Stijn Schauvliege

Influence of a constant rate infusion of dexmedetomidine on cardiopulmonary function and recovery quality in isoflurane anaesthetized horses

OBJECTIVE To investigate the influence of a dexmedetomidine constant rate infusion (CRI) in horses anaesthetized with isoflurane. STUDY DESIGN Prospective, randomized, blinded, clinical study. ANIMALS Forty adult healthy horses (weight mean 491 ± SD 102 kg) undergoing elective surgery. METHODS After sedation [dexmedetomidine, 3.5 μg kg(-1) intravenously (IV)] and induction IV (midazolam 0.06 mg kg(-1), ketamine 2.2 mg kg(-1)), anaesthesia was maintained with isoflurane in oxygen/air (FiO(2) 55-60%). Horses were ventilated and dobutamine was administered when hypoventilation [arterial partial pressure of CO(2) > 8.00 kPa (60 mmHg)] and hypotension [arterial pressure 70 mmHg] occurred respectively. During anaesthesia, horses were randomly allocated to receive a CRI of dexmedetomidine (1.75 μg kg(-1) hour(-1) ) (D) or saline (S). Monitoring included end-tidal isoflurane concentration, cardiopulmonary parameters, and need for dobutamine and additional ketamine. All horses received 0.875 μg kg(-1) dexmedetomidine IV for the recovery period. Age and weight of the horses, duration of anaesthesia, additional ketamine and dobutamine, cardiopulmonary data (anova), recovery scores (Wilcoxon Rank Sum Test), duration of recovery (t-test) and attempts to stand (Mann-Whitney test) were compared between groups. Significance was set at p < 0.05. RESULTS Heart rate and arterial partial pressure of oxygen were significantly lower in group D compared to group S. An interaction between treatment and time was present for cardiac index, oxygen delivery index and systemic vascular resistance. End-tidal isoflurane concentration and heart rate significantly increased over time. Packed cell volume, systolic, diastolic and mean arterial pressure, arterial oxygen content, stroke volume index and systemic vascular resistance significantly decreased over time. Recovery scores were significantly better in group D, with fewer attempts to stand and significantly longer times to sternal position and first attempt to stand. CONCLUSIONS AND CLINICAL RELEVANCE A dexmedetomidine CRI produced limited cardiopulmonary effects, but significantly improved recovery quality.

Role of Heat-Stable Enterotoxins in the Induction of Early Immune Responses in Piglets after Infection with Enterotoxigenic Escherichia coli

Enterotoxigenic Escherichia coli (ETEC) strains that produce heat-stable (ST) and/or heat - labile (LT) enterotoxins are cause of post – weaning diarrhea in piglets. However, the relative importance of the different enterotoxins in host immune responses against ETEC infection has been poorly defined. In the present study, several isogenic mutant strains of an O149:F4ac+, LT+ STa+ STb+ ETEC strain were constructed that lack the expression of LT in combination with one or both types of ST enterotoxins (STa and/or STb). The small intestinal segment perfusion (SISP) technique and microarray analysis were used to study host early immune responses induced by these mutant strains 4 h after infection in comparison to the wild type strain and a PBS control. Simultaneously, net fluid absorption of pig small intestinal mucosa was measured 4 h after infection, allowing us to correlate enterotoxin secretion with gene regulation. Microarray analysis showed on the one hand a non-toxin related general antibacterial response comprising genes such as PAP, MMP1 and IL8. On the other hand, results suggest a dominant role for STb in small intestinal secretion early after post-weaning infection, as well as in the induced innate immune response through differential regulation of immune mediators like interleukin 1 and interleukin 17.

