Cardiorespiratory,sedative and antinociceptive effects of dexmedetomidine alone or in combination with methadone,morphine or tramadol in dogs

ObjectiveTo evaluate the cardiorespiratory, sedative and antinociceptive effects of dexmedetomidine alone or in combination with methadone, morphine or tramadol in dogs.Study designExperimental, blinded, randomized, crossover study.AnimalsSix mixed breed dogs (two males and four females) weighing 10 ± 4 kg.MethodsThe animals were randomly divided into four treatments: D (10 μg kg^?1 of dexmedetomidine), DM (dexmedetomidine 10 μg kg^?1 and methadone 0.5 mg kg^?1); DMO (dexmedetomidine 10 μg kg^?1 and morphine 0.5 mg kg^?1), and DT (dexmedetomidine 10 μg kg^?1 and tramadol 2 mg kg^?1). The combinations were administered intramuscularly in all treatments. The variables evaluated were heart rate (HR), respiratory rate (f_R), rectal temperature (RT), systolic arterial pressure (SAP), sedation scale and pedal withdrawal reflex. These variables were measured at T0 (immediately before the administration of the protocol) and every 15 minutes thereafter until T105.ResultsA decrease in HR and f_R occurred in all the treatments compared with T0, but no significant difference was observed between the treatments. The RT decreased from T45 onward in all the treatments. The SAP did not show a difference between the treatments, but in the DT treatment, the SAP was lower at T30 and T45 compared with T0. The D treatment had lower scores of sedation at T15 to T75 compared with the other treatments, and the DMO and DM treatments showed higher scores at T60 and T75 compared with DT.Conclusions and clinical relevanceThe treatments with morphine and methadone added to the dexmedetomidine showed higher sedation scores than the control treatment and the treatment with tramadol added to the dexmedetomidine showed no relevant differences in any of the variables evaluated in the study.     

Comparative study on the sedative effects of morphine, methadone, butorphanol or tramadol, in combination with acepromazine, in dogs

Objective  To compare the effects of morphine (MOR), methadone (MET), butorphanol (BUT) and tramadol (TRA), in combination with acepromazine, on sedation, cardiorespiratory variables, body temperature and incidence of emesis in dogs.
Study design  Prospective randomized, blinded, experimental trial.
Animals  Six adult mixed-breed male dogs weighing 12.0 ± 4.3 kg.
Methods  Dogs received intravenous administration (IV) of acepromazine (0.05 mg kg⁻¹) and 15 minutes later, one of four opioids was randomly administered IV in a cross-over design, with at least 1-week intervals. Dogs then received MOR 0.5 mg kg⁻¹; MET 0.5 mg kg⁻¹; BUT 0.15 mg kg⁻¹; or TRA 2.0 mg kg⁻¹. Indirect systolic arterial pressure (SAP), heart rate (HR), respiratory rate ( f _R), rectal temperature, pedal withdrawal reflex and sedation were evaluated at regular intervals for 90 minutes.
Results  Acepromazine administration decreased SAP, HR and temperature and produced mild sedation. All opioids further decreased temperature and MOR, BUT and TRA were associated with further decreases in HR. Tramadol decreased SAP whereas BUT decreased f _R compared with values before opioid administration. Retching was observed in five of six dogs and vomiting occurred in one dog in MOR, but not in any dog in the remaining treatments. Sedation scores were greater in MET followed by MOR and BUT. Tramadol was associated with minor changes in sedation produced by acepromazine alone.
Conclusions and clinical relevance  When used with acepromazine, MET appears to provide better sedation than MOR, BUT and TRA. If vomiting is to be avoided, MET, BUT and TRA may be better options than MOR.     

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

ObjectiveTo 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 a₂-agonists.Databases usedPubmed 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.ConclusionsDifferent 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.     

