Thermography as an early predictive measurement for evaluating epidural and femoral-sciatic block success in dogs.

OBJECTIVE: To evaluate skin temperature increase as an early predictive measure for evaluating epidural and femoral-sciatic block success in dogs. STUDY DESIGN: Prospective clinical trial. ANIMALS: A total of 29 dogs undergoing orthopaedic surgery on one hindlimb. METHODS: Dogs were anaesthetized and placed into lateral recumbency with the affected limb uppermost and the coat was clipped. Baseline infrared thermographic images (T0) of the affected limb, of the paw pad of the affected leg and of the ipsilateral paw pad were taken. Subsequently, dogs were administered either an epidural (EPI; n=11) or a femoral-sciatic block (FS; n=18) using bupivacaine 1 mg kg-1. Then, 2 minutes after placement of the block, thermographic images were obtained every 3 minutes for a total of four measurements (T1-T4) and surgery was commenced. Rescue analgesia consisting of fentanyl 1 µg kg-1 was administered if needed. A regional block was considered successful if the dose of fentanyl administered was less than the lower 95% confidence interval of the geometric mean of the total fentanyl used in each group. A ≥ 1 °C increase of skin temperature was considered as the minimum increase required for detection of a successful block. RESULTS: A total of 12 out of 18 blocks in the FS and eight of 11 in the EPI group were considered successful based on fentanyl consumption. Out of these, only four of 12 in the FS and one of eight in the EPI group developed an increase in temperature of ≥ 1 °C. Contrarily, four of six of the nonsuccessful cases in the FS and three of three in the EPI group developed an increase in temperature of ≥ 1 °C. CONCLUSIONS AND CLINICAL RELEVANCE: Contrary to reports in humans, thermography did not indicate regional block success prior to surgery in dogs. However further studies under more controlled conditions are needed to determine whether thermography can be used to indicate failure of regional blockade.

Modulation of spinal shape with growth following implantation of a novel surgical implant.

PURPOSE: First, to determine whether scoliosis development could be limited or reversed by growth when a novel modular hinged implant was fixed to the convexity of a scoliosis created by contralateral rib and laminar tethering and unilateral rib resection in a sheep model. Second, to assess the effect and performance of the implant in normal non-tethered sheep. METHODS: At 5 weeks, 20 Scottish Blackface lambs underwent surgery to create a right sided scoliosis by (i) tethering the left lamina of T5-L1 and the left lower six ribs and (ii) resecting a segment of their right lower six ribs [1, 2]. Twelve weeks later, through an antero-lateral thoracotomy, a mobile bi-planar hinged implant was inserted onto the right side of the spine of eight animals (group 1). For comparison, 12 sheep were tethered only but had no implant insertion (group 2). In addition, seven had no tethering but were implanted (group 3) and normal growth patterns were observed in five that had no surgery (group 4). Curve progression was assessed by plain radiography and CT over a 1-year period. RESULTS: Before implant insertion the trial animals had a scoliosis of 35º ± 16º and a lordosis of 44º ± 20º (n = 8, mean ± SD). Surgery immediately reduced these values to 25º ± 14º, p < 0.01 and 35º ± 18º, p < 0.001, with scoliosis continuing to decrease during the next three months. Spinal flexibility was retained. In the un-tethered sheep, a scoliosis of 10º ± 6º was created on the opposite side to the implant (p < 0.05) with no significant change in alignment in the sagittal plane (1º ± 6º). The implant did not cause any adverse effect on growth or affect neurological function. CONCLUSIONS: In the un-tethered animals the effect of the implant was to create a scoliotic deformity and in the tethered to improve deformity while maintaining spinal motion. We believe that the results are promising and that devices of similar construct may be of use in children with scoliosis, potentially changing current methods of clinical care.

Creation of an ovine model of progressive structural lordo-scoliosis using a unilateral laminar tether.

