Successful blood transfusion in a Holstein cow experiencing hemorrhagic shock under general anesthesia.

A 2-year-old Holstein cow weighing 530 kg at 2 mo gestation was scheduled for a paracostal laparotomy and abomasotomy following diagnosis of a reticular foreign body causing obstruction and abomasal impaction. Hemorrhagic shock occurred during surgery, with a rapid, approximately 60% decrease in arterial blood pressure, and reflex tachycardia with a 2-fold increase in heart rate. Following identification of hemorrhagic shock, arterial blood pressure was supported by reducing the inhalant anesthetic requirement, positive inotropic support (IV dobutamine infusion), and IV fluid therapy. Hypertonic saline was administered IV for initial resuscitation of arterial blood pressure, followed by a whole blood transfusion to replenish red blood cells, support oxygencarrying capacity, and provide intravascular volume to maintain cardiac output and tissue perfusion. A gradual increase in arterial blood pressure and a decrease in heart rate were observed in response to treatment. This case report demonstrates the physiologic compensatory response to hemorrhagic shock and the treatment to stabilize cardiovascular parameters in an anesthetized cow. Key clinical message: This case illustrates the physiological reponses to acute hemorrhage under general anesthesia and the effects of various treatment interventions.

Transfusion sanguine réussie chez une vache Holstein en état de choc hémorragique sous anesthésie générale. Une vache Holstein de 2 ans pesant 530 kg à 2 mois de gestation devait subir une laparotomie paracostale et une abomasotomie à la suite du diagnostic d'un corps étranger réticulaire provoquant une obstruction et une impaction abomasale. Un choc hémorragique est survenu pendant la chirurgie, avec une diminution rapide d'environ 60 % de la pression artérielle et une tachycardie réflexe avec une augmentation du double de la fréquence cardiaque. À la suite de l'identification d'un choc hémorragique, la pression artérielle a été soutenue en réduisant le besoin d'anesthésique inhalé, un soutien inotrope positif (perfusion de dobutamine IV) et une thérapie avec des fluides IV. Une solution saline hypertonique a été administrée par voie intraveineuse pour la restauration initiale de la pression artérielle, suivie d'une transfusion de sang total pour rétablir la quantité de globules rouges, soutenir la capacité de transport d'oxygène et fournir un volume intravasculaire pour maintenir le débit cardiaque et la perfusion tissulaire. Une augmentation progressive de la pression artérielle et une diminution de la fréquence cardiaque ont été observées en réponse au traitement. Ce rapport de cas démontre la réponse physiologique compensatoire au choc hémorragique et le traitement pour stabiliser les paramètres cardiovasculaires chez une vache anesthésiée.Message clinique clé :Ce cas illustre les réponses physiologiques à une hémorragie aiguë sous anesthésie générale et les effets de diverses interventions thérapeutiques.(Traduit par Dr Serge Messier).

Intrahepatic Injection of Sodium Pentobarbital as an Alternative to Intraperitoneal Injection for the Euthanasia of Rats (Rattus norvegicus).

The most commonly accepted method of rat euthanasia in North America is intraperitoneal injection of sodium pentobarbital (PB). However, misinjection can occur, and intraperitoneal PB may cause pain and distress. The objective of this study was to test an alternative method of euthanasia: intrahepatic injection of PB. A pilot study was conducted to develop a method of intrahepatic injections (evaluated using CT scans and test injections), followed by a full study comparing intraperitoneal (n = 14) and intrahepatic PB injections (n = 66) in adult rats. Full study outcomes were: 1) time from injection to loss of right- ing reflex (LORR), 2) time from injection to cessation of heartbeat (CHB), 3) number of failed euthanasia attempts, and 4) confirmation of successful intrahepatic injection or misinjection via necropsy. All injections were performed by a veterinary student. CT revealed that intrahepatic injections were feasible. Times (median [range]) to LORR and CHB were faster after successful intrahepatic injections (LORR, 3 s [1 to 5 s]; CHB, 8 s [2 to 242 s]) than after intraperitoneal injections (LORR, 89.5 s [73 to 110 s], CHB: 284.5 s [237 to 423 s]). The misinjection rate was higher with intrahepatic injections (59%) than with intraperitoneal injections (29%), but intrahepatic misinjection still resulted in fast and successful euthanasia (LORR, 29 s [1 to 96 s]; CHB, 216 s [12 to 330 s]), with the injectate distributed between the intraperitoneal and intrahepatic locations. The number of failed euthanasia attempts with intrahepatic injections was low (n = 2). Intrahepatic injections show potential as an alternative to intraperitoneal injections for rat euthanasia.

