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Cardiopulmonary Bypass and the Pharmacokinetics of Drugs

An Update

  • Review Article
  • Clinical Pharmacokinetics and Disease Processes
  • Published:
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Summary

Cardiopulmonary bypass is accompanied by profound changes in the organism that may alter the pharmacokinetics of drugs. Drug distribution can be altered, for example, by changes in blood flow and by haemodilution, with a decrease in protein binding; a decrease in the elimination of some drugs can be caused by impairment of renal or hepatic clearance, due, for example, to lowered perfusion and hypothermia.

The subject was reviewed in the Journal in 1982, and the emphasis of the present review is on new data related to specific drugs. The following substances are dealt with: benzodiazepines, cephalosporins, digitalis glycosides, general anaesthetics, glyceryl trinitrate (nitroglycerin), lignocaine (lidocaine), muscle relaxants, nitroprusside, opiates, papaverine and propranolol. For many of these substances an abrupt decrease has been observed in serum concentration upon initiation of bypass, which is explained by haemodilution and an increase in distribution due to decreased protein binding. For nitrates and some opiates, adsorption to the bypass apparatus was shown to be important. The gradual increase in serum concentrations seen during cardiopulmonary bypass with some drugs after the initial fall is usually explained by redistribution of the drug and/or decrease in its elimination. The same phenomena are thought to explain why in the post-bypass period a concentration increase occurs, or at least a slower decrease than expected. However, drug elimination has been directly measured in only a few studies. The short duration of the bypass procedure and the continuous changes during the process hamper a rigorous pharmacokinetic evaluation. Studies allowing more precise understanding of the mechanisms underlying the observed concentration changes are needed, but are difficult to design. Similarly, more data are awaited on the pharmacodynamic and clinical consequences of the concentration changes.

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References

  • Aaltonen L, Kanto J, Arola M, Iisalo E, Pakkanen A. Effect of age and cardiopulmonary bypass on the pharmacokinetics of lorazepam. Acta Pharmacologica et Toxicologica 51: 126–131, 1982

    Article  PubMed  CAS  Google Scholar 

  • Akl BF, Richardson G. Serum cefazolin levels during cardiopulmonary bypass. Annals of Thoracic Surgery 29: 109–112, 1980

    Article  PubMed  CAS  Google Scholar 

  • Arden JR, Holley FO, Stansky DR. Increased sensitivity to etomidate in the elderly: initial distribution versus altered brain response. Anesthesiology 65: 19–27, 1986

    Article  PubMed  CAS  Google Scholar 

  • Avram MJ, Shanks CA, Henthorn TK, Ronai AK, Kinzer J. Metocurine kinetics in patients undergoing operations requiring cardiopulmonary bypass. Clinical Pharmacology and Therapeutics 42: 576–581, 1987

    Article  PubMed  CAS  Google Scholar 

  • Benowitz N, Forsyth RP, Melmon KL, Rowland M. Lidocaine disposition kinetics in monkey and man. Clinical Pharmacology and Therapeutics 16: 99–109, 1974

    PubMed  CAS  Google Scholar 

  • Bentley JB, Conahan TJ, Cork RC. Fentanyl sequestration in lungs during cardiopulmonary bypass. Clinical Pharmacology and Therapeutics 34: 703–706, 1983

    Article  PubMed  CAS  Google Scholar 

  • Bjorksten AR, Crankshaw DP, Morgan DJ, Prideaux PR. The effects of cardiopulmonary bypass on plasma concentrations and protein binding of methohexital and thiopental. Journal of Cardiothoracic Anesthesia 2: 281–289, 1988

    Article  PubMed  CAS  Google Scholar 

  • Bogaert MG. Clinical pharmacokinetics of glyceryl trinitrate following the use of systemic and topical preparations. Clinical Pharmacokinetics 12: 1–11, 1987

