Goal Directed Perfusion: theory, clinical results, and key rules

Goal Directed Perfusion: theory, clinical results, and key rules M. Ranucci Director of Clinical Research Dept of Cardiothoracic and Vascular Anesthesia and Intensive Care IRCCS Policlinico S.Donato Ranuuci, M et al. 2005

Outline Theory: postoperative organ dysfunction and oxygen dependency Clinical results: the hypothesis generated by retrospective data Key rules: the GDP laws

Outline Theory: postoperative organ dysfunction and oxygen dependency Clinical results: the hypothesis generated by retrospective data Key rules: the GDP laws

Performing perioperative optimization of the high-risk surgical patients. If this debt is paid back within 8 hours, the incidence of postoperative complications decreases, and if it is never paid then cell dysfunction and death occur. BJA 2006;97:4-11

Lactate

Hemodynamic optimization 70 60 50 40 30 20 10 0 Cardiac Index > 4,5 L/min/m2 O 2 delivery > 600 ml/min /m2 O 2 consumption > 170 ml/min/m2 Control PAC control PAC hemodynamic optimization

FROM NON-CARDIAC SURGERY TO CPB-CARDIAC OPERATIONS

THE ASSOCIATION BETWEEN ORGAN FAILURE AND LOW OXYGEN CONTENT/ DELIVERY Low HCT levels on CPB have been associated with: AKI Stroke Low cardiac output

THE ASSOCIATION BETWEEN ORGAN FAILURE AND LOW OXYGEN CONTENT/ DELIVERY Low HCT levels on CPB have been associated with: KIDNEY BRAIN HEART

Cardiac Output Preload Chang MC. New Horizons 1999;7:35-45

THE ASSOCIATION BETWEEN ORGAN FAILURE AND LOW OXYGEN CONTENT/ DELIVERY Low HCT levels on CPB have been associated with: KIDNEY BRAIN HEART

Crude risk of Low Output Failure (LOF) by Nadir Hematocrit during CPB. Surgenor SD, et al. Circulation 2006;114(Suppl):43 8i.

THE ASSOCIATION BETWEEN ORGAN FAILURE AND LOW OXYGEN CONTENT/ DELIVERY Low HCT levels on CPB have been associated with: KIDNEY BRAIN HEART

Possible perfusion-related risk factors CPB itself Perfusion pressure Perfusion flow Loss of pulsatility Severe hemodilution Poor oxygen delivery Hemolysis

PRESSURE

FLOW

OXYGEN CONTENT OXYGEN DELIVERY

STRUCTURE OF THE KIDNEY(after A.Despopoulos & S.Silbernagl, Color Atlas of Physiology, 2003)

Kidney and oxygen supply Renal medulla is chronically hypoxemic A low oxygen content (hemodilution) further worsen kidney hypoxia Low blood flow is a major determinant of reduced oxygen supply

12%

0.3 16,000 consecutive patients at the IRCCS PSD Riskof AKI stage 2 0.2 0.1 8% 0.0 10 15 20 25 30 35 40 Nadir HCT (%) on CPB

HCT DO 2 VCO 2 DO 2 /VCO 2 AKI (creatinine change within first 48h)

DO 2 262ml/min/m 2 DO 2 /VCO 2 5.3 Hct 23.5%

Measurements and calculations PA-catheter: Systemic haemodynamics Renal vein catheter: Renal blood flow (RBF) Renal oxygen extraction (SaO 2 -SrvO 2 ) / SaO 2 Filtration fraction (FF), the renal extraction of Cr 51 -EDTA Calculations: Glomerular Filtration Rate (GFR) = FF x RBF x (1-Hct) Renal Oxygen Consumption (RVO 2 ) = RBF x (CaO 2 - CvO 2 ) Renal Oxygen Delivery (RDO 2 ) = RBF x CaO 2 Urinary excretion of NAG (every 30 minutes) Lukas lannemyr, M D, Dpt of Cardiothoracic anaesthesia and intensive care, Sahlgrenska University Hospital, Gothenburg, Sweden