A Pharmacokinetic-Pharmacodynamic Study of Intravenous Midazolam and Flumazenil in Adult New Zealand White-Californian Rabbits (Oryctolagus cuniculus).

Flumazenil, a competitive GABAA receptor antagonist, is commonly used in rabbits to shorten sedation or postanesthetic recovery after benzodiazepine administration. However, no combined pharmacokinetic (PK) and pharmacodynamic (PD) data are available to guide its administration in this species. In a prospective, randomized, blinded, crossover study design, the efficacy of IV flumazenil (FLU; 0.05 mg/kg) or saline control (SAL; equal volume) to reverse the loss of righting reflex (LORR) induced by IV midazolam (1.2 mg/kg) was investigated in 15 New Zealand white rabbits (2.73 to 4.65 kg, 1 y old). Rabbits were instrumented with arterial (central auricular artery) and venous (marginal auricular vein) catheters. After baseline blood sampling, IV midazolam was injected (T0). Flumazenil or saline (FLU/SAL) was injected 30 s after LORR. Arterial blood samples were collected at 1 and 3 min after midazolam injection, and at 1, 3, 6, 10, 15, 21, 28, 36, 45 and 60 min after injection with flumazenil. Plasma samples for midazolam, 1-OH-midazolam and flumazenil were analyzed using high performance liquid chromatography-high-resolution mass spectrometry and the time to return of righting reflex (ReRR) was compared between groups (Wilcoxon test). FLU terminal half-life, plasma clearance and volume of distribution were 26.3 min [95%CI: 23.3 to 29.3], 18.74 mL/min/kg [16.47 to 21.00] and 0.63 L/kg [0.55 to 0.71], respectively. ReRR was 25 times faster in rabbits treated with FLU (23 [8 to 44] s) compared with SAL (576 [130 to 1141] s; 95%CI [425 to 914 s]). Return of sedation (lateral recumbency) occurred in both groups (7/13 in FLU; 12/13 in SAL) with return of LORR in a few animals (4/13 in FLU; 7/13 in SAL) at 1540 [858 to 2328] s. In the population and anesthesia protocol studied, flumazenil quickly and reliably reversed sedation induced by midazolam injection. However, the potential return of sedation after flumazenil administration warrants careful monitoring in the recovery period.

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.

Systematic Review: Anaesthetic Protocols and Management as Confounders in Rodent Blood Oxygen Level Dependent Functional Magnetic Resonance Imaging (BOLD fMRI)-Part A: Effects of Changes in Physiological Parameters.

Background: To understand brain function in health and disease, functional magnetic resonance imaging (fMRI) is widely used in rodent models. Because animals need to be immobilised for image acquisition, fMRI is commonly performed under anaesthesia. The choice of anaesthetic protocols and may affect fMRI readouts, either directly or via changing physiological balance, and thereby threaten the scientific validity of fMRI in rodents. Methods: The present study systematically reviewed the literature investigating the influence of different anaesthesia regimes and changes in physiological parameters as confounders of blood oxygen level dependent (BOLD) fMRI in rats and mice. Four databases were searched, studies selected according to pre-defined criteria, and risk of bias assessed for each study. Results are reported in two separate articles; this part of the review focuses on effects of changes in physiological parameters. Results: A total of 121 publications was included, of which 49 addressed effects of changes in physiological parameters. Risk of bias was high in all included studies. Blood oxygenation [arterial partial pressure of oxygen (paO2)], ventilation [arterial partial pressure of carbon dioxide (paCO2)] and arterial blood pressure affected BOLD fMRI readouts across various experimental paradigms. Conclusions: Blood oxygenation, ventilation and arterial blood pressure should be monitored and maintained at stable physiological levels throughout experiments. Appropriate anaesthetic management and monitoring are crucial to obtain scientifically valid, reproducible results from fMRI studies in rodent models.

Hypoventilation following oxygen administration associated with alfaxalone-dexmedetomidine-midazolam anesthesia in New Zealand White rabbits.