    Article  PubMed  CAS  Google Scholar 

  • Boscoe MJ, Dawling S, Thompson MA, Jones RM. Lorazepam in open-heart surgery — plasma concentrations before, during and after bypass following different dose regimens. Anaesthesia and Intensive Care 12: 9–13, 1984

    PubMed  CAS  Google Scholar 

  • Bovill JG, Sebel PS. Pharmacokinetics of high-dose fentanyl. British Journal of Anaesthesia 52: 795–801, 1980

    Article  PubMed  CAS  Google Scholar 

  • Buzello W, Schluermann D, Schindler M, Spillner G. Hypothermic cardiopulmonary bypass and neuromuscular blockade by pancuronium and vecuronium. Anesthesiology 62: 201–204, 1985

    Article  PubMed  CAS  Google Scholar 

  • Carruthers SG, Cleland J, Kely JG, Lyons SM, McDevitt DG. Plasma and tissue digoxin concentrations in patients undergoing cardiopulmonary bypass. British Heart Journal 37: 313–320, 1975

    Article  PubMed  CAS  Google Scholar 

  • Coltart DJ, Chamberlain DA, Howard MR, Kettlewell MG, Mercer JL. Effect of cardiopulmonary bypass on plasma digoxin concentrations. British Heart Journal 33: 334–338, 1971

    Article  PubMed  CAS  Google Scholar 

  • Dasta JF, Jacobi J, Wu LS, Sokoloski T, Beckley P. Loss of nitroglycerin to cardiopulmonary bypass apparatus. Critical Care Medicine 11: 50–52, 1983

    Article  PubMed  CAS  Google Scholar 

  • Dasta JF, Weber RJ, Wu LS, Sokoloski TD, Kakos GS. Influence of cardiopulmonary bypass on nitroglycerin clearance. Journal of Clinical Pharmacology 26: 165–168, 1986

    PubMed  CAS  Google Scholar 

  • D’Hollander AA, Duvaldestin P, Henzel D, Nevelsteen M, Bomblet JP. Variations in pancuronium requirement, plasma concentration, and urinary excretion induced by cardiopulmonary bypass with hypothermia. Anesthesiology 58: 505–509, 1983

    Article  PubMed  Google Scholar 

  • Fischler M, Levron JC, Trang H, Brodaty D, Dubois C. Pharmacokinetics of phenoperidine in patients undergoing cardiopulmonary bypass. British Journal of Anaesthesia 57: 877–882, 1985

    Article  PubMed  CAS  Google Scholar 

  • Flezzani P, Alvis MJ, Jacobs JR, Schilling MM, Bai S. Sufentanil disposition during cardiopulmonary bypass. Canadian Journal of Anaesthesia 34: 566–569, 1987

    Article  PubMed  CAS  Google Scholar 

  • Flynn PJ, Hughes R, Walton B. Use of atracurium in cardiac surgery involving cardiopulmonary bypass with induced hypothermia. British Journal of Anaesthesia 56: 967–972, 1984

    Article  PubMed  CAS  Google Scholar 

  • Futter ME, Whalley DG, Wynands JE, Bevan DR. Pancuronium requirements during hypothermic cardiopulmonary bypass in man. Anaesthesia and Intensive Care 11: 216–219, 1983

    PubMed  CAS  Google Scholar 

  • Giacomini KM, Swezey SE, Giacomini JC, Blaschke TF. Administration of heparin causes in vitro release of non-esterifled fatty acids in human plasma. Life Sciences 27: 771–780, 1980

    Article  PubMed  CAS  Google Scholar 

  • Goldmann DA, Hopkins CC, Karchmer AW, Abel RM, Mc-Enany MT. Cephalotin prophylaxis in cardiac valve surgery. Journal of Thoracic and Cardiovascular Surgery 73: 470–479, 1977

    PubMed  CAS  Google Scholar 

  • Holley FO, Ponganis KV, Stanski DR. Effect of cardiopulmonary bypass on the pharmacokinetics of drugs. Clinical Pharmacokinetics 7: 234–251, 1982

