The hemodynamic response to constant dobutamine infusion

Yogev, Dotan; Basheer, Maamoun; Perlman, Amichai; Blotnick, Simcha; Caraco, Yoseph; Muszkat, Mordechai

doi:10.1097/fpc.0000000000000338

Cited by 3 publications

(3 citation statements)

References 30 publications

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“…In healthy individuals, HR and renin responses to dobutamine in incremental doses were more than 3‐fold greater among β1‐AR Arg389 compared with Gly389 homozygotes 23 . In the same study population, no significant difference was found in haemodynamic response to dobutamine constant infusion between β1‐AR 389 genotypes 24 . The difference in the effect on chronotropy in neonates, compared to adults, may be explained by developmental physiology as well as differences in β‐AR signalling in the immature heart.…”

Section: Discussionmentioning

confidence: 77%

“…23 In the same study population, no significant difference was found in haemodynamic response to dobutamine constant infusion between β1-AR 389 genotypes. 24 The difference in the effect on chronotropy in neonates, compared to adults, may be explained by developmental physiology as well as differences in β-AR signalling in the immature heart. It has been discussed before in the field of pharmacokinetics that true genotype-phenotype relationship may not be fully apparent until the gene is fully expressed.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacogenetics may explain part of the interindividual variability of dobutamine pharmacodynamics in neonates

Hallik

Soeorg

Kahre

et al. 2022

Brit J Clinical Pharma

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To determine whether the known single nucleotide polymorphisms in adrenoreceptor associated genes affect the haemodynamic response to dobutamine in critically ill neonates. Methods: Alleles in the known genetic single nucleotide polymorphisms in β1and β2-adrenoceptor (AR) genes and Gs protein α-subunit gene (GNAS) possibly affecting inotropic effect were identified in patients of neonatal dobutamine pharmacokineticpharmacodynamic study. Linear mixed-effect models were used to describe the effect of genetic polymorphisms to heart rate (HR), left ventricular output (LVO) and right ventricular output (RVO) during dobutamine treatment. Results: Twenty-six neonates (5 term, 21 preterm) were studied. Dobutamine plasma concentration and exposure time respective HR (adjusted to gestational age) is dependent on β1-AR Arg389Gly polymorphism so that in G/G (Gly) homozygotes and G/C heterozygotes dobutamine increases HR more than in C/C (Arg) homozygotes, with parameter estimate (95% CI) of 38.3 (15.8-60.7) beats/min per AUC of 100 μg L À1 h, P = .0008. LVO (adjusted to antenatal glucocorticoid administration

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Pharmacogenetics may explain part of the interindividual variability of dobutamine pharmacodynamics in neonates

Hallik

Soeorg

Kahre

et al. 2022

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…23 In the same study population, no significant difference was found in haemodynamic response to dobutamine constant infusion between β1-AR 389 genotypes. 24 The difference in the effect on chronotropy in neonates, compared to adults, may be explained by developmental physiology as well as differences in β-AR signalling in the immature heart. As in neonates, especially in the premature and critically ill with cardiac failure, HR is already high before treatment, the lower HR in response to dobutamine treatment in Arg389 β1-AR subjects may refer to better response to inotropic treatment, with sequence variant specific difference in the change in contractility not captured by our measurement methods.…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenetics may explain part of the interindividual variability of dobutamine pharmacodynamics in neonates

Hallik

Soeorg

Kahre

et al. 2022

Preprint

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Aim: To determine whether the known single nucleotide polymorphisms in adrenoreceptor associated genes affect the hemodynamic response to dobutamine in critically ill neonates. Methods: Alleles in the known genetic single nucleotide polymorphisms in β1 and β2 adrenoceptor (AR) genes and Gs protein α-subunit gene (GNAS) possibly affecting inotropic effect were identified in patients of neonatal dobutamine pharmacokinetic-pharmacodynamic study. Linear mixed-effect models were used to describe the effect of genetic polymorphisms to heart rate (HR), left ventricular output (LVO) and right ventricular output (RVO) during dobutamine treatment. Results: 26 neonates (5 term, 21 preterm) were studied. Dobutamine plasma concentration and exposure time respective HR (adjusted to gestational age) is dependent on β1-AR Arg389Gly polymorphism so that in G/G (Gly) homozygotes and G/C heterozygotes dobutamine increases HR more than in C/C (Arg) homozygotes, with parameter estimate (95% CI) of 38.3 (15.8 – 60.7) bpm per AUC of 100 mg·h, p=0.0005. LVO (adjusted to antenatal glucocorticoid administration and illness severity) and RVO (adjusted to gestational age and illness severity) is dependent on GNAS c.393C>T polymorphism so that in T/T homozygotes and C/T heterozygotes but not in C/C homozygotes LVO and RVO increase with dobutamine treatment, 24.5 (6.2 – 42.9) mL kg-1 min-1 per AUC of 100 mg·h, p=0.0116 and 33.2 (12.1 – 54.3) mL kg-1 min-1 per AUC of 100 mg·h, p=0.0025, respectively. Conclusion: In critically ill neonates, β1-AR Arg389Gly and GNAS c.393C>T polymorphisms may play a role in the haemodynamic response to dobutamine during the first hours and days of life.

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