Cardiopulmonary and sedative effects of intravenous or epidural methadone in conscious dogs

Cardiopulmonary and sedative effects of intravenous or epidural methadone were compared. Six beagles were randomly assigned to group MIV (methadone 0.5 mg/kg IV + NaCl 0.9% epidurally) or MEP (methadone 0.5 mg/kg epidurally + NaCl 0.9% IV). Cardiopulmonary, blood gas and sedation were assessed at time (T) 0, 15, 30, 60, 120, 240 and 480 min after drug administration. Compared to T0, heart rate decreased at T15–T120 in MIV (p < .001) and T15–T240 in MEP (p < .05); mean arterial pressure was reduced at T15–T60 in MEP (p < .01); respiratory rate was higher at T15 and T30 in both groups (p < .05); pH was lower at T15–T120 in MIV (p < .01) and T15, T30 and T120 in MEP (p < .05); PaCO₂ was higher at T15–T60 in MIV (p < .01) and T15, T30 and T120 in MEP (p < .01); sedation scores were higher at T15 and T30 in MIV and T15–T60 in MEP (p < .05). At T120 and T240, sedation score was higher in group MEP compared with group MIV (p < .01) In conclusion, cardiopulmonary and sedative effects of identical methadone doses are similar when administered IV or epidurally to conscious healthy dogs.     

Anaesthetic,analgesic and cardiorespiratory effects of intramuscular medetomidine‐ketamine combination alone or with morphine or tramadol for orchiectomy in cats

ObjectivesTo compare the anaesthetic, analgesic and cardiorespiratory effects of intramuscular (IM) medetomidine and ketamine administered alone or combined with morphine or tramadol, for orchiectomy in cats.Study designRandomised, blinded, prospective clinical study.AnimalsThirty client-owned cats.Materials and methodsCats (n = 10 in each group) received a combination of medetomidine (60 μgkg^?1) and ketamine (10 mg kg^?1) alone (MedK); combined with morphine (0.2 mg kg^?1) (MedKM), or combined with tramadol (2 mg kg^?1) (MedKT) IM. Time of induction, surgical and recovery events were recorded, and physiological parameters measured and recorded. Analgesia was evaluated with a visual analogue scale, a composite scoring system and the von Frey mechanical threshold device, every hour from three to eight hours post-drug administration injection. Data were analyzed with a linear mixed model, Kruskal–Wallis or Chi-square tests (p < 0.05).ResultsMedian (IQR) induction and recovery times (minutes) were not significantly (p = 0.125) different between groups: 5.6 (2.7–8.0), 7.4 (5.1–9.6) and 8.0 (5.8–14.9) for induction and 128.5 (95.1–142.8), 166.4 (123.1–210.0) and 142.9 (123.4–180.2) for recovery, with MedK, MedKT and MedKM, respectively. Two cats (MedKM) required alfaxalone for endotracheal intubation. In all groups, three or four cats required additional isoflurane for surgery. Arterial oxygen tension overall (mean ± SD: 66 ± 2 mmHg) was low. Surgery resulted in increased systolic arterial blood pressure (p < 0.001), haemoglobin saturation (p < 0.001), respiratory (p = 0.003) and heart rates (p = 0.002). Pain scores did not differ significantly between groups. Von Frey responses decreased over time; changes over time varied by treatment (p < 0.001), MedK returning to baseline values more rapidly than MedKM and MedKT. No cat required rescue analgesics.Conclusion and clinical relevanceAll three protocols can provide adequate anaesthesia and analgesia for orchiectomy in cats. However, rescue intervention to maintain surgical anaesthesia may be required in some cats. Oxygen supplementation is advised.     

Cardiopulmonary effects of an infusion of remifentanil or morphine in horses anesthetized with isoflurane and dexmedetomidine

