Pharmacokinetic and pharmacodynamic considerations when treating patients with sepsis and septic shock

Clinical Pharmacokinetics

Volumn 41, Issue 14, 2002, Pages 1135-1151

  De Paepe, Peter ^a   Belpaire, Frans M ^a   Buylaert, Walter A ^b  

^a GHENT UNIVERSITY   (Belgium)

^b GHENT UNIVERSITY HOSPITAL   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

AMIKACIN; AMINOGLYCOSIDE ANTIBIOTIC AGENT; ANALGESIC AGENT; ANESTHETIC AGENT; AZTREONAM; BRONCHODILATING AGENT; CEFEPIME; CEFOXITIN; CEFTAZIDIME; CHLORZOXAZONE; CIPROFLOXACIN; CLINDAMYCIN; DOBUTAMINE; DOPAMINE; DOPEXAMINE; FLEROXACIN; GENTAMICIN; HEXOBARBITAL; HYPERTENSIVE FACTOR; INDOCYANINE GREEN; MIDAZOLAM; MORPHINE; NALOXONE; NORADRENALIN; OROSOMUCOID; PHENAZONE; PHENYTOIN; THEOPHYLLINE; TOBRAMYCIN; UNINDEXED DRUG; ANTIINFECTIVE AGENT; NARCOTIC ANTAGONIST;

AEROBIC METABOLISM; BLOOD BRAIN BARRIER; CAPILLARY PERMEABILITY; CRITICAL ILLNESS; DRUG ABSORPTION; DRUG BINDING; DRUG CONTRAINDICATION; DRUG DISTRIBUTION; DRUG EFFECT; DRUG ELIMINATION; DRUG EXCRETION; DRUG METABOLISM; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG TOXICITY; FLUID RETENTION; HUMAN; HYPOALBUMINEMIA; KIDNEY FAILURE; LIPID SOLUBILITY; LIVER BLOOD FLOW; LIVER CLEARANCE; LIVER DISEASE; LUNG EDEMA; NEPHROTOXICITY; OTOTOXICITY; PATHOPHYSIOLOGY; PH MEASUREMENT; PRIORITY JOURNAL; PROTEIN BINDING; REVIEW; SEPSIS; SEPTIC SHOCK; TISSUE PERFUSION; TREATMENT PLANNING; CLINICAL TRIAL; METABOLISM; PHARMACOKINETICS; PHARMACOLOGY; TISSUE DISTRIBUTION;

ANALGESICS; ANESTHETICS; ANTI-INFECTIVE AGENTS; BRONCHODILATOR AGENTS; CLINICAL TRIALS; HUMANS; NARCOTIC ANTAGONISTS; PHARMACOKINETICS; PHARMACOLOGY; SEPSIS; SHOCK, SEPTIC; TISSUE DISTRIBUTION;

EID: 0036438587     PISSN: 03125963     EISSN: None     Source Type: Journal    
DOI: 10.2165/00003088-200241140-00002     Document Type: Review

References (131)

1. Bone RC, Balk R, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Crit Care Med 1992; 20: 864-74
2. Clowes GHA, Vucini M, Weidner MG. Circulatory and metabolic alterations associated with survival and death in peritonitis. Ann Surg 1966; 163: 866-85
3. Siegel J, Greenspan M, Del Guercio LRM. Abnormal vascular tone, defective oxygen transport, and myocardial failure in human septic shock. Ann Surg 1967; 165: 504-17
4. Centers for Disease Control. Increase in national hospital discharge survey rates for septicemia, United States, 1979-1987. MMWR Morb Mortal Wkly Rep 1990; 39: 31-4
5. Bone RC, Sepsis, the sepsis syndrome, multi-organ failure: A plea for comparable definitions. Ann Intern Med 1991; 114: 332-3
6. Sands KE, Bates DW, Lanken PN, et al. Epidemiology of sepsis syndrome in 8 academic medical centers. JAMA 1997; 278: 234-40
7. Parrillo JE. Pathogenetic mechanisms of septic shock. N Engl J Med 1993; 328: 1471-7
8. Power BM, Millar Forbes A, Vernon van Heerden P, et al. Pharmacokinetics of drugs used in critically ill adults. Clin Pharmacokinet 1998; 34: 25-56
9. Bodenham A, Shelly MP, Park GR. The altered pharmacokinetics and pharmacodynamics of drugs commonly used in critically ill patients. Clin Pharmacokinet 1988; 14: 347-73
10. Heffner JE. A wake-up call in the intensive care unit. N Engl J Med 2000; 342: 1520-2
