Antinociceptive and Cardiorespiratory Effects of a Single Dose of Dexmedetomidine in Laboratory Mice Subjected to Craniotomy under General Anaesthesia with Isoflurane and Carprofen or Meloxicam

Pain refinement represents an important aspect of animal welfare in laboratory animals. Refining analgesia regimens in mice undergoing craniotomy has been sparsely investigated. Here, we sought to investigate the effect of dexmedetomidine in combination with other analgesic drugs on intraoperative anti-nociceptive effects and cardiorespiratory stability. All mice were anaesthetised with isoflurane and received local lidocaine infiltration at the surgical site. Mice were randomised into treatment groups consisting of either carprofen 5 mg kg−1 or meloxicam 5 mg kg−1 with or without dexmedetomidine 0.1 mg kg−1 administered subcutaneously. Intra-anaesthetic heart rates, breathing rates, isoflurane requirements, and arterial oxygen saturations were continuously monitored. We found that administration of dexmedetomidine significantly improved heart and breathing rate stability during two of four noxious stimuli (skin incision and whisker stimulation) compared to non-dexmedetomidine-treated mice and lowered isoflurane requirements throughout anaesthesia by 5–6%. No significant differences were found between carprofen and meloxicam. These results demonstrate that dexmedetomidine reduces nociception and provides intra-anaesthetic haemodynamic and respiratory stability in mice. In conclusion, the addition of dexmedetomidine to anaesthetic regimes for craniotomy offers a refinement over current practice for laboratory mice

Systematic Review: Anesthetic Protocols and Management as Confounders in Rodent Blood Oxygen Level Dependent Functional Magnetic Resonance Imaging (BOLD fMRI)—Part B: Effects of Anesthetic Agents, Doses and Timing

In rodent models the use of functional magnetic resonance imaging (fMRI) under anesthesia is common. The anesthetic protocol might influence fMRI readouts either directly or via changes in physiological parameters. As long as those factors cannot be objectively quantified, the scientific validity of fMRI in rodents is impaired. In the present systematic review, literature analyzing in rats and mice the influence of anesthesia regimes and concurrent physiological functions on blood oxygen level dependent (BOLD) fMRI results was investigated. Studies from four databases that were searched were selected following pre-defined criteria. Two separate articles publish the results; the herewith presented article includes the analyses of 83 studies. Most studies found differences in BOLD fMRI readouts with different anesthesia drugs and dose rates, time points of imaging or when awake status was compared to anesthetized animals. To obtain scientifically valid, reproducible results from rodent fMRI studies, stable levels of anesthesia with agents suitable for the model under investigation as well as known and objectively quantifiable effects on readouts are, thus, mandatory. Further studies should establish dose ranges for standardized anesthetic protocols and determine time windows for imaging during which influence of anesthesia on readout is objectively quantifiable

Comparison of recovery quality following Medetomidine versus Xylazine balanced isoflurane anaesthesia in horses: a retrospective analysis

Medetomidine partial intravenous anaesthesia (PIVA) has not been compared to xylazine PIVA regarding quality of recovery. This clinical retrospective study compared recoveries following isoflurane anaesthesia balanced with medetomidine or xylazine. The following standard protocol was used: sedation with 7 µg·kg−1 medetomidine or 1.1 mg·kg−1 xylazine, anaesthesia induction with ketamine/diazepam, maintenance with isoflurane and 3.5 µg·kg−1·h−1 medetomidine or 0.7 mg·kg−1·h−1 xylazine, and sedation after anaesthesia with 2 µg·kg−1 medetomidine or 0.3 mg·kg−1 xylazine. Recovery was timed and, using video recordings, numerically scored by two blinded observers. Influence of demographics, procedure, peri-anaesthetic drugs, and intraoperative complications (hypotension, hypoxemia, and tachycardia) on recovery were analysed using regression analysis (p < 0.05). A total of 470 recoveries (medetomidine 279, xylazine 191) were finally included. Following medetomidine, recoveries were significantly longer (median (interquartile range): 57 (43–71) min) than xylazine (43 (32–59) min) (p < 0.001). However, the number of attempts to stand was similar (medetomidine and xylazine: 2 (1–3)). Poorer scores were seen with increased pre-anaesthetic dose of xylazine, intraoperative tetrastarch, or salbutamol. However, use of medetomidine or xylazine did not influence recovery score, concluding that, following medetomidine–isoflurane PIVA, recovery is longer, but of similar quality compared to xylazine