Effects of a constant rate infusion of detomidine on cardiovascular function, isoflurane requirements and recovery quality in horses

OBJECTIVE To examine the influence of a detomidine constant rate infusion (CRI) on cardiovascular function, isoflurane requirements and recovery quality in horses undergoing elective surgery. STUDY DESIGN Prospective, randomized, blinded, clinical trial. ANIMALS Twenty adult healthy horses. METHODS After sedation (detomidine, 10 μg kg(-1) intravenously [IV]) and induction of anaesthesia (midazolam 0.06 mg kg(-1) , ketamine 2.2 mg kg(-1) IV), anaesthesia was maintained with isoflurane in oxygen/air (inspiratory oxygen fraction 55%). When indicated, the lungs were mechanically ventilated. Dobutamine was administered when MAP<70 mmHg. The horses were randomly allocated to one of two groups and throughout anaesthesia, received either a detomidine (5 μg kg(-1)  hour(-1) ) (D) or saline (S) CRI, with the anaesthetist unaware of the treatment. Monitoring included end-tidal isoflurane concentration, arterial pH, PaCO(2) , PaO(2) , dobutamine administration rate, heart rate (HR), arterial pressure, cardiac index (CI), systemic vascular resistance (SVR), stroke index and oxygen delivery index (ḊO(2) I). For recovery from anaesthesia, all horses received 2.5 μg kg(-1) detomidine IV. Recovery quality and duration were recorded in each horse. For statistical analysis, anova, Pearson chi-square and Wilcoxon rank sum tests were used as relevant. RESULTS Heart rate (p=0.0176) and ḊO(2) I (p= 0.0084) were lower and SVR higher (p=0.0126) in group D, compared to group S. Heart rate (p=0.0011) and pH (p=0.0187) increased over time. Significant differences in isoflurane requirements were not detected. Recovery quality and duration were comparable between treatments. CONCLUSIONS AND CLINICAL RELEVANCE A detomidine CRI produced cardiovascular effects typical for α(2) -agonists, without affecting isoflurane requirements, recovery duration or recovery quality.

Effects of a constant-rate infusion of dexmedetomidine on the minimal alveolar concentration of sevoflurane in ponies

REASONS FOR PERFORMING STUDY Dexmedetomidine has been administered in the equine as a constant-rate infusion (CRI) during inhalation anaesthesia, preserving optimal cardiopulmonary function with calm and coordinated recoveries. Inhalant anaesthetic sparing effects have been demonstrated in other species, but not in horses. OBJECTIVES To determine the effects of a CRI of dexmedetomidine on the minimal alveolar concentration (MAC) of sevoflurane in ponies. METHODS Six healthy adult ponies were involved in this prospective, randomised, crossover, blinded, experimental study. Each pony was anaesthetised twice (3 weeks washout period). After induction with sevoflurane in oxygen (via nasotracheal tube), the ponies were positioned on a surgical table (T0), and anaesthesia was maintained with sevoflurane (expired sevoflurane fraction 2.5%) in 55% oxygen. The ponies were randomly allocated to treatment D (dexmedetomidine 3.5 µg/kg bwt i.v. [T10-T15] followed by a CRI of dexmedetomidine at 1.75 µg/kg bwt/h) or treatment S (bolus and CRI of saline at the same volume and rate as treatment D). After T60, MAC determination, using a classic bracketing technique, was initiated. Stimuli consisted of constant-current electrical stimuli at the skin of the lateral pastern region. Triplicate MAC estimations were obtained and averaged in each pony. Monitoring included pulse oximetry, electrocardiography, anaesthetic gas monitoring, arterial blood pressure measurement and arterial blood gases. Normocapnia was maintained by mechanical ventilation. Analysis of variance (treatment and period as fixed factors) was used to detect differences between treatments (α= 0.05). RESULTS An intravenous (i.v.) dexmedetomidine CRI decreased mean ± s.d. sevoflurane MAC from 2.42 ± 0.55 to 1.07 ± 0.21% (mean MAC reduction 53 ± 15%). CONCLUSIONS AND POTENTIAL RELEVANCE A dexmedetomidine CRI at the reported dose significantly reduces the MAC of sevoflurane.

Romifidine as a constant rate infusion in isoflurane anaesthetized horses: a clinical study.

