Skip to main content
SpringerLink
Log in

Pathophysiology and Pharmacokinetics Following Burn Injury

  • Clinical Pharmacokinetics and Disease Processes
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

Therapy for inpatient burn victims is a clear challenge for the clinician, since directly following injury the pharmacokinetic parameters of many drugs will change drastically. Blood flow to the tissues is decreased; the rate of distribution and elimination of intravenous drugs administered during this time is reduced, and absorption of oral drugs may be slowed. Approximately 48 hours after injury, the blood flow increases, as does internal core temperature: the rates may increase as a result.

Immediately after injury, plasma albumin level rapidly decreases and remains significantly depressed even at 60 days post-burn. Thus, the protein binding of acidic and neutral drugs will decrease and higher amounts of free fraction will be available at the biophase. On the other hand, α1-acid glycoprotein increases in concentration and remains elevated at least 20 days post-burn. Basic drugs exhibit increased protein binding and will most probably need an increased dosage to achieve the appropriate pharmacological effect.

Hepatic metabolism is also affected: the rate of phase I metabolism will decrease, while phase II metabolism is unimpaired and may possibly increase. Other liver functions, such as protein synthesis, are also impaired. The effect on phase I drug metabolism is believed to be due to oxygen-derived free radicals released during the course of injury.

In those patients with full-thickness burns, the epidermal layer is destroyed. Topical drugs have less of a barrier to cross and, consequently, less drug is needed to achieve effectiveness. In addition, the stomach has been found to secrete excess protons which will eventually lead to ulcers in the majority of patients. Hyperchlorhydria may affect the dissolution and disintegration of orally administered drugs in tablet form, as well as the partitioning of the neutral un-ionised species between the stomach and bloodstream. In the small intestine decreased nutrient absorption and DNA synthesis occurs, but the effect this may have on drug absorption is questionable.

This paper focuses on the epidemiology of burn injuries and the way in which the pathophysiology following such injury alters the pharmacokinetics of a drug. Specific examples are provided. Some mention is made of burn management, therapeutic drug monitoring in burn patients, experimental design considerations, and future research topics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aikawa N, Martyn JAJ, Burke JF. Pulmonary artery characterisation and thermodilution cardiac output determination in the management of critically ill burned patients. American Journal of Surgery 135: 811–817, 1978

    Article  PubMed  CAS  Google Scholar 

  • Anggard E, Jonsson CE. Formation of prostaglandins in the skin following burn injury. In Ramwell & Pharriss (Eds) Prostaglandins in cellular biology, pp. 269–284, Plenum Press, New York, 1972

    Chapter  Google Scholar 

  • Arturson G. Pathophysiologic aspects of the burn syndrome. Acta Chirurgica Scandinavica 274(Suppl.): 1–135, 1961

    PubMed  Google Scholar 

  • Bloedow DC, Goodfellow LA, Marvin J, Heimbach D. Meperidine disposition in burn patients. Research Communications in Chemical Pathology and Pharmacology 54: 87–99, 1986a

    PubMed  CAS  Google Scholar 

  • Bloedow DC, Hansbrough JF, Hardin T, Simons M. Postburn scrum drug binding and serum protein concentrations. Journal of Clinical Pharmacology 26: 147–151, 1986b

    PubMed  CAS  Google Scholar 

  • Boykin Jr JV, Crute SL, Haynes Jr BW. Cimetidine therapy for burn shock: a quantitative assessment. Journal of Trauma 25: 864–870, 1985

    Article  PubMed  CAS  Google Scholar 

  • Boykin Jr JV. Manson NH. Mechanisms of cimetidine protection following thermal injury. American Journal of Medicine 83(Suppl. 6A): 76–81, 1987

    Article  PubMed  Google Scholar 

  • Carter EA, Udall JN, Kirkham SE, Walker WA. Thermal injury and gastrointestinal function. I. Small intestine nutrient absorption and DNA synthesis. Journal of Burn Care and Rehabilitation 7: 469–474, 1986

    Article  PubMed  CAS  Google Scholar 

  • Chatterjee BF, Barancik JI, Frattianne RB, Waltz RC, Fife D, Northeastern Ohio trauma study: V. Burn injury. Journal of Trauma 26: 844–847, 1986

    Article  PubMed  CAS  Google Scholar 

  • Ciaccio El, Fruncillo RJ. Decreased aryl hydrocarbon hydroxylase after a 15% burn injury. Biochemical Pharmacology 28: 3151–3152, 1979

    Article  PubMed  CAS  Google Scholar 

  • Curreri PW. Heck EL. Brown L. et al. Stimulated neutrophil antibacterial function and prediction of wound sepsis in burned patients. Surgery 74: 6. 1973

    PubMed  CAS  Google Scholar 

  • Czaja A, McAlhany JC. Pruitt BA Acute gastroduodenal disease after thermal injury: an endoscopic evaluation of incidence and natural history. New England Journal of Medicine 29: 925–929, 1976

    Google Scholar 

  • Czaja AJ, Rizzo TA, Smith WR, Pruitt BA. Acute lier disease after cutaneous thermal injury. Journal of Trauma 15: 887–894, 1975

    Article  PubMed  CAS  Google Scholar 

  • Daniels JC, Larson DL, Abston S, Ritzmann S. Serum protein profiles in thermal burns. I. Serum electrophoretic patterns, immunoglobulins and transport proteins. Journal of Trauma 14: 137–152, 1974

    Article  PubMed  CAS  Google Scholar 

  • Demling RH. Burns. New England Journal of Medicine 313: 1389–1398, 1985

    Article  PubMed  CAS  Google Scholar 

  • Demling RH. Fluid replacement in the burned patient. Surgical Clinics of North America 67(1): 15–30, 1987

    PubMed  CAS  Google Scholar 

  • Dorr MB. The effect of thermal injury on oxidative drug metabolism. Abstract. Pharmaceutical Research 5(Suppl.): 5–162, 1988

    Google Scholar 

  • Ecklund J, Granberg P, Liljedahl S. Studies on renal function in burns. Acta Chirurgica Scandinavica 136: 627–640, 1979

    Google Scholar 

  • Elberg JJ, Scroder HA, Glent-Madsen L, Hall KV, Burns: epidemiology and the effect of a prevention programme. Burns. Including Thermal Injury 13: 391–393, 1987

    Article  CAS  Google Scholar 

  • Florence AT. Attwood D. Physicochemical Principles of Pharmacy. Macmillan Press Ltd, London. 1981

    Google Scholar 

  • Frolich S. Serum cholinesterase deficiency in major burns. Burns 4: 123–128, 1978

    Article  Google Scholar 

  • Fruncillo RJ, DiGiregono GJ. The effect of thermal injury on drug metabolism in the rat. Journal of Trauma 23: 523–529, 1983

    Article  PubMed  CAS  Google Scholar 

  • Fruncillo RJ, DiGregorio GJ. Pharmacokinetics of pentobarbital, quimdine, lidocaine and theophylline in the thermally injured rat. Journal of Pharmaceutical Sciences 73: 1117–1121, 1984

    Article  PubMed  CAS  Google Scholar 

  • Garrelts JC, Peterie JD. Altered vancomycin dose vs. serum concentration relationship in burn patients. Clinical Pharmacology and Therapeutics 44: 9–13, 1988

    Article  PubMed  CAS  Google Scholar 

  • Gault DT, Everitt AS, Gordon PW, Eve MD, Moody FM. Scrum cholinesterase levels after thermal injury. Is treatment required? Burns. Including Thermal Injury 13: 208–212, 1987

    Article  CAS  Google Scholar 

  • Harrison HN, Blackmore WP, Bales HW, Reeder W. The absorption of 14-C labeled sulfamylon acetate through burned skin. I. Experimental methods and initial observations. Journal of Trauma 12: 986–993, 1972

    Article  PubMed  CAS  Google Scholar 

  • Heidman M. Complement activation by thermal injury and its possible consequences for immune defense. In Ninnemann JL (Ed.) The immune consequences of thermal injury. p. 127 Williams and Wilkins, Baltimore. 1981

