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Antibiotic Pharmacokinetics Following Fluid Resuscitation From Traumatic Shock

Antibiotic Pharmacokinetics Following Fluid Resuscitation From Traumatic Shock Abstract Objective: To describe the pharmacokinetic profile of aztreonam and vancomycin hydrochloride in a clinically relevant experimental model of hemorrhagic shock and trauma. Methods: Ten mongrel pigs (mean±SD weight, 26.7±6.4 kg) were anesthetized with fentanyl citrate and ventilated, and an indwelling catheter was placed in the jugular vein. On day 3, all pigs were subjected to fentanyl administration, ventilation, soft-tissue injury, and an arterial hemorrhage (mean±SD, 40%±8%). After a 1-hour shock period, baseline hemodynamics were restored by reinfusing shed blood plus twice the shed volume as lactated Ringer's solution. Aztreonam and vancomycin were infused on day 1, after resuscitation on day 3, and on days 4 and 8. Serial plasma samples were collected for 6 hours after treatment, and differences were compared with analysis of variance. Results: Aztreonam clearance initially decreased with trauma, but subsequently increased by 48% (P<.02) by day 8. Aztreonam steady-state volume decreased by 34% (P=.05, baseline value vs that on day 8). Vancomycin clearance was increased between 25% and 52% (P<.001) on days 3, 4, and 8 compared with the baseline value. Vancomycin steady-state volume initially increased with trauma (P=.009), but it subsequently decreased by 29% (P<.001) on day 8. These data cannot be explained by changes in plasma volume per se because levels of plasma sodium, potassium, chloride, and calcium were within normal reference ranges at all time points. Neither liver nor renal functions were severely impaired because levels of serum urea nitrogen, bilirubin, liver enzymes, creatinine, and plasma proteins were within normal reference ranges. Furthermore, our previous work demonstrated that systemic and splanchnic organ oxygen delivery and demand were near normal immediately after fluid resuscitation and for at least 3 days thereafter; thus, there were probably no major perfusion abnormalities in the liver or kidney. Conclusions: For at least 5 days after trauma, clearance and steady-state volume of aztreonam and vancomycin are altered. These changes suggest that the interval and magnitude of dosing should be adjusted, relative to the standard recommended dosages of each antibiotic, to maximize their efficacy. Similar studies should be done for other antibiotics.(Arch Surg. 1995;130:1321-1329) References 1. Dellinger EP, Oreskovich MR, Wertz MJ, Hamaski V, Lenard ES. Risk of infection following laparotomy for penetrating abdominal injury . Arch Surg . 1984; 119:20-27.Crossref 2. Nichols RL, Smith JW, Klein DB, et al. Risk of infection after penetrating abdominal trauma . N Engl J Med . 1984;311:1065-1070.Crossref 3. Jones RC, Thal ER, Johnson NA, Gollihar LN. Evaluation of antibiotic therapy following penetrating abdominal trauma . Ann Surg . 1985;201:576-585.Crossref 4. Fabian TC, Croce MA, Payne LW, Minard G, Pritchard FE, Kudsk KA. Duration of antibiotic therapy for penetrating abdominal trauma: a prospective trial . Surgery . 1992;112:788-795. 5. Croce MA, Fabian TC, Stewart RM, Pritchard FE, Minard G, Trenthem LL, Kudsk KA. Empiric monotherapy versus combination therapy of nosocomial pneumonia in trauma patients . J Trauma . 1993;35:303-309.Crossref 6. Fabian TC, Hess MM, Croce MA, et al. Superiority of aztreonam/clindamycin compared with gentamicin/clindamycin in patients with penetrating abdominal trauma . Am J Surg . 