Drug Res (Stuttg) 2013; 63(10): 495-500
DOI: 10.1055/s-0033-1343470
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Pharmacokinetic Assessment of Sufentanil in Cardiac Surgery

J. L. Manfio
1   Laboratory of Clinical Pharmacology and Therapeutics, Pharmacy Department, School of Pharmaceutical Sciences, University of Sao Paulo – Sao Paulo (SP), Brazil
3   Biocinese – Biopharmaceutical Studies Center – Toledo (PR), Brazil
,
L. M. Santos
2   Anesthesia Department, Heart Institute – Clinical Hospitals, Faculty of Medicine, University of Sao Paulo – Sao Paulo (SP), Brazil
,
M. J. C. Carmona
2   Anesthesia Department, Heart Institute – Clinical Hospitals, Faculty of Medicine, University of Sao Paulo – Sao Paulo (SP), Brazil
,
M. B. dos Santos
3   Biocinese – Biopharmaceutical Studies Center – Toledo (PR), Brazil
,
S. RCJ. Santos
1   Laboratory of Clinical Pharmacology and Therapeutics, Pharmacy Department, School of Pharmaceutical Sciences, University of Sao Paulo – Sao Paulo (SP), Brazil
› Author Affiliations
Further Information

Publication History

received 20 July 2012

accepted 01 March 2013

Publication Date:
18 June 2013 (online)

Abstract

Plasma monitoring and pharmacokinetic assessment are important tools used in therapeutic control. Sufentanil is responsible for the hemodynamic stabilization of patients, providing better suppression of the neuroendocrine response compared to its analogue fentanyl. This study aims to use the plasma monitoring of sufentanil in patients undergoing cardiac surgery with extracorporeal circulation (ECC, group 1) or without ECC (group 2) to assess the pharmacokinetics of the compound.

The 42 patients in this study received 0.5 μg/kg of sufentanil through bolus injection followed by a maintenance infusion of 0.5 μg/kg.h. Serial blood samples were collected during the post induction intraoperative period and during the postoperative period until 36 h after sufentanil administration. The plasma concentrations were determined by a validated method utilizing liquid chromatography coupled to mass spectrometry. The pharmacokinetic modeling was performed using a 3-compartment model fit.

The surgical patients included in the protocol were adults of both genders, with 30 patients in the ECC group and 12 in the group without ECC. The plasma concentrations obtained were significantly different between the 2 groups. During the extracorporeal circulation procedure, intense fluctuations were observed in the sufentanil plasma concentrations. Compared with the results of group 2, the ECC procedure reduced the terminal or gamma half-life from 36.35±6.37 h to 23.25±2.75 h in group 1. In addition, the ECC procedure promoted higher fluctuations in the sufentanil plasma concentrations without causing alterations in the area under the curve, distribution volume, clearance or the distributional (alpha) and rapid elimination (beta) half-lives (t1/2α and t1/2β, respectively).

 
  • References

  • 1 Bovill Jg, Sebel Ps, Blackburn Cl et al. The pharmacokinetics of sufentanil in surgical patients. Anesthesiology 1984; v.61: 502-506
  • 2 Bassanezi BSB, Filho AGO. Analgesia Pós Operatória. Ver Col Bras Cir 2006; v. 33 n.2
  • 3 Scott B. Opioids in cardiac surgery: Cardiopulmonary bypass and inflammatory response. Int J Cardiol 1998; v.64 (sup. 01) 535-541
  • 4 Scholz J, Steinfath M, Schulz M. Clinical Pharmacokinetics of alfentanil, fentanil and sufentanil – An Update. Clin Pharmacokinet 1996; v.31, n.4: 275-292
  • 5 Ahonen J, Olkkola KT, Hynynen M et al. Comparison of alfentanil, fentanyl and sufentanil for total intravenous anaesthesia with propofol in patients undergoing coronary artery bypass surgery. British J of Anaeth 2000; v.85, n.4: 533-540
  • 6 Barvais L, Heitz D, Schmartz D et al. Pharmacokinetic Model-driven infusion of sufentanil and midazolam during cardiac surgery: assessment of the prospective predictive accuracy and the quality of anesthesia. J of Cardiothor. and Vascular Anesth 2000; v. 14, n.4: 402-408
  • 7 Cross DA, Nikas D. The effects of carbon dioxide management on plasma levels of fentanyl and sufentanil during hypothermic cardiopulmonary bypass. J of Cardiothor and Vascular Anesth 1994; v.8, n.6: 649-652
  • 8 Flezzani P, Alvis MJ, Jacobs JR et al. Sufentanil disposition during cardiopulmonary bypass. Can J Anaesth 1987; v 34: 566-569
  • 9 Gepts E, Shafer SL, Camu F et al. Linearity of pharmacokinetics and model estimation of sufentanil. Anesthesiology 1995; v 83: 1194-1204
  • 10 Hudson RJ, Bergstrom RG, Thomson IR et al. Pharmacokinetics of sufentanil in patients undergoing abdominal aortic surgery. Anesthesiology 1989; v.70: 426-431
  • 11 Hudson RJ, Henderson BT, Thomson IR et al. Pharmacokinetics of sufentanil in Patients undergoing coronary artery bypass graft surgery. J of Cardiothoracic and Vascular Anesthesia 2001; v15, n.6: 693-699
  • 12 Ionescu TI, Taverne RHT, Houweling PL et al. Pharmacokinetic study of extradural and intrathecal sufentanil anaesthesia for major surgery. British J of Anaesth 1991; v.66: 458-464
  • 13 Schraag S, Mohl U, Hirsch M et al. Recovery from opioid anaesthesia: the clinical implication of context-sensitive half-times. Anesth Analg. 1998; v.86: 184-190
  • 14 Schwartz AE, Matteo RS, Ornstein E et al. Pharmacokinetics of sufentanil in neurosurgical patients undergoing hyperventilation. Br J Anaesth 1989; v.63: 385-388
  • 15 Thomson IR, Herderson BT, Singh K et al. Anesthesiology 1998; v 89: 852-861
  • 16 Zhao Y, Duan J-L, Wu X-M et al. Two-stage analysis of pharmacokinetics of sufentanil administered by target-controlled infusion in Chinese patients. Chinese Medical Journal. 2009; v.122, n.17: 1979-1984
  • 17 Manfio JL, Santos VJ, Lanchote VL et al. Development and validation of a LC-MS/MS method for the determination of sufentanil and morphine in human plasma. Jour. AOAC internat 2011; v 94: 136-142
  • 18 Okutani R, Philbin D, Rosow C et al. Effect of hypothermic hemodilutional cardiopulmonary bypass on plasma sufentanil and catecholamine concentrations in humans. Anesth Analg 1988; v.67: 667-670
  • 19 Gedney Ja, Ghosh S. Pharmacokinetics of analgesics, sedatives and anaesthetic agents during cardiopulmonary bypass. Review Article. British J Anaesthesia 1995; v.75: 344-351
  • 20 Rosen DA, Rosen KR. Elimination of drugs and toxins during cardiopulmonary bypass. J Cardiothor and Vasc Anest 1997; v.11, n.3: 337-340
  • 21 Wilkinson Gr. Pharmacokinetics: The dynamics of drug absorption, distribution and elimination. In: Hardman JG, Limbird LE. (ed Goodman & Gilman’s – The Pharmacological Basis of Therapeutics. Chicago: McGraw-Hill Medical Publishing Division; 2001: 3-29
  • 22 Hughes MA, Glass PS, Jacobs JR. Context-sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology 1992; 76: 334-341