JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ypsilantis, P. Articles by Simopoulos, C. Search for Related Content PubMed PubMed Citation Articles by Ypsilantis, P. Articles by Simopoulos, C. Related Collections Critical Care Mechanisms Ventilation Pharmacology

---

CRITICAL CARE AND TRAUMA

Organ Toxicity and Mortality in Propofol-Sedated Rabbits Under Prolonged Mechanical Ventilation

Petros Ypsilantis, DVM, PhD^*#, Maria Politou, MD^*#, Dimitrios Mikroulis, MD, PhD, Michail Pitiakoudis, MD, PhD^*, Maria Lambropoulou, MD, PhD, Christina Tsigalou, MD, Vasilios Didilis, MD, PhD, Georgios Bougioukas, MD, PhD, Nikolaos Papadopoulos, MD, PhD, Constantinos Manolas, MD, PhD^||, and Constantinos Simopoulos, MD, PhD^*

From the *Laboratory of Experimental Surgery and Surgical Research, Cardiothoracic Surgery Clinic, Laboratory of Histology and Embryology, and ||First Clinic of Surgery, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece; and Laboratory of Biochemistry, University General Hospital of Alexandroupolis, Alexandroupolis, Greece. #These authors contributed equally to this work.

Address correspondence and reprint requests to Petros Ypsilantis, DVM, PhD, Laboratory of Experimental Surgery and Surgical Research, University General Hospital of Alexandroupolis, Dragana 68100 Alexandroupolis, Greece. Address e-mail to pipsil{at}med.duth.gr.

BACKGROUND: Prolonged administration of propofol at large doses has been implicated in propofol infusion syndrome in intensive care unit patients. In this study we investigated organ toxicity and mortality of propofol sedation at large doses in prolonged mechanically ventilated rabbits and determined the role of propofol's lipid vehicle.

METHODS: Eighteen healthy male rabbits were endotracheally intubated and sedated with propofol 2% (Group P), sevoflurane (Group S) or sevoflurane while receiving Intralipid 10% (Group SI). Sedation lasted 48 h or until death (Group P) or the maximum surviving period of Group P (Groups S and SI). The initial propofol infusion rate (20 mg · kg^–1 · h^–1) or sevoflurane concentration (1.5%) was adjusted, if needed, to maintain a standard level of sedation. Blood biochemical analysis was performed in serial blood samples and histologic examination in the heart, lungs, liver, gallbladder, kidneys, urinary bladder, and quadriceps femoris muscle at autopsy.

RESULTS: The mortality rate was 100% (surviving period, 26–38 h) for Group P, whereas 0% for Groups S and SI. The initial propofol infusion rate had to be increased up to 65.7 ± 4.6 mg · kg^–1 · h^–1 and sevoflurane concentration up to 4%. Serum liver function indices, lipids and creatine kinase were significantly increased (P < 0.05) in Groups P and SI and lactate was increased only in Group P, whereas amylase was increased in all groups. In Group P, histologic examination revealed myocarditis, pulmonary edema with interstitial pneumonia, hepatitis, steatosis, and focal liver necrosis, cholangitis, gallbladder necrosis, acute tubular necrosis of the kidneys, focal loss of the urinary bladder epithelium, and rhabdomyolysis of skeletal muscles; in Group S, low-grade bronchitis and incipient inflammation of the liver and the kidneys; and in Group SI, low-grade bronchitis, liver steatosis and hepatitis, and incipient inflammation of the gallbladder, kidneys, and urinary bladder.

CONCLUSIONS: Continuous infusion of 2% propofol at large doses for the sedation of rabbits undergoing prolonged mechanical ventilation induced fatal multiorgan dysfunction syndrome similar to the propofol infusion syndrome seen in humans. Our novel findings including lung, liver, gallbladder, and urinary bladder injury were also noted. The role of propofol's lipid vehicle in the manifestation of the syndrome was minor. Sevoflurane proved to be a safe alternative medication for prolonged sedation.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999