Analgesia in clinically relevant rodent models of sepsis

Jeger, Victor; Hauffe, Till; Nicholls-Vuille, Flora; Béttex, Dominique; Rudiger, Alain

doi:10.1177/0023677216675009

Cited by 14 publications

(12 citation statements)

References 62 publications

(96 reference statements)

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“…However, sex as well as strain differences have been reported, which should be taken into consideration for the translation of our results to other setups [10, 30]. …”

Section: Discussionmentioning

confidence: 93%

“…Therefore, we could reach our main goal of improving animal welfare by reducing distress in severe animal experiments without detecting heart rate changes over time. To our knowledge, there are no reports of nalbuphine and its effect on behaviour changes in experimental sepsis so far [10]. Further research is needed to implement robust, user-independent items for score-sheets to assess pain and distress in experimental sepsis.…”

Section: Discussionmentioning

confidence: 99%

“…Heart rate was recorded continuously by a wireless data acquisition system (TR180 SmartPad, Millar, Houston, TX, USA). Heart rate readings were recorded with PowerLab and analysed with LabChart Pro (see Jeger et al [10] for picture) by a blinded investigator (M.A.). Delta heart rate was calculated as heart rate at time point x minus heart rate at baseline.…”

Section: Methodsmentioning

confidence: 99%

“…This line was subsequently attached to a swivel-tether system (UNO BV, Zevenaar, the Netherlands) allowing the rat to have unrestrained movement in its cage and free access to food and water (see Jeger et al [10] for picture).…”

Section: Methodsmentioning

confidence: 99%

“…Evidence for appropriate analgesia in septic animals is scarce and guidelines are missing. We recently reviewed different analgesic regimens in sepsis models [10]. …”

Section: Introductionmentioning

confidence: 99%

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

Jeger

Arrigo

Hildenbrand

et al. 2017

ICMx

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BackgroundSepsis 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.MethodsMale 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.ResultsIn 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.ConclusionsIn anaesthetised rats, nalbuphine depresses respiratory rate, heart rate, and blood pressure. In awake animals, nalbuphine analgesia improves animal welfare during sepsis.

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“…However, sex as well as strain differences have been reported, which should be taken into consideration for the translation of our results to other setups [10, 30]. …”

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Evidence for appropriate analgesia in septic animals is scarce and guidelines are missing. We recently reviewed different analgesic regimens in sepsis models [10]. …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations