The use of intravenous lipid emulsion as an antidote in veterinary toxicology

Objective – To review the use of IV lipid emulsion (ILE) for the treatment of toxicities related to fat‐soluble agents; evaluate current human and veterinary literature; and to provide proposed guidelines for the use of this emerging therapy in veterinary medicine and toxicology. Data Sources – Human and veterinary medical literature. Human Data Synthesis – Human data are composed mostly of case reports describing the response to treatment with ILE as variant from mild improvement to complete resolution of clinical signs, which is suspected to be due to the variability of lipid solubility of the drugs. The use of ILE therapy has been advocated as an antidote in cases of local anesthetic and other lipophilic drug toxicoses, particularly in the face of cardiopulmonary arrest and unsuccessful cardiopulmonary cerebral resuscitation. Veterinary Data Synthesis – The use of ILE therapy in veterinary medicine has recently been advocated by animal poison control centers for toxicoses associated with fat‐soluble agents, but there are only few clinical reports documenting successful use of this therapy. Evidence for the use of ILE in both human and veterinary medicine is composed primarily from experimental animal data. Conclusions – The use of ILE appears to be a safe therapy for the poisoned animal patient, but is warranted only with certain toxicoses. Adverse events associated with ILE in veterinary medicine are rare and anecdotal. Standard resuscitation protocols should be exhausted before considering this therapy and the potential side effects should be evaluated before administration of ILE as a potential antidote in cases of lipophilic drug toxicoses. Further research is waranted.     

Dose requirement and cardiopulmonary effects of diluted and undiluted propofol for induction of anaesthesia in dogs

ObjectiveTo compare the dose, cardiopulmonary effects and quality of anaesthetic induction in dogs using propofol (10 mg mL^–1) and diluted propofol (5 mg mL^–1).Study designRandomized, blinded, clinical study.AnimalsA total of 28 client-owned dogs (12 males/16 females).MethodsFollowing intramuscular acepromazine (0.02 mg kg^–1) and methadone (0.2 mg kg^–1), propofol (UP, 10 mg mL^–1) or diluted propofol (DP, 5 mg mL^–1) was administered intravenously (0.2 mL kg^–1 minute^–1) by an anaesthetist unaware of the allocated group to achieve tracheal intubation. Sedation, intubation and induction quality were scored from 0 to 3. Pre- and post-induction pulse rate (PR), respiratory rate (f_R) and systolic (SAP), mean (MAP) and diastolic (DAP) arterial blood pressure were compared. Time to first breath and induction dose were recorded. Data were analysed for normality and Mann–Whitney U or Student t tests were performed where appropriate. Significance was set at p < 0.05. Data are presented as mean ± standard deviation or median (range).ResultsThe propofol dose administered to achieve induction was lower in the DP group (2.62 ± 0.48 mg kg^–1) than in the UP group (3.48 ± 1.17 mg kg^–1) (p = 0.021). No difference was observed in pre- and post-induction PR, SAP, MAP, DAP and f_R between groups. The differences between post-induction and pre-induction values of these variables were also similar between groups. Time to first breath did not differ between groups. Sedation scores were similar between groups. Quality of tracheal intubation was marginally better with UP 0 (0–1) than with DP 1 (0–2) (p = 0.036), but overall quality of induction was similar between groups [UP 0 (0–1) and DP 0 (0–1), p = 0.549].Conclusion and clinical relevanceDiluting propofol reduced the dose to induce anaesthesia without significantly altering the cardiopulmonary variables.     

Dose and cardiopulmonary effects of propofol alone or with midazolam for induction of anesthesia in critically ill dogs

ObjectiveTo determine the dose and cardiopulmonary effects of propofol alone or with midazolam for induction of anesthesia in American Society of Anesthesiologists status ≥III dogs requiring emergency abdominal surgery.Study designProspective, randomized, blinded, clinical trial.AnimalsA total of 19 client-owned dogs.MethodsDogs were sedated with fentanyl (2 μg kg^–1) intravenously (IV) for instrumentation for measurement of heart rate, arterial blood pressure, cardiac index, systemic vascular resistance index, arterial blood gases, respiratory rate and rectal temperature. After additional IV fentanyl (3 μg kg^–1), the quality of sedation was scored and cardiopulmonary variables recorded. Induction of anesthesia was with IV propofol (1 mg kg^–1) and saline (0.06 mL kg^–1; group PS; nine dogs) or midazolam (0.3 mg kg^–1; group PM; 10 dogs), with additional propofol (0.25 mg kg^–1) IV every 6 seconds until endotracheal intubation. Induction/intubation quality was scored, and anesthesia was maintained with isoflurane. Variables were recorded for 5 minutes with the dog in lateral recumbency, breathing spontaneously, and then in dorsal recumbency with mechanical ventilation for the next 15 minutes. A general linear mixed model was used with post hoc analysis for multiple comparisons between groups (p < 0.05).ResultsThere were no differences in group demographics, temperature and cardiopulmonary variables between groups or within groups before or after induction. The propofol doses for induction of anesthesia were significantly different between groups, 1.9 ± 0.5 and 1.1 ± 0.5 mg kg^–1 for groups PS and PM, respectively, and the induction/intubation score was significantly better for group PM.Conclusions and clinical relevanceMidazolam co-induction reduced the propofol induction dose and improved the quality of induction in critically ill dogs without an improvement in cardiopulmonary variables, when compared with a higher dose of propofol alone.     

