End-of-Surgery Serum Lactate concentration
as a major predictor of postoperative
outcome. A multicentre prospective study.
Eric Vibert, Emmanuel Boleslawski, Cyril Cosse, Rene Adam,
Denis Castaing, Daniel Cherqui, Salima Naili, Jean-Marc
Régimbeau, Antonio Sa Cunha, Stéphanie Truant, Maher Fleyfel,
François René Pruvot, Catherine Paugam, Olivier Farges
ACHBT Hepatectomy Registry
PST-AST = 450 UI/L
PST-ALT = 420 UI/L
AUROC = 0.61 AUROC = 0.57
French Multicentric Study : 651 pts in 9 HPB Centers
Postoperative Peak of Transaminase is not a relevant endpoint to predict outcome
2014
Objectives of the study
After an elective liver resection:
1. Is Arterial Lactate Concentration at the end
of surgery (LCT-EOS) predictive of outcome ?
2. If yes, is there pre- or intraoperative
predictors of an increase in LCT-EOS ?
Study endpoints
• End of surgery arterial Lactate Concentration
– Between 1 and 4 hours after end of liver transection
• Postoperative outcome (90-day outcome)
– High Clinical Comprehensive Index (> 3rd quartile)
– Mortality
– Severe morbidity (Clavien’s grade III-V)
ACHBT Web Prospective Registry
1342 Consecutive Hepatectomies in 4 Hospitals
Training Cohort
June 2012 – December 2014
In Paul Brousse Hosp.
Validation Cohort
June 2012 – December 2014
In Beaujon, Lille, Amiens Hosp.
565 Patients 777 Patients
519 Patients 466 Patients
Dosage of Art. LCT routinely at
the end of sugery (92%)
Dosage of Art. LCT according
to surgical complexity (60%)
519 Patients in the Training Cohort
Patients
Age (yr), median (IQR) 62 (18-87)
Gender, male 298 (57%)
BMI (kg/m²), mean ± DS 25.1 ± 4.8
Diabetes 100 (19%)
Cirrhosis 62 (12%)
Preoperative Portal Vein Occlusion 67 (13%)
Major Hepatectomy 236 (45.5%)
Laparoscopy 59 (12%)
Synchronous Major Procedure 81 (16%)
Inflow Occlusion 348 (67%)
Blood Loss > 500 cc 176 (34%)
Diagnosis
Metastatic disease 259 (50%)
Primary malignancy 199 (38%)
Benign and Living Donor 51 (10%)
Parasitosis 10 (2%)
Postoperative Outcome in the 2 cohorts
Training cohort
n = 519
Validation cohort
n = 466
P value
Grade of Clavien N(%) N(%)
0.0001
Grade 0 212 (40.8) 121 (30.0)
Grade I 36 (6.9) 41 (8.8)
Grade II 164 (31.6) 164 (35.2)
Grade III 88 (16.9) 69 (14.8)
Grade IV 9 (1.7) 41 (8.8)
Grade V 10 (1.9) 30 (6.4)
CCI , median (95%CI) 20.92 (18.91-22.93) 24.24 (22.42-26.06) <0.0001
CCI > 3rd Quartile 124 (23.9) 192 (41.2) 0.0001
3 steps to evaluate LCT-EOS prognostic impact
1. Building models of outcome in the training cohort
- LCT-EOS cut-off was determined by ROC-curves for the 3 endpoints
(High CCI, Mortality, Severe Morb)
- Uni- and Multivariate analyses of pre- and intraoperative factors,
including LCT-EOS, were performed for the 3 endpoints.
- AUROC of each model (which included or not LCT-EOS) were
compared to evaluate the additive value of LCT-EOS
2. Testing the models in the validation cohort (Real Life)
– AUROC of each model with / without LCT-OES
– Calibration : Prediction vs Observation ?
3. Calculate Se, Sp, Accuracy of models in the entire cohort
Firt Step : Building Models
Training Cohort : LCT-EOS cut-offs
End Point LCT-EOS cut-off AUROC
High CCI (>3rd quartile) 3.0 mmol/L 0.86 (95%CI 0.82 – 0.89)
90-day Mortality 3.0 mmol/L 0.87 (95%CI 0.83 – 0.91)
90-day Severe Morbidity 2.8 mmol/L 0.76 (95%CI 0.72 – 0.80)
High CCI > 3rd Q.
Mortality.