PURPOSE: To characterise changes in vertebral dimension in an ovine model of scoliosis and determine whether a reproducible curvature could be created that would be suitable for future testing of curve modifying surgical implants. METHODS: At a mean age of 5 weeks, 28 Scottish blackface sheep were anaesthetised. A 4 mm braided synthetic tape was laid under the left lamina of T5 and L1 and tightened to 'hand' tension. A scoliosis was then created by binding the six lowest ribs on the same side just distal to their rib angles and resecting a segment from each of the opposite ribs. Radiographs were taken at 4 weekly intervals, and CT images at 2, 5 and 7 months post tethering, to determine multi-planar curve progression. 20 animals were assessed at age 3 months, 12 at 41 weeks and 10 at 1 year with comparisons to five control animals. RESULTS: A significant bi-planar deformity was produced in all animals (scoliosis 32 ± 13º and lordosis 53 ± 21º 2 months post tethering; mean ± SD, n = 22). During the next 5 months the scoliosis decreased slightly (p = 0.08) but the sagittal deformity remained static: 21 ± 18° and 53 ± 19°, respectively (n = 12). The values at 7 months were associated with a mean 6 ± 4º rotational deformity. There was approximately twice as much growth in the right anterior aspects of the apical vertebrae as in the left posterior. CONCLUSIONS: With appropriate care it was possible to obtain a reproducible curvature in immature sheep. The methods described are suitable for use in studies of growth modulation and other spinal devices.

Transfixation pinning and casting of a comminuted metacarpal fracture in a 870 kg bull.

OBJECTIVE: To report metacarpal fracture repair in a bull. STUDY DESIGN: Clinical report. ANIMALS: Simmental bull (n = 1; 870 kg). METHODS: A comminuted right metacarpal fracture was repaired using 2 transfixation pins (6 mm diameter) through the distal metaphysis and diaphysis of the radius and a full limb synthetic resin cast. RESULTS: Slight bending of both pins occurred 1 day after surgery. Both pins were loose and removed at 31 days and a full-limb cast reapplied. The cast was changed at approximately -4 week intervals. On day 50, the right carpus had moderate overextension and a valgus deformity. An exercise program was started on day 62, and on day 110, the cast was replaced with a Robert-Jones-bandage. At 130 days there was circumferential callus formation and the bull was discharged. At 6.5 months, overextension of the right carpus had resolved and carpal valgus had improved. The bull returned to at 7.5 months after surgery, and was successfully used for 4 years. CONCLUSION: For highly valuable cattle like this breeding bull, a surgical treatment of such a fracture should be attempted despite a primarily poor prognosis.

Clinical effects of isoflurane and sevoflurane in lambs.

OBJECTIVE: To compare isoflurane and sevoflurane in lambs undergoing prolonged anaesthesia for spinal surgery. STUDY DESIGN: Prospective randomised clinical study. ANIMALS: Eighteen Scottish blackface lambs 3-6 weeks of age and weighing 10-17 kg. METHODS: After intramuscular medetomidine, anaesthesia was induced and maintained with either isoflurane (group I) or sevoflurane (group S) delivered in oxygen. Meloxicam, morphine, a constant rate infusion of ketamine and atracurium were given intravenously (IV) during surgery. Lungs were ventilated to maintain normocapnia. with peak inspiratory pressures of 20-25 cmH(2) O. Ephedrine or dextran 40% was administered when mean arterial pressure (MAP) was <55 mmHg. Intrathecal morphine, and IV meloxicam and edrophonium were injected before recovery. Time to loss of palpebral reflex (TLPR) upon induction, cardiorespiratory variables, time at first swallowing and other movement, tracheal extubation, vocalisation, spontaneous head lifting (>1 minute), reunion with the ewe, and the number of MAP treatments were recorded. Statistical analysis utilised anova, Mann-Whitney, t-test or Pearson's correlation test as relevant. p < 0.05 was considered significant. RESULTS: End-tidal carbon dioxide (mean ± SD) was significantly lower in group S (5.5 ± 0.6 kPa) than in group I (5.8 ± 0.5 kPa) while MAP (70 ± 11 mmHg) and diastolic arterial blood pressure (60 ± 11 mmHg) were higher in group S than in group I (65 ± 12 and 54 ± 11 mmHg, respectively). No differences were found with TLPR and MAP treatments. Time (median, range) from end of anaesthesia to ewe-lamb reunion was briefer (p = 0.018) in group S (48, 20-63 minutes). CONCLUSION: Isoflurane and sevoflurane are both suitable for maintaining general anaesthesia in lambs although sevoflurane, as used in this study, allows a more rapid reunion with the ewe. CLINICAL RELEVANCE: The principal advantage of sevoflurane over isoflurane during prolonged anaesthesia in lambs is a more rapid recovery.

The effects of age, isoflurane and sevoflurane on atracurium in lambs.