Regional ventilation distribution and dead space in anaesthetized horses treated with and without continuous positive airway pressure: novel insights by electrical impedance tomography and volumetric capnography

Objective: The aim of this study was to evaluate the effect of continuous positive airway pressure (CPAP) on regional distribution of ventilation and dead space in anaesthetized horses. Study design: Randomized, experimental, crossover study. Animals: A total of eight healthy adult horses. Methods: Horses were anaesthetized twice with isoflurane in 50% oxygen and medetomidine as continuous infusion in dorsal recumbency, and administered in random order either CPAP (8 cmH2O) or NO CPAP for 3 hours. Electrical impedance tomography (and volumetric capnography (VCap) measurements were performed every 30 minutes. Lung regions with little ventilation [dependent silent spaces (DSSs) and nondependent silent spaces (NSSs)], centre of ventilation (CoV) and dead space variables, as well as venous admixture were calculated. Statistical analysis was performed using multivariate analysis of variance and Pearson correlation. Results: Data from six horses were statistically analysed. In CPAP, the CoV shifted to dependent parts of the lungs (p < 0.001) and DSSs were significantly smaller (p < 0.001), while no difference was seen in NSSs. Venous admixture was significantly correlated with DSS with the treatment time taken as covariate (p < 0.0001; r = 0.65). No differences were found for any VCap parameters. Conclusions and clinical relevance: In dorsally recumbent anaesthetized horses, CPAP of 8 cmH2O results in redistribution of ventilation towards the dependent lung regions, thereby improving ventilation-perfusion matching. This improvement was not associated with an increase in dead space indicative for a lack in distension of the airways or impairment of alveolar perfusion

Electrocardiographic alterations during intravascular application of three different test doses of bupivacaine and epinephrine: experimental study in neonatal pigs

Background Origin of electrocardiographic (ECG) alterations during intravascular injection of local anaesthetic solutions is controversial. The aim of this study was to elucidate whether epinephrine, bupivacaine or their combination is responsible for ECG alteration. Methods Forty-five piglets were randomized into three groups. After induction of general anaesthesia using sevoflurane and peripheral venous cannulation, the trachea was intubated, the lungs were artificially ventilated, and anaesthesia was maintained by sevoflurane. Under steady state 0.2 ml kg−1 and after 10 min 0.4 ml kg−1 of one of the following three test solutions was administered i.v.: bupivacaine 0.125% (Group 1), bupivacaine 0.125%+epinephrine 1:200 000 (Group 2), and plain epinephrine 1:200 000 (Group 3). The ECG was analysed for alterations in heart rate and T-elevation. Results After injection of 0.2 or 0.4 ml kg−1 test solution, an increase in heart rate of at least 10% was found in none of Group 1 and in all of Groups 2 and 3. After application of 0.2 ml kg−1 test solution, T-elevation was found in 7% of Group 1 and in 93% of Groups 2 and 3. The injection of 0.4 ml kg−1 revealed a T-elevation in 27%, 100%, and 100%, respectively, in Groups 1, 2, and 3. Conclusions This animal model demonstrated that increases in heart rate and T-elevation in the ECG during i.v. application of a common test dose (0.2 ml kg−1) of bupivacaine are caused by epinephrine addition. Whether higher doses of bupivacaine alone can cause similar ECG changes or not requires further studie

Electrocardiographic changes during continuous intravenous application of bupivacaine in neonatal pigs

Background It is controversial as to whether T-wave elevation is caused by local anaesthetics, epinephrine, or their combination. It has been shown that T-elevation after intravascular injection of a small bupivacaine test dose is caused by epinephrine and not by bupivacaine. The aim of this study was to investigate ECG changes with higher doses of i.v. bupivacaine. Methods Thirty neonatal pigs were anaesthetized with sevoflurane and their tracheas intubated and artificially ventilated. Under steady-state conditions, bupivacaine was continuously infused (flow rate 3.2 ml kg−1 min−1) by a syringe infusion pump through a central venous catheter. Group 1 received bupivacaine 0.125%, Group 2 bupivacaine 0.5%. The ECG was continuously printed and subsequently analysed for alterations in heart rate, ventricular de- and repolarization, and arrhythmias at 1.25, 2.5, and 5 mg kg−1 bupivacaine infused. Results Sinus rhythm persisted in all pigs. Heart rate decreased progressively in both groups, but this was significantly more pronounced in Group 1. T-wave elevation occurred in 40% and 0% (Groups 1 and 2) at 1.25 mg kg−1, in 80% and 0% at 2.5 mg kg−1, and in 93% and 80% at 5 mg kg−1 bupivacaine infused. There were significant differences between the two groups at 1.25 and 2.5 mg kg−1 infused. Conclusions Higher doses of i.v. infused bupivacaine can cause T-elevation. With slower injection technique, T-elevation can already be detected at lower bupivacaine doses administere