OBJECTIVE To evaluate the effects of a constant rate infusion (CRI) of romifidine on the requirement of isoflurane, cardiovascular performance and recovery in anaesthetized horses undergoing arthroscopic surgery. STUDY DESIGN Randomized blinded prospective clinical trial. ANIMALS Thirty horses scheduled for routine arthroscopy. METHODS After premedication (acepromazine 0.02 mg kg(-1), romifidine 80 microg kg(-1), methadone 0.1 mg kg(-1)) and induction (midazolam 0.06 mg kg(-1) ketamine 2.2 mg kg(-1)), anaesthesia was maintained with isoflurane in oxygen. Horses were assigned randomly to receive a CRI of saline (group S) or 40 microg kg(-1) hour(-1) romifidine (group R). The influences of time and treatment on anaesthetic and cardiovascular parameters were evaluated using an analysis of variance. Body weight (t-test), duration of anaesthesia (t-test) and recovery score (Wilcoxon Rank Sum Test) were compared between groups. Significance was set at p < 0.05. RESULTS All but one horse were positioned in the dorsal recumbent position and ventilated from the start of anaesthesia. End tidal isoflurane concentrations were similar in both groups at similar time points and over the whole anaesthetic period. Cardiac output was significantly lower in horses of the R group, but there were no significant differences between groups in cardiac index, body weight or age. All other cardiovascular parameters were similar in both groups. Quality of recovery did not differ significantly between groups, but more horses in group R stood without ataxia at the first attempt. One horse from group S had a problematic recovery. CONCLUSIONS AND CLINICAL RELEVANCE No inhalation anaesthetic sparing effect or side effects were observed by using a 40 microg kg(-1) hour(-1) romifidine CRI in isoflurane anaesthetized horses under clinical conditions. Cardiovascular performance remained acceptable. Further studies are needed to identify the effective dose of romifidine that will induce an inhalation anaesthetic sparing effect in anaesthetized horses.

Comparison of the influence of two different constant-rate infusions (dexmedetomidine versus morphine) on anaesthetic requirements, cardiopulmonary function and recovery quality in isoflurane anaesthetized horses

Twenty adult healthy horses undergoing elective surgery were involved in this prospective, blinded, clinical study. Horses were randomly allocated to receive a constant rate infusion (CRI) of morphine or dexmedetomidine. After induction, anaesthesia was maintained with isoflurane in oxygen/air and mechanical ventilation applied. The end-tidal isoflurane concentration (FÉISO) was initially set at 0.9% and adjusted by the anaesthetist, to maintain a light surgical plane of anaesthesia, according to an objective flow-chart. The cardiopulmonary function was only minimally different between groups and maintained within clinically normal ranges. Less ketamine was required, FÉISO was lower after 1h and fewer alterations in the anaesthetic depth were needed in horses receiving dexmedetomidine, with better recoveries. One horse receiving morphine developed post-operative colic and pulmonary oedema and two showed box-walking behaviour. This study showed that a dexmedetomidine CRI produced a more stable anaesthetic depth, reduced isoflurane requirements and better recoveries, without post-operative complications compared with a morphine CRI.

Partial intravenous anaesthesia in the horse: a review of intravenous agents used to supplement equine inhalation anaesthesia. Part 2: opioids and alpha‐2 adrenoceptor agonists

OBJECTIVE To review the literature with regard to the use of different intravenous agents as supplements to inhalational anaesthesia in horses. The Part 2 of this review will focus in the use of opioids and α2 -agonists. DATABASES USED Pubmed and Web of Science. Search terms: horse, inhalant anaesthesia, balanced anaesthesia, partial intravenous anaesthesia, opioids, morphine, pethidine, butorphanol, methadone, fentanyl, alfentanil, remifentanil, sufentanil, xylazine, romifidine, detomidine, medetomidine and dexmedetomidine. CONCLUSIONS Different drugs and their combinations can be administered systemically in anaesthetized horses aiming to reduce the amount of the volatile agent while improving the recovery qualities and providing a multimodal analgesic approach. However, full studies as to whether these techniques improve cardiopulmonary status are not always available and potential disadvantages should also be considered.

