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

Abstract

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.

Protective Effect of Arbidol Against Pulmonary Fibrosis and Sepsis in Mice

“…As the most common source of infection in patients with sepsis comes from the abdominal cavity, in recent years, the abdominal infection model has been gradually used as a commonly used animal model of sepsis. Animal models of fecal peritonitis have been widely used in sepsis research ( Dyson et al, 2011 ; Rudiger et al, 2013 ; Jeger et al, 2017 ; Sulzbacher et al, 2020 ). Since our laboratory cannot perform virus tests, in this study, we used fecal diluent-induced sepsis mice to simulate the cytokine storm symptoms of COVID-19 to a certain extent.…”

Conventional Echocardiography and Two-Dimensional Speckle Tracking in Healthy Sevoflurane-Anesthetized Dogs Undergoing Continuous Rate Infusion of Nalbuphine

“…In addition, one study in humans demonstrated that patients from the intensive care unit who received nalbuphine showed desirable analgesia with hemodynamic stability compared to those receiving sufentanil [28]. Other authors, however, demonstrate significant reductions of HR and arterial pressure using CRI of nalbuphine during inhalation anesthesia in rats with sepsis [29]. Transmitral flow and mitral annular motion were used to assess the effects of nalbuphine on left ventricular diastolic function.…”

The Influence of Pain and Analgesia in Rodent Models of Sepsis

“…However, continuous infusion of nalbuphine reduced facial grimace scores at 24 h in a cecal slurry model in rats. 35 Although clinical scoring was unaffected, the facial grimace scoring suggested that this nonsurgical model did cause pain in the absence of an invasive procedure. This finding suggests that additional studies defining the role of pain and analgesia in nonsurgical models of sepsis are warranted.…”