    Google Scholar 

  • Kremer JMH, Wilting J. Janseen LHM Drug binding to alpha 1-acid glycoprotein in health and disease. Pharmacological Reviews 1: 1–48, 1988

    Google Scholar 

  • Koch-Weser J. Serum drug concentrations in clinical perspective. Therapeutic Drug Monitoring 3: 3–16, 1981

    PubMed  CAS  Google Scholar 

  • Lee JB, Patak RV, Mookerjee BK. Renal prostaglandins and the regulation of blood pressure and sodium and water homeostasis. American Journal of Medicine 60: 798–816, 1976

    Article  PubMed  CAS  Google Scholar 

  • Levy Rl, Moskowitz J. Cardiovascular research. Decades of progress, a decade of promise. Science 217: 121–129, 1982

    Article  PubMed  CAS  Google Scholar 

  • Loirat P, Rohan J, Baillet A, Beaufils F, David R, et al. Increased glomerular filtration in patients with major burns and its effect on the pharmacokinelics of tobramycin. New England Journal of Medicine 299: 915–919, 1978

    Article  PubMed  CAS  Google Scholar 

  • Lyngdorf P, Occupational burn injuries. Burns. Including Thermal Injury 13: 294–297, 1987

    Article  CAS  Google Scholar 

  • Marathe PH, Dwersteg JR, Pavlin EG, Haschke RH, Heimbach DM, el al. Effect of thermal injury on the pharmacokinetics and pharmacodynamics of atracurium in humans. Anesthesiology 70: 752–755, 1989

    Article  PubMed  CAS  Google Scholar 

  • Marshall Jr WG, Dimick AR. The natural history of major burns with multiple system failure. Journal of Trauma 23: 102–105, 1983

    Article  PubMed  Google Scholar 

  • Martin CJ, Wytah R, Muir IF. Exposure treatment in the burned patient: a computer simulation of the thermal environment and its effect on evaporation and heat loss. Clinical Physics and Physiological Measurement 4: 323–326, 1985

    Article  Google Scholar 

  • Martyn JAJ. Clinical pharmacology and drug therapy in the burned patient. Anesthesiology 65: 67–75, 1986

    Article  PubMed  CAS  Google Scholar 

  • Martyn JAJ, Goldhill DR, Goudsouzian NG. Clinical pharmacology of muscle relaxants in patients with burn injury. Journal of Clinical Pharmacology 26: 680–685, 1986

    PubMed  CAS  Google Scholar 

  • Martyn JAJ, Greenblatt DJ. Lorazepam conjugation is unimpaired in burn trauma. Clinical Pharmacology and Therapeutics 43: 250–255, 1988

    Article  PubMed  CAS  Google Scholar 

  • Martyn JAJ, Greenblatt DJ, Abernathy DR. Increased cimetidine clearance in burn patients. Journal of the American Medical Association 253: 1288–1291, 1985

    Article  PubMed  CAS  Google Scholar 

  • Martyn JAJ, Greenblatl DJ, Hagen J, Hoaglin DC. Alteration by burn injury of the pharmacokinetics and pharmacodynamics of cimetidine in children. European Journal of Clinical Pharmacology 36: 361–367, 1989

    Article  PubMed  CAS  Google Scholar 

  • Martyn JAJ, Greenblatt DJ, Quinby WC. Diazepam kinetics following burns. Anesthesia and Analgesia 62: 293–297, 1983

    PubMed  CAS  Google Scholar 

  • Merrell SW, Saffle JR, Sullivan JJ, Larsen CM, Warden GD, Increased survival after major thermal injury. A nine-year review. American Journal of Surgery 154: 623–627, 1987

    Article  PubMed  CAS  Google Scholar 

  • Moran K. Munster AM. Alterations of the host defense mechanism in burned patients. Surgical Clinics of North America 67(1): 47–56, 1987

    PubMed  CAS  Google Scholar 

  • Munster AM. Immunologie alterations following injury. Advances in Orthopaedic Surgery 328: 1985

  • Notan RE. Biopharmaceutics and clinical pharmacokinetics, 3rd ed., pp. 119–149, Marcell Dekker Inc., New York. 1980