OBJECTIVE: To investigate the relationship between oxygen administration and ventilation in rabbits administered intramuscular alfaxalone-dexmedetomidine-midazolam. STUDY DESIGN: Prospective, randomized, blinded study. ANIMALS: A total of 25 New Zealand White rabbits, weighing 3.1-5.9 kg and aged 1 year. METHODS: Rabbits were anesthetized with intramuscular alfaxalone (4 mg kg-1), dexmedetomidine (0.1 mg kg-1) and midazolam (0.2 mg kg-1) and randomized to wait 5 (n = 8) or 10 (n = 8) minutes between drug injection and oxygen (100%) administration (facemask, 1 L minute-1). A control group (n = 9) was administered medical air 10 minutes after drug injection. Immediately before (PREoxy/air5/10) and 2 minutes after oxygen or medical air (POSToxy/air5/10), respiratory rate (fR), pH, PaCO2, PaO2, bicarbonate and base excess were recorded by an investigator blinded to treatment allocation. Data [median (range)] were analyzed with Wilcoxon, Mann-Whitney U and Kruskal-Wallis tests and p < 0.05 considered significant. RESULTS: Hypoxemia (PaO2 < 88 mmHg, 11.7 kPa) was observed at all PRE times: PREoxy5 [71 (61-81) mmHg, 9.5 (8.1-10.8) kPa], PREoxy10 [58 (36-80) mmHg, 7.7 (4.8-10.7) kPa] and PREair10 [48 (32-64) mmHg, 6.4 (4.3-8.5) kPa]. Hypoxemia persisted when breathing air: POSTair10 [49 (33-66) mmHg, 6.5 (4.4-8.8) kPa]. Oxygen administration corrected hypoxemia but was associated with decreased fR (>70%; p = 0.016, both groups) and hypercapnia (p = 0.016, both groups). Two rabbits (one per oxygen treatment group) were apneic (no thoracic movements for 2.0-2.5 minutes) following oxygen administration. fR was unchanged when breathing air (p = 0.5). PaCO2 was higher when breathing oxygen than air (p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: Early oxygen administration resolved anesthesia-induced hypoxemia; however, fR decreased and PaCO2 increased indicating that hypoxemic respiratory drive is an important contributor to ventilation using the studied drug combination.

Prevalence and management of pain in dogs in the emergency service of a veterinary teaching hospital.

A prospective, observational, cross-sectional study documenting the prevalence of pain in dogs presented to the emergency service of a veterinary teaching hospital and their handling (times to triage, examination, treatment) was conducted. Pain was assessed and compared using a validated and an unvalidated pain assessment scale. Sedation was monitored using a validated scale. A first evaluation was completed in 109 dogs. A second evaluation was completed for 95 dogs: 36 (38%) were identified as painful and 53% (19/36) were provided analgesia in the clinic. The remainder either did not receive analgesia (6/36, 17%) or were prescribed an analgesic for administration at home (11/36, 31%). Of dogs receiving analgesia in the clinic, most showed a decrease in pain score (15/19, 79%). Pain assessment scales were positively correlated (r = 0.69, P < 0.0001) but the unvalidated scale was insensitive in discriminating changes. Between painful and non-painful dogs, progression did not differ: admission to treatment [P = 0.96, 95% confidence interval (CI): -23 to 22 minutes] and examination to treatment (P = 0.73, 95% CI: 14 to 20 minutes). Suboptimal analgesic use suggests focused training in pain assessment and analgesic use guided by a validated pain assessment scale, is warranted.

