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Impact of the C2/C6 ratio of high-molecular-weight hydroxyethyl starch on pharmacokinetics and blood coagulation in pigs.
Anesthesiology. 2007 Sep; 107(3):442-51.A

Abstract

BACKGROUND

High-molecular-weight, low-substituted hydroxyethyl starch (HES) may not affect blood coagulation more than low-molecular-weight, low-substituted HES. The authors assessed in vivo the effect of a lowered C2/C6 ratio on pharmacokinetic characteristics and the impact on blood coagulation of high-molecular-weight, low-substituted HES.

METHODS

A prospective, randomized, parallel study in 30 pigs compared HES 650/0.42/2.8 with HES 650/0.42/5.6. Before, during, and after infusion of 30 ml/kg body weight HES, blood samples were collected over 630 min to measure HES concentrations and plasmatic coagulation and to assess blood coagulation in whole blood by Thrombelastography (TEG; Haemoscope Corporation, Niles, IL). Pharmacokinetic parameters were estimated using a two-compartment model.

RESULTS

The elimination constant was 0.009 +/- 0.001 min(-1) for HES 650/0.42/2.8 and 0.007 +/- 0.001 min(-1) for HES 650/0.42/5.6 (P < 0.001); the area under the plasma concentration-time curve was 1,374 +/- 340 min x g/l for HES 650/0.42/2.8 and 1,697 +/- 411 min x g/l for HES 650/0.42/5.6 (P = 0.026). The measured plasma HES concentrations were not different between HES 650/0.42/2.8 and HES 650/0.42/5.6. Both HES solutions equally affected blood coagulation: Thrombelastographic coagulation index decreased similarly at the end of infusion of HES 650/0.42/2.8 and at the end of infusion of HES 650/0.42/5.6 (P = 0.293). Also, activated partial thromboplastin and prothrombin times increased similarly for HES 650/0.42/2.8 and HES 650/0.42/5.6 (P = 0.831).

CONCLUSION

Reducing the C2/C6 ratio in high-molecular, low-substituted HES solutions results in a slightly faster HES elimination. However, the blood coagulation compromising effect was unaffected.

Authors+Show Affiliations

Department of Anesthesiology, University Hospital Lausanne, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17721247

Citation

Schramm, Sebastian, et al. "Impact of the C2/C6 Ratio of High-molecular-weight Hydroxyethyl Starch On Pharmacokinetics and Blood Coagulation in Pigs." Anesthesiology, vol. 107, no. 3, 2007, pp. 442-51.
Schramm S, Thyes C, Frascarolo P, et al. Impact of the C2/C6 ratio of high-molecular-weight hydroxyethyl starch on pharmacokinetics and blood coagulation in pigs. Anesthesiology. 2007;107(3):442-51.
Schramm, S., Thyes, C., Frascarolo, P., Buclin, T., Burki, M., Fisch, A., Burmeister, M. A., Asmis, L., & Spahn, D. R. (2007). Impact of the C2/C6 ratio of high-molecular-weight hydroxyethyl starch on pharmacokinetics and blood coagulation in pigs. Anesthesiology, 107(3), 442-51.
Schramm S, et al. Impact of the C2/C6 Ratio of High-molecular-weight Hydroxyethyl Starch On Pharmacokinetics and Blood Coagulation in Pigs. Anesthesiology. 2007;107(3):442-51. PubMed PMID: 17721247.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of the C2/C6 ratio of high-molecular-weight hydroxyethyl starch on pharmacokinetics and blood coagulation in pigs. AU - Schramm,Sebastian, AU - Thyes,Caroline, AU - Frascarolo,Philippe, AU - Buclin,Thierry, AU - Burki,Marco, AU - Fisch,Andreas, AU - Burmeister,Marc-Alexander, AU - Asmis,Lars, AU - Spahn,Donat R, PY - 2007/8/28/pubmed PY - 2007/10/27/medline PY - 2007/8/28/entrez SP - 442 EP - 51 JF - Anesthesiology JO - Anesthesiology VL - 107 IS - 3 N2 - BACKGROUND: High-molecular-weight, low-substituted hydroxyethyl starch (HES) may not affect blood coagulation more than low-molecular-weight, low-substituted HES. The authors assessed in vivo the effect of a lowered C2/C6 ratio on pharmacokinetic characteristics and the impact on blood coagulation of high-molecular-weight, low-substituted HES. METHODS: A prospective, randomized, parallel study in 30 pigs compared HES 650/0.42/2.8 with HES 650/0.42/5.6. Before, during, and after infusion of 30 ml/kg body weight HES, blood samples were collected over 630 min to measure HES concentrations and plasmatic coagulation and to assess blood coagulation in whole blood by Thrombelastography (TEG; Haemoscope Corporation, Niles, IL). Pharmacokinetic parameters were estimated using a two-compartment model. RESULTS: The elimination constant was 0.009 +/- 0.001 min(-1) for HES 650/0.42/2.8 and 0.007 +/- 0.001 min(-1) for HES 650/0.42/5.6 (P < 0.001); the area under the plasma concentration-time curve was 1,374 +/- 340 min x g/l for HES 650/0.42/2.8 and 1,697 +/- 411 min x g/l for HES 650/0.42/5.6 (P = 0.026). The measured plasma HES concentrations were not different between HES 650/0.42/2.8 and HES 650/0.42/5.6. Both HES solutions equally affected blood coagulation: Thrombelastographic coagulation index decreased similarly at the end of infusion of HES 650/0.42/2.8 and at the end of infusion of HES 650/0.42/5.6 (P = 0.293). Also, activated partial thromboplastin and prothrombin times increased similarly for HES 650/0.42/2.8 and HES 650/0.42/5.6 (P = 0.831). CONCLUSION: Reducing the C2/C6 ratio in high-molecular, low-substituted HES solutions results in a slightly faster HES elimination. However, the blood coagulation compromising effect was unaffected. SN - 0003-3022 UR - https://www.unboundmedicine.com/medline/citation/17721247/Impact_of_the_C2/C6_ratio_of_high_molecular_weight_hydroxyethyl_starch_on_pharmacokinetics_and_blood_coagulation_in_pigs_ L2 - https://pubs.asahq.org/anesthesiology/article-lookup/doi/10.1097/01.anes.0000278879.76613.1c DB - PRIME DP - Unbound Medicine ER -