Advertisement

Clinical Pharmacokinetics

, Volume 47, Issue 10, pp 635–654 | Cite as

Influence of Burns on Pharmacokinetics and Pharmacodynamics of Drugs Used in the Care of Burn Patients

  • Benoit Blanchet
  • Vincent Jullien
  • Christophe Vinsonneau
  • Michel Tod
Review Article

Abstract

The pharmacokinetics and pharmacodynamics of drugs are significantly altered in the burn patient, and the burn patient population shows wide inter- and intraindividual variation in drug handling. Burn injury evolves in two phases. The first phase corresponds to the burn shock, which occurs during the first 48 hours after thermal injury. In this phase, hypovolaemia, oedema, hypoalbuminaemia and a low glomerular filtration rate are observed, which result in a slower rate of drug distribution and lower renal clearance. The second phase (beyond 48 hours after injury) is a hyperdynamic state with high blood flow in the kidneys and liver, an increased α1-acid-glycoprotein level and loss of the drug with exudate leakage. As a result, protein binding, drug distribution and clearance may be altered.

Because of the alteration in these variables, wide intraindividual variation of pharmacokinetic parameters occurs depending upon the time since thermal injury and fluid resuscitation. Interindividual variations may be correlated with the percentage of the body surface area that is burnt, creatinine clearance, albuminaemia or the α1-acid-glycoprotein level. A number of important variations in pharmacodynamic parameters have been described, but their mechanisms are poorly understood.

From a practical point of view, for the subpopulation of burn patients who eliminate drugs extremely rapidly, higher doses and/or shorter dosing intervals are required to avoid treatment inefficacy. Drug concentration measurements help to take into account interindividual variability. However, adaptation of doses based on Bayesian methods is frequently not possible because the distribution of pharmacokinetic parameters is poorly characterized in this population. Methods based only on individual data or on a surrogate marker for efficacy may be used to optimize the dosing regimen in this population.

Keywords

Morphine Vancomycin Pharmacokinetic Parameter Teicoplanin Thermal Injury 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

