PMID- 34883383
OWN - NLM
STAT- MEDLINE
DCOM- 20220127
LR  - 20220127
IS  - 1872-7565 (Electronic)
IS  - 0169-2607 (Linking)
VI  - 214
DP  - 2022 Feb
TI  - Robust K-PD model for activated clotting time prediction and UFH dose 
      individualisation during cardiopulmonary bypass.
PG  - 106553
LID - S0169-2607(21)00627-1 [pii]
LID - 10.1016/j.cmpb.2021.106553 [doi]
AB  - BACKGROUND AND OBJECTIVE: Activated clotting time (ACT) is a point-of-care test 
      used to monitor the effect of unfractionated heparin (UFH) during cardiopulmonary 
      bypass (CPB). This test sometimes returns aberrant values, which can lead to the 
      administration of an inappropriate dosing regimen. The development of a 
      population-robust K-PD model of UFH could allow the individualisation and 
      automation of UFH therapy during CPB. METHODS: We conducted a prospective 
      observational study to collect ACT measurements from patients undergoing surgery 
      using CPB. The ACT data were split into a development and validation cohort. The 
      development cohort was used to estimate a standard and robust population K-PD 
      model characterised by a residual error following a normal distribution and 
      student's t-distribution. The ACT prediction performance using Bayesian estimates 
      of individual K-PD parameters was evaluated by comparing predicted versus 
      observed ACTs. Using estimates of the robust K-PD model, a Bayesian 
      individualisation strategy to automate UFH administration was proposed and 
      evaluated using Monte Carlo simulations. RESULTS: A total of 295 patients were 
      included in the study, and 1561 ACTs were collected. In patients without outlier 
      values, Bayesian estimates (based on four ACT measurements) from both standard 
      and robust K-PD models had similar performances, with a median prediction bias 
      close to 0 s. In patients with outlier measurements, the use of the robust K-PD 
      model greatly improved the prediction bias and root-mean-square error (RMSE), 
      with a mean prediction bias of 3.25 s, IQR = [-19.9; 46.03] versus -86 s 
      IQR = [-135.7; -63.8] for the standard model. Monte Carlo simulations showed that 
      the robust Bayesian individualisation strategy allowed the ACT to be maintained 
      above the target using only two to three ACT measurements. CONCLUSIONS: The use 
      of a robust K-PD model reduced prediction bias and RMSE in patients with outlier 
      ACT measurements. The Bayesian individualisation strategy using robust estimates 
      of individual parameters may help automate UFH dosing regimens. Proper clinical 
      validation is warranted before its use in daily clinical practice.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Chaux, Robin
AU  - Chaux R
AD  - U1059, Dysfonction Vasculaire et Hemostase, INSERM, Saint-Etienne, France; Unite 
      de Recherche Clinique, Innovation, Pharmacologie, Hopital Nord, CHU de 
      Saint-Etienne, Saint-Etienne Cedex 2, Saint-Etienne F-42055, France.
FAU - Lanoiselee, Julien
AU  - Lanoiselee J
AD  - U1059, Dysfonction Vasculaire et Hemostase, INSERM, Saint-Etienne, France; 
      Departement d'Anesthesie-Reanimation, Hopital Nord, CHU de Saint-Etienne, 
      Saint-Etienne F-42055, France.
FAU - Magand, Clement
AU  - Magand C
AD  - Departement d'Anesthesie-Reanimation, Hopital Nord, CHU de Saint-Etienne, 
      Saint-Etienne F-42055, France.
FAU - Zufferey, Paul
AU  - Zufferey P
AD  - U1059, Dysfonction Vasculaire et Hemostase, INSERM, Saint-Etienne, France; 
      Departement d'Anesthesie-Reanimation, Hopital Nord, CHU de Saint-Etienne, 
      Saint-Etienne F-42055, France.
FAU - Delavenne, Xavier
AU  - Delavenne X
AD  - U1059, Dysfonction Vasculaire et Hemostase, INSERM, Saint-Etienne, France.
FAU - Ollier, Edouard
AU  - Ollier E
AD  - U1059, Dysfonction Vasculaire et Hemostase, INSERM, Saint-Etienne, France; Unite 
      de Recherche Clinique, Innovation, Pharmacologie, Hopital Nord, CHU de 
      Saint-Etienne, Saint-Etienne Cedex 2, Saint-Etienne F-42055, France. Electronic 
      address: edouard.ollier@univ-st-etienne.fr.
LA  - eng
PT  - Journal Article
PT  - Observational Study
DEP - 20211127
PL  - Ireland
TA  - Comput Methods Programs Biomed
JT  - Computer methods and programs in biomedicine
JID - 8506513
RN  - 0 (Anticoagulants)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Anticoagulants
MH  - Bayes Theorem
MH  - *Cardiopulmonary Bypass
MH  - *Heparin
MH  - Humans
MH  - Whole Blood Coagulation Time
COIS- Declaration of Competing Interest There are no competing interests to declare.
EDAT- 2021/12/10 06:00
MHDA- 2022/01/28 06:00
CRDT- 2021/12/09 20:22
PHST- 2021/06/15 00:00 [received]
PHST- 2021/11/17 00:00 [revised]
PHST- 2021/11/24 00:00 [accepted]
PHST- 2021/12/10 06:00 [pubmed]
PHST- 2022/01/28 06:00 [medline]
PHST- 2021/12/09 20:22 [entrez]
AID - S0169-2607(21)00627-1 [pii]
AID - 10.1016/j.cmpb.2021.106553 [doi]
PST - ppublish
SO  - Comput Methods Programs Biomed. 2022 Feb;214:106553. doi: 
      10.1016/j.cmpb.2021.106553. Epub 2021 Nov 27.