Prévalence et gestion de la douleur chez des chiens présentés au service d'urgence d'un hôpital d'enseignement vétérinaire. Une étude prospective, observationnelle et transversale a été réalisée pour documenter la prévalence de la douleur chez les chiens présentés au service d'urgence d'un hôpital universitaire vétérinaire ainsi que leur gestion (délai pour le triage, examen et traitement). Une échelle validée d'évaluation de la douleur a été utilisée pour évaluer la douleur à l'admission et suivant le traitement en clinique. A titre de comparaison, une échelle non validée d'évaluation de la douleur a également été utilisé et le degré de sédation a été documenté à l'aide d'une échelle de sédation validée. Une première évaluation a été complétée chez 109 chiens. Sur les 95 chiens pour lesquels une deuxième évaluation a été complétée, 36 (38 %) ont été identifiés comme étant en douleur et 53 % (19/36) ont reçu de l'analgésie en clinique. Les chiens restants n'ont soit pas reçu d'analgésie (6/36, 17 %) ou ont reçu une prescription pour un traitement analgésique à la maison (11/36, 31 %). Pour les chiens ayant reçu un traitement analgésique en clinique, la grande majorité ont démontré une diminution de leur score de douleur (15/19, 79 %). Une corrélation positive entre les deux échelles d'évaluation de la douleur était présente (r = 0,69, P < 0,0001), mais l'échelle non validée n'était pas sensible pour distinguer les changements de score de douleur. Il n'y avait pas de différence significative entre les chiens en douleur et non en douleur concernant le délai entre l'admission et le traitement (P = 0,96, 95 % CI : ­23 à 22 minutes) ou entre l'examen et le traitement (P = 0,73, 95 % CI : 14 à 20 minutes). L'administration d'analgésie était suboptimal dans la population étudiée, suggérant qu'un entraînement ciblé pour reconnaître et traiter la douleur à l'aide d'une échelle validée est recommandé.(Traduit par Dr Frédérik Rousseau-Blass).

Agreement between invasive and oscillometric arterial blood pressure measurements using the LifeWindow multiparameter monitor and two cuff sizes in anesthetized adult horses.

OBJECTIVE: To assess agreement between oscillometric noninvasive blood pressure (NIBP) measurements using LifeWindow monitors (LW9xVet and LW6000V) and invasive blood pressure (IBP). To assess the agreement of NIBP readings using a ratio of cuff width to mid-cannon circumference of 25% and 40%. STUDY DESIGN: Prospective, randomized clinical study. ANIMALS: A total of 43 adult horses undergoing general anesthesia in dorsal recumbency for different procedures. METHODS: Anesthetic protocols varied according to clinician preference. IBP measurement was achieved after cannulation of the facial artery and connection to an appropriately positioned transducer connected to one of two LifeWindow multiparameter monitors (models: LW6000V and LW9xVet). Accuracy of monitors was checked daily using a mercury manometer. For each horse, NIBP was measured with two cuff widths (corresponding to 25% or 40% of mid-cannon bone circumference), both connected to the same monitor, and six paired IBP/NIBP readings were recorded (at least 3 minutes between readings). NIBP values were corrected to the relative level of the xiphoid process. A Bland-Altman analysis for repeated measures was used to assess bias (NIBP-IBP) and limits of agreement (LOAs). RESULTS: The 40% cuff width systolic arterial pressure [SAP; bias 7.9 mmHg, LOA -26.6 to 42.3; mean arterial pressure (MAP): bias 4.9 mmHg, LOA -28.2 to 38.0; diastolic arterial pressure (DAP): bias 4.2 mmHg, LOA -31.4 to 39.7)] performed better than the 25% cuff width (SAP: bias 26.4 mmHg, LOA -21.0 to 73.9; MAP: bias 15.7 mmHg, LOA -23.8 to 55.2; DAP: bias 10.9 mmHg, LOA -33.2 to 54.9). CONCLUSIONS AND CLINICAL RELEVANCE: Using the LifeWindow multiparameter monitor in anesthetized horses, the 40% cuff width provided better agreement with IBP; however, both cuff sizes and both monitor models failed to meet American College of Veterinary Internal Medicine Consensus Statement Guidelines.

Dynamic prediction of fluid responsiveness during positive pressure ventilation: a review of the physiology underlying heart-lung interactions and a critical interpretation.

OBJECTIVE: Cardiovascular responses to hypovolemia and hypotension are depressed during general anesthesia. A considerable number of anesthetized and critically ill animals may not benefit hemodynamically from a fluid bolus; therefore, it is important to have measures for accurate prediction of fluid responsiveness. Static measures of preload, such as central venous pressure, do not provide accurate prediction of fluid responsiveness, whereas dynamic measures of cardiovascular function, obtained during positive pressure ventilation, are highly predictive. This review describes key physiological concepts behind heart-lung interactions during positive pressure ventilation, factors that can modify this relationship and provides the basis for a rational interpretation of the information obtained from dynamic measurements, with a focus on pulse pressure variation (PPV). DATABASE USED: PubMed. Search items used were: heart-lung interaction, positive pressure ventilation, pulse pressure variation, dynamic index of fluid therapy, goal-directed hemodynamic therapy, dogs, cats, pigs, horses and rabbits. CONCLUSIONS: The veterinary literature suggests that targeting specific PPV thresholds should guide fluid therapy in lieu of conventional assessments. Understanding the physiology of heart-lung interactions during intermittent positive pressure ventilation provides a rational basis for interpreting the literature on dynamic indices of fluid responsiveness, including PPV. Clinical trials are needed to evaluate whether goal-directed fluid therapy based on PPV results in improved outcomes in veterinary patient populations.