The synergistic necrohemorrhagic action of Clostridium perfringens perfringolysin and alpha toxin in the bovine intestine and against bovine endothelial cells

Bovine necrohemorrhagic enteritis is a major cause of mortality in veal calves. Clostridium perfringens is considered as the causative agent, but there has been controversy on the toxins responsible for the disease. Recently, it has been demonstrated that a variety of C. perfringens type A strains can induce necrohemorrhagic lesions in a calf intestinal loop assay. These results put forward alpha toxin and perfringolysin as potential causative toxins, since both are produced by all C. perfringens type A strains. The importance of perfringolysin in the pathogenesis of bovine necrohemorrhagic enteritis has not been studied before. Therefore, the objective of the current study was to evaluate the role of perfringolysin in the development of necrohemorrhagic enteritis lesions in calves and its synergism with alpha toxin. A perfringolysin-deficient mutant, an alpha toxin-deficient mutant and a perfringolysin alpha toxin double mutant were less able to induce necrosis in a calf intestinal loop assay as compared to the wild-type strain. Only complementation with both toxins could restore the activity to that of the wild-type. In addition, perfringolysin and alpha toxin had a synergistic cytotoxic effect on bovine endothelial cells. This endothelial cell damage potentially explains why capillary hemorrhages are an initial step in the development of bovine necrohemorrhagic enteritis. Taken together, our results show that perfringolysin acts synergistically with alpha toxin in the development of necrohemorrhagic enteritis in a calf intestinal loop model and we hypothesize that both toxins act by targeting the endothelial cells.

Cardiovascular effects of epidural administration of methadone, ropivacaine 0.75% and their combination in isoflurane anaesthetized dogs

OBJECTIVE To compare the cardiovascular effects of four epidural treatments in isoflurane anaesthetised dogs. STUDY DESIGN Prospective, randomized. experimental study. ANIMALS Six female, neutered Beagle dogs (13.3±1.0 kg), aged 3.6±0.1 years. METHODS Anaesthesia was induced with propofol (8.3±1.1 mg kg(-1)) and maintained with isoflurane in a mixture of oxygen and air [inspiratory fraction of oxygen (FiO(2))=40%], using intermittent positive pressure ventilation. Using a cross-over model, NaCl 0.9% (P); methadone 1% 0.1 mg kg(-1) (M); ropivacaine 0.75% 1.65 mg kg(-1) (R) or methadone 1% 0.1 mg kg(-1) + ropivacaine 0.75% 1.65 mg kg(-1) (RM) in equal volumes (0.23 mL kg(-1)) using NaCl 0.9%, was administered epidurally at the level of the lumbosacral space. Treatment P was administered to five dogs only. Cardiovascular and respiratory variables, blood gases, and oesophageal temperature were recorded at T-15 and for 60 minutes after epidural injection (T0). RESULTS Mean overall heart rate (HR in beats minute(-1)) was significantly lower after treatment M (119±16) (p=0.0019), R (110±18) (p< 0.0001) and RM (109±13) (p<0.0001), compared to treatment P (135±21). Additionally, a significant difference in HR between treatments RM and M was found (p=0.04). After both ropivacaine treatments, systemic arterial pressures (sAP) were significantly lower compared to other treatments. No significant overall differences between treatments were present for central venous pressure, cardiac output, stroke volume, systemic vascular resistance, oxygen delivery and arterial oxygen content (CaO(2)). Heart rate and sAP significantly increased after treatment P and M compared to baseline (T-15). With all treatments significant reductions from baseline were observed in oesophageal temperature, packed cell volume and CaO(2) . A transient unilateral Horners syndrome occurred in one dog after treatment R. CONCLUSIONS AND CLINICAL RELEVANCE Clinically important low sAPs were observed after the ropivacaine epidural treatments in isoflurane anaesthetised dogs. Systemic arterial pressures were clinically acceptable when using epidural methadone.

Drugs for Cardiovascular Support in Anesthetized Horses

Despite the use of balanced anesthesia and fluids, drugs for cardiovascular support are often needed in anesthetized horses. Antimuscarinics can be used to treat bradycardia unrelated to hypertension. Vasopressors can be useful when hypotension is caused by vasodilation and/or when the effect of fluids and inotropes is insufficient. In most cases, however, inotropes, including sympathomimetics, calcium salts, and phosphodiesterase inhibitors, are preferred. Of the β-sympathomimetics, dobutamine remains the agent of choice. Calcium salts are mainly useful in hypocalcemic patients. Phosphodiesterase inhibitors may offer an alternative solution, but more research is needed.