OBJECTIVE: To determine the effects of age, sevoflurane and isoflurane on atracurium-induced neuromuscular blockade in 3-16 week-old lambs. STUDY DESIGN: Prospective randomized experimental trial. ANIMALS: Twenty-six Scottish blackface ewe-lambs were anaesthetized for spinal surgery when either 3-6 (mean age 4.6 weeks; n = 18) or 12-16 weeks (mean age 13.7 weeks; n = 15) of age; seven animals were anaesthetized at both ages. METHODS: After intramuscular injection of medetomidine (10 µg kg(-1)) anaesthesia was induced in the younger lambs either with isoflurane or sevoflurane in oxygen delivered by mask, and in the older lambs with ketamine (4 mg kg(-1)), and midazolam (0.2 mg kg(-1) ) administered intravenously (IV). In both groups anaesthesia was maintained with fixed end-tidal concentrations of either sevoflurane (2.8%) or isoflurane (1.8%) delivered in oxygen. Before surgery meloxicam (0.6 mg kg(-1)), morphine (0.5 mg kg(-1)) and ketamine (1 mg kg(-1) followed by 10 µg kg(-1) minute(-1) ) were administered IV. The lungs were ventilated mechanically to maintain normocapnia. Neuromuscular block was achieved with a loading dose (LD) of atracurium (0.5 mg kg(-1) IV). The peroneal nerve was stimulated (train-of-four every 12 seconds). Evoked responses in the digital extensor muscles were evaluated by palpation and observation. Maintenance doses (MD) of atracurium (0.17 mg kg(-1) IV) were administered when the first twitch (T1) returned. The onset and duration of LD action (T1 absent) and the duration of MD were recorded. Data were analysed using Student's t test, Mann-Whitney U test, repeated-measures anova, Wilcoxon's matched pairs test or Pearson correlation coefficient as relevant (p < 0.05). RESULTS: Onset of LD action developed significantly (p < 0.05) more rapidly in isoflurane compared with sevoflurane-anaesthetized lambs (55 ± 18 cf. 80 ± 37 seconds). Duration of action of LDs and MDs was longer (p < 0.05) in lambs aged 12-16 than 3-6 weeks (33 ± 5.4 cf. 25 ± 6.4 and 26 ± 4.2 cf. 18 ± 5.5 minutes) but were independent of the anaesthetic used. CONCLUSIONS AND CLINICAL RELEVANCE: The effect of atracurium is age-dependent in lambs being prolonged in older animals. The onset of neuromuscular blockade is more rapid in isoflurane compared with sevoflurane-anaesthetized lambs.

Laparoscopic-assisted implantation of a urinary catheter in male sheep.

OBJECTIVE-To evaluate a laparoscopic technique for implantation of a urinary catheter in the right paramedian area in male sheep and to determine feasibility, benefits, and risks for this technique. DESIGN-Evaluation study. ANIMALS-6 Healthy male sheep (mean +/- SD body weight, 42.16 +/- 11.95 kg [92.75 +/- 26.29 lb]). PROCEDURES-Each sheep was anesthetized and positioned in dorsal recumbency. A 10-mm laparoscope was inserted in the right paramedian area between the xiphoid and preputial orifice. After creation of capnoperitoneum, grasping forceps were inserted in the left paramedian area at the level of the teats and used to immobilize the urinary bladder. A pigtail balloon catheter was implanted transcutaneously in the right paramedian area between the preputial orifice and teats and directed into the urinary bladder by use of laparoscopic guidance. The catheter was removed 10 days after implantation. Fourteen days after initial surgery, a second laparoscopy was performed to evaluate pathologic changes. RESULTS-Inadvertent insertion of the first trocar into the rumen of 1 sheep was the only intraoperative complication encountered. Laparoscopic-assisted implantation of the urinary catheter was successfully performed in all sheep. No postoperative complications were detected. CONCLUSIONS AND CLINICAL RELEVANCE-Laparoscopic-assisted implantation of a urinary catheter in the right paramedian area was successfully performed and may be a feasible method for use in sheep. This method can be considered as an alternative to tube cystotomy performed by laparotomy.

Thiolated chitosans: design and in vivo evaluation of a mucoadhesive buccal peptide drug delivery system.