11. Pentel P, Benowitz N. Pharmacokinetic and pharmacodynamic considerations in drug therapy of cardiac emergencies. Clin Pharmacokinet 1984; 9: 273-308
12. Jellet LB, Heazlewood VJ. Pharmacokinetics in acute illness. Med J Aust 1990; 153: 534-41
13. Neugebauer E, Dietrich A, Lechleuthner A, et al. Pharmacotherapy in shock syndromes: The neglected field of pharmacokinetics and pharmacodynamics. Circ Shock 1992; 36: 312-20
14. Park GR. Pharmacokinetics and pharmacodynamics in the critically ill patient. Xenobiotica 1993; 23: 1195-230
15. Wagner BKJ, O'Hara D. Pharmacokinetics and pharmacodynamics of sedatives and analgesics in the treatment of agitated critically ill patients. Clin Pharmacokinet 1997; 33: 426-53
16. Kennedy JM, Van Riji A. Effects of surgery on the pharmacokinetic parameters of drugs. Clin Pharmacokinet 1998; 35: 293-12
17. Verbeeck RK, Horsmans Y. Effect of hepatic insufficiency on pharmacokinetics and drug dosing. Pharm World Sci 1998; 20: 183-92
18. McKindley DS, Hanes S, Boucher BA. Hepatic drug metabolism in critical illness. Pharmacotherapy 1998; 18: 759-78
19. Shedlofsky SI, Israel BC, McClain CJ, et al. Endotoxin administration to humans inhibits hepatic cytochrome P450-mediated drug metabolism. J Clin Invest 1994; 94: 2209-14
20. Shedlofsky SI, Israel BC, Tosheva R, et al. Endotoxin depresses hepatic cytochrome P450-mediated drug metabolism in women. Br J Clin Pharmacol 1997; 43: 627-32
21. Shelly MP, Mendel L, Park GR. Failure of critically ill patients to metabolise midazolam. Anaesthesia 1987; 42: 619-26
22. Macnab MSP, Macrae DJ, Guy E, et al. Profound reduction in morphine clearance and liver blood flow in shock. Intensive Care Med 1986; 12: 366-9
23. Groeger JS, Inturrisi CE. High-dose naloxone: Pharmacokinetics in patients in septic shock. Crit Care Med 1987; 15: 751-6
24. Beckhouse MJ, Whyte M, Byth PL, et al. Altered aminoglycoside pharmacokinetics in the critically ill. Anaesth Intensive Care 1988; 16: 418-22
25. Marik PE. Aminoglycoside volume of distribution and illness in critically ill septic patients. Anaesth Intensive Care 1993; 21: 172-3
26. Kinowski J, de la Coussaye J, Bressolle F, et al. Multiple-dose pharmacokinetics of amikacin and ceftazidime in critically ill patients with septic multiple-organ failure during intermittent hemofiltration. Antimicrob Agents Chemother 1993; 37: 464-73
27. Lugo G, Castaneda-Hernandez G. Relationship between hemodynamic and vital support measures and pharmacokinetic variability of amikacin in critically ill patients with sepsis. Crit Care Med 1997; 25: 806-11
28. Mann HJ, Fuhs DW, Awang R, et al. Altered aminoglycoside pharmacokinetics in critically ill patients with sepsis. Clin Pharm 1987; 6: 148-53
29. Chelluri L, Warren J, Jastremski MS. Pharmacokinetics of a 3 mg/kg body weight loading dose of gentamicin or tobramycin in critically ill patients. Chest 1989; 95: 1295-7
30. Triginer C, Izquierdo I, Fernández R, et al. Gentamicin volume of distribution in critically ill septic patients. Intensive Care Med 1990; 16: 303-6
31. Tholl DA, Shikuma LR, Miller TQ, et al. Physiologic response of stress and aminoglycoside clearance in critically ill patients. Crit Care Med 1993; 21: 248-51