    Article  PubMed  CAS  Google Scholar 

  • Holley FO, Ponganis KV, Stanski DR. Effects of cardiac surgery with cardiopulmonary bypass on lidocaine disposition. Clinical Pharmacology and Therapeutics 35: 617–626, 1984

    Article  PubMed  CAS  Google Scholar 

  • Hug CC, De Lange S, Burm AGL. Alfentanil pharmacokinetics in patients before and after cardiopulmonary bypass (CPB). Anesthesia and Analgesia 62: 266, 1983

    Google Scholar 

  • Hug CC, Moldenhauer CC. Pharmacokinetics and dynamics of fentanyl infusions in cardiac surgical patients. Anesthesiology 57: A45, 1982

    Article  Google Scholar 

  • Kanto J, Himberg JJ, Heikkilä H, Arola M, Jalonen J. Midazolam kinetics before, during and after cardiopulmonary bypass surgery. International Journal of Clinical and Pharmacological Research 2: 123–126, 1985

    Google Scholar 

  • Koren G, Crean P, Klein J, Goresky G, Villamater J. Sequestration of fentanyl by the cardiopulmonary bypass (CPBP). European Journal of Clinical Pharmacology 27: 51–56, 1984a

    PubMed  CAS  Google Scholar 

  • Koren G, Goresky G, Crean P, Klein J, MacLeod SM. Pediatric fentanyl dosing based on pharmacokinetics during cardiac surgery. Anesthesia and Analgesia 63: 577–582, 1984b

    Article  PubMed  CAS  Google Scholar 

  • Koska AJ, Romagnoli A, Kramer WG. Effect of cardiopulmonary bypass on fentanyl distribution and elimination. Clinical Pharmacology and Therapeutics 29: 100–105, 1981

    Article  PubMed  Google Scholar 

  • Kramer WG, Romagnoli A. Papaverine disposition in cardiac surgery patients and the effect of cardiopulmonary bypass. European Journal of Clinical Pharmacology 27: 127–130, 1984

    Article  PubMed  CAS  Google Scholar 

  • Krasula RW, Hastreiter AR, Levitsky S, Yanagi R, Soyka LF. Serum, atrial, and urinary digoxin levels during cardiopulmonary bypass in children. Circulation 49: 1047–1052, 1974

    Article  PubMed  CAS  Google Scholar 

  • Kumar K, Crankshaw DP, Morgan DJ, Beemer GH. The effect of cardiopulmonary bypass on plasma protein binding of alfentanil. European Journal of Clinical Pharmacology 35: 47–52, 1988

    Article  PubMed  CAS  Google Scholar 

  • Lerman J, Gregory GA, Eger El. Hematocrit and the solubility of volatile anesthetics in blood. Anesthesia and Analgesia 63: 911–914, 1984

    Article  PubMed  CAS  Google Scholar 

  • Loomis CW, Brunet D, Milne B, Cervenko FW, Johnson GD. Arterial isoflurane concentration and EEG burst suppression during cardiopulmonary bypass. Clinical Pharmacology and Therapeutics 40: 304–313, 1986

    Article  PubMed  CAS  Google Scholar 

  • Lowry KG, Dundee JW, McClean E, Lyons SM, Carson IW. Pharmacokinetics of diazepam and midazolam when used for sedation following cardiopulmonary bypass. British Journal of Anaesthesia 57: 883–885, 1985

    Article  PubMed  CAS  Google Scholar 

  • Lunn JK, Stanley TH, Eisele J, Webster L, Woodward A. High dose fentanyl anesthesia for coronary artery surgery: plasma fentanyl concentrations and influence of nitrous oxide on cardiovascular responses. Anesthesia and Analgesia 58: 390–395, 1979

    Article  PubMed  CAS  Google Scholar 

  • McAllister RG, Bourne DW, Tan TG, Erickson JL, Wachtel CC. Effects of hypothermia on propranolol kinetics. Clinical Pharmacology and Therapeutics 25: 1–7, 1979