The cardiopulmonary effects of romifidine in dogs with and without prior or concurrent administration of glycopyrrolate

Objective To determine the electrocardiographic and cardiopulmonary effects of romifidine with and without prior or concurrent administration of glycopyrrolate. Study design Randomized crossover experimental study. Animals Six (three male, three female) cross‐bred dogs weighing 23 ± 2.4 kg. Methods Baseline cardiopulmonary measurements were obtained in conscious dogs and one of five treatments was administered. Glycopyrrolate (G) 0.01 mg kg^?1, or saline (S) 0.5 mL, were administered IM as premedication (Gp or Sp), or G was administered concurrently (Gc) with romifidine (RO). Treatments were as follows T1, Sp + RO 40 µg kg^?1; T2, Gp + RO (40 µg kg^?1); T3, Sp + RO 120 µg kg^?1; T4, Gp + RO (120 µg kg^?1); T5, Sp + Gc + RO (120 µg kg^?1). Romifidine or RO + Gc was administered subcutaneously 20 minutes after premedication (time 0), and further measurements were taken 10, 20, 30, 60 and 90 minutes after RO. The main treatment effect was evaluated using two‐way anova for repeated measures, followed by one‐way anova and a post‐hoc least squares difference test with a modified Bonferroni correction (p < 0.02). A Student's t‐test was used to compare the effect of romifidine at 20 and 60 minutes versus baseline values (p < 0.05). Results Both low‐ and high‐dose RO (T1, T3) significantly decreased heart rate (HR), respiratory rate (RR), cardiac index (CI) and stroke volume index, and increased arterial blood pressure (SAP), systemic vascular resistance (SVR), pulmonary arterial occlusion pressure (PAOP) and central venous pressure. High‐dose RO produced greater increases in SVR and SAP measurements. Neither dose of RO produced an alteration in blood gas values or the alveolar to arterial oxygen gradient. Glycopyrrolate significantly increased HR and CI from 10 to 90 minutes between T1/T2 and T3/T4. Increases in SAP were dose related with significant differences between T1/T3 and T2/T4 at 90 and 10 minutes, respectively, and were highest in animals receiving Gp or Gc. High‐dose RO groups (T3, T4) had higher values for SVR than low‐dose RO groups (T1, T2), unrelated to G administration. There was an increase in PAOP in all treatments. The oxygen extraction ratio was increased with all treatments: larger increases were observed in T1, T3 and T4 compared with only minimal changes in T2. Concurrent G administration was associated with an increased frequency of high‐grade second‐degree atrioventricular heart block with variable conduction at 10 and 20 minutes. Conclusions Romifidine produced effects consistent with other selective α₂‐adrenoreceptor agonists. Glycopyrrolate offset the decrease in HR and partially offset the decrease in CI associated with RO administration. Glycopyrrolate premedication produced an initial tachycardia and added to the increase in SAP associated with RO. Concurrent G administration was associated with a higher frequency of dysrhythmias and is not recommended. Despite the decrease in RR, RO sedation did not alter blood gas values. Clinical relevance It appears likely that G administration prior to or concurrent with RO produces an increase in myocardial workload and oxygen demand suggesting that this combination should not be used in dogs with cardiomyopathy or heart failure. The improvement in oxygen extraction ratio with T2 suggests that G may be beneficial with lower doses of RO, nevertheless, the use of G and RO in cardiovascularly compromised patients is not advised.     

The effects of maxillary nerve block,ethmoidal nerve block and their combination on cardiopulmonary responses to nasal stimulation in anesthetized Beagle dogs

ObjectiveTo describe an approach for ethmoidal nerve block (E_BLOCK) and to compare the effects of a maxillary nerve block (M_BLOCK), E_BLOCK and their combination (M-E_BLOCK) on heart rate (HR), systolic (SAP), mean (MAP), diastolic (DAP) arterial pressures and respiratory rate (f_R) during nasal stimulation in dogs.Study designProspective, blinded, randomized, crossover placebo-controlled study.AnimalsBeagle dogs (five cadavers, nine live dogs), with a median (interquartile range) weight of 10.5 (10.3–11.0) kg.MethodsThe accuracy of iohexol injections (each 1 mL) at the maxillary and ethmoidal foramina in cadavers was evaluated using computed tomography. Then, anesthetized dogs were administered four bilateral treatments separated by 1 week, saline or 2% lidocaine 1 mL per injection: injections of saline at the maxillary and ethmoidal foramina (Control), injections of lidocaine at the maxillary foramina and saline at the ethmoidal foramina (M_BLOCK), injections of saline at the maxillary foramina and lidocaine at the ethmoidal foramina (E_BLOCK) and injections of lidocaine at all foramina (M-E_BLOCK). The ventral nasal meatus was bilaterally stimulated using cotton swabs, and HR, SAP, MAP, DAP and f_R were continuously recorded. Values for each variable were compared before and after stimulation using Wilcoxon signed-rank test. Changes in variables among treatments were analyzed using Mann–Whitney U and Kruskal–Wallis tests (p ≤ 0.05).ResultsComputed tomography revealed iohexol distribution around the openings of the target foramina in all cadavers. In living dogs, HR, SAP, MAP, DAP and f_R significantly increased after stimulation within each treatment (p < 0.03). Physiologic responses were significantly attenuated, but not absent, in the M-E_BLOCK [HR (p = 0.019), SAP, MAP, DAP and f_R (all p ≤ 0.001)] compared with those in the Control.Conclusions and clinical relevanceConcurrent injections of lidocaine at the maxillary and ethmoidal foramina attenuated HR, arterial pressure and f_R responses to nasal stimulation in Beagle dogs.     

