–2.32 0.27 2 measurements (n=147) 1.14 0.71–1.85 0.58 3 measurements (n=316) 1.22 0.81-1.84 0.35 *Results controlled for with known predictors of > 4 OTPD: age, weight, BMI, terminal creatinine, donor management bundle met at all 3 time points, standard criteria status, gender, thyroid hormone administration, and CDC high risk status.

RESULTS – INDIVIDUAL ORGANS Lower mean lactate levels found in DNDDs whose organs were utilized: Used Not Used p Hearts 2.6 + 2.9 3.1 + 3.2 < 0.01 Lungs 2.4 + 3.0 3.1 + 3.1 Livers 2.7 + 2.9 3.6 + 3.7

CONCLUSIONS Lactate measurements are inconsistently drawn in DNDDs during donor management Lower mean lactate levels remained independent predictors of ≥ 4 OTPD Terminal lactate < 2 mmol/L: independently associated with > 4 OTPD Inclusion of a lactate level < 2 mmol/L into existing DMG Bundles should be considered

QUESTIONS