References

  1. 1.
    Arturson G. Pathophysiology of the burn wound and pharmacological treatment: the Rudi Hermans Lecture, 1995. Burns 1996 Jun; 22(4): 255–74PubMedCrossRefGoogle Scholar
  2. 2.
    Demling RH. The burn edema process: current concepts. J Burn Care Rehabil 2005 May–Jun; 26(3): 207–27PubMedGoogle Scholar
  3. 3.
    Kramer GC, Lund T, Herndon DN. Pathophysiology of burn shock and burn edema. In: Herndon DN, editor. Philadelphia: Elsevier Health Sciences, 2007: 93–106Google Scholar
  4. 4.
    Lund T, Wiig H, Reed RK. Acute postburn edema: role of strongly negative interstitial fluid pressure. Am J Physiol 1988 Nov; 255 (5 Pt 2): H1069-74Google Scholar
  5. 5.
    Arturson G, Jakobsson OP. Oedema measurements in a standard burn model. Burns Incl Therm Inj 1985 Oct; 12(1): 1–7PubMedCrossRefGoogle Scholar
  6. 6.
    Jeschke MG. The hepatic response to thermal injury. In: Herndon DN, editor. Philadelphia: Elsevier Health Sciences, 2007: 361–78Google Scholar
  7. 7.
    Bloedow DC, Hansbrough JF, Hardin T, et al. Postburn serum drug binding and serum protein concentrations. J Clin Pharmacol 1986 Feb; 26(2): 147–51PubMedGoogle Scholar
  8. 8.
    Martyn JA, Abernethy DR, Greenblatt DJ. Plasma protein binding of drugs after severe burn injury. Clin Pharmacol Ther 1984 Apr; 35(4): 535–9PubMedCrossRefGoogle Scholar
  9. 9.
    Weinbren MJ. Pharmacokinetics of antibiotics in burns patients. J Antimicrob Chemother 2001 May; 47(5): 720PubMedCrossRefGoogle Scholar
  10. 10.
    Zaske D, Cipolle RJ, Solem LD, et al. Rapid individualization of gentamicin dosage regimens in 66 burn patients. Burns 1978; 7: 215–20CrossRefGoogle Scholar
  11. 11.
    Palayret D, Manelli JC, Perez-Cappelano R, et al. Clinical and pharmacokinetic study of amikacin in septicemia complicating major burns [in French]. Nouv Presse Med 1979; 8(42): 3503–6PubMedGoogle Scholar
  12. 12.
    Vinçon G, Sanchez R, Perro G, et al. Pharmacokinetics of amikacin in burn patients of middle-degree severity [in French]. Therapie 1986 Nov–Dec; 41(6): 417–20PubMedGoogle Scholar
  13. 13.
    Kopcha RG, Fant WK, Warden GD. Increased dosing requirements for amikacin in burned children. J Antimicrob Chemother 1991 Nov; 28(5): 747–52PubMedCrossRefGoogle Scholar
  14. 14.
    Conil JM, Georges B, Breden A, et al. Increased amikacin dosage requirements in burn patients receiving a once-daily regimen. Int J Antimicrob Agents 2006 Sep; 28(3): 226–30PubMedCrossRefGoogle Scholar
  15. 15.
    Glew RH, Moellering Jr RC, Burke JF. Gentamicin dosage in children with extensive burns. J Trauma 1976 Oct; 16(10): 819–23PubMedCrossRefGoogle Scholar
  16. 16.
    Zaske DE, Sawchuk RJ, Gerding DN, et al. Increased dosage requirements of gentamicin in burn patients. J Trauma 1976 Oct; 16(10): 824–8PubMedCrossRefGoogle Scholar
  17. 17.
    Sawchuk RJ, Zaske DE, Cipolle RJ, et al. Kinetic model for gentamicin dosing with the use of individual patient parameters. Clin Pharmacol Ther 1977 Mar; 21(3): 362–9PubMedGoogle Scholar
  18. 18.
    Polk RE, Mayhall CG, Smith J, et al. Gentamicin and tobramycin penetration into burn eschar: pharmacokinetics and microbiological effects. Arch Surg 1983 Mar; 118(3): 295–302PubMedCrossRefGoogle Scholar
  19. 19.
    Ristuccia AM, Gayle Jr WE, Wasserman AJ, et al. Penetration of gentamicin into burn wounds. J Trauma 1982 Nov; 22(11): 944–9PubMedCrossRefGoogle Scholar
  20. 20.
    Hollingsed TC, Harper DJ, Jennings JP, et al. Aminoglycoside dosing in burn patients using first-dose pharmacokinetics. J Trauma 1993 Sep; 35(3): 394–8PubMedCrossRefGoogle Scholar
  21. 21.
    Hoey LL, Tschida SJ, Rotschafer JC, et al. Wide variation in single, daily-dose aminoglycoside pharmacokinetics in patients with burn injuries. J Burn Care Rehabil 1997 Mar–Apr; 18(2): 116–24PubMedCrossRefGoogle Scholar
