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Effect of a single dose of tobramycin on systemic inflammatory response-induced acute kidney injury in a 6-hour porcine model*

Lipcsey, Miklós; Carlsson, Markus; Larsson, Anders; Algotsson, Lars LU ; Eriksson, Mats; Lukinius, Agneta and Sjölin, Jan (2009) In Critical Care Medicine 37(10). p.2782-2790
Abstract
OBJECTIVE:: To evaluate whether the addition of tobramycin further compromises renal function in inflammatory response-induced acute kidney injury. Effective antibiotic treatment in septic shock is crucial for the outcome. The combination of aminoglycosides with different beta-lactam antibiotics offers a broad antimicrobial coverage, rapid bacterial killing, synergistic effects, and low antibiotic-induced endotoxin release. However, aminoglycosides have nephrotoxic effects that may aggravate sepsis-induced acute kidney injury. DESIGN:: Prospective, randomized, placebo-controlled experimental study. SETTING:: University research unit. SUBJECTS:: Twenty-four healthy pigs. INTERVENTIONS:: The animals were anesthetized and randomized to four... (More)
OBJECTIVE:: To evaluate whether the addition of tobramycin further compromises renal function in inflammatory response-induced acute kidney injury. Effective antibiotic treatment in septic shock is crucial for the outcome. The combination of aminoglycosides with different beta-lactam antibiotics offers a broad antimicrobial coverage, rapid bacterial killing, synergistic effects, and low antibiotic-induced endotoxin release. However, aminoglycosides have nephrotoxic effects that may aggravate sepsis-induced acute kidney injury. DESIGN:: Prospective, randomized, placebo-controlled experimental study. SETTING:: University research unit. SUBJECTS:: Twenty-four healthy pigs. INTERVENTIONS:: The animals were anesthetized and randomized to four groups. Groups I (n = 8) and II (n = 8) received endotoxin infusion for 6 hrs, whereas groups III (n = 4) and IV (n = 4) received saline. Groups I and III received 7 mg/kg of tobramycin 20 mins after the initiation of the protocol, whereas groups II and IV received saline. MEASUREMENTS AND MAIN RESULTS:: The renal elimination rate of a bolus dose of cefuroxime was chosen as the primary end point. Renal function was also evaluated by urine output, creatinine clearance, plasma cystatin C, plasma urea, and urine NAG (N-acetyl-beta-D-glucoaminidase). After 3 hrs, there were significantly lower cefuroxime elimination rates in the two endotoxin groups than in the nonendotoxin groups. No difference in cefuroxime elimination rates between groups I and II could be detected at any time point. Similarly, there were changes indicating acute kidney injury in urine output, creatinine clearance, and plasma cystatin C in the endotoxin groups with no differences between groups I and II. Plasma urea and urine NAG did not differ between any of the groups. CONCLUSIONS:: The result of this study does not lend any support to the hypothesis that a single dose of tobramycin enhances the risk of acute renal failure in cases with systemic inflammatory response-induced acute kidney injury. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Critical Care Medicine
volume
37
issue
10
pages
2782 - 2790
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000270234700015
  • pmid:19707126
  • scopus:70349668735
ISSN
1530-0293
DOI
10.1097/CCM.0b013e3181a988f8
language
English
LU publication?
yes
id
17a67cd2-1ccb-4b77-a967-06920d274840 (old id 1469335)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19707126?dopt=Abstract
date added to LUP
2009-09-07 15:44:43
date last changed
2017-04-30 11:38:20
@article{17a67cd2-1ccb-4b77-a967-06920d274840,
  abstract     = {OBJECTIVE:: To evaluate whether the addition of tobramycin further compromises renal function in inflammatory response-induced acute kidney injury. Effective antibiotic treatment in septic shock is crucial for the outcome. The combination of aminoglycosides with different beta-lactam antibiotics offers a broad antimicrobial coverage, rapid bacterial killing, synergistic effects, and low antibiotic-induced endotoxin release. However, aminoglycosides have nephrotoxic effects that may aggravate sepsis-induced acute kidney injury. DESIGN:: Prospective, randomized, placebo-controlled experimental study. SETTING:: University research unit. SUBJECTS:: Twenty-four healthy pigs. INTERVENTIONS:: The animals were anesthetized and randomized to four groups. Groups I (n = 8) and II (n = 8) received endotoxin infusion for 6 hrs, whereas groups III (n = 4) and IV (n = 4) received saline. Groups I and III received 7 mg/kg of tobramycin 20 mins after the initiation of the protocol, whereas groups II and IV received saline. MEASUREMENTS AND MAIN RESULTS:: The renal elimination rate of a bolus dose of cefuroxime was chosen as the primary end point. Renal function was also evaluated by urine output, creatinine clearance, plasma cystatin C, plasma urea, and urine NAG (N-acetyl-beta-D-glucoaminidase). After 3 hrs, there were significantly lower cefuroxime elimination rates in the two endotoxin groups than in the nonendotoxin groups. No difference in cefuroxime elimination rates between groups I and II could be detected at any time point. Similarly, there were changes indicating acute kidney injury in urine output, creatinine clearance, and plasma cystatin C in the endotoxin groups with no differences between groups I and II. Plasma urea and urine NAG did not differ between any of the groups. CONCLUSIONS:: The result of this study does not lend any support to the hypothesis that a single dose of tobramycin enhances the risk of acute renal failure in cases with systemic inflammatory response-induced acute kidney injury.},
  author       = {Lipcsey, Miklós and Carlsson, Markus and Larsson, Anders and Algotsson, Lars and Eriksson, Mats and Lukinius, Agneta and Sjölin, Jan},
  issn         = {1530-0293},
  language     = {eng},
  number       = {10},
  pages        = {2782--2790},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Critical Care Medicine},
  title        = {Effect of a single dose of tobramycin on systemic inflammatory response-induced acute kidney injury in a 6-hour porcine model*},
  url          = {http://dx.doi.org/10.1097/CCM.0b013e3181a988f8},
  volume       = {37},
  year         = {2009},
}