ObjectiveTo examine the cardiopulmonary effects of infusions of remifentanil or morphine, and their influence on recovery of horses anesthetized with isoflurane and dexmedetomidine.Study designRandomized crossover study with 7-day rest periods.AnimalsSix adult horses (507 ± 61 kg).MethodsAfter the horses were sedated with xylazine, anaesthesia was induced with ketamine and diazepam, and maintained with isoflurane. After approximately 60 minutes, a dexmedetomidine infusion was started (0.25 μg kg^?1 then 1.0 μg^?1 kg^?1 hour^?1) in combination with either saline (group S), morphine (0.15 mg kg^?1 then 0.1 mg kg^?1 hour^?1; group M), or remifentanil (6.0 μg kg^?1 hour^?1; group R) for 60 minutes. Mean arterial pressure, heart rate, end-tidal carbon dioxide tension, and end-tidal isoflurane concentration were recorded every 5 minutes. Core body temperature, cardiac output, right ventricular and arterial blood-gas values were measured every 15 minutes. Cardiac index, systemic vascular resistance (SVR), intrapulmonary shunt fraction, alveolar dead space, oxygen delivery and extraction ratio were calculated. Recoveries were videotaped and scored by two observers blinded to the treatment. Data were analyzed using repeated measures anova followed by Dunnett’s or Bonferroni’s significant difference test. Recovery scores were analyzed using a Kruskal–Wallis test.ResultsNo significant differences were found among groups. Compared to baseline, heart rate decreased and SVR increased significantly in all groups, and cardiac index significantly decreased in groups S and M. Hemoglobin concentration, oxygen content and oxygen delivery significantly decreased in all groups. The oxygen extraction ratio significantly increased in groups M and R. Lactate concentration significantly increased in group S. Recovery scores were similar among groups.Conclusions and clinical relevanceDexmedetomidine alone or in combination with remifentanil or morphine infusions was infused for 60 minutes without adverse effects in the 6 healthy isoflurane-anesthetized horses in this study.     

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.     

Evaluation of the perioperative stress response from dexmedetomidine infusion alone,with butorphanol bolus or remifentanil infusion compared with ketamine and morphine infusions in isoflurane-anesthetized horses

ObjectiveTo evaluate perioperative stress-related hormones in isoflurane-anesthetized horses administered infusions of dexmedetomidine alone or with butorphanol or remifentanil, compared with ketamine–morphine.Study designRandomized, prospective, nonblinded clinical study.AnimalsA total of 51 horses undergoing elective surgical procedures.MethodsHorses were premedicated with xylazine, anesthesia induced with ketamine–diazepam and maintained with isoflurane and one of four intravenous infusions. Partial intravenous anesthesia (PIVA) was achieved with dexmedetomidine (1.0 μg kg^–1 hour^–1; group D; 12 horses); dexmedetomidine (1.0 μg kg^–1 hour^–1) and butorphanol bolus (0.05 mg kg^–1; group DB; 13 horses); dexmedetomidine (1.0 μg kg^–1 hour^–1) and remifentanil (3.0 μg kg^–1 hour^–1; group DR; 13 horses); or ketamine (0.6 mg kg^–1 hour^–1) and morphine (0.15 mg kg^–1, 0.1 mg kg^–1 hour^–1; group KM; 13 horses). Infusions were started postinduction; butorphanol bolus was administered 10 minutes before starting surgery. Blood was collected before drugs were administered (baseline), 10 minutes after ketamine–diazepam, every 30 minutes during surgery and 1 hour after standing. Mean arterial pressure (MAP), pulse rate, end-tidal isoflurane concentration, cortisol, nonesterified fatty acids (NEFA), glucose and insulin concentrations were compared using linear mixed models. Significance was assumed when p < 0.05.ResultsWithin D, cortisol was lower at 120–180 minutes from starting surgery compared with baseline. Cortisol was higher in KM than in D at 60 minutes from starting surgery. Within all groups, glucose was higher postinduction (except DR) and 60 minutes from starting surgery, and insulin was lower during anesthesia and higher after standing compared with baseline. After standing, NEFA were higher in KM than in DB. In KM, MAP increased at 40–60 minutes from starting surgery compared with 30 minutes postinduction.Conclusions and clinical relevanceDexmedetomidine suppressed cortisol release more than dexmedetomidine–opioid and ketamine–morphine infusions. Ketamine–morphine PIVA might increase catecholamine activity.     

Peritoneal concentrations of transforming growth factor beta in horses with colic