    PubMed  CAS  Google Scholar 

  • Miller KW, Chan KKH, McCoy HG, Fischer RP, Lindsay WG. Cephalotin kinetics: before, during and after cardiopulmonary bypass surgery. Clinical Pharmacology and Therapeutics 26: 54–62, 1979

    PubMed  CAS  Google Scholar 

  • Miller KW, McCoy HG, Chan KKH, Fischer RP, Lindsay WG. Effect of cardiopulmonary bypass on cefazoline disposition. Clinical Pharmacology and Therapeutics 27: 551–556, 1980

    Google Scholar 

  • Mizuta E, Tsubotani A, Watanabe K, Sugimura S. A method for the pharmacokinetic analysis of serum cefotiam levels during cardiopulmonary bypass. Chemical and Pharmaceutical Bulletin 33: 3534–3539, 1985

    Article  CAS  Google Scholar 

  • Moore RA, Geller EA, Gallagher JD, Clark DL. Effect of hypothermic cardiopulmonary bypass on nitroprusside metabolism. Clinical Pharmacology and Therapeutics 37: 680–683, 1985

    Article  PubMed  CAS  Google Scholar 

  • Morgan DJ, Crankshaw DP, Prideaux PR, Chan HNJ, Boyd MD. Thiopentone levels during cardiopulmonary bypass. Anaesthesia 41: 4–10, 1986

    Article  PubMed  CAS  Google Scholar 

  • Morrell DF, Harrison GG. Lignocaine kinetics during cardiopulmonary bypass. British Journal of Anaesthesia 55: 1173–1177, 1983

    Article  PubMed  CAS  Google Scholar 

  • Morrison J, Killip T. Serum digitalis and arrhythmia in patients undergoing cardiopulmonary bypass. Circulation 47: 341–352, 1973

    Article  PubMed  CAS  Google Scholar 

  • Nancherla AR, Narang PK, Kim YD, Howard C, Gallelli JF. Sodium thiopental kinetics during cardiopulmonary bypass. Anesthesia and Analgesia 65: S111, 1986

    Google Scholar 

  • Nimmo WS, Peacock JE. Effect of anaesthesia and surgery on pharmacokinetics and pharmacodynamics. British Medical Bulletin 44: 286–301, 1988

    PubMed  CAS  Google Scholar 

  • Oduro A, Tomlinson AA, Voice A, Davies GK. The use of etomidate infusions during anaesthesia for cardiopulmonary bypass. Anaesthesia 38S: 66–69, 1983

    Article  Google Scholar 

  • Pentel P, Benowitz N. Pharmacokinetic and pharmacodynamic considerations in drug therapy of cardiac emergencies. Clinical Pharmacokinetics 9: 273–308, 1984

    Article  PubMed  CAS  Google Scholar 

  • Plachetka JR, Salomon NW, Copeland JG. Plasma propranolol before, during and after cardiopulmonary bypass. Clinical Pharmacology and Therapeutics 30: 745–751, 1981

    Article  PubMed  CAS  Google Scholar 

  • Polk RE, Archer GL, Lower R. Cefamandole kinetics during cardiopulmonary bypass. Clinical Pharmacology and Therapeutics 23: 473–480, 1978

    PubMed  CAS  Google Scholar 

  • Price SL, Brown DL, Carpenter RL, Unadkat JD, Crosby SS. Isoflurane elimination via a bubble oxygenator during extracorporeal circulation. Journal of Cardiothoracic Anesthesia 2: 41–44, 1988

    Article  PubMed  CAS  Google Scholar 

  • Rosen DA, Rosen KR, Davidson B, Nahrwold ML, Broadman L. Absorption of fentanyl by the membrane oxygenator. Anesthesiology 63: A281, 1985

    Article  Google Scholar 

  • Roth RA, Wiersma DA. Role of the lung in total body clearance of circulating drugs. Clinical Pharmacokinetics 4: 355–367, 1979