32. Oparaoji EC, Cornwell EE, Hekmat E, et al. Aminoglycoside volume of distribution in postoperative patients with septic shock. Clin Pharm 1993; 12: 131-4
33. Peterson AK, Duffull SB. Population analysis of once-daily dosing of gentamicin in patients with neutropenia. Aust N Z J Med 1998; 28: 311-5
34. Tang GJ, Tang JJ, Lin BS, et al. Factors affecting gentamicin pharmacokinetics in septic patients. Acta Anaesthesiol Scand 1999; 43: 726-30
35. Kieft H, Hoepelman AIM, Knupp CA, et al. Pharmacokinetics of cefepime in patients with sepsis syndrome. J Antimicrob Chemother 1993; 32: 117-22
36. Pazin GJ, Schwartz SN, Ho M, et al. Treatment of septicemic patients with cefoxitin: Pharmacokinetics in renal insufficiency. Rev Infect Dis 1979; 1: 189-94
37. Lipman J, Scribante J, Gous AGS, et al. Pharmacokinetic profiles of high-dose intravenous ciprofloxacin in severe sepsis. Antimicrob Agents Chemother 1998; 42: 2235-9
38. Schrenzel J, Cerruti F, Herrmann M, et al. Single-dose pharmacokinetics of oral fleroxacin in bacteremic patients. Antimicrob Agents Chemother 1994; 38: 1219-24
39. Winslade NE, Smith IL, Simons GW, et al. Pharmacokinetics and extravascular penetration of aztreonam in patients with abdominal sepsis. Rev Infect Dis 1985; 7: S716-23
40. Cornwell EE, Belzberg H, Berne TV, et al. Pharmacokinetics of aztreonam in critically ill surgical patients. Am J Health Syst Pharm 1997; 54: 537-40
41. Mann HJ, Townsend RJ, Fuhs DW, et al. Decreased hepatic clearance of clindamycin in critically ill patients with sepsis. Clin Pharm 1987; 6: 154-9
42. Toft P, Heslet L, Hansen M, et al. Theophylline and ethylenediamine pharmacokinetics following administration of aminophylline to septic patients with multiorgan failure. Intensive Care Med 1991; 17: 465-8
43. Poloyac SM, Tosheva RT, Gardner BM, et al. The effect of endotoxin administration on the pharmacokinetics of chlorzoxazone in humans. Clin Pharmacol Ther 1999; 66: 554-62
44. Gavin TJ, Fabian TC, Wilson JD, et al. Splanchnic and systemic hemodynamic responses to portal vein endotoxin after resuscitation from hemorrhagic shock. Surgery 1994; 115: 310-24
45. Astiz ME, DeGent GE, Lin RY, et al. Microvascular function and rheologic changes in hyperdynamic sepsis. Crit Care Med 1995; 23: 265-71
46. Dahn MS, Lange P, Lobdell K, et al. Splanchnic and total body oxygen consumption differences in septic and injured patients. Surgery 1987; 101: 69-80
47. Ruokonen E, Takala J, Kari A, et al. Regional blood flow and oxygen transport in septic shock. Crit Care Med 1993; 21: 1296-303
48. Meier-Hellmann A, Reinhart K, Bredle DL, et al. Epinephrine impairs splanchnic perfusion in septic shock. Crit Care Med 1997; 25: 399-404
49. Reinelt H, Radermacher P, Kiefer P, et al. Impact of exogenous β-adrenergic receptor stimulation on hepatosplanchnic oxygen kinetics and metabolic activity in septic shock. Crit Care Med 1999; 27: 325-31
50. Takala J, Ruokonen E. Blood flow and adrenergic drugs in septic shock. In: Vincent JL, editor. Update in Intensive Care and Emergency Medicine. Berlin: Springer-Verlag, 1991: 144-52
51. Kiefer P, Tugtekin I, Wiedeck H, et al. Effect of a dopexamine-induced increase in cardiac index on splanchnic hemodynamics in septic shock. Am J Respir Crit Care Med 2000; 161: 775-9