Reasons for performing the study: In man, peritoneal transforming growth factor beta (TGF‐β) is associated with peritoneal diseases and subsequent adhesion formation. No studies on plasma and peritoneal TGF‐β concentrations in horses with colic are available. Objectives: 1) To determine both plasma and peritoneal TGF‐β₁ and TGF‐β₃ concentrations in horses with different types of colic (not previously subjected to abdominal surgery); 2) to compare these concentrations according to the type of peritoneal fluid (transudate, modified transudate and exudate); and 3) to compare and correlate plasma and peritoneal concentrations of TGF‐β₁ and TGF‐β₃ and the types of peritoneal fluid according to the colic group and outcome. Methods: Peritoneal fluid and plasma samples from 78 horses with colic and 8 healthy horses were obtained. Patients were classified according to diagnosis (obstructions, enteritis, ischaemic disorders and peritonitis), peritoneal fluid analysis (transudate, modified transudate and exudate), and outcome (survivors and nonsurvivors). Plasma and peritoneal TGF‐β₁ and TGF‐β₃ concentrations were determined by ELISA. Data were analysed by parametric and nonparametric tests. P≤0.05 was considered as statistically significant. Results: Concentrations of peritoneal fluid TGF‐β₁ were significantly (P = 0.01) higher in horses with peritonitis in comparison with all other colic groups and controls. Horses with ischaemic lesions had significantly (P = 0.01) higher concentrations of peritoneal TGF‐β₁ in comparison with controls and the group of horses with obstructions. Peritoneal TGF‐β₁ concentration also was significantly (P = 0.01) higher in exudates in comparison with transudates. Peritoneal TGF‐β₁ and TGF‐β₃ concentrations and plasma TGF‐β₁ concentration were significantly increased in nonsurvivors compared to survivors (P = 0.001, P = 0.004 and P = 0.05, respectively). Conclusions: Peritoneal TGF‐β₁ concentration was higher in horses with severe gastrointestinal diseases (ischaemic intestinal lesions and peritonitis), in horses with an altered peritoneal fluid (exudate), and in nonsurvivors. Potential relevance: Peritoneal TGF‐β concentration increases in horses with severe gastrointestinal disease as an anti‐inflammatory response.     

Sedative and cardiovascular effects of romifidine, alone and in combination with butorphanol, in the horse

The behavioural and sedative effects of intravenous (iv) romifidine (40 and 80 μg/kg bodyweight [bwt]) alone or in combination with iv butorphanol (50 μg/kg bwt) were investigated in four ponies and one Thoroughbred horse. Apparent sedation, as judged by the lowering of the head, and by the response to imposed touch, visual and sound stimuli was assessed. The combination with butorphanol reduced the animals' response to imposed stimuli when compared with the effect of the same dose of romifidine alone. Following the administration of romifidine/butorphanol combinations muzzle tremor was noted and some animals attempted to walk forward. In a separate series, the cardiopulmonary effects of iv romifidine (80 μg/kg bwt) alone, or in combination with butorphanol (50 μg/kg bwt) were investigated. Romifidine and the romifidine/butorphanol combination caused similar cardiovascular changes, these being bradycardia with heart block, and hypertension followed by hypotension. Romifidine caused a transient decrease in arterial oxygen tensions and arterial carbon dioxide tensions had increased significantly by the end of the 90 min recording period. Romifidine/butorphanol combinations produced significantly higher arterial carbon dioxide tensions during the first 15 mins after drug administration than did romifidine alone. Butorphanol at 50 μg/kg bwt iv reduced the response to imposed stimuli in horses sedated with romifidine. The combination produced no cardiovascular changes beyond those induced by romifidine alone, but did increase the degree of respiratory depression.     

Polymorphism of inhibin βB gene and its relationship with litter size in sheep

The inhibin β_B (INHBB) gene was studied as a candidate gene for the prolificacy of Small Tail Han and Hu sheep. According to the sequence of exon 1 and 2 of bovine INHBB gene, six pairs of primers were designed to detect single nucleotide polymorphisms of exon 1 and 2 of INHBB gene in both high (Small Tail Han and Hu sheep) and low prolificacy breeds (Dorset, Texel and German Mutton Merino sheep) by polymerase chain reaction‐single strand conformation polymorphism (PCR‐SSCP). Three pairs of primers (primers 1‐1, 1‐2 and 1‐3) were used to amplify the exon 1, and others (primers 2‐1, 2‐2 and 2‐3) to the exon 2. Only the products amplified by primer 2‐3 displayed polymorphism. For primer 2‐3, three genotypes (AA, AB and BB) were detected in Hu sheep and only AA genotype in other breeds. In Hu sheep, frequency of AA, AB and BB genotypes was 0.636, 0.046 and 0.318, respectively. Sequencing revealed 276A > G mutation (based on the amplification region of primer 2‐3) which did not cause any amino acid change because it lay in the 3′ untranslated region. The ewes with genotype BB had 0.58 (P < 0.01) lambs more than those with AA in Hu sheep.