    Article  PubMed  CAS  Google Scholar 

  • Schiavello R, Mezza A, Feo L, Sciarra M, Monaco C. Compartmental analysis of lidocaine kinetics during extracorporeal circulation. Journal of Cardiothoracic Anesthesia 2: 290–296, 1988

    Article  PubMed  CAS  Google Scholar 

  • Sato Y, Kanazawa H, Okazaki H, Kosuge T, Imaizumi K. A comparison of the penetration characteristics of latamoxef and cephalothin into right atrial appendage and pericardial fluid of adult patient undergoing open-heart surgery. Japanese Journal of Antibiotics 37: 678–679, 1984

    Google Scholar 

  • Shanks CA, Ramzan IM, Walker JS, Brown KF. Gallamine disposition in open-heart surgery involving cardiopulmonary bypass. Clinical Pharmacology and Therapeutics 33: 792–799, 1983

    Article  PubMed  CAS  Google Scholar 

  • Skacel M, Knott C, Reynolds F, Aps C. Extracorporeal circuit sequestration of fentanyl and alfentanil. British Journal of Anaesthesia 58: 947–949, 1986

    Article  PubMed  CAS  Google Scholar 

  • Sprigge JS, Wynands JE, Whalley DG, Bevan DR, Townsend GE. Fentanyl infusion anesthesia for aortocoronary bypass surgery: plasma levels and hemodynamic response. Anesthesia and Analgesia 61: 972–978, 1982

    Article  PubMed  CAS  Google Scholar 

  • Stanley TH. Arterial pressure and deltoid muscle gas tension during cardiopulmonary bypass in man. Canadian Anaesthetists’ Society Journal 25: 286–290, 1978

    Article  PubMed  CAS  Google Scholar 

  • Storstein L, Nitter-Hauge S, Fjeld N. Effect of cardiopulmonary bypass with heparin administration on digitoxin pharmacokinetics, serum electrolytes, free fatty acids, and renal function. Journal of Cardiovascular Pharmacology 1: 191–204, 1979

    Article  PubMed  CAS  Google Scholar 

  • Tinker JH. Anesthetic management of cardiopulmonary bypass. In Barash PG (Ed.) ASA refresher courses in anesthesiology, Vol. 15, pp. 197–208, JB Lippincott Company, Philadelphia, 1987

    Google Scholar 

  • Walker JS, Shanks CA, Brown KF. Alcuronium kinetics in patients undergoing cardiopulmonary bypass surgery. British Journal of Clinical Pharmacology 15: 237–244, 1983

    Article  PubMed  CAS  Google Scholar 

  • Walker JS, Shanks CA, Brown KF. Altered d-tubocurarine disposition during cardiopulmonary bypass surgery. Clinical Pharmacology and Therapeutics 35: 686–694, 1984

    Article  PubMed  CAS  Google Scholar 

  • Williams DJ, Steele TW. Cephalothin prophylaxis assay during cardiopulmonary bypass. Journal of Thoracic and Cardiovascular Surgery 71: 207–211, 1976

    PubMed  CAS  Google Scholar 

  • Wood M, Shand DG, Wood AJJ. Propranolol binding in plasma during cardiopulmonary bypass. Anesthesiology 51: 512–516, 1979

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Emergency Medicine, Department of Anaesthesiology and Heymans Institute of Pharmacology, University Hospital and State University of Ghent, Belgium

    W. A. Buylaert, L. L. Herregods, E. P. Mortier & M. G. Bogaert

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  1. W. A. Buylaert
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  2. L. L. Herregods
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  3. E. P. Mortier
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  4. M. G. Bogaert
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Buylaert, W.A., Herregods, L.L., Mortier, E.P. et al. Cardiopulmonary Bypass and the Pharmacokinetics of Drugs. Clin-Pharmacokinet 17, 10–26 (1989). https://doi.org/10.2165/00003088-198917010-00002

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