g/l mmhg 3 2,5 Results Systemic variables Cardiac Index *** *** ** 100 90 80 70 60 50 40 30 20 10 0 Mean Arterial Pressure Pre CPB 30' CPB 60' Post CPB * L/min/m 2 2 1,5 1 0,5 140 120 100 80 Haemoglobin *** *** *** 0 Pre CPB 30' CPB 60' Post CPB 60 40 * p < 0.05, ** p < 0.01, ** p < 0.001 20 0 Pre CPB 30' CPB 60' Post CPB

ml/min ml/min mmhg/ml/min ml/min Results Renal variables Renal blood flow 700 600 500 400 300 200 100 0 Pre CPB 30' CPB 60' Post CPB *** p < 0.001 Glomerular filtration rate 80 60 40 20 0 Pre CPB 30' CPB 60' Post CPB 0,2 0,15 0,1 0,05 0 15 10 5 0 Renal vascular resistance Pre CPB 30' CPB 60' Post CPB Renal oxygen consumption *** Pre CPB 30' CPB 60' Post CPB

RDO 2 ml/min Systemic and renal oxygen delivery 400 350 * * 140 120 300 100 DO 2 I ml/min/m 2 250 200 150 100 DO2I RDO2 * ** * 80 60 40 50 20 0 * p < 0.05, ** p < 0.01 vs Pre Pre CPB CPB 30' CPB 60' Post CPB 0

0,2 0,15 Renal oxygen extraction - oxygen supply demand relationship *** * * 0,1 0,05 0 Pre CPB 30' CPB 60' Post CPB * p < 0.05, *** p < 0.001 vs Pre

ml/min NAG excretion 14 NAG/U-creatinine 12 10 *** *** 8 6 4 2 0 * Pre CPB CPB 30' CPB 60' CPB 120' Post CPB30' Post CPB60' 24 hpost CPB * * p < 0.05, *** p < 0.001 vs Pre

BEFORE CPB DO2 600 ml/min DO2 85 ml/min (14%) O2ER 10%

ON CPB DO2 680 ml/min DO2 68 ml/min (10%) O2ER 15%

AFTER CPB DO2 610 ml/min DO2 76 ml/min (12%) O2ER 17%

Outline Theory: postoperative organ dysfunction and oxygen dependency Clinical results: the hypothesis generated by retrospective data Key rules: the GDP laws

SvO2 not sensitive

Single center retrospective cohort study 16.790 non congenital adult patients undergone cardiac surgery on pump from 2000 to december 2013 793 (4,7%) AKI stage 2/3 in postop (increasing serum creatinine more than 200%)

Nadir Hct value during CPB was confirmed as an indipendent determinant of AKI (increase of 7% per 1% point of nadir Hct value

Some factors (egfr and EF) have been improving in the last period Others (diabetes, redo and nonelective operations, non isolated CABG, peoperative use of IABP and duration CPB) show a significantly higher severity.

AKI rate significantly increased until 2005, despite no significant change in RRS Starting 2006 AKI rate decline, despite the increase in the RRS

7.7% 7.5% CENTRIFUGAL PUMPS

4.8% 3.7% NO ANGIOGRAPHY ON THE DAY OF SURGERY P=0.028

5.8% 3.1% GOAL DIRECTED PERFUSION P=0.001

Effect of Goal Directed Perfusion

Outline Theory: postoperative organ dysfunction and oxygen dependency Clinical results: the hypothesis generated by retrospective data Key rules: the GDP laws

Gas flow temperature GDP monitor Pump flow measured Low prime oxygenators Same old perfusionist as in the 90 s

THE FIVE GDP LAWS 1. Limit hemodilution on CPB 0.25 AKI rate (% with 95% CI) 0.20 0.15 0.10 0.05 0.00 16 18 20 22 24 26 28 30 32 34 36 38 Nadir HCT on CPB (%)