1994;167:291-296.Crossref 7. Chaudry IH, Ayala A. Mechanism of increased susceptibility to infection following hemorrhage . Am J Surg . 1993;165:59S-67S.Crossref 8. Livingston DH, Malangoni MA. An experimental study of susceptibility to infection after hemorrhagic shock . Surg Gynecol Obstet . 1988;168:138-142. 9. Livingston DH, Shumate CR, Polk HC, Malangoni MA. More is better: antibiotic management after hemorrhagic shock . Ann Surg . 1988;208:451-459.Crossref 10. Livingston DH, Wang MT. Continuous infusion of cefazolin is superior to intermittent dosing in decreasing infection after hemorrhagic shock . Am J Surg . 1993;165:203-207.Crossref 11. Griffeth LK, Rosen GM, Tschanz C, Rauckman EJ. Effects of model traumatic injury on hepatic drug metabolism in the rat, I: in vivo antipyrine metabolism . Drug Metab Dispos . 1983;11:517-525. 12. Griffeth LK, Rosen GM, Rauckman EJ. Effects of model traumatic injury on hepatic drug metabolism in the rat, II: in vivo metabolism of hexobarbital and zoxazolamine . Drug Metab Dispos . 1984;12:582-587. 13. Griffeth LK, Rosen GM, Rauckman EJ. Effects of model traumatic injury on hepatic drug metabolism in the rat, III: differential responses of cytochrome P-450 subpopulations . Drug Metab Dispos . 1984;12:588-595. 14. Griffeth LK, Rosen GM, Rauckman EJ. Effects of model traumatic injury on hepatic drug metabolism in the rat, IV: glucuronidation . Drug Metab Dispos . 1985;12:391-397. 15. Griffeth LK, Rosen GM, Rauckman EJ. Effects of model traumatic injury on hepatic drug metabolism in the rat, V: sulfation and acetylation . Drug Metab Dispos . 1985;12:391-397. 16. Dickson PL, DiPiro JT, Michael KA, Cheung RPF, Hall EM. Effect of hemorrhagic shock on cefazolin and gentamicin pharmacokinetics in dogs . Antimicrob Agents Chemother . 1987;31:389-392.Crossref 17. Fabian TC, Croce MA, Stewart RM, Dockter ME, Proctor KG. Neutrophil CD18 expression and blockade following traumatic shock and endotoxin challenge . Ann Surg . 1994;220:552-563.Crossref 18. Stewart RM, Fabian TC, Fabian MJ, et al. Gastric and extragastric actions of the histamine antagonist ranitidine during posttraumatic sepsis . Surgery . 1995; 117:68-82.Crossref 19. McGinty MP, Stewart RM, Fabian MJ, Fabian TC, Proctor KG. Gamma scintigraphy and early hepatocellular dysfunction during posttraumatic sepsis . Surgery . 1994;116:535-543. 20. Bertino JS, Booker LA, Franck PA, Jenkins PL, Franck KR, Nafziger AN. Incidence of and significant risk factors for aminoglycoside-associated nephrotoxicity in patients dosed by using individualized pharmacokinetic monitoring . J Infect Dis . 1993;167:173-179.Crossref 21. Meulemans A, Mohler J, Vittecoq D, et al. High-performance liquid chromatographic analysis of azthreonam in tissues and body fluids . J Chromatogr . 1986; 377:466-470.Crossref 22. D'Argenio DZ, Schumitzky A. A program package for simulation and parameter estimation in pharmacokinetic systems . Comput Methods Programs Biomed . 1979;9:115-134.Crossref 23. Rodvold KA, Blum RA, Fischer JH, et al. Vancomycin pharmacokinetics in patients with various degrees of renal function . Antimicrob Agents Chemother . 1988;32:848.Crossref 24. Swabb EA, Sugerman AA, Platt TB, Pilkiewicz FG, Frantz M. Single-dose pharmacokinetics of the monobactam aztreonam (SQ 26,776) in healthy subjects . Antimicrob Agents Chemother . 1982;21:944-949.Crossref 25. Swabb EA, Sugerman AA, Frantz M, Platt TB, Stern M. Renal handling of the monobactam aztreonam in healthy subjects . Clin Pharmacol Ther . 