52. Smithies M, Yee TH, Jackson L, et al. Protecting the gut and the liver in the critically ill: Effect of dopexamine. Crit Care Med 1994; 22: 789-95
53. Maynard ND, Bihari DJ, Dalton RN, et al. Increasing splanchnic blood flow in the critically ill. Chest 1995; 108: 1648-54
54. Meier-Hellmann A, Bredle DL, Specht M, et al. The effects of low-dose dopamine on splanchnic blood flow and oxygen uptake in patients with septic shock. Intensive Care Med 1997; 23: 31-7
55. Nevière R, Mathieu MD, Chagnon JL, et al. The contrasting effects of dobutamine and dopamine on gastric mucosal perfusion in septic patients. Am J Respir Crit Care Med 1996; 154: 1684-8
56. Marik PE, Mohedin M. The contrasting effects of dopamine and norepinephrine on systemic and splanchnic oxygen utilization in hyperdynamic sepsis. JAMA 1994; 272: 1354-7
57. Fink MP. Adequacy of gut oxygenation in endotoxemia and sepsis. Crit Care Med 1993; 21: S4-8
58. Benet LZ, Kroetz DL, Sheiner LB. Pharmacokinetics: The dynamics of drug absorption, distribution, and elimination. In: Goodman LS, Gilman A, editors. The Pharmacological Basis of Therapeutics. New York: Macmillan Publishing Co Inc., 1996: 3-27
59. van Lambalgen AA, Bronsveld W. van den Bos GC, et al. Distribution of cardiac output, oxygen consumption and lactate production in canine endotoxin shock. Cardiovasc Res 1984; 18: 195-205
60. Lundberg D. The pharmacological basis of treatment with high dose corticosteroids in circulatory shock. Acta Chir Scand 1985; 526: 7-12
61. Whitworth PW, Cryer HM, Garrison RN, et al. Hypoperfusion of the intestinal microcirculation without decreased cardiac output during live Escherichia coil sepsis in rats. Circ Shock 1989; 27: 111-22
62. Hollenberg SM, Ahrens TS, Astiz ME, et al. Practice parameters for hemodynamic support of sepsis in adult patients in sepsis. Crit Care Med 1999; 27: 639-60
63. Hinshaw LB. Sepsis/septic shock: Participation of the microcirculation, an abbreviated review. Crit Care Med 1996; 24: 1072-8
64. Flournoy DJ, Beller BK, Archer LT, et al. Relationship of serum gentamicin levels and methylprednisolone sodium succinate treatment in baboons challenged with Escherichia coli LD100. Clin Ther 1983; 5: 417-21
65. Beller BK, Archer LT, Passey RB, et al. Effectiveness of modified steroid/antibiotic therapies for lethal sepsis in the dog. Arch Surg 1983; 118: 1293-9
66. Hinshaw LB, Beller BK, Chang ACK. et al. Evaluation of naloxone for therapy of Escherichia coli shock. Arch Surg 1984; 119: 1410-8
67. Kreuzer F, Cain SM. Regulation of the peripheral vasculature and tissue oxygenation in health and disease. Crit Care Clin 1985; 1: 453-70
68. Ishihara H, Matsui A, Muraoka M, et al. Detection of capillary protein leakage by indocyanine green and glucose dilutions in septic patients. Crit Care Med 2000; 28: 620-6
69. Elsasser S, Schächinger H, Strobel W. Adjunctive drug treatment in severe hypoxic respiratory failure. Drugs 1999; 58: 429-46
70. Moore RD, Smith CR, Lietman PS. The association of aminoglycoside plasma levels with mortality in patients with gram-negative bacteremia. J Infect Dis 1984; 149: 443-8
71. Niemiec PW, Allo MD, Miller CF, et al. Effect of altered volume of distribution on aminoglycoside levels in patients in surgical intensive care. Arch Surg 1987; 122: 207-12