    Google Scholar 

  • O’Neill JA. Pruitt BA. Moncrief JA. Studies of renal function during early poslburn period. Presented at the Third International Congress on Research. Burns. Prague. September 20-25, 1970

  • Overman JA. Carrithers JA. Quantitative alterations in lymphocyte subpopulations in burn patients Clinical and Laboratory Science 2: 52–55, 1989

    Google Scholar 

  • Pegg SP, Miller PM, Sticklen EJ, Storie WJ, Epidemiology of industrial burns in Brisbane. Burns. Including Thermal Injury 12: 484–490, 1986

    Article  CAS  Google Scholar 

  • Perry S, Inturrisi CE. Analgesia and morphine disposition in burn patients. Journal of Burn Care and Rehabilitation 4: 276–279, 1983

    Article  Google Scholar 

  • Pippenger CE. Massoud N. Therapeutic drug monitoring. In Benet et al. (Eds) Pharmacokinetic basis for drug treatment, pp. 367–393, Raven Press, New York. 1984

    Google Scholar 

  • Polk HC. Consensus summary on infection. Journal of Trauma 19: 894. 1979

    PubMed  CAS  Google Scholar 

  • Pond SM. Pharmacokinetic drug interactions. In Benet et al. (Eds) Pharmacokinetic basis for drug treatment, pp. 195–220, Raven Press, New York. 1984

    Google Scholar 

  • Pruitt BA. Fluid and electrolyte replacement in the bumed patient. Surgical Clinics of North America 12: 1291–1312, 1978

    Google Scholar 

  • Punch JD, Smith DJ, Robson MC. Hospital care of major burns. Postgraduate Medicine 85: 205–215, 1989

    PubMed  CAS  Google Scholar 

  • Rossignol AM, Locke JA, Boyle CM, Burke JF. Epidemiology of work-related burn injuries in Massachusetts requiring hospitalization. Journal of Trauma 26: 1097–1101, 1986

    Article  PubMed  CAS  Google Scholar 

  • Rossman I. Clinical geriatrics. 2nd ed., pp. 23–52, 132-137, 224-229, JB Lippincott, Philadelphia. 1979

    Google Scholar 

  • Sawchuk RJ, Rector TS. Drug kinetics in burn patients. Clinical Pharmacokinelics 5: 548–556, 1980

    Article  CAS  Google Scholar 

  • Wachtel TL. Major burns. Postgraduate Medicine 85: 178–196, 1989

    PubMed  CAS  Google Scholar 

  • Walstad RA, Aanderud L, Thurmann-Nielson E. Pharmacokinetics and tissue concentrations of ceftazidime in burn patients. European Journal of Clinical Pharmacology 35: 543–549, 1988

    Article  PubMed  CAS  Google Scholar 

  • Waxman K, Rebello T, Pinderski L, O’Neal K, Khan N, et al. Protein loss across burn wounds. Journal of Trauma 27: 136–140, 1987

    Article  PubMed  CAS  Google Scholar 

  • Wolfe RR, Herndon DN, Jahoor F, Miyoshi H, Wolfe M. Effect of severe burn injury on substrate cycling by glucose and fatty acids. New England Journal of Medicine 317: 403–408, 1987

    Article  PubMed  CAS  Google Scholar 

  • Zaske DE, Sawchuk RJ, Gerding DN, Strate RG. Increased dosage requirements of gentamycin in burn patients. Journal of Trauma 16: 824–828, 1976

    Article  PubMed  CAS  Google Scholar 

  • Zaske DE, Sawchuk RJ, Strate RG. The necessity of increased doses of amikacin in burn patients. Surgery 84: 603–608, 1978

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Pharmacy, Department of Pharmacology/Toxicology, Washington State University, Pullman, Washington, 99164-6510, USA

    Peter L. Bonate

Authors
  1. Peter L. Bonate
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bonate, P.L. Pathophysiology and Pharmacokinetics Following Burn Injury. Clin Pharmacokinet 18, 118–130 (1990). https://doi.org/10.2165/00003088-199018020-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-199018020-00003

Keywords

Search

Navigation