A comparison of cardiopulmonary function,recovery quality,and total dosages required for induction and total intravenous anesthesia with propofol versus a propofol‐ketamine combination in healthy Beagle dogs

ObjectiveTo compare cardiopulmonary function, recovery quality, and total dosages required for induction and 60 minutes of total intravenous anesthesia (TIVA) with propofol (P) or a 1:1 mg mL⁻¹ combination of propofol and ketamine (KP).Study designRandomized crossover study.AnimalsTen female Beagles weighing 9.4 ± 1.8 kg.MethodsDogs were randomized for administration of P or KP in a 1:1 mg mL⁻¹ ratio for induction and maintenance of TIVA. Baseline temperature, pulse, respiratory rate (f_R), noninvasive mean blood pressure (MAP), and hemoglobin oxygen saturation (SpO₂) were recorded. Dogs were intubated and spontaneously breathed room air. Heart rate (HR), f_R, MAP, SpO₂, end tidal carbon dioxide tension (Pe’CO₂), temperature, and salivation score were recorded every 5 minutes. Arterial blood gas analysis was performed at 10, 30, and 60 minutes, and after recovery. At 60 minutes the infusion was discontinued and total drug administered, time to extubation, and recovery score were recorded. The other treatment was performed 1 week later.ResultsKP required significantly less propofol for induction (4.0 ± 1.0 mg kg⁻¹ KP versus 5.3 ±1.1 mg kg⁻¹ P, p = 0.0285) and maintenance (0.3 ± 0.1 mg kg⁻¹ minute⁻¹ KP versus 0.6 ±0.1 mg kg⁻¹ minute⁻¹ P, p = 0.0018). Significantly higher HR occurred with KP. Both P and KP caused significantly lower MAP compared to baseline. MAP was significantly higher with KP at several time points. P had minimal effects on respiratory variables, while KP resulted in significant respiratory depression. There were no significant differences in salivation scores, time to extubation, or recovery scores.Conclusions and clinical relevanceTotal intravenous anesthesia in healthy dogs with ketamine and propofol in a 1:1 mg mL⁻¹ combination resulted in significant propofol dose reduction, higher HR, improved MAP, no difference in recovery quality, but more significant respiratory depression compared to propofol alone.     

The effect of focused extracorporeal shock wave therapy on collagen matrix and gene expression in normal tendons and ligaments

Reasons for performing study: Extracorporeal shock wave therapy (ESWT) is frequently used in equine practice, but little is known about its biological action. Objectives: To study the effects of ESWT on matrix structure and gene expression levels in normal, physiologically loaded tendinous structures in ponies. Methods: Six Shetland ponies, free of lameness and with ultrasonographically normal flexor and extensor tendons and suspensory ligaments (SL), were used. ESWT was applied at the origin of the suspensory ligament and the mid‐metacarpal region of the superficial digital flexor tendon (SDFT) 6 weeks prior to sample taking, and at the mid‐metacarpal region (ET) and the insertion on the extensor process of the distal phalanx (EP) of the common digital extensor tendon 3 h prior to tendon sampling. In all animals one forelimb was treated and the other limb was used as control. After euthanasia, tendon tissue was harvested for real‐time PCR to determine gene expression levels and additional samples were taken for histological evaluation and biochemical analyses Results: Histologically a disorganisation of the normal collagen structure was observed 3 h after ESWT, remnants of which were still visible after 6 weeks. While degraded collagen levels showed an increase at 3 h post treatment (P = 0.012) they were reduced at 6 weeks post ESWT (P = 0.039). Gene expression for both COL1 (P = 0.004) and MMP14 (P = 0.020) was upregulated at 6 weeks after treatment. Conclusions: Exposure of normal tendinous tissue to ESWT is not uneventful; it leads to a disorganisation of matrix structure and changes in degraded collagen levels. The upregulation of COL1 expression 6 weeks after ESWT may be indicative for repair. Potential relevance: The observed disorganisation of the collagen network warrants caution when using ESWT. Exposing noninjured tissue to ESWT should be avoided and it may be advisable to restrict exercise in recently treated patients. However, the induced tissue disorganisation might also be a trigger for repair in chronic tendinopathies.