THE FIVE GDP LAWS 2. Always stay at a DO2 > 270 ml/min/m2

THE FIVE GDP LAWS 3. Increase the DO2 by acting on pump flow, PaO2

Perfusion. 2015 Jul 23. pii: 0267659115595281. [Epub ahead of print] The effects of hyperoxaemia on tissue oxygenation in patients with a nadir haematocrit lower than 20% during cardiopulmonary bypass. Sevuk U(1), Altindag R(2), Baysal E(2), Yaylak B(2), Adiyaman MS(2), Akkaya S(2), Ay N(3), Alp V(3). Excessive haemodilution and the resulting anaemia during CPB is accompanied by a decrease in the total arterial oxygen content, which may impair tissue oxygen delivery. Hyperoxic ventilation has been proven to improve tissue oxygenation in different pathophysiological states of anaemic tissue hypoxia. The aim of this study was to examine the influence of arterial hyperoxaemia on tissue oxygenation during CPB. Records of patients undergoing isolated CABG with CPB were retrospectively reviewed. Patients with nadir haematocrit levels below 20% during CPB were included in the study. Tissue hypoxia was defined as hyperlactataemia (lactate >2.2 mmol/l) coupled with low ScVO2 (ScVO2 <70%) during CPB. One hundred patients with normoxaemia and 100 patients with hyperoxaemia were included in the study. Patients with hyperoxaemia had lower tissue hypoxia incidence than patients with normoxaemia (p<0.001). Compared with patients without tissue hypoxia, patients with tissue hypoxia had significantly lower PaO2 values (p<0.001) and nadir haematocrit levels (p<0.001). Nadir haematocrit levels <18% (OR: 5.3; 95% CI: 2.67-10.6; p<0.001) and hyperoxaemia (OR: 0.28; 95% CI: 0.14-0.56; p<0.001) were independently associated with tissue hypoxia.conclusions: Hyperoxaemia during CPB may be protective against tissue hypoxia in patients with nadir haematocrit levels <20%.

THE FIVE GDP LAWS 4. Transfuse RBC based on SvO2 and O2ER rather than HCT

THE FIVE GDP LAWS 5. Avoid the anaerobic zone by checking lactates and VCO2

DO 2, VO 2, SvO 2, and Lactates...and VCO2 VCO 2 VO (ml/min) 2 (ml/min) 300 250 200 150 100 50 0 OXYGEN DEBT Critical DO 2 SvO 2 (%) 90 80 70 60 50 40 30 25 Lac (mmol/l) 12 10 8 6 4 2 0 0 100 200 300 400 500 600 700 800 900 1,000 DO 2 (ml/min)

THE GDP CONCEPT: VCO 2 VO (ml/min) 2 (ml/min) 300 250 200 150 100 50 0 OXYGEN DEBT Critical DO 2 WE WANT THE PATIENT IN THIS ZONE SvO 2 (%) 90 80 70 60 50 40 30 25 Lac (mmol/l) 12 10 8 6 4 2 0 0 100 200 300 400 500 600 700 800 900 1,000 DO 2 (ml/min)

AKI 2 rate (%) 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 5 0 1994 2014 KEEP THE PATIENT HERE 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 Lowest HCT on CPB

Peak Arterial Blood Lactate (mmol/l) 3,0 Critical DO2 2,5 2,0 GDP: KEEP THE PATIENT HERE 1,5 1,0 200 220 240 260 280 300 320 340 360 380 Lowest Oxygen Delivery (ml/min/mq)

KEEP THE PATIENT HERE

H E R E HERE

AKI 2 rate (%) 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 5 0 Same HCT Higher Pump Flow GDP in 2014 1994 2014 20 years of CPB technologies improvements Centrifugal vs roller pumps Biocompatible circuits Flow monitoring Less transfusions 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 Lowest HCT on CPB