Gender differences in the association between life history of body silhouettes and asthma incidence : results from the SAPALDIA cohort study

Background: The association of obesity and asthma has been described in children and adults. However, whether a different life course of weight in men and women may explain gender differences in asthma incidence, has not been addressed. Objectives: Using data from the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults, we investigated the role of overweight/obesity as measured by body silhouettes at different life stages in men and women for asthma incidence. Methods: Our analysis included 5417 subjects who were asthma free at age 8, followed up to 2011, and had complete covariate information. The main predictor of interest was self-reported body silhouettes at age 8, menarche, 30, 45, menopause, and 60, and additionally changes in body silhouette number across these different time points. Asthma incidence was defined as newly reported doctor-diagnosed asthma after the body silhouette time point. Asthma incidence and its association with body silhouettes was analysed using sex stratified logistic regression, adjusting for age, atopy, urbanity, smoking, parental asthma, education and study area. Results: Men at age 60 had an increased risk of asthma incidence per unit increase in body silhouette number (OR 1.93, 95% CI 1.13–3.30). This association was stronger in women at age 60 (OR 2.78, 95% CI 1.49–5.18) and observed also at menopause (OR 1.35, 95% CI 1.03–1.78), as well as per unit change in body silhouette number between age 45 – menopause (OR 1.74, 95% CI 1.15–2.63). Conclusion: In this longitudinal study, the risk of incident asthma increased in men and women with a larger body silhouette in late adulthood. In women, this risk appeared present between age 45 and menopause. At age 60, both men and women were at higher risk of asthma incidence per unit increase in body silhouette, the risk being more pronounced in women. The age-related increase of obesity may underlie gender differences in asthma incidence at higher ages

Causal effects of body mass index on airflow obstruction and forced mid-expiratory flow: a mendelian randomization study taking interactions and age-specific instruments into consideration toward a life course perspective

Obesity has complex links to respiratory health. Mendelian randomization (MR) enables assessment of causality of body mass index (BMI) effects on airflow obstruction and mid-expiratory flow. In the adult SAPALDIA cohort, recruiting 9,651 population-representative samples aged 18–60 years at baseline (female 51%), BMI and the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) as well as forced mid-expiratory flow (FEF25–75%) were measured three times over 20 follow-up years. The causal effects of BMI in childhood and adulthood on FEV1/FVC and FEF25–75% were assessed in predictive (BMI averaged over 1st and 2nd, lung function (LF) averaged over 2nd and 3rd follow-up; N = 2,850) and long-term cross-sectional models (BMI and LF averaged over all follow-ups; N = 2,728) by Mendelian Randomization analyses with the use of weighted BMI allele score as an instrument variable and two-stage least squares (2SLS) method. Three different BMI allele scores were applied to specifically capture the part of BMI in adulthood that likely reflects tracking of genetically determined BMI in childhood. The main causal effects were derived from models containing BMI (instrumented by BMI genetic score), age, sex, height, and packyears smoked as covariates. BMI interactions were instrumented by the product of the instrument (BMI genetic score) and the relevant concomitant variable. Causal effects of BMI on FEV1/FVC and FEF25–75% were observed in both the predictive and long-term cross-sectional models. The causal BMI- LF effects were negative and attenuated with increasing age, and stronger if instrumented by gene scores associated with childhood BMI. This non-standard MR approach interrogating causal effects of multiplicative interaction suggests that the genetically rooted part of BMI patterns in childhood may be of particular relevance for the level of small airway function and airflow obstruction later in life. The methodological relevance of the results is first to point to the importance of a life course perspective in studies on the etiological role of BMI in respiratory health, and second to point out novel methodological aspects to be considered in future MR studies on the causal effects of obesity related phenotypes