  22. 22.
    Loirat P, Rohan J, Baillet A, et al. Increased glomerular filtration rate in patients with major burns and its effect on the pharmacokinetics of tobramycin. N Engl J Med 1978 Oct 26; 299(17): 915–9PubMedCrossRefGoogle Scholar
  23. 23.
    Sawchuk RJ, Zaske DE. Pharmacokinetics of dosing regimens which utilize multiple intravenous infusions: gentamicin in burn patients. J Pharmacokinet Biopharm 1976 Apr; 4(2): 183–95PubMedGoogle Scholar
  24. 24.
    Freeman CD, Nicolau DP, Belliveau PP, et al. Once-daily dosing of aminoglycosides: review and recommendations for clinical practice. J Antimicrob Chemother 1997 Jun; 39(6): 677–86PubMedCrossRefGoogle Scholar
  25. 25.
    Zaske DE, Sawchuk RJ, Strate RG. The necessity of increased doses of amikacin in burn patients. Surgery 1978 Nov; 84(5): 603–8PubMedGoogle Scholar
  26. 26.
    Lesne-Hulin A, Bourget P, Le Bever H, et al. Étude pilote de la pharmacocinétique de l’association amikacine-teicoplanine chez le sujet gravement brûlé infecté. Med Mal Infect 1997; 27: 306–13CrossRefGoogle Scholar
  27. 27.
    Conil JM, Georges B, Fourcade O, et al. Intermittent administration of ceftazidime to burns patients: influence of glomerular filtration. Int J Clin Pharmacol Ther 2007 Mar; 45(3): 133–42PubMedGoogle Scholar
  28. 28.
    Conil JM, Georges B, Lavit M, et al. A population pharmacokinetic approach to ceftazidime use in burn patients: influence of glomerular filtration, gender and mechanical ventilation. Br J Clin Pharmacol 2007 Jul; 64(1): 27–35PubMedCrossRefGoogle Scholar
  29. 29.
    Walstad RA, Aanderud L, Thurmann-Nielsen E. Pharmacokinetics and tissue concentrations of ceftazidime in burn patients. Eur J Clin Pharmacol 1988; 35(5): 543–9PubMedCrossRefGoogle Scholar
  30. 30.
    Zong G, Xiao G, Zhang Y. The pharmacokinetics of ceftazidime in the burned patients [in Chinese]. Zhonghua Zheng Xing Shao Shang Wai Ke Za Zhi 1994 Sep; 10(5): 385–8PubMedGoogle Scholar
  31. 31.
    Conil JM, Georges B, Lavit M, et al. Pharmacokinetics of ceftazidime and cefepime in burn patients: the importance of age and creatinine clearance. Int J Clin Pharmacol Ther 2007 Oct; 45(10): 529–38PubMedGoogle Scholar
  32. 32.
    Dailly E, Pannier M, Jolliet P, et al. Population pharmacokinetics of ceftazidime in burn patients. Br J Clin Pharmacol 2003 Dec; 56(6): 629–34PubMedCrossRefGoogle Scholar
  33. 33.
    Drugeon HB, Pannier M, Courtieu AL. Pharmacokinetics of azlocillin in the burn patient [in French]. Presse Med 1984 Mar 29; 13(13): 805–7PubMedGoogle Scholar
  34. 34.
    Friedrich LV, White RL, Kays MB, et al. Aztreonam pharmacokinetics in burn patients. Antimicrob Agents Chemother 1991 Jan; 35(1): 57–61PubMedCrossRefGoogle Scholar
  35. 35.
    Bonapace CR, White RL, Friedrich LV, et al. Pharmacokinetics of cefepime in patients with thermal burn injury. Antimicrob Agents Chemother 1999 Dec; 43(12): 2848–54PubMedGoogle Scholar
  36. 36.
    Sampol E, Jacquet A, Viggiano M, et al. Plasma, urine and skin pharmacokinetics of cefepime in burns patients. J Antimicrob Chemother 2000 Aug; 46(2): 315–7PubMedCrossRefGoogle Scholar
  37. 37.
    Boucher BA, Hickerson WL, Kuhl DA, et al. Imipenem pharmacokinetics in patients with burns. Clin Pharmacol Ther 1990 Aug; 48(2): 130–7PubMedCrossRefGoogle Scholar
  38. 38.
    Dailly E, Kergueris MF, Pannier M, et al. Population pharmacokinetics of imipenem in burn patients. Fundam Clin Pharmacol 2003 Dec; 17(6): 645–50PubMedCrossRefGoogle Scholar
  39. 39.
    Shikuma LR, Ackerman BH, Weaver RH, et al. Thermal injury effects on drug disposition: a prospective study with piperacillin. J Clin Pharmacol 1990 Jul; 30(7): 632–7PubMedGoogle Scholar
  40. 40.