1983;33: 609-614.Crossref 26. Golper TA, Noonan HM, Elzinga L, et al. Vancomycin pharmacokinetics, renal handling, and nonrenal clearances in normal human subjects . Clin Pharmacol Ther . 1988;43:565-570.Crossref 27. Gibaldi M, Perrier D. Pharmacokinetics . 2nd ed. New York, NY: Marcel Dekker Inc; 1982:199-219. 28. Zurick AM, Urzua J, Yared JP, Estafanous FG. Comparison of hemodynamic and hormonal effects of large single-dose fentanyl anesthesia and halothane/nitrous oxide anesthesia for coronary artery surgery . Anesth Analg . 1982;61: 521-526.Crossref 29. Reich DL, Silvay G. Ketamine: an update on the first twenty-five years of clincal experience . Can J Anaesth . 1989;36:186-197.Crossref 30. Samanta A, Roffe C, Woods KL. Accidental self-administration of xylazine in a veterinary nurse . Postgrad Med J . 1990;66:244-245.Crossref 31. Behrman SW, Fabian TC, Kudsk KA, Proctor KG. Microcirculatory flow changes after initial resuscitation of hemorrhagic shock with 7.5% hypertonic saline/6% dextran 70 . J Trauma . 1991;31:589-598.Crossref 32. Gavin TJ, Fabian TC, Wilson JD, et al. Splanchnic and systemic hemodynamic responses to portal vein endotoxin after resuscitation from hemorrhagic shock . Surgery . 1994;115:310-324. 33. Spiers JP, Fabian TC, Kudsk KA, Proctor KG. Resuscitation of hemorrhagic shock with hypertonic saline/dextran or lactated Ringer's supplemented with AICA riboside . Circ Shock . 1993;40:29-36. 34. Mann HJ, Fuhs DW, Awang R, Ndemo FA, Cerra FB. Altered aminoglycoside pharmacokinetics in critically ill patients with sepsis . Clin Pharm . 1987;6:148-153. 35. Niemiec PW, Allo MD, Miller CF. Effect of altered volume of distribution on aminoglycoside levels in patients in surgical intensive care . Arch Surg . 1987; 122:207-212.Crossref 36. Dasta JF, Armstrong DK. Variability in aminoglycoside pharmacokinetics in critically ill surgical patients . Crit Care Med . 1988;16:327-330.Crossref 37. Boccazzi A, Langer M, Mandelli M, Ranzi AM, Urso R. The pharmacokinetics of aztreonam and penetration into the bronchial secretions of critically ill patients . J Antimicrob Chemother . 1989;23:401-407.Crossref 38. Ericsson CD, Fischer RP, Rowlands BJ, Hunt C, Miller-Crotchett P, Reed L. Prophylactic antibiotics in trauma: the hazards of underdosing . J Trauma . 1989; 29:1356-1361.Crossref 39. Moore R, Smith C, Lietman P. Increased risk of renal dysfunction due to interaction of liver disease and aminoglycosides . Am J Med . 1986;80:1093-1097.Crossref 40. Zaske DE, Sawchuk RJ, Gerding DN. Increased dosage requirements of gentamicin in burn patients . J Trauma . 1976;16:824-828.Crossref 41. Livingston DH, Malangoni MA. Increasing antibiotic dose decreases polymicrobial infection after hemorrhagic shock . Surg Gynecol Obstet . 1993;176: 418-422. 42. Rall TW. Hypnotics and sedatives: ethanol . In: Gilman AG, Rail TW, Nies AS, Taylor P, eds. The Pharmacological Basis of Therapeutics . 8th ed. Elmsford, NY: Pergamon Press Inc; 1990:345-382. 43. Wang P, Ba ZA, Chaudry IH. Endothelial cell dysfunction occurs after hemorrhage in nonheparinized but not in preheparinized models . J Surg Res . 1993; 54:499-506.Crossref 44. Rana MW, Singh G, Wang P, Ayala A, Zhou M, Chaudry IH. Protective effects of preheparinization on microvasculature during and following hemorrhagic shock . J Trauma . 1992;32:420-426.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Surgery American Medical Association

Antibiotic Pharmacokinetics Following Fluid Resuscitation From Traumatic Shock

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Publisher
American Medical Association
Copyright
Copyright © 1995 American Medical Association. All Rights Reserved.