Severe Morbidity
2012-2014 : 519 Patients with
systematic dosage of Lactate
at the end of surgery
Variables Hazard ratio 95% CI
For high CCI (> 3rd quartile)
Major hepatectomy 2.0 1.1 - 4.6
Associated procedure 3.6 1.3 – 10
Transection > 90 min 1.8 1.0 - 3.4
Blood Loss > 500 cc 2.3 1.2 - 4.4
LCT-EOS > 3 mmol/L 2.2 1.1 - 4.2
For 90-day Mortality
Diabetes 7.34 2.1 – 25
Cirrhosis 4.34 1.9 – 28
Associated procedure 4.31 1.5 – 28
Length of Surgery > 300 min 2.6 1.1 - 5.4
LCT-EOS > 3 mmol/L 3.4 2.5 - 5.2
For 90-day Severe Morbidity
BMI > 28 2.5 1.2 – 5.2
Associated procedure 2.9 1.4 – 6.2
Ischemia duration > 30 min 2.2 1.2 – 4.2
Transection > 90 min 1.9 1.0 – 3.4
Blodd Loss > 500 cc 2.7 1.4 – 5.1
LCT – EOS > 2.8 mmol/L 2.0 1.1-3.9
Predictive Models for the 3 endpoints
0.75 (0.68-0.82)
0.77 (0.71-0.83)
0.69 (0.64-0.73)
0.74 (0.70-0.78)
0.68 (0.65-0.71)
0.72 (0.65-0.71)
Second Step : Validate Models in
the « real-life » Cohort…
Impact of LCT-EOS in validation cohort
The role of LCT-EOS was more important for predicting High-CCI
and Mortality than severe morbidity
0.73 (0.70-0.76)
0.85 (0.78-0.92)
0.69 (0.65-0.73)
0.72 (0.69-0.75)
0.71 (0.68-0.74)
0.76 (0.68-0.74)
High CCI Mortality Severe Morb.
Model Calibration in the Validation cohort
predicted (%) real (%) predicted (%) real (%) predicted (%) real (%)
0 17 17,1 1,08 1,25 20,6 20,8
1 17,95 18,1 2,5 2,09 21,5 21,5
2 18,74 19,5 3,7 3,05 22,3 22,9
3 19,53 20,3 5,16 4,22 23,15 24,5
4 20,32 20,8 6,36 5,06 24,75 25,8
5 21,26 22,4 7,78 6,4 26,5 28,3
High CCI score 90-day mortality Severe morbidity
N. of risk factors
Result of model (Prediction) VS Real Outcome in Validation cohort according to the N. of risk factors
High CCI Mortality Severe Morb.
Third Step : Use all patients to
calculated Se, Sp and Accuracy
End point
Models
without LCT
Models
with LCT
Increased
Accuracy with
LCT
High CCI
Score
DOR 4.69 5.46
Sensitivity 71% 74% 16%
Specificity 66% 66%
Mortality
DOR 2.35 3.16
Sensitivity 69% 74% 34%
Specificity 51% 52%
Severe
Morbidity
DOR 2.55 2.99
Sensitivity 71% 74% 17%
Specificity 65% 65%
“Diagnostic accuracy is defined as the proportion of all tests that give a correct
result (Scott et al. 2008)”
Objectives of the study
After an elective liver resection:
1. Is Arterial Lactate Concentration at the end
of surgery (LCT-EOS) predictive of outcome ?
2. If yes, is there pre- or intraoperative
predictors of an increase in LCT-EOS ?
Variables Hazard ratio 95% CI
Diabetes 2.2 1.1 - 4.6
Major Hepatectomy 3.7 2.1 – 6.5
Repeat Hepatectomy 2.7 1.2 – 6.0
Synchronous Major Procedure 2.4 1.1 - 5.0
Inflow occlusion 2.0 1.0 – 3.8
Transfusion 2.3 1.1 - 4.5
Pre- and Intraoperative factors
predictive of LCT-EOS > 3 mmol/L
Results of Multivariate analyis in the Training Cohort
Conclusions
• This multicentric study including a training cohort of 519
patients and validation cohort of 466 patients over a 24
months with a prospective outcome evaluation period
demonstrated that
Arterial Lactate concentration at the End of Surgery is an
early, convenient and reliable endpoint for postop. outcomes
LCT-EOS must be used to explore the impact of pre- and/or
intraoperatives factors on the outcome of liver resection
• LCT-EOS > 3 mmol/L is a surrogate endpoint that
determine the need for critical care after hepatectomy

Arterial Lactate Concentration is a major pronostic factor after elective surgery (ESA Meeting 2015à

  • 1.