    Bourget P, Lesne-Hulin A, Le Reveille R, et al. Clinical pharmacokinetics of piperacillin-tazobactam combination in patients with major burns and signs of infection. Antimicrob Agents Chemother 1996 Jan; 40(1): 139–45PubMedGoogle Scholar
  41. 41.
    Adam D, Zellner PR, Koeppe P, et al. Pharmacokinetics of ticarcillin/clavulanate in severely burned patients. J Antimicrob Chemother 1989 Nov; 24 Suppl. B: 121–9PubMedCrossRefGoogle Scholar
  42. 42.
    Yoshida T, Homma K, Azami K, et al. Pharmacokinetics of meropenem in experimentally burned rats. J Dermatol 1993 Apr; 20(4): 208–13PubMedGoogle Scholar
  43. 43.
    Cerra FB, Siegel JH, Coleman B, et al. Septic autocannibalism: a failure of exogenous nutritional support. Ann Surg 1980; 192(4): 570–80PubMedCrossRefGoogle Scholar
  44. 44.
    Rotschafer JC, Crossley K, Zaske DE, et al. Pharmacokinetics of vancomycin: observations in 28 patients and dosage recommendations. Antimicrob Agents Chemother 1982 Sep; 22(3): 391–4PubMedCrossRefGoogle Scholar
  45. 45.
    Garrelts JC, Peterie JD. Altered vancomycin dose vs serum concentration relationship in burn patients. Clin Pharmacol Ther 1988 Jul; 44(1): 9–13PubMedCrossRefGoogle Scholar
  46. 46.
    Brater DC, Bawdon RE, Anderson SA, et al. Vancomycin elimination in patients with burn injury. Clin Pharmacol Ther 1986 Jun; 39(6): 631–4PubMedCrossRefGoogle Scholar
  47. 47.
    Rybak MJ, Albrecht LM, Berman JR, et al. Vancomycin pharmacokinetics in burn patients and intravenous drug abusers. Antimicrob Agents Chemother 1990 May; 34(5): 792–5PubMedCrossRefGoogle Scholar
  48. 48.
    Zokufa HZ, Solem LD, Rodvold KA, et al. The influence of serum albumin and alpha l-acid glycoprotein on vancomycin protein binding in patients with burn injuries. J Burn Care Rehabil 1989 Sep–Oct; 10(5): 425–8PubMedCrossRefGoogle Scholar
  49. 49.
    Potel G, Moutet J, Bernareggi A, et al. Pharmacokinetics of teicoplanin in burn patients. Scand J Infect Dis 1990; 72: 29–34Google Scholar
  50. 50.
    Steer JA, Papini RP, Wilson AP, et al. Pharmacokinetics of a single dose of teicoplanin in burn patients. J Antimicrob Chemother 1996 Mar; 37(3): 545–53PubMedCrossRefGoogle Scholar
  51. 51.
    Rio Y, Giorgi C, Schockmel G, et al. Treatment of septicemias and skin infections in burn patient by teicoplanin: study of its skin diffusion [in French]. Pathol Biol 1987 May; 35(5): 603–7PubMedGoogle Scholar
  52. 52.
    Lesne-Hulin A, Bourget P, Le Bever H, et al. Therapeutic monitoring of teicoplanin in a severely burned patient [in French]. Ann Fr Anesth Reanim 1997; 16(4): 374–7PubMedCrossRefGoogle Scholar
  53. 53.
    Potel G, Meignier M, Baron D, et al. Pharmacokinetics of fosfomycin in normal and burn patients: effect of probenecid. Drugs Exp Clin Res 1989; 15(4): 177–84PubMedGoogle Scholar
  54. 54.
    Lesne-Hulin A, Bourget P, Le Bever H, et al. Pharmacokinetics of fusidic acid in patients with seriously infected burns [in French]. Pathol Biol 1999 May; 47(5): 486–90PubMedGoogle Scholar
  55. 55.
    Sun H, Maderazo EG, Krusell AR. Serum protein-binding characteristics of vancomycin. Antimicrob Agents Chemother 1993 May; 37(5): 1132–6PubMedCrossRefGoogle Scholar
  56. 56.
    Albrecht LM, Rybak MJ, Warbasse LH, et al. Vancomycin protein binding in patients with infections caused by Staphylococcus aureus. DICP 1991 Jul–Aug; 25(7–8): 713–5PubMedGoogle Scholar
  57. 57.
    Conil JM, Favarel H, Laguerre J, et al. Continuous administration of vancomycin in patients with severe burns [in French]. Presse Med 1994 Nov 5; 23(34): 1554–8PubMedGoogle Scholar
  58. 58.
    Van der Auwera P, Martin A, Arnould JP, et al. Pharmacology of enoxacin given orally in severely burned patients. Rev Infect Dis 1988; 10 Suppl. 1: S107–8Google Scholar
  59. 59.