ISSN
0004-0010
eISSN
1538-3644
DOI
10.1001/archsurg.1995.01430120075012
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Abstract

Abstract Objective: To describe the pharmacokinetic profile of aztreonam and vancomycin hydrochloride in a clinically relevant experimental model of hemorrhagic shock and trauma. Methods: Ten mongrel pigs (mean±SD weight, 26.7±6.4 kg) were anesthetized with fentanyl citrate and ventilated, and an indwelling catheter was placed in the jugular vein. On day 3, all pigs were subjected to fentanyl administration, ventilation, soft-tissue injury, and an arterial hemorrhage (mean±SD, 40%±8%). After a 1-hour shock period, baseline hemodynamics were restored by reinfusing shed blood plus twice the shed volume as lactated Ringer's solution. Aztreonam and vancomycin were infused on day 1, after resuscitation on day 3, and on days 4 and 8. Serial plasma samples were collected for 6 hours after treatment, and differences were compared with analysis of variance. Results: Aztreonam clearance initially decreased with trauma, but subsequently increased by 48% (P<.02) by day 8. Aztreonam steady-state volume decreased by 34% (P=.05, baseline value vs that on day 8). Vancomycin clearance was increased between 25% and 52% (P<.001) on days 3, 4, and 8 compared with the baseline value. Vancomycin steady-state volume initially increased with trauma (P=.009), but it subsequently decreased by 29% (P<.001) on day 8. These data cannot be explained by changes in plasma volume per se because levels of plasma sodium, potassium, chloride, and calcium were within normal reference ranges at all time points. Neither liver nor renal functions were severely impaired because levels of serum urea nitrogen, bilirubin, liver enzymes, creatinine, and plasma proteins were within normal reference ranges. Furthermore, our previous work demonstrated that systemic and splanchnic organ oxygen delivery and demand were near normal immediately after fluid resuscitation and for at least 3 days thereafter; thus, there were probably no major perfusion abnormalities in the liver or kidney. Conclusions: For at least 5 days after trauma, clearance and steady-state volume of aztreonam and vancomycin are altered. These changes suggest that the interval and magnitude of dosing should be adjusted, relative to the standard recommended dosages of each antibiotic, to maximize their efficacy. Similar studies should be done for other antibiotics.(Arch Surg. 1995;130:1321-1329) References 1. Dellinger EP, Oreskovich MR, Wertz MJ, Hamaski V, Lenard ES. Risk of infection following laparotomy for penetrating abdominal injury . Arch Surg . 1984; 119:20-27.Crossref 2. Nichols RL, Smith JW, Klein DB, et al. Risk of infection after penetrating abdominal trauma . N Engl J Med . 1984;311:1065-1070.Crossref 3. Jones RC, Thal ER, Johnson NA, Gollihar LN. Evaluation of antibiotic therapy following penetrating abdominal trauma . Ann Surg . 1985;201:576-585.Crossref 4. Fabian TC, Croce MA, Payne LW, Minard G, Pritchard FE, Kudsk KA. Duration of antibiotic therapy for penetrating abdominal trauma: a prospective trial . Surgery . 1992;112:788-795. 5. Croce MA, Fabian TC, Stewart RM, Pritchard FE, Minard G, Trenthem LL, Kudsk KA. Empiric monotherapy versus combination therapy of nosocomial pneumonia in trauma patients . J Trauma . 1993;35:303-309.Crossref 6. Fabian TC, Hess MM, Croce MA, et al. Superiority of aztreonam/clindamycin compared with gentamicin/clindamycin in patients with penetrating abdominal trauma . Am J Surg . 