72. Dasta JF, Armstrong DK. Variability in aminoglycoside pharmacokinetics in critically ill surgical patients. Crit Care Med 1988; 16: 327-30
73. Reimann IR, Meier-Hellmann A, Reinhart K, et al. Comments to consensus document: Once daily dosing of aminoglycosides from N. Anaizi: A supplement to dosage and monitoring in critically ill patients. Int J Clin Pharmacol Ther 1997; 35: 397
74. Zaske DE, Cipolle RJ, Strate RG. Gentamicin dosage requirements: Wide interpatient variations in 242 surgery patients with normal renal function. Surgery 1980; 87: 164-9
75. Hassan E, Ober J. Predicted and measured aminoglycoside pharmacokinetic parameters in critically ill patients. Crit Care Med 1986; 14: 394-8
76. Zaske DE, Cipolle RJ, Rotschafer JC, et al. Gentamicin pharmacokinetics in 1640 patients: Method for control of serum concentrations. Antimicrob Agents Chemother 1982; 21: 407-11
77. Whipple JK, Ausman RK, Franson T, et al. Effect of individualized pharmacokinetic dosing on patient outcome. Crit Care Med 1991; 19: 1480-5
78. Nau R, Sörgel F, Prange HW. Pharmacokinetic optimisation of the treatment of bacterial central nervous system infections. Clin Pharmacokinet 1998; 35: 223-46
79. Lamy M. Acute-phase proteins and protease-antiproteases in the inflammatory reaction. In: Bihari D, Cerra FB, editors. New Horizons: Multiple Organ Failure. Fullerton (CA): Society of Critical Care Medicine, 1989: 193-217
80. Zielmann S, Mielck F, Kahl R. A rational basis for the measurement of free phenytoin concentration in critically ill trauma patients. Ther Drug Monit 1994; 16: 139-44
81. Vree TB, Shimoda M, Driessen JJ, et al. Decreased plasma albumin concentration results in increased volume of distribution and decreased elimination of midazolam in intensive care patients. Clin Pharmacol Ther 1989; 46: 537-44
82. Tuchschmidt J, Oblitas D, Fried JC. Oxygen consumption in sepsis and septic shock. Crit Care Med 1991; 19: 664-71
83. Elston AC, Bayliss MK, Park GR. Effect of renal failure on drug metabolism by the liver. Br J Anaesth 1993; 71: 282-90
84. Beal AL, Cerra FB. Multiple organ failure syndrome in the 1990s: Systemic inflammatory response and organ dysfunction. JAMA 1994; 271: 226-33
85. Cerra FB, Siegel JH, Coleman B, et al. Septic autocannibalism: A failure of exogenous nutritional support. Ann Surg 1980; 192: 570-80
86. Shargel L, Yu ABC. Applied biopharmaceutics and pharmacokinetics. Stamford: Appleton and Lange, 1999: 353-98
87. Belpaire FM, Bogaert MG. The fate of xenobiotics in living organisms. In: Wermuth CG, editor. The Practice of Medicinal Chemistry. London: Academia Press, 1996: 593-614
88. Hebert MF. Guide to drug dosage in hepatic disease. In: Holford N, editor. Clinical Pharmacokinetics: Drug Data Handbook. Auckland (NZ): Adis International 1998: 121-79
89. Gump FE, Price JB, Kinney JM. Whole body and splanchnic blood flow and oxygen consumption measurements in patients with intraperitoneal infection. Ann Surg 1970; 171: 321-8
90. Wilmore DW, Goodwin CW, Aulick LH, et al. Effect of injury and infection on visceral metabolism and circulation. Ann Surg 1980; 192: 491-504
91. Wang P, Ba ZF, Chaudry IH. Hepatic extraction of indocyanine green is depressed early in sepsis despite increased hepatic blood flow and cardiac output. Arch Surg 1991; 126: 219-24