    Sawada Y, Ohkubo T, Kudo M, et al. Concentration of orally administered antimicrobial agent in burn scar tissue, granulation tissue, normal skin and serum. Burns 1993 Dec; 19(6): 529–30PubMedCrossRefGoogle Scholar
  60. 60.
    Potel G, Meignier M, Touze MD, et al. Pharmacokinetics of pefloxacin in burn patients [in French]. Pathol Biol 1987 Jun; 35 (5 Pt 2): 777–80PubMedGoogle Scholar
  61. 61.
    Metz R, Weber G, Sorgel F, et al. Pharmacokinetics of ciprofloxacin in patients with burn injuries. Rev Infect Dis 1989; 11 Suppl. 5: S1012–3Google Scholar
  62. 62.
    Garrelts JC, Jost G, Kowalsky SF, et al. Ciprofloxacin pharmacokinetics in burn patients. Antimicrob Agents Chemother 1996 May; 40(5): 1153–6PubMedGoogle Scholar
  63. 63.
    Lesne-Hulin A, Bourget P, Ravat F, et al. Clinical pharmacokinetics of ciprofloxacin in patients with major burns. Eur J Clin Pharmacol 1999 Sep; 55(7): 515–9PubMedCrossRefGoogle Scholar
  64. 64.
    Varela JE, Cohn SM, Brown M, et al. Pharmacokinetics and burn eschar penetration of intravenous ciprofloxacin in patients with major thermal injuries. J Antimicrob Chemother 2000 Mar; 45(3): 337–42PubMedCrossRefGoogle Scholar
  65. 65.
    Kiser TH, Hoody DW, Obritsch MD, et al. Levofloxacin pharmacokinetics and pharmacodynamics in patients with severe burn injury. Antimicrob Agents Chemother 2006 Jun; 50(6): 1937–45PubMedCrossRefGoogle Scholar
  66. 66.
    Forrest A, Nix DE, Ballow CH, et al. Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. Antimicrob Agents Chemother 1993 May; 37(5): 1073–81PubMedCrossRefGoogle Scholar
  67. 67.
    Forrest A, Ballow CH, Nix DE, et al. Development of a population pharmacokinetic model and optimal sampling strategies for intravenous ciprofloxacin. Antimicrob Agents Chemother 1993 May; 37(5): 1065–72PubMedCrossRefGoogle Scholar
  68. 68.
    Boucher BA, King SR, Wandschneider HL, et al. Fluconazole pharmacokinetics in burn patients. Antimicrob Agents Chemother 1998 Apr; 42(4): 930–3PubMedGoogle Scholar
  69. 69.
    Rayatt S, Wienbren M, Clarke J. Fluconazole use in burns patients. Burns 2000 Feb; 26(1): 109–10PubMedCrossRefGoogle Scholar
  70. 70.
    Ziemniak JA, Watson WA, Saffle JR, et al. Cimetidine kinetics during resuscitation from burn shock. Clin Pharmacol Ther 1984 Aug; 36(2): 228–33PubMedCrossRefGoogle Scholar
  71. 71.
    Martyn JA, Greenblatt DJ, Hagen J, et al. Alteration by burn injury of the pharmacokinetics and pharmacodynamics of Cimetidine in children. Eur J Clin Pharmacol 1989; 36(4): 361–7PubMedCrossRefGoogle Scholar
  72. 72.
    Martyn JA, Greenblatt DJ, Abernethy DR. Increased Cimetidine clearance in burn patients. JAMA 1985 Mar 1; 253(9): 1288–91PubMedCrossRefGoogle Scholar
  73. 73.
    Martyn JA, Bishop AL, Oliveri MF. Pharmacokinetics and pharmacodynamics of ranitidine after burn injury. Clin Pharmacol Ther 1992 Apr; 51(4): 408–14PubMedCrossRefGoogle Scholar
  74. 74.
    Martyn JA, Matteo RS, Greenblatt DJ, et al. Pharmacokinetics of d-tubocurarine in patients with thermal injury. Anesth Anaig 1982 Mar; 61(3): 241–6Google Scholar
  75. 75.
    Marathe PH, Dwersteg JF, Pavlin EG, et al. Effect of thermal injury on the pharmacokinetics and pharmacodynamics of atracurium in humans. Anesthesiology 1989 May; 70(5): 752–5PubMedCrossRefGoogle Scholar
  76. 76.
    Bowdle TA, Neal GD, Levy RH, et al. Phenytoin pharmacokinetics in burned rats and plasma protein binding of phenytoin in burned patients. J Pharmacol Exp Ther 1980 Apr; 213(1): 97–9PubMedGoogle Scholar
  77. 77.
    Denson DD, Concilus RR, Warden G, et al. Pharmacokinetics of continuous intravenous infusion of methadone in the early post-burn period. J Clin Pharmacol 1990 Jan; 30(1): 70–5PubMedGoogle Scholar
  78. 78.