    End-of-Surgery Serum Lactateconcentration as a major predictor of postoperative outcome. A multicentre prospective study. Eric Vibert, Emmanuel Boleslawski, Cyril Cosse, Rene Adam, Denis Castaing, Daniel Cherqui, Salima Naili, Jean-Marc Régimbeau, Antonio Sa Cunha, Stéphanie Truant, Maher Fleyfel, François René Pruvot, Catherine Paugam, Olivier Farges ACHBT Hepatectomy Registry
  • 2.
    PST-AST = 450UI/L PST-ALT = 420 UI/L AUROC = 0.61 AUROC = 0.57 French Multicentric Study : 651 pts in 9 HPB Centers Postoperative Peak of Transaminase is not a relevant endpoint to predict outcome 2014
  • 3.
    Objectives of thestudy After an elective liver resection: 1. Is Arterial Lactate Concentration at the end of surgery (LCT-EOS) predictive of outcome ? 2. If yes, is there pre- or intraoperative predictors of an increase in LCT-EOS ?
  • 4.
    Study endpoints • Endof surgery arterial Lactate Concentration – Between 1 and 4 hours after end of liver transection • Postoperative outcome (90-day outcome) – High Clinical Comprehensive Index (> 3rd quartile) – Mortality – Severe morbidity (Clavien’s grade III-V)
  • 5.
  • 6.
    1342 Consecutive Hepatectomiesin 4 Hospitals Training Cohort June 2012 – December 2014 In Paul Brousse Hosp. Validation Cohort June 2012 – December 2014 In Beaujon, Lille, Amiens Hosp. 565 Patients 777 Patients 519 Patients 466 Patients Dosage of Art. LCT routinely at the end of sugery (92%) Dosage of Art. LCT according to surgical complexity (60%)
  • 7.
    519 Patients inthe Training Cohort Patients Age (yr), median (IQR) 62 (18-87) Gender, male 298 (57%) BMI (kg/m²), mean ± DS 25.1 ± 4.8 Diabetes 100 (19%) Cirrhosis 62 (12%) Preoperative Portal Vein Occlusion 67 (13%) Major Hepatectomy 236 (45.5%) Laparoscopy 59 (12%) Synchronous Major Procedure 81 (16%) Inflow Occlusion 348 (67%) Blood Loss > 500 cc 176 (34%) Diagnosis Metastatic disease 259 (50%) Primary malignancy 199 (38%) Benign and Living Donor 51 (10%) Parasitosis 10 (2%)
  • 8.
    Postoperative Outcome inthe 2 cohorts Training cohort n = 519 Validation cohort n = 466 P value Grade of Clavien N(%) N(%) 0.0001 Grade 0 212 (40.8) 121 (30.0) Grade I 36 (6.9) 41 (8.8) Grade II 164 (31.6) 164 (35.2) Grade III 88 (16.9) 69 (14.8) Grade IV 9 (1.7) 41 (8.8) Grade V 10 (1.9) 30 (6.4) CCI , median (95%CI) 20.92 (18.91-22.93) 24.24 (22.42-26.06) <0.0001 CCI > 3rd Quartile 124 (23.9) 192 (41.2) 0.0001
  • 9.
    3 steps toevaluate LCT-EOS prognostic impact 1. Building models of outcome in the training cohort - LCT-EOS cut-off was determined by ROC-curves for the 3 endpoints (High CCI, Mortality, Severe Morb) - Uni- and Multivariate analyses of pre- and intraoperative factors, including LCT-EOS, were performed for the 3 endpoints. - AUROC of each model (which included or not LCT-EOS) were compared to evaluate the additive value of LCT-EOS 2. Testing the models in the validation cohort (Real Life) – AUROC of each model with / without LCT-OES – Calibration : Prediction vs Observation ? 3. Calculate Se, Sp, Accuracy of models in the entire cohort
  • 10.
    Firt Step :Building Models
  • 11.
    Training Cohort :LCT-EOS cut-offs End Point LCT-EOS cut-off AUROC High CCI (>3rd quartile) 3.0 mmol/L 0.86 (95%CI 0.82 – 0.89) 90-day Mortality 3.0 mmol/L 0.87 (95%CI 0.83 – 0.91) 90-day Severe Morbidity 2.8 mmol/L 0.76 (95%CI 0.72 – 0.80) High CCI > 3rd Q. Mortality. Severe Morbidity 2012-2014 : 519 Patients with systematic dosage of Lactate at the end of surgery
  • 12.
