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Jeger V, Arrigo M, Hildenbrand FF, et al. Improving animal welfare using continuous nalbuphine infusion in a long-term rat model of sepsis. Intensive Care Med Exp. 2017;5(1):23doi: 10.1186/s40635-017-0137-2.
Jeger, V., Arrigo, M., Hildenbrand, F. F., Müller, D., Jirkof, P., Hauffe, T., Seifert, B., Arras, M., Spahn, D. R., Bettex, D., & Rudiger, A. (2017). Improving animal welfare using continuous nalbuphine infusion in a long-term rat model of sepsis. Intensive care medicine experimental, 5(1), 23. https://doi.org/10.1186/s40635-017-0137-2
Jeger, Victor, et al. "Improving animal welfare using continuous nalbuphine infusion in a long-term rat model of sepsis." Intensive care medicine experimental vol. 5,1 (2017): 23. doi: https://doi.org/10.1186/s40635-017-0137-2
Jeger V, Arrigo M, Hildenbrand FF, Müller D, Jirkof P, Hauffe T, Seifert B, Arras M, Spahn DR, Bettex D, Rudiger A. Improving animal welfare using continuous nalbuphine infusion in a long-term rat model of sepsis. Intensive Care Med Exp. 2017 Dec;5(1):23. doi: 10.1186/s40635-017-0137-2. Epub 2017 Apr 20. PMID: 28429311; PMCID: PMC5399012.
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Intensive Care Med Exp. 2017 Dec;5(1):23. doi: 10.1186/s40635-017-0137-2. Epub 2017 Apr 20.

Improving animal welfare using continuous nalbuphine infusion in a long-term rat model of sepsis.

Intensive care medicine experimental

Victor Jeger, Mattia Arrigo, Florian F Hildenbrand, Daniel Müller, Paulin Jirkof, Till Hauffe, Burkhardt Seifert, Margarete Arras, Donat R Spahn, Dominique Bettex, Alain Rudiger

Affiliations

  1. Institute of Anaesthesiology, University of Zurich and University Hospital Zurich, Zurich, Switzerland.
  2. Department of Medicine, University of Zurich and University Hospital Zurich, Zurich, Switzerland.
  3. Department of Cardiology, University Heart Centre, University Hospital Zurich, Zurich, Switzerland.
  4. Institute of Clinical Chemistry, University of Zurich and University Hospital Zurich, Zurich, Switzerland.
  5. Department of Surgery, University of Zurich and University Hospital Zurich, Zurich, Switzerland.
  6. Epidemiology, Biostatistics and Prevention Institute (EBPI), Department of Biostatistics, University of Zurich, Zurich, Switzerland.
  7. Institute of Anaesthesiology, University of Zurich and University Hospital Zurich, Zurich, Switzerland. [email protected].

PMID: 28429311 PMCID: PMC5399012 DOI: 10.1186/s40635-017-0137-2

Abstract

BACKGROUND: Sepsis research relies on animal models to investigate the mechanisms of the dysregulated host response to infection. Animal welfare concerns request the use of potent analgesics for the Refinement of existing sepsis models, according to the 3Rs principle. Nevertheless, adequate analgesia is often missing, partly because the effects of analgesics in this particular condition are unknown. We evaluated the use of nalbuphine, an opioid with kappa agonistic and mu antagonistic effects, in rats with and without experimental sepsis.

METHODS: Male Wistar rats were anesthetized with isoflurane and instrumented with a venous line for drug administration. Arterial cannulation allowed for blood pressure measurements and blood sampling in short-term experiments of non-septic animals. Nalbuphine (or placebo) was administered intravenously at a dose of 1 mg/kg/h. Long-term (48 h) experiments in awake septic animals included repetitive clinical scoring with the Rat Grimace Scale and continuous heart rate monitoring by telemetry. Sepsis was induced by intraperitoneal injection of faecal slurry. Nalbuphine plasma levels were measured by liquid chromatography-high resolution mass spectrometry.

RESULTS: In anesthetized healthy animals, nalbuphine led to a significant reduction of respiratory rate, heart rate, and mean arterial pressure during short-term experiments. In awake septic animals, a continuous nalbuphine infusion did not affect heart rate but significantly improved the values of the Rat Grimace Scale. Nalbuphine plasma concentrations remained stable between 4 and 24 h of continuous infusion in septic rats.

CONCLUSIONS: In anaesthetised rats, nalbuphine depresses respiratory rate, heart rate, and blood pressure. In awake animals, nalbuphine analgesia improves animal welfare during sepsis.

Keywords: 3R; Analgesia; Animal welfare; Faecal peritonitis; Nalbuphine; Rat model; Sepsis

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