    Furman WR, Munster AM, Cone EJ. Morphine pharmacokinetics during anesthesia and surgery in patients with burns. J Burn Care Rehabil 1990 Sep–Oct; 11(5): 391–4PubMedCrossRefGoogle Scholar
  79. 79.
    Herman RA, Veng-Pedersen P, Miotto J, et al. Pharmacokinetics of morphine sulfate in patients with burns. J Burn Care Rehabil 1994 Mar–Apr; 15(2): 95–103PubMedCrossRefGoogle Scholar
  80. 80.
    Perreault S, Choiniere M, du Souich PB, et al. Pharmacokinetics of morphine and its glucuronidated metabolites in burn injuries. Ann Pharmacother 2001 Dec; 35(12): 1588–92PubMedCrossRefGoogle Scholar
  81. 81.
    Han T, Harmatz JS, Greenblatt DJ, et al. Fentanyl clearance and volume of distribution are increased in patients with major burns. J Clin Pharmacol 2007 Jun; 47(6): 674–80PubMedCrossRefGoogle Scholar
  82. 82.
    Bloedow DC, Goodfellow LA, Marvin J, et al. Meperidine disposition in burn patients. Res Commun Chem Pathol Pharmacol 1986 Oct; 54(1): 87–99PubMedGoogle Scholar
  83. 83.
    Macfie AG, Magides AD, Reilly CS. Disposition of alfentanil in burns patients. Br J Anaesth 1992 Nov; 69(5): 447–50PubMedCrossRefGoogle Scholar
  84. 84.
    Martyn JA, Greenblatt DJ, Quinby WC. Diazepam kinetics in patients with severe burns. Anesth Analg 1983 Mar; 62(3): 293–7PubMedGoogle Scholar
  85. 85.
    Martyn J, Greenblatt DJ. Lorazepam conjugation is unimpaired in burn trauma. Clin Pharmacol Ther 1988 Mar; 43(3): 250–5PubMedCrossRefGoogle Scholar
  86. 86.
    Cone JB, Wallace BH, Olsen KM, et al. The pharmacokinetics of ibuprofen after burn injury. J Burn Care Rehabil 1993 Nov–Dec; 14(6): 666–9PubMedCrossRefGoogle Scholar
  87. 87.
    Galizia JP, Imbenotte M, Hochart D, et al. Pharmacokinetic study of propofol in burn patients [in French]. Ann Fr Anesth Reanim 1989; 8 Suppl.: R157PubMedCrossRefGoogle Scholar
  88. 88.
    Murat I, Billard V, Vernois J, et al. Pharmacokinetics of propofol after a single dose in children aged 1–3 years with minor burns: comparison of three data analysis approaches. Anesthesiology 1996 Mar; 84(3): 526–32PubMedCrossRefGoogle Scholar
  89. 89.
    Martyn J, Goldhill DR, Goudsouzian NG. Clinical pharmacology of muscle relaxants in patients with burns. J Clin Pharmacol 1986 Nov–Dec; 26(8): 680–5PubMedGoogle Scholar
  90. 90.
    Dwersteg JF, Pavlin EG, Heimbach DM. Patients with burns are resistant to atracurium. Anesthesiology 1986 Nov; 65(5): 517–20PubMedCrossRefGoogle Scholar
  91. 91.
    Leibel WS, Martyn JA, Szyfelbein SK, et al. Elevated plasma binding cannot account for the burn-related d-tubocurarine hyposensitivity. Anesthesiology 1981 May; 54(5): 378–82PubMedCrossRefGoogle Scholar
  92. 92.
    Cederholm I, Bengtsson M, Bjorkman S, et al. Long term high dose morphine, ketamine and midazolam infusion in a child with burns. Br J Clin Pharmacol 1990 Dec; 30(6): 901–5PubMedCrossRefGoogle Scholar
  93. 93.
    Han TH, Lee JH, Kwak IS, et al. The relationship between bispectral index and targeted propofol concentration is biphasic in patients with major burns. Acta Anaesthesiol Scand 2005 Jan; 49(1): 85–91PubMedCrossRefGoogle Scholar
  94. 94.
    Sakabu SA, Hansbrough JF, Cooper M, et al. Cyclosporine A for prolonging allograft survival in patients with massive burns. J Burn Care Rehabil 1990; 11(5): 410–8PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • Benoit Blanchet
    • 1
  • Vincent Jullien
    • 2
  • Christophe Vinsonneau
    • 3
  • Michel Tod
    • 1
    • 4
  1. 1.Department of Pharmacy-ToxicologyGH Cochin-Saint Vincent-de-PaulParisFrance
  2. 2.Department of Clinical Pharmacology, GH Cochin-Saint Vincent-de-PaulUniversité Paris DescartesParisFrance
  3. 3.Intensive Care Unit, GH Cochin-Saint Vincent-de-PaulUniversité Paris DescartesParisFrance
  4. 4.Université de LyonLyonFrance

Personalised recommendations