1994;167:291-296.Crossref 7. Chaudry IH, Ayala A. Mechanism of increased susceptibility to infection following hemorrhage . Am J Surg . 1993;165:59S-67S.Crossref 8. Livingston DH, Malangoni MA. An experimental study of susceptibility to infection after hemorrhagic shock . Surg Gynecol Obstet . 1988;168:138-142. 9. Livingston DH, Shumate CR, Polk HC, Malangoni MA. More is better: antibiotic management after hemorrhagic shock . Ann Surg . 1988;208:451-459.Crossref 10. Livingston DH, Wang MT. Continuous infusion of cefazolin is superior to intermittent dosing in decreasing infection after hemorrhagic shock . Am J Surg . 1993;165:203-207.Crossref 11. Griffeth LK, Rosen GM, Tschanz C, Rauckman EJ. Effects of model traumatic injury on hepatic drug metabolism in the rat, I: in vivo antipyrine metabolism . Drug Metab Dispos . 1983;11:517-525. 12. Griffeth LK, Rosen GM, Rauckman EJ. Effects of model traumatic injury on hepatic drug metabolism in the rat, II: in vivo metabolism of hexobarbital and zoxazolamine . Drug Metab Dispos . 1984;12:582-587. 13. Griffeth LK, Rosen GM, Rauckman EJ. Effects of model traumatic injury on hepatic drug metabolism in the rat, III: differential responses of cytochrome P-450 subpopulations . Drug Metab Dispos . 1984;12:588-595. 14. Griffeth LK, Rosen GM, Rauckman EJ. Effects of model traumatic injury on hepatic drug metabolism in the rat, IV: glucuronidation . Drug Metab Dispos . 1985;12:391-397. 15. Griffeth LK, Rosen GM, Rauckman EJ. Effects of model traumatic injury on hepatic drug metabolism in the rat, V: sulfation and acetylation . Drug Metab Dispos . 1985;12:391-397. 16. Dickson PL, DiPiro JT, Michael KA, Cheung RPF, Hall EM. Effect of hemorrhagic shock on cefazolin and gentamicin pharmacokinetics in dogs . Antimicrob Agents Chemother . 1987;31:389-392.Crossref 17. Fabian TC, Croce MA, Stewart RM, Dockter ME, Proctor KG. Neutrophil CD18 expression and blockade following traumatic shock and endotoxin challenge . Ann Surg . 1994;220:552-563.Crossref 18. Stewart RM, Fabian TC, Fabian MJ, et al. Gastric and extragastric actions of the histamine antagonist ranitidine during posttraumatic sepsis . Surgery . 1995; 117:68-82.Crossref 19. McGinty MP, Stewart RM, Fabian MJ, Fabian TC, Proctor KG. Gamma scintigraphy and early hepatocellular dysfunction during posttraumatic sepsis . Surgery . 1994;116:535-543. 20. Bertino JS, Booker LA, Franck PA, Jenkins PL, Franck KR, Nafziger AN. Incidence of and significant risk factors for aminoglycoside-associated nephrotoxicity in patients dosed by using individualized pharmacokinetic monitoring . J Infect Dis . 1993;167:173-179.Crossref 21. Meulemans A, Mohler J, Vittecoq D, et al. High-performance liquid chromatographic analysis of azthreonam in tissues and body fluids . J Chromatogr . 1986; 377:466-470.Crossref 22. D'Argenio DZ, Schumitzky A. A program package for simulation and parameter estimation in pharmacokinetic systems . Comput Methods Programs Biomed . 1979;9:115-134.Crossref 23. Rodvold KA, Blum RA, Fischer JH, et al. Vancomycin pharmacokinetics in patients with various degrees of renal function . Antimicrob Agents Chemother . 1988;32:848.Crossref 24. Swabb EA, Sugerman AA, Platt TB, Pilkiewicz FG, Frantz M. Single-dose pharmacokinetics of the monobactam aztreonam (SQ 26,776) in healthy subjects . Antimicrob Agents Chemother . 1982;21:944-949.Crossref 25. Swabb EA, Sugerman AA, Frantz M, Platt TB, Stern M. Renal handling of the monobactam aztreonam in healthy subjects . Clin Pharmacol Ther . 