Morphine pharmacokinetics and pharmacodynamics in preterm and term neonates: secondary results from the NEOPAIN trial K.J.S. Anand, B.J. Anderson, N.H.G.

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Presentation transcript:

Morphine pharmacokinetics and pharmacodynamics in preterm and term neonates: secondary results from the NEOPAIN trial K.J.S. Anand, B.J. Anderson, N.H.G. Holford, R.W. Hall, T. Young, B. Shephard, N.S. Desai, B.A. Barton British Journal of Anaesthesia Volume 101, Issue 5, Pages 680-689 (November 2008) DOI: 10.1093/bja/aen248 Copyright © 2008 British Journal of Anaesthesia Terms and Conditions

Fig 1 Quality of fit of pharmacokinetic data. (a) Displays individual Bayesian concentration predictions based on values of the parameters for the specific individual. (b) Displays the predicted typical (population) concentrations, which are based on population parameters and covariate information. (c) The y-axis displays the ratio of measured concentrations to those predicted from NONMEM post hoc, step-based on values of parameters for the specific individual. (d) The y-axis displays the ratio of measured concentrations to those predicted from PK analysis. (e) The weighted residuals for each subject in the two populations with values for each subject joined by vertical lines. British Journal of Anaesthesia 2008 101, 680-689DOI: (10.1093/bja/aen248) Copyright © 2008 British Journal of Anaesthesia Terms and Conditions

Fig 2 (a) Individual predicted clearances (CL) for morphine, standardized to a 70 kg person, from the NONMEM post hoc step, are plotted against PMA. The dashed line represents the non-linear relation between clearance and age. (b) Magnification of (a) to reveal the shift to the right for maturation of clearance in preterm neonates (solid line). British Journal of Anaesthesia 2008 101, 680-689DOI: (10.1093/bja/aen248) Copyright © 2008 British Journal of Anaesthesia Terms and Conditions

Fig 3 (a) Individual predicted volumes of distribution (V) for morphine, standardized to a 70 kg person, from the NONMEM post hoc step, are plotted against PMA. The dashed line represents the non-linear relation between clearance and age. (b) Magnification of (a) to reveal increased V in ventilator-dependent preterm neonates with no relationship to PMA (solid line). British Journal of Anaesthesia 2008 101, 680-689DOI: (10.1093/bja/aen248) Copyright © 2008 British Journal of Anaesthesia Terms and Conditions

Fig 4 The relationship between volumes of distribution (V) for morphine and PNA reveals increased V in ventilator-dependent preterm neonates with no relationship to PNA (solid line). British Journal of Anaesthesia 2008 101, 680-689DOI: (10.1093/bja/aen248) Copyright © 2008 British Journal of Anaesthesia Terms and Conditions

Fig 5 The lack of relationship between morphine concentrations and heart rate changes occurring with ETT suctioning. British Journal of Anaesthesia 2008 101, 680-689DOI: (10.1093/bja/aen248) Copyright © 2008 British Journal of Anaesthesia Terms and Conditions

Fig 6 The lack of relationship between morphine concentrations and PIPP scores associated with ETT suctioning. British Journal of Anaesthesia 2008 101, 680-689DOI: (10.1093/bja/aen248) Copyright © 2008 British Journal of Anaesthesia Terms and Conditions