The effect of lipopolysaccharide (LPS) on inflammatory markers in blood and brain and on behavior in individually-housed pigs.

Most of us have experienced deterioration of mood while ill. In humans, immune activation is associated with lethargy and social withdrawal, irritability and aggression; changes in social motivation could, in theory, lead to less functional interactions. This might also be the case for animals housed in close confinement. Tail biting in pigs is an example of damaging social behavior, and sickness is thought to be a risk factor for tail biting outbreaks. One possible mechanism whereby sickness may influence behavior is through cytokines. To identify possible mediators between immune activation and behavioral change, we injected 16 gilts with lipopolysaccharide (LPS; O111:B4; 1.5 µg kg-1 IV through a permanent catheter). In LPS-treated pigs, a significant increase in cortisol, TNF-α, IL-1 receptor antagonist, IL-6, and IL-8 was observed alongside decreased activity within the first 6 h after the injection. CRP was elevated at 12 and 24 h after injection, and food intake was reduced for the first 24 h after injection. Three days post-injection, LPS pigs had lower levels of noradrenaline in their hypothalamus, hippocampus and frontal cortex compared to saline-injected pigs. Pigs injected with LPS also had higher levels of the pro-inflammatory cytokine IFN-γ in their frontal cortex compared to saline-injected pigs. Thus, a low dose of LPS can induce changes in brain cytokine levels and neurotransmitter levels that persist after inflammatory and stress markers in the periphery have returned to baseline levels.

Dexmedetomidine or fentanyl? Cardiovascular stability and analgesia during propofol-ketamine total intravenous anaesthesia in experimental pigs.

OBJECTIVE: To compare cardiovascular function and response to nociception during total intravenous anaesthesia in pigs with propofol, ketamine and either dexmedetomidine or fentanyl administered as a continuous infusion. STUDY DESIGN: Blinded, randomized, balanced, crossover study ANIMALS: Eight immunocastrated male, mixed breed pigs with a mean ± standard deviation body weight of 26.4 ± 1.9 kg for dexmedetomidine and 27.5 ± 3.8 kg for fentanyl treatment. METHODS: The animals were anaesthetized twice with either propofol-ketamine-dexmedetomidine (DEX) or fentanyl (FENT). DEX was infused at 2, 4 and 8 µg kg-1 hour-1 and FENT at 25, 50 and 100 µg kg-1 hour-1. Each infusion rate was administered for 80 minutes prior to commencing the next. Heart rate (HR), 3-lead electrocardiogram, systolic, mean and diastolic arterial blood pressure (SAP, MAP, DAP) in addition to cardiac output measured by transpulmonary thermodilution was used to monitor cardiovascular function. Mechanical and electrical stimulation (nociceptive withdrawal reflex, NWR) was used to elicit nociceptive responses. Similar anaesthetic depth was determined based on the NWR response. Cardiovascular parameters were compared statistically at this time. Additionally, response to nociceptive stimulation and cardiovascular response over time were compared. RESULTS: DEX-treated pigs had significantly higher HR, SAP, DAP, MAP, systemic vascular resistance, haemoglobin concentration, content of oxygen in arterial and venous blood and oxygen delivery index than FENT-treated pigs at similar anaesthetic depth, whereas stroke volume index was significantly higher in FENT. Motoric response to mechanical nociceptive stimulation was abolished prior to any decrease in NWR response in FENT, whereas the two responses decreased more in unison in DEX. The cardiovascular response to nociception was less pronounced in DEX than in FENT. CONCLUSIONS AND CLINICAL RELEVANCE: Propofol combined with ketamine and either fentanyl or dexmedetomidine provides stable cardiovascular conditions in normovolaemic, healthy pigs. Based on cardiovascular response and depression of NWR, dexmedetomidine apparently provides superior analgesia to fentanyl.

The influence of acute pulmonary hypertension on cardiac output measurements: calibrated pulse contour analysis, transpulmonary and pulmonary artery thermodilution against a modified Fick method in an animal model.