92. Bersten AD, Hersch M, Cheung H, et al. The effect of various sympathomimetics on the regional circulations in hyperdynamic sepsis. Surgery 1992; 112: 549-61
93. Wyler F, Forsyth RP, Nies AS, et al. Endotoxin-induced regional circulatory changes in the unanesthetized monkey. Circ Res 1969; 24: 777-86
94. Wang P, Ba ZF, Chaudry IH, et al. Increase in hepatic blood flow during early sepsis is due to increased portal blood flow. Am J Physiol 1991; 261: R1507-12
95. Wang P, Zhou M, Rana MW, et al. Differential alterations in microvascular perfusion in various organs during early and late sepsis. Am J Physiol 1992; 263: G38-43
96. Wang P, Ba ZF, Tait SM, et al. Alterations in circulating blood volume during polymicrobial sepsis. Circ Shock 1993; 40: 92-8
97. Wang P, Ba ZF, Chaudry IH. Hepatocellular dysfunction occurs earlier than the onset of hyperdynamic circulation during sepsis. Shock 1995; 3: 21-6
98. Ayuse T, Brienza N, Revelly JP, et al. Alterations in liver hemodynamics in an intact porcine model of endotoxin shock. Am J Physiol 1995; 268: H1106-14
99. Garrison RN, Ratcliffe DJ, Fry DE. Hepatocellular function and nutrient blood flow in experimental peritonitis. Surgery 1982; 92: 713-9
100. Gutierrez G, Bismar H, Dantzker DR, et al. Comparison of gastric intramucosal pH with measures of oxygen transport and consumption in critically ill patients. Crit Care Med 1992; 20: 451-7
101. De Backer D, Creteur J, Noordally O, et al. Does hepatosplanchnic VO2/DO2 dependency exist in critically ill patients? Am J Respir Crit Care Med 1998; 157: 1219-25
102. Gutierrez G, Clark C, Brown SD, et al. Effect of dobutamine on oxygen consumption and gastric mucosal pH in septic patients. Am J Respir Crit Care Med 1994; 150: 324-9
103. Marik PE. Gastric intramucosal pH: A better predictor of multi-organ dysfunction syndrome than oxygen-derived variables in patients with sepsis. Chest 1993; 104: 225-9
104. Maynard N, Bihari D, Beale R, et al. Assessment of splanchnic oxygenation by gastric tonometry in patients with acute circulatory failure. JAMA 1993; 270: 1203-10
105. Creteur J, De Backer D, Vincent JL. A dobutamine test can disclose hepatosplanchnic hypoperfusion in septic patients. Am J Respir Crit Care Med 1999; 160: 839-45
106. Levy B, Bollaert PE, Charpentier C, et al. Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism and gastric tonometric variables in septic shock: A prospective randomized study. Intensive Care Med 1997; 23: 282-7
107. Perkins MW, Dasta JF, DeHaven B. Physiologic implications of mechanical ventilation on pharmacokinetics. Drug Intell Clin Pharm 1989; 23: 316-23
108. Bonnet F, Richard C, Glaser P, et al. Changes in hepatic flow induced by continuous positive pressure ventilation in critically ill patients. Crit Care Med 1982; 10: 703-5
109. Jardin F, Farcot JC, Boisante L, et al. Influence of positive end-expiratory pressure on left ventricular performance. N Engl J Med 1981; 304: 387-92
110. Zamacona MK, Suarez E, Aguilera L, et al. Serum protein binding of propofol in critically ill patients. Acta Anaesthesiol Scand 1997; 41: 1267-72