1983;33: 609-614.Crossref 26. Golper TA, Noonan HM, Elzinga L, et al. Vancomycin pharmacokinetics, renal handling, and nonrenal clearances in normal human subjects . Clin Pharmacol Ther . 1988;43:565-570.Crossref 27. Gibaldi M, Perrier D. Pharmacokinetics . 2nd ed. New York, NY: Marcel Dekker Inc; 1982:199-219. 28. Zurick AM, Urzua J, Yared JP, Estafanous FG. Comparison of hemodynamic and hormonal effects of large single-dose fentanyl anesthesia and halothane/nitrous oxide anesthesia for coronary artery surgery . Anesth Analg . 1982;61: 521-526.Crossref 29. Reich DL, Silvay G. Ketamine: an update on the first twenty-five years of clincal experience . Can J Anaesth . 1989;36:186-197.Crossref 30. Samanta A, Roffe C, Woods KL. Accidental self-administration of xylazine in a veterinary nurse . Postgrad Med J . 1990;66:244-245.Crossref 31. Behrman SW, Fabian TC, Kudsk KA, Proctor KG. Microcirculatory flow changes after initial resuscitation of hemorrhagic shock with 7.5% hypertonic saline/6% dextran 70 . J Trauma . 1991;31:589-598.Crossref 32. Gavin TJ, Fabian TC, Wilson JD, et al. Splanchnic and systemic hemodynamic responses to portal vein endotoxin after resuscitation from hemorrhagic shock . Surgery . 1994;115:310-324. 33. Spiers JP, Fabian TC, Kudsk KA, Proctor KG. Resuscitation of hemorrhagic shock with hypertonic saline/dextran or lactated Ringer's supplemented with AICA riboside . Circ Shock . 1993;40:29-36. 34. Mann HJ, Fuhs DW, Awang R, Ndemo FA, Cerra FB. Altered aminoglycoside pharmacokinetics in critically ill patients with sepsis . Clin Pharm . 1987;6:148-153. 35. Niemiec PW, Allo MD, Miller CF. Effect of altered volume of distribution on aminoglycoside levels in patients in surgical intensive care . Arch Surg . 1987; 122:207-212.Crossref 36. Dasta JF, Armstrong DK. Variability in aminoglycoside pharmacokinetics in critically ill surgical patients . Crit Care Med . 1988;16:327-330.Crossref 37. Boccazzi A, Langer M, Mandelli M, Ranzi AM, Urso R. The pharmacokinetics of aztreonam and penetration into the bronchial secretions of critically ill patients . J Antimicrob Chemother . 1989;23:401-407.Crossref 38. Ericsson CD, Fischer RP, Rowlands BJ, Hunt C, Miller-Crotchett P, Reed L. Prophylactic antibiotics in trauma: the hazards of underdosing . J Trauma . 1989; 29:1356-1361.Crossref 39. Moore R, Smith C, Lietman P. Increased risk of renal dysfunction due to interaction of liver disease and aminoglycosides . Am J Med . 1986;80:1093-1097.Crossref 40. Zaske DE, Sawchuk RJ, Gerding DN. Increased dosage requirements of gentamicin in burn patients . J Trauma . 1976;16:824-828.Crossref 41. Livingston DH, Malangoni MA. Increasing antibiotic dose decreases polymicrobial infection after hemorrhagic shock . Surg Gynecol Obstet . 1993;176: 418-422. 42. Rall TW. Hypnotics and sedatives: ethanol . In: Gilman AG, Rail TW, Nies AS, Taylor P, eds. The Pharmacological Basis of Therapeutics . 8th ed. Elmsford, NY: Pergamon Press Inc; 1990:345-382. 43. Wang P, Ba ZA, Chaudry IH. Endothelial cell dysfunction occurs after hemorrhage in nonheparinized but not in preheparinized models . J Surg Res . 1993; 54:499-506.Crossref 44. Rana MW, Singh G, Wang P, Ayala A, Zhou M, Chaudry IH. Protective effects of preheparinization on microvasculature during and following hemorrhagic shock . J Trauma . 1992;32:420-426.Crossref

Journal

Archives of SurgeryAmerican Medical Association

Published: Dec 1, 1995

References