Norepinephrine kinetics and dynamics in septic shock and trauma patients

• Published in: British journal of anaesthesia : BJA Vol. 95; no. 6; pp. 782 - 788
• Main Authors: Beloeil, H., Mazoit, J.-X., Benhamou, D., Duranteau, J.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.12.2005; Oxford University Press; Oxford Publishing Limited (England)
• Subjects: Adult; Aged; Aged, 80 and over; Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Body Weight; Chromatography, High Pressure Liquid; complications; complications, septic shock; Critical Care - methods; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Male; Medical sciences; Middle Aged; Models, Biological; norepinephrine; Norepinephrine - administration & dosage; Norepinephrine - blood; pharmacokinetics; septic shock; Severity of Illness Index; Sex Factors; Shock, Septic - blood; sympathetic nervous system; sympathetic nervous system, norepinephrine; trauma patients; Vasoconstrictor Agents - administration & dosage; Vasoconstrictor Agents - blood; Wounds and Injuries - blood; pharmacokinetics; complications, septic shock; trauma patients; sympathetic nervous system, norepinephrine; Shock; American; Multicenter study; Body weight; Variability; HPLC chromatography; septic shock; pharmacokinetics; sympathetic nervous system; Anesthesia; Complication; Arterial pressure; Blood pressure; Human; Dopamine; complications; Catecholamine; Sympathetic nervous system; Trauma; Infection; Arterial blood; Distribution volume; Neurotransmitter; Informed consent; Norepinephrine; Pharmacokinetics; norepinephrine; trauma patients
• ISSN: 0007-0912; 1471-6771
• DOI: 10.1093/bja/aei259

There is considerable variability in the inter-patient response to norepinephrine. Pharmacokinetic studies of dopamine infusion in volunteers and in patients have also shown large variability. The purpose of this study was to define the pharmacokinetics of norepinephrine in septic shock and trauma patients. After Ethical Committee approval and written informed family consent, 12 patients with septic shock and 11 trauma patients requiring norepinephrine infusion were studied. Norepinephrine dose was increased in three successive steps of 0.1 mg kg−1 min−1 at 15-min intervals (20% maximum allowed increase in arterial pressure). Arterial blood was sampled before and at 0.5, 13, and 15 min after each infusion rate change and 30 s, 1, 2, 5, 10, and 15 min after return to baseline dosing. Norepinephrine was assayed by HPLC. The pharmacokinetics were modelled using NONMEM (one-compartment model). The effects of group, body weight (BW), gender and SAPS II (Simplified Acute Physiology Score II) [Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. J Am Med Assoc 1993; 270: 2957–63] patients score on clearance (CL) and volume of distribution (V) were tested. Group, gender, and BW did not influence CL or V. CL was negatively related to SAPS II. CL and T1/2 varied from 3 litre min−1 and 2 min, respectively, when SAPS II=20 to 0.9 litre min−1 and 6.8 min when SAPS II=60. In trauma patients and in septic shock patients, norepinephrine clearance is negatively related to SAPS II.