a non-trivial challenge for a perfusionist

Transcription

1 DO 2 -guided nephroprotective perfusion - a non-trivial challenge for a perfusionist Dirk Buchwald, Krzysztof Klak

2 xygenium oxygen - Colorless and odorless gas - Most common chemical element on earth atomic oxygen: O molecular oxygen: dioxygen O 2 trioxygen (ozone) O 3 tetraoxygen O 4 octaoxygen O 8 - Third most prevalent chemical element in the universe Highly reactive with most chemical elements of the periodic table Page 2

3 Dependence of biological processes on continuous oxygen supply using the example of the human brain from Siegenthaler, Klinische Pathophysiologie, 2006 Page 3

4 Circulation. 2009;119: Incidence: over 30 % of all patients - Independently associated with increased mortality Page 4

5 Oxygen utilization (in normothermia, under resting condition) Parameter CO = 5 l/min VO 2total. = 225 ml/min % of CO S v O 2 (%) % of total- O 2 -consumption Q blood /VO 2 (ml/min blood /ml O2 ) modified from Lücke, M: Erste Hilfe bei Notfällen und Unfällen and Reinhart K in: Lewis, Pfeiffer (eds): Practical Applications of Fiberoptics in Critical Care Monitoring, Springer Verlag Berlin - Heidelberg - NewYork 1990, pp Page 5

6 Why is the kidney so sensitive to hypoxia, although the oxygen extraction rate is so low? Page 6

7 QO 2kidney = 2.7 mmol/min/kg, QO 2heart = 4.3 mmol/min/kg This high oxygen consumption is largely driven by the high renal blood flow, since the renal oxygen extraction is low. 80 % of the oxygen consumption - tubular sodium transport. Basal metabolic rate % of oxygen utilization. Page 7

8 Renal unique feature: Increase in RBF increase in GFR increase in oxygen demand In kidney an increase in oxygen supply also increases the oxygen demand (peculiarity of the kidney) Cortex - 20% of CO - tissue po 2 of mmhg Medulla % RBF - tissue po 2 of mmhg. The segments of the medulla are most vulnerable to the injury caused by low oxygen delivery Page 8

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11 Requirements for a nephroprotective perfusion: Oxygen delivery should be above 262 ml/min/m 2 The ratio of oxygen delivery to CO 2 production should be above 5,3 Page 11

12 Definition of DO 2i : oxygen delivery per square meter of BSA DO 2i = Q B Hb S ao , 36 ml g + 0, 0031 ml BSA dl mm Hg pao 2 10 dl l where: DO 2i oxygen delivery index ml/min/m 2 Q B blood flow l/min Hb hemoglobin g/dl S a O 2 arterial saturation % po 2 arterial oxygen partial pressure mm Hg BSA body surface area m 2 Page 12

13 Control of DO 2i during CPB DO 2i = Q B Hb S ao , 36 ml g + 0, 0031 ml BSA dl mm Hg pao 2 10 dl l RAP Hemodilution Page 13

14 Definition of VCO 2 : carbon dioxide production where: VCO 2 carbon dioxide production ml/min Q G oxygenator gas flow l/min pco 2ex end-tidal carbon dioxide partial pressure mm Hg parameter not directly controllable through the CPB Page 14

15 How can one determine DO 2 and VCO 2 during CPB? Page 15

16 p a O 2 S a O 2 Hb S v O 2 GDP-Monitor Inline-BGA Monitor DO 2 VCO 2 pco 2exp Capnograph Q blood Q gas Page 16

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19 condensed water obstructs gas escape port Page 19

20 recalibration CDI 500 DO 2 rise DO 2 decline crystalloid administration pump flow increase Packed red blood cells administration pump stop low level alarm Page 20

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22 How can we verify whether the DO 2 -guided perfusion has a clinically relevant influence on the renal function? Page 22

23 Definition of the renal failure Page 23

24 Classification of acute renal failure AKIN (Acute Kidney Injury Network) RIFLE (Risk Injury Failure Loss Endstage renal disease) RIFLE- Stage AKIN- Stage Risk 1 Injury 2 Failure 3 Creatinine criterion serum creatinine 1,5-2,0 x baseline or increase >0,3 mg/dl serum creatinine 2,0-3,0 x baseline serum creatinine > 3x baseline OR Disadvantage: Creatinine increases not before GFR falls more than 50%. Urine output criterion hourly urine output <0,5ml/h/kg for 6-12 h hourly urine output <0,5 ml/h/kg for > 12 h hourly urine output < 0,3 ml/h/kg > 24 h or Anuria > 12 h Kidney International Supplements (2012) 2, 8 12; doi: /kisup Page 24