111. Park GR, Pichard L, Tinel M, et al. What changes drug metabolism in critically ill patients? Anaesthesia 1994; 49: 188-91
112. Park GR, Miller E, Navapurkar V. What changes drug metabolism in critically ill patients? Serum inhibits the metabolism of midazolam in human microsomes. Anaesthesia 1996; 51: 11-5
113. Park GR, Miller E. What changes drug metabolism in critically ill patients? Effect of pre-existing disease on the metabolism of midazolam. Anaesthesia 1996; 51: 431-4
114. Park GR. Molecular mechanisms of drug metabolism in the critically ill. Br J Anaesth 1996; 77: 32-49
115. Morgan ET. Regulation of cytochromes P450 during inflammation and infection. Drug Metab Rev 1997; 29: 1129-88
116. Iber H, Sewer MB, Barclay TB, et al. Modulation of drug metabolism in infectious and inflammatory diseases. Drug Metab Rev 1999; 31: 29-41
117. Tsutsumi M, Lasker JM, Shimizu M, et al. The intralobular distribution of ethanol-inducible P450 2E1 in rat and human liver. Hepatology 1989; 10: 437-46
118. Muller CM, Scierka A, Stiller RL. Nitric oxide mediates hepatic cytochrome P450 dysfunction induced by endotoxin. Anesthesiology 1996; 84: 1435-42
119. Rowland M, Tozer TN. Clinical Pharmacokinetics: Concepts and Applications. Philadelphia (PA): Williams and Wilkins, 1994: 156-83
120. van Dalen R, Vree TB. Pharmacokinetics of antibiotics in critically ill patients. Intensive Care Med 1990; 16: S235-8
121. Duchin KL, Schrier RW. Interrelationship between renal haemodynamics, drug kinetics and drug action. Clin Pharmacokinet 1978; 3: 58-71
122. Bock HA. Pathophysiology of acute renal failure in septic shock: From prerenal to renal failure. Kidney Int 1998; 53: S15-8
123. Milne RW, Nation RL, Somogyi AA, et al. The influence of renal function on the renal clearance of morphine and its glucuronide metabolites in intensive-care patients. Br J Clin Pharmacol 1992; 34: 53-9
124. Davies G, Kingswood C, Street M. Pharmacokinetics of opioids in renal dysfunction. Clin Pharmacokinet 1996; 31: 410-22
125. D'Honneur G, Gilton A, Sandouk P, et al. Plasma and cerebrospinal fluid concentrations of morphine and morphine glucuronides after oral morphine. Anesthesiology 1994; 81: 87-93
126. Bauer TM, Haberthür C, Riem Ha H, et al. Prolonged sedation due to accumulation of conjugated metabolites of midazolam. Lancet 1995; 346: 145-7
127. St Peter WL, Redic-Kill KA, Halstenson CE. Clinical pharmacokinetics of antibiotics in patients with impaired renal function. Clin Pharmacokinet 1992; 22: 169-210
128. Jones EM, McMullin CM, Hedges AJ, et al. The pharmacokinetics of intravenous ciprofloxacin 400mg 12 hourly in patients with severe sepsis: The effect of renal function and intra-abdominal disease. J Antimicrob Chemother 1997; 40: 121-4
129. Wheeler AP, Bernard GR. Treating patients with severe sepsis. N Engl J Med 1999; 340: 207-14
130. De Paepe P, Belpaire FM, Rosseel MT, et al. The influence of hypovolemia on the pharmacokinetics and the electroencephalographic effect of propofol in the rat. Anesthesiology 2000; 93: 1482-90
131. Silverman HJ, Penaranda R, Orens JB, et al. Impaired β-adrenergic receptor stimulation of cyclic adenosine monophosphate in human septic shock: Association with myocardial hyporesponsiveness to catecholamines. Crit Care Med 1993; 21: 31-9