Incomplete reporting of experimental studies and items associated with risk of bias in veterinary research.

In in vivo research, the reporting of core items of study design is persistently poor, limiting assessment of study quality and study reproducibility. This observational cohort study evaluated reporting levels in the veterinary literature across a range of species, journals and research fields. Four items (randomisation, sample size estimation, blinding and data exclusion) were assessed as well as availability of study data in publicly accessible repositories. From five general and five subject-specific journals, 120 consecutively published papers (12 per journal) describing in vivo experimental studies were selected. Item reporting was scored using a published scale (items ranked as fully, partially or not reported) according to completeness of reporting. Papers in subject-specific journals had higher median reporting levels (50.0 per cent vs 33.3 per cent, P=0.007). In subject-specific journals, randomisation (75.0 per cent vs 41.7 per cent, P=0.0002) and sample size estimation (35.0 per cent vs 16.7 per cent, P=0.025) reporting was approximately double that of general journals. Blinding (general 48.3 per cent, subject-specific 50.0 per cent, P=0.86) and data exclusion (general 53.3 per cent, subject-specific 63.3 per cent, P=0.27) were similarly reported. A single paper made study data readily accessible. Incomplete reporting remains prevalent in the veterinary literature irrespective of journal type, research subject or species. This impedes evaluation of study quality and reproducibility, raising concerns regarding wasted financial and animal resources.

ARRIVE has not ARRIVEd: Support for the ARRIVE (Animal Research: Reporting of in vivo Experiments) guidelines does not improve the reporting quality of papers in animal welfare, analgesia or anesthesia.

Poor research reporting is a major contributing factor to low study reproducibility, financial and animal waste. The ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines were developed to improve reporting quality and many journals support these guidelines. The influence of this support is unknown. We hypothesized that papers published in journals supporting the ARRIVE guidelines would show improved reporting compared with those in non-supporting journals. In a retrospective, observational cohort study, papers from 5 ARRIVE supporting (SUPP) and 2 non-supporting (nonSUPP) journals, published before (2009) and 5 years after (2015) the ARRIVE guidelines, were selected. Adherence to the ARRIVE checklist of 20 items was independently evaluated by two reviewers and items assessed as fully, partially or not reported. Mean percentages of items reported were compared between journal types and years with an unequal variance t-test. Individual items and sub-items were compared with a chi-square test. From an initial cohort of 956, 236 papers were included: 120 from 2009 (SUPP; n = 52, nonSUPP; n = 68), 116 from 2015 (SUPP; n = 61, nonSUPP; n = 55). The percentage of fully reported items was similar between journal types in 2009 (SUPP: 55.3 ± 11.5% [SD]; nonSUPP: 51.8 ± 9.0%; p = 0.07, 95% CI of mean difference -0.3-7.3%) and 2015 (SUPP: 60.5 ± 11.2%; nonSUPP; 60.2 ± 10.0%; p = 0.89, 95%CI -3.6-4.2%). The small increase in fully reported items between years was similar for both journal types (p = 0.09, 95% CI -0.5-4.3%). No paper fully reported 100% of items on the ARRIVE checklist and measures associated with bias were poorly reported. These results suggest that journal support for the ARRIVE guidelines has not resulted in a meaningful improvement in reporting quality, contributing to ongoing waste in animal research.

Morbidity and Mortality Conferences: A Mini Review and Illustrated Application in Veterinary Medicine.

This mini review presents current knowledge on the role of morbidity and mortality conferences (M&MCs) as a powerful educational tool and driver to improve patient care. Although M&MCs have existed since the early twentieth century, formal evaluation of their impact on education and patient care is relatively recent. Over time, M&MCs have evolved from single discipline discussions with a tendency to focus on individual errors and assign blame, to multidisciplinary, standardized presentations incorporating error analysis techniques, and educational theory. Current evidence shows that M&MCs can provide a valuable educational experience and have the potential to generate measurable improvements in patient care.