25 Detection of renal failure by means of biological marker Cell division cycle IGFBP-7 TIMP-2 Release with damage of tubule cells Insulin-like-growth-factor-binding-protein-7 Tissue inhibitor of metalloproteinase-2 Page 25

26 C IGFBP-7 x C TIMP-2 cut-off value > 0,3 ng 2 /ml 2 NephroCheck / Astute Early detection of ARF in urine Shows kidney injury before structural damage occurs (creatinine rise, decrease of GFR) Early diagnosis in potentially reversible stage of renal injury Page 26

27 Extended definition of oxygen undersupply Page 27

28 Definition of cumulative oxygen undersupply CU DO2 DO 2i Δt ΔDO 2i DO 2ithreshold = 272 ml/min/m 2 t (time) CU DO 2i = DO 2iactual DO 2ithreshold dt if DO 2iactual - DO 2ithreshold < 0 ml/min/m 2 Page 28

29 Technical feasibility Clinical implementation Observational study (RUB ethics committee Nr ) 30 patients Continuous recording of DO 2 und DO 2 /VCO 2 Calculation of the cumulative oxygen undersupply (AUC DO 2 /t) No change in perfusion management No patient selection Measurement of biological marker in urine for early diagnosis of ARF Page 29

30 Results Page 30

31 scheduled: 30 patients included: 27 patients 3x technical error n = patients developed ARF Stage 1 or 2 within 3 days ARF according to diuresis- or creatinine criterion 26% 11% 63% no ARF ARF Stage 1 ARF Stage 2 Page 31

32 Biological marker IGFBP-7 und TIMP-2 Null hypothesis H 0 : There is no correlation between postoperative renal failure stage and urine concentration of biological marker > 0,3 ng 2 /ml 2 Time of analysis p-value statistical significance arrival on ICU 0, h postoperative 0,0127 significant H 0 proved wrong: There is a significant correlation between postoperative renal failure and urine concentration of biological marker Page 32

33 Cumulative oxygen undersupply CU DO2 i Null hypothesis H 0 : There is no correlation between the cumulative oxygen undersupply and postoperative renal failure stage oxygen undersupply CU DO2 i p-value statistical significance > 200 mlo 2 /m 2 and < 500 mlo 2 /m 2 0,4559 > 500 mlo 2 /m 2 and < 1000 mlo 2 /m 2 0,2388 > 1000 mlo 2 /m 2 0,0166 significant In patients with cumulative oxygen undersupply > 1000 mlo 2 /m 2 the occurrence of postoperative renal failure is probable. Page 33

34 Cumulative oxygen undersupply CU DO2 i Null hypothesis H 0 : There is no correlation between the duration of oxygen undersupply and postoperative renal failure stage Duration of oxygen undersupply p-value statistical significance t > 5 min and t < 10 min 0,4093 t > 10 min and t < 15 min 0,5061 t > 15 min 0,0236 significant In patients with duration of undersupply of DO 2i > 15 min the occurrence of postoperative renal failure is probable. Page 34

35 Duration of ECC Null hypothesis H 0 : There is no correlation between the bypass time and postoperative renal failure stage CPB duration p-value statistical significance < 100 min 0,2467 > 100 min and < 120 min 0,6559 > 120 min and < 140 min 0,4559 In considered time frame until 140 minutes of CPB time the null hypothesis was confirmed. Page 35

36 Conclusions Perfusion Department During low-flow phases of the CPB and/or too low hemoglobin level DO 2i can fall below the critical value of 272 ml/min/m 2 for longer time periods, although the venous saturation (gold standard) is high enough. DO 2i below critical level (also for short time periods) -> cumulative pathological effect for renal function The biological markers IGFBP-7 and TIMP-2 sensitively detect renal failure. The implementation of DO 2 -guided perfusion as Goal Directed Perfusion (GDP) is for perfusionists technically (and intellectually) practicable, requires however extended perception compared to the daily CPB routine. Page 36

37 Coming soon: G.I.F.T. Trial Goal Directed Perfusion Trial Multicenter study (11 centers, patients per center, max. 700 patients) PI Ranucci, Milano CONTROL (N=350) TREATMENT (N=350) GDP monitor GDP monitor No blood prime (withdrawal) Priming volume and nature according to local standards No blood prime (withdrawal) Priming volume and nature according to local standards Perfusion targeted on BSA and C Perfusion targeted on DO ml/min/m 2 Perfusion pressure according to local standards Transfusion triggered by Hct according to local standards Postoperative care according to local standards Perfusion pressure according to local standards Transfusion triggered by S V O 2 < 68% and/or O 2 ER > 40% Postoperative care according to local standards Page 37

38 Disclosure Perfusion Department Speaker s fee, travel expenditures, hotel room from Sorin Group Thank you for your attention. Page 38