PURPOSE: Intravenous application of pituitary adenylate cyclase-activating polypeptide (PACAP) has been identified as a promising strategy for the treatment of type 2 diabetes. To generate a more applicable formulation, it was the aim of this study to develop a sustained buccal delivery system for this promising therapeutic peptide. METHODS: 2-Iminothiolane was covalently bound to chitosan to improve the mucoadhesive and permeation-enhancing properties of chitosan used as drug carrier matrix. The resulting chitosan-4-thiobutylamidine conjugate was homogenized with the enzyme inhibitor and permeation mediator glutathione (gamma-Glu-Cys-Gly), Brij 35, and PACAP (formulation A). The mixture was lyophilized and compressed into flat-faced discs (18 mm in diameter). One formulation was additionally coated on one side with palm wax (formulation B). Tablets consisting of unmodified chitosan and PACAP (formulation C) or of unmodified chitosan, Brij 35, and PACAP (formulation D) served as controls. Bioavailability studies were performed in pigs by buccal administration of these test formulations. Blood samples were analyzed via an ELISA method. RESULTS: Formulations A and B led to an absolute bioavailability of 1%, whereas PACAP did not reach the systemic circulation when administered via formulations C and D. Moreover, in the case of formulations A and B, a continuously raised plasma level of the peptide drug being in the therapeutic range could be maintained over the whole period of application (6 h). Formulations A and B were removed by moderate force from the buccal mucosa after 6 h, whereas formulations C and D detached from the mucosa 4 h after application. CONCLUSION: The study reveals this novel mucoadhesive delivery system to be a promising approach for buccal delivery of PACAP.

The use of thiolated polymers as carrier matrix in oral peptide delivery--proof of concept.

It was the aim of this study to develop an oral delivery system for the peptide drug antide. The stability of the therapeutic peptide towards gastrointestinal peptidases was evaluated. The therapeutic agent and the permeation mediator glutathione were embedded in the thiolated polymer chitosan-4-thio-butylamidine conjugate (chitosan-TBA conjugate) and compressed to tablets. Drug release studies were performed in the dissolution test apparatus according to the Pharmacopoeia Europea using the paddle method and demineralized water as release medium. In order to avoid mucoadhesion of these delivery systems already in the oral cavity and oesophagus tablets were coated with a triglyceride. These tablets were orally given to pigs (weight: 50+/-2 kg; Edelschwein Pietrain). Moreover, antide was administered intravenously, subcutaneously and orally in solution. Results showed stability of antide towards pepsin, trypsin and chymotrypsin. In contrast, antide was rapidly degraded by elastase. Consequently a stomach-targeted delivery system was designed. Drug release studies demonstrated an almost zero-order controlled release of antide over 8 h. In vivo studies demonstrated a relative bioavailability of 34.4% for the subcutaneous administration. Oral administration of antide in solution led to no detectable concentrations of the drug in plasma at all. In contrast, administering antide being incorporated in the thiolated polymer resulted in a significant uptake of the peptide. The absolute and relative bioavailability was determined to be 1.1% and 3.2%, respectively.

Impact of extracorporeal membrane oxygenation modality on cytokine release during rescue from infant hypoxia.

The treatment of acute respiratory failure in infants by means of extracorporeal membrane oxygenation (ECMO) is thought to be associated with a treatment-related inflammatory reaction, which may deteriorate the underlying disease process. The aim of this study was to compare the venoarterial (VA) and venovenous (VV) modality of ECMO with regard to their pulmonary and serological cytokine release during rescue from acute hypoxia. The inflammatory response was measured in piglets undergoing hypoxic ventilation with a gas mixture of 92% N2 and 8% O2, which were then rescued through VA- (n = 5) or VV-ECMO (n = 5). The effect of cannulation and anesthesia on the inflammatory response was deducted from regularly ventilated control animals (n = 5). The concentrations of the proinflammatory interleukins (IL)-1beta and IL-8 increased in the bronchoalveolar lavage fluid of all groups over a study period of 5 h but were significantly higher (P < 0.05) during VA-ECMO treatment, whereas the anti-inflammatory IL-10 concentrations were significantly higher in the bronchoalveolar lavage fluid of VV-treated animals (P < 0.001). No statistical difference between groups was found in the serum concentrations of cytokines. We conclude that in this animal model rescue from hypoxia by means of the VA modality of ECMO leads to a more pronounced inflammatory reaction of the lung than when applying the VV modality.