Pharmacokinetics of midazolam and its major metabolite 1-hydroxymidazolam in the ball python (Python regius) after intracardiac and intramuscular administrations.

Midazolam is a benzodiazepine with sedative, muscle relaxant, anxiolytic, and anticonvulsant effects. Twelve ball pythons (Python regius) were used in a parallel study evaluating the pharmacokinetics of 1 mg/kg midazolam following a single intracardiac (IC) or intramuscular (IM) administration. Blood was collected from a central venous catheter placed 7 days prior, or by cardiocentesis, at 15 time points starting just prior to and up to 72 hr after drug administration. Plasma concentrations of midazolam and 1-hydroxymidazolam were determined by the use of high-performance liquid chromatography tandem-mass spectrometry and pharmacokinetic parameters were estimated using noncompartmental analysis. The mean ± SD terminal half-lives of IC and IM midazolam were 12.04 ± 3.25 hr and 16.54 ± 7.10 hr, respectively. The area under the concentration-time curve extrapolated to infinity, clearance, and apparent volume of distribution in steady-state of IC midazolam were 19,112.3 ± 3,095.9 ng*hr/ml, 0.053 ± 0.008 L hr-1  kg-1 , and 0.865 ± 0.289 L/kg, respectively. The bioavailability of IM midazolam was estimated at 89%. Maximum plasma concentrations following an IM administration were reached 2.33 ± 0.98 hr and 24.00 ± 14.12 hr postinjection for midazolam and 1-hydroxymidazolam, respectively, and 22.33 ± 20.26 hr postinjection for 1-hydroxymidazolam following IC administration.

A porcine animal model to mimic the restart of enteral nutrition (refeeding-model).

With the aim towards establishing an animal model of total parenteral nutrition (TPN), 12 piglets aged 9 weeks (mean body weight 21 kg) were surgically provided with central venous catheters. Six piglets were nourished parenterally with the objective to reach a 14-d period of TPN; the other six piglets served as control and were fed normally. Only one animal from each group could be monitored over the whole period. Nine piglets were euthanised on d 13 and one on d 12. No animal showed fever or signs of septicaemia during the study. The levels of Ca, Mg, Na and P in the blood were within the normal range as were those for blood glucose and plasma creatinine. Symptoms of the TPN included: transient diarrhoea, occasional appearance of faecal blood and occasional absence of defecation. A reduced small intestine length and altered mucosal morphology and function were observed. One animal showed bile stasis at the end of the study. All TPN animals showed a remarkably high level of blood urea early in the morning. The intestinal symptoms observed may resemble the human situation during TPN. However, due to the fast growth rate, pigs aged 9 weeks have higher nutrient requirements per kg body weight. Consequently, the osmolality of the nutrient solution was necessarily high. Whether the significantly higher blood urea observed in the TPN group reflected a catabolic metabolism during the starving period at night-time could not be conclusively shown. Alternatively, it could reflect a slower growth rate and a resulting quantitative excess of amino acids (AA), or could have been the consequence of a suboptimal AA composition. A permanent infusion would be favourable in order not to overcharge the capacity for glucose uptake and amino acid metabolism during the infusion.

Percutaneously inserted long-term central venous catheters in pigs of different sizes.

Pigs are used for long-term biomedical experiments requiring repeated injections, infusions and collections of blood samples. Thus, it is necessary for vascular catheters to be indwelling to avoid undue stress to the animals and the use of restraints. We propose a refined model of percutaneous insertion of long-term central venous catheters to minimize the surgical trauma and postoperative complications associated with catheter insertion. Different sizes of needles (18 Ga versus 21 Ga) for initial puncture of the veins were compared. In conventional pigs weighing less than 30 kg, catheter insertion may be facilitated by using a microintroducer set with a 21 Ga needle. In pigs weighing 50 kg, a standard 18 Ga needle may be preferable.

Use of tissue plasminogen activator in catheters used for extracorporeal renal replacement therapy.

BACKGROUND: Intraluminal thrombosis of central venous catheters used for renal replacement therapy (RRT) decreases the ability to provide adequate treatment. Alteplase is a recombinant tissue plasminogen activator that has been used to improve the function of catheters used for RRT in humans. OBJECTIVES: To retrospectively review alteplase instillation in dysfunctional catheters used for RRT in dogs and cats. ANIMALS: Seventeen dogs and 8 cats receiving RRT for kidney failure. METHODS: Medical records of patients in which alteplase was used for RRT catheter dysfunction from 2004 to 2012 were retrospectively reviewed to characterize reasons for use, improvement in function, increase in blood flow, and duration of improvement. RESULTS: Alteplase was instilled 43 times in 29 catheters, most commonly because of suspicion that the catheter would not provide sufficient flow on the next treatment (n = 21). The second most common reason was inability to start a dialysis treatment (n = 12). Catheter function improved after alteplase instillation in 34 of 43 treatments (79%). Median blood flow rate increased by 13% (18 mL/min) in the dialysis session after alteplase instillation. Seven of 29 catheters (24%) were treated with alteplase on >1 occasion (median time to second treatment, 8 days), and 1 catheter had to be replaced because of intractable dysfunction. CONCLUSIONS AND CLINICAL IMPORTANCE: Alteplase is effective at improving function of central venous catheters used to provide RRT, but the results are short-lived.