BACKGROUND: In critically ill patients with significant pulmonary hypertension (PH), close perioperative cardiovascular monitoring is mandatory, considering the increased morbidity and mortality in this patient group. Although the pulmonary artery catheter is still the standard for the diagnosis of PH, its use to monitor cardiac output (CO) in patients with PH is decreasing as a result of increased morbidity and possible influence of tricuspid regurgitation on the measurements. However, continuous CO measurement methods have never been evaluated under PH regarding their agreement and trending ability. In this study, we evaluated the influence of acute PH and different CO states on transpulmonary thermodilution (TPTD) and calibrated pulse contour analysis (PiCCO; both assessed with PiCCO plus™), intermittent pulmonary artery thermodilution (PATD), and continuous thermodilution (CCO) compared with a modified Fick method (FICK) in an animal model. METHODS: Nine healthy pigs were studied under anesthesia. PH of 25 and 40 mm Hg (by administration of the thromboxane analog U46619), CO decreases, and CO increases were induced to test the different CO measurement techniques over a broad range of hemodynamic situations. Before each step, a new baseline data set was collected. CO values were compared using Bland-Altman analysis; trending abilities were assessed via concordance and polar plot analysis. The influence of pulmonary pressure on CO measurements was analyzed using linear mixed models. RESULTS: A mean bias of -0.26 L/min with prediction intervals of -0.88 to 1.4 L/min was measured between TPTD and FICK. Their concordance rate was 100% (94%-100% confidence interval), and the mean polar angle -3° with radial limits of agreement of ±28° indicated good trending abilities. PATD compared with FICK also showed good trending ability. Comparisons of PiCCO and CCO versus FICK revealed low agreement and poor trending results with concordance rates of 84% (71%-93%) and 88% (74%-95%), mean polar angles from -17° and -19°, and radial limits of agreement of ±45° and 40°. Pulmonary pressures influenced only the difference between FICK and PiCCO, as assessed by linear mixed models. CONCLUSIONS: TPTD compared with FICK was able to track all changes induced during the study period, including those by PH. It yielded better agreement than PATD both compared with FICK. PiCCO and CCO were not mapping all changes correctly, and when used clinically in unstable patients, regular controls with intermittent techniques are required. Acute pharmacologically induced PH did influence the difference between FICK and PiCCO.

The effects of cardiac output and pulmonary arterial hypertension on volumetric capnography derived-variables during normoxia and hypoxia.

The aim of this study was to test the effect of cardiac output (CO) and pulmonary artery hypertension (PHT) on volumetric capnography (VCap) derived-variables. Nine pigs were mechanically ventilated using fixed ventilatory settings. Two steps of PHT were induced by IV infusion of a thromboxane analogue: PHT25 [mean pulmonary arterial pressure (MPAP) of 25 mmHg] and PHT40 (MPAP of 40 mmHg). CO was increased by 50% from baseline (COup) with an infusion of dobutamine≥5 µg kg(-1) min(-1) and decreased by 40% from baseline (COdown) infusing sodium nitroglycerine≥30 µg kg(-1) min(-1) plus esmolol 500 µg kg(-1) min(-1). Another state of PHT and COdown was induced by severe hypoxemia (FiO2 0.07). Invasive hemodynamic data and VCap were recorded and compared before and after each step using a mixed random effects model. Compared to baseline, the normalized slope of phase III (SnIII) increased by 32% in PHT25 and by 22% in PHT40. SnIII decreased non-significantly by 4% with COdown. A combination of PHT and COdown associated with severe hypoxemia increased SnIII by 28% compared to baseline. The elimination of CO2 per breath decreased by 7% in PHT40 and by 12% in COdown but increased only slightly with COup. Dead space variables did not change significantly along the protocol. At constant ventilation and body metabolism, pulmonary artery hypertension and decreases in CO had the biggest effects on the SnIII of the volumetric capnogram and on the elimination of CO2.

Comparison of sedation scores and propofol induction doses in dogs after intramuscular premedication with butorphanol and either dexmedetomidine or medetomidine.

OBJECTIVE: To compare sedation scores and propofol induction doses in dogs receiving either dexmedetomidine or medetomidine, both with butorphanol intramuscularly (IM) prior to general anaesthesia. STUDY DESIGN: Prospective, 'blinded', randomized, clinical study. ANIMALS: Fifty client-owned dogs scheduled for elective diagnostic imaging procedures. METHODS: Dogs were allocated to receive butorphanol 0.1 mg kg(-1) with either medetomidine (group M) 0.01 mg kg(-1) or dexmedetomidine (group D) 0.005 mg kg(-1) IM. Sedation was scored before and 20 minutes after pre-anaesthetic medication using a composite simple descriptive sedation score giving a score of 0 to 15 (0 = no sedation; 15 = profound sedation). Forty-five minutes after pre-anaesthetic medication, propofol was administered in increments of 0.5 mg kg(-1) over 15 seconds until tracheal intubation was possible. The time required to check intubation conditions between each propofol aliquot was 15 seconds. Total propofol dose required to perform tracheal intubation and the number of dogs achieving a clinically desired sedation score of ≥9/15 was recorded in each group. Sedation score and propofol dose were compared using the Mann-Whitney U-test. Results are reported as median (range). Statistical significance was set at p < 0.05. RESULTS: The sedation score 20 minutes after pre-anaesthetic medication was significantly higher in group M [11 (2-14)] than in group D [7 (0-14)]. There was no significant difference between propofol dose requirements in group M [1.5 (1-2.5) mg kg(-1)] or D at [1.5 (1-3) mg kg(-1)]. Significantly more dogs in group M achieved a sedation score of ≥9/15 than in group D. CONCLUSIONS AND CLINICAL RELEVANCE: Combined IM with butorphanol, medetomidine 0.01 mg kg(-1) produced effective sedation more frequently than dexmedetomidine 0.005 mg kg(-1) in dogs undergoing sedation prior to anaesthesia for elective procedures but this did not affect the propofol dose required for induction of anaesthesia significantly.