Use of the activated coagulation time and heparin dose-response curve for the determination of protamine dosage in vascular surgery

Abstract Sequential design methods for binary response variables exist for determination of the concentration or dose associated with the 50% point along the dose–response curve; the up-and-down method of Dixon and Mood is now commonly used in anesthesia research. There have been important developments in statistical methods that (1) allow the design of experiments for the measurement of the response at any point (quantile) along the dose–response curve, (2) demonstrate the risk of certain statistical methods commonly used in literature reports, (3) allow the estimation of the concentration or dose—the target dose—associated with the chosen quantile without the assumption of the symmetry of the tolerance distribution, and (4) set bounds on the probability of response at this target dose. This article details these developments, briefly surveys current use of the up-and-down method in anesthesia research, reanalyzes published reports using the up-and-down method for the study of the epidural relief of pain during labor, and discusses appropriate inferences from up-and-down method studies.

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A Screening Procedure for Substances Which Inhibit Dextran Edema in the Rat

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1958.193.2.275 ◽

1958 ◽

Vol 193 (2) ◽

pp. 275-282 ◽

Cited By ~ 20

Author(s):

Jacob C. Stucki ◽

Charles R. Thompson

Keyword(s):

Dose Response ◽

Response Curve ◽

Intraperitoneal Administration ◽

Dose Response Curve ◽

Screening Procedure ◽

Adrenergic Agents ◽

Adrenergic Drugs ◽

Before And After ◽

Quantitative Bioassay

Determination of foot volume by mercury displacement before and after the intraperitoneal administration of dextran to rats demonstrated that pronounced edema occurs one-half to three-fourths of an hour after dextran, reaches a maximum in 1 1/2 hours, and gradually subsides over the next several hours. Inhibiting substances prevent the edema entirely, reduce its severity or delay its appearance. A method was presented for screening compounds for ability to inhibit dextran edema. A dose-response curve developed for chlorpromazine suggests that the technique might also be suitable for quantitative bioassay. It was found that strongly vasoconstrictor adrenergic agents inhibited edema while adrenergic drugs with other predominating activities did not. Atropine, Dibenamine, morphine, reserpine, hydroxyzine and meprobamate were inactive. Chlorpromazine, the antihistaminics and anesthetic doses of phenobarbital were active. Cortisone and phenylbutazine were inactive but the salicylates were moderately active.

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Determination of a Dose-Response Curve for Intrathecal Sufentanil in Labor

Anesthesiology ◽

10.1097/00000542-199409001-01148 ◽

1994 ◽

Vol 81 (SUPPLEMENT) ◽

pp. A1149 ◽

Cited By ~ 2

Author(s):

T. Van Decar ◽

R. Callicot ◽

R. Jones ◽

N. Herman

Keyword(s):

Dose Response ◽

Response Curve ◽

Dose Response Curve

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A comparison of acceleromyography and mechanomyography for determination of the dose–response curve of rocuronium in children

Anaesthesia ◽

10.1111/j.1365-2044.1997.104-az0101.x ◽

1997 ◽

Vol 52 (4) ◽

pp. 345-349 ◽

Cited By ~ 20

Author(s):

A. McCluskey ◽

G. Meakin ◽

J. M. Hopkinson ◽

R. D. Baker

Keyword(s):

Dose Response ◽

Response Curve ◽

Dose Response Curve

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Adjusting Heparin Infusion Rates from the Initial Response to Activated Coagulation Time

Drug Intelligence & Clinical Pharmacy ◽

10.1177/106002808301700904 ◽

1983 ◽

Vol 17 (9) ◽

pp. 632-634 ◽

Cited By ~ 6

Author(s):

Paul G. Hattersley ◽

J. Chris Mitsuoka ◽

Robert J. Ignoffo ◽

Jeffrey H. King ◽

Nabil A. Musallam

Keyword(s):

Mathematical Model ◽

Mathematical Description ◽

Response Curve ◽

Initial Response ◽

Heparin Dose ◽

Coagulation Time ◽

Heparin Infusion ◽

The Mean ◽

Activated Coagulation Time ◽

Heparin Dosage

A mathematical description of the dose-response curve of heparin to the activated coagulation time is applied retrospectively to 20 patients treated with continuous heparin infusion. The adjusted heparin dose was compared with a calculated prediction using the theoretical mathematical model. The main actual dose was 28 U/kg/h, and the mean predicted dose was 25.8 U/kg/h. The correlation coefficient was 0.862 (p30.05). These data are used to develop a dosing adjustment chart. Special considerations prior to using the calculation or dosing adjustment chart are discussed. The use of this model may allow the clinician to determine more rapidly a therapeutic heparin dosage than previous empiric approaches.

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