    Variables Hazard ratio95% CI For high CCI (> 3rd quartile) Major hepatectomy 2.0 1.1 - 4.6 Associated procedure 3.6 1.3 – 10 Transection > 90 min 1.8 1.0 - 3.4 Blood Loss > 500 cc 2.3 1.2 - 4.4 LCT-EOS > 3 mmol/L 2.2 1.1 - 4.2 For 90-day Mortality Diabetes 7.34 2.1 – 25 Cirrhosis 4.34 1.9 – 28 Associated procedure 4.31 1.5 – 28 Length of Surgery > 300 min 2.6 1.1 - 5.4 LCT-EOS > 3 mmol/L 3.4 2.5 - 5.2 For 90-day Severe Morbidity BMI > 28 2.5 1.2 – 5.2 Associated procedure 2.9 1.4 – 6.2 Ischemia duration > 30 min 2.2 1.2 – 4.2 Transection > 90 min 1.9 1.0 – 3.4 Blodd Loss > 500 cc 2.7 1.4 – 5.1 LCT – EOS > 2.8 mmol/L 2.0 1.1-3.9
  • 13.
    Predictive Models forthe 3 endpoints 0.75 (0.68-0.82) 0.77 (0.71-0.83) 0.69 (0.64-0.73) 0.74 (0.70-0.78) 0.68 (0.65-0.71) 0.72 (0.65-0.71)
  • 14.
    Second Step :Validate Models in the « real-life » Cohort…
  • 15.
    Impact of LCT-EOSin validation cohort The role of LCT-EOS was more important for predicting High-CCI and Mortality than severe morbidity 0.73 (0.70-0.76) 0.85 (0.78-0.92) 0.69 (0.65-0.73) 0.72 (0.69-0.75) 0.71 (0.68-0.74) 0.76 (0.68-0.74) High CCI Mortality Severe Morb.
  • 16.
    Model Calibration inthe Validation cohort predicted (%) real (%) predicted (%) real (%) predicted (%) real (%) 0 17 17,1 1,08 1,25 20,6 20,8 1 17,95 18,1 2,5 2,09 21,5 21,5 2 18,74 19,5 3,7 3,05 22,3 22,9 3 19,53 20,3 5,16 4,22 23,15 24,5 4 20,32 20,8 6,36 5,06 24,75 25,8 5 21,26 22,4 7,78 6,4 26,5 28,3 High CCI score 90-day mortality Severe morbidity N. of risk factors Result of model (Prediction) VS Real Outcome in Validation cohort according to the N. of risk factors High CCI Mortality Severe Morb.
  • 17.
    Third Step :Use all patients to calculated Se, Sp and Accuracy
  • 18.
    End point Models without LCT Models withLCT Increased Accuracy with LCT High CCI Score DOR 4.69 5.46 Sensitivity 71% 74% 16% Specificity 66% 66% Mortality DOR 2.35 3.16 Sensitivity 69% 74% 34% Specificity 51% 52% Severe Morbidity DOR 2.55 2.99 Sensitivity 71% 74% 17% Specificity 65% 65% “Diagnostic accuracy is defined as the proportion of all tests that give a correct result (Scott et al. 2008)”
  • 19.
    Objectives of thestudy After an elective liver resection: 1. Is Arterial Lactate Concentration at the end of surgery (LCT-EOS) predictive of outcome ? 2. If yes, is there pre- or intraoperative predictors of an increase in LCT-EOS ?
  • 20.
    Variables Hazard ratio95% CI Diabetes 2.2 1.1 - 4.6 Major Hepatectomy 3.7 2.1 – 6.5 Repeat Hepatectomy 2.7 1.2 – 6.0 Synchronous Major Procedure 2.4 1.1 - 5.0 Inflow occlusion 2.0 1.0 – 3.8 Transfusion 2.3 1.1 - 4.5 Pre- and Intraoperative factors predictive of LCT-EOS > 3 mmol/L Results of Multivariate analyis in the Training Cohort
  • 21.
    Conclusions • This multicentricstudy including a training cohort of 519 patients and validation cohort of 466 patients over a 24 months with a prospective outcome evaluation period demonstrated that Arterial Lactate concentration at the End of Surgery is an early, convenient and reliable endpoint for postop. outcomes LCT-EOS must be used to explore the impact of pre- and/or intraoperatives factors on the outcome of liver resection • LCT-EOS > 3 mmol/L is a surrogate endpoint that determine the need for critical care after hepatectomy