Attenuation of propofol tolerance conferred by remifentanil co-administration does not reduce propofol toxicity in rabbits under prolonged mechanical ventilation.
Abstract | BACKGROUND: MATERIALS AND METHODS: Eighteen healthy male rabbits were mechanically ventilated and received propofol (group P, n = 6), propofol plus remifentanil (group PR, n = 6), or remifentanil plus sevoflurane (group RS, n = 6) in order to be kept under sedation (group P) or sedation/ analgesia (groups PR and RS) for up to 48 h. Initial propofol and remifentanil infusion rates (IRs) were adjusted, if needed, to maintain the desired level of sedation and analgesia, respectively (groups P and PR). In group RS, remifentanil was infused at IRs equivalent to those of group PR. Propofol IRs were recorded, propofol concentrations were measured in the arterial plasma, and blood biochemical parameters and organ histopathology were assessed. RESULTS: Animals survived for 29-36 h in group P and 22-38 h in group PR (100% mortality rate). Tolerance was developed to propofol's sedative effect. The onset of tolerance was delayed and its magnitude was decreased in group PR compared with group P. Propofol was accumulated in the systemic circulation. Propofol clearance rate was gradually decreased. Arterial lactate, and serum aspartate aminotransferase (AST), lactate dehydrogenase (LDH), bilirubin, cholesterol, triglycerides, and creatine kinase (CK) levels were increased. The heart, lungs, liver, gallbladder, kidneys, urinary bladder, and skeletal muscles were seriously injured in groups P and PR. In group RS, mortality was 0%, while there was only mild injury of the lungs, liver, gallbladder, kidneys, and urinary bladder. CONCLUSIONS:
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Authors | Petros Ypsilantis, Maria Politou, Dimitrios Mikroulis, Maria Lambropoulou, Ioannis Bougioukas, Georgios Theodoridis, Christina Tsigalou, Constantinos Manolas, Nikolaos Papadopoulos, Georgios Bougioukas, Constantinos Simopoulos |
Journal | The Journal of surgical research
(J Surg Res)
Vol. 168
Issue 2
Pg. 253-61
(Jun 15 2011)
ISSN: 1095-8673 [Electronic] United States |
PMID | 20036388
(Publication Type: Journal Article)
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Copyright | Copyright © 2011 Elsevier Inc. All rights reserved. |
Chemical References |
- Anesthetics, Inhalation
- Anesthetics, Intravenous
- Methyl Ethers
- Piperidines
- Sevoflurane
- Remifentanil
- Propofol
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Topics |
- Anesthetics, Inhalation
(administration & dosage)
- Anesthetics, Intravenous
(administration & dosage, blood, toxicity)
- Animals
- Drug Interactions
- Drug Tolerance
- Gallbladder
(pathology)
- Kidney
(pathology)
- Liver
(pathology)
- Lung
(pathology)
- Male
- Methyl Ethers
(administration & dosage)
- Multiple Organ Failure
(chemically induced, pathology)
- Muscle, Skeletal
(pathology)
- Myocardium
(pathology)
- Piperidines
(pharmacology)
- Propofol
(administration & dosage, blood, toxicity)
- Rabbits
- Remifentanil
- Sevoflurane
- Urinary Bladder
(pathology)
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