Pharmacokinetic and pharmacodynamic modelling of intravenous,intramuscular and subcutaneous buprenorphine in conscious cats

ObjectiveTo describe simultaneous pharmacokinetics (PK) and thermal antinociception after intravenous (IV), intramuscular (IM) and subcutaneous (SC) buprenorphine in cats.Study designRandomized, prospective, blinded, three period crossover experiment.AnimalsSix healthy adult cats weighing 4.1 ± 0.5 kg.MethodsBuprenorphine (0.02 mg kg^?1) was administered IV, IM or SC. Thermal threshold (TT) testing and blood collection were conducted simultaneously at baseline and at predetermined time points up to 24 hours after administration. Buprenorphine plasma concentrations were determined by liquid chromatography tandem mass spectrometry. TT was analyzed using anova (p < 0.05). A pharmacokinetic-pharmacodynamic (PK-PD) model of the IV data was described using a model combining biophase equilibration and receptor association-dissociation kinetics.ResultsTT increased above baseline from 15 to 480 minutes and at 30 and 60 minutes after IV and IM administration, respectively (p < 0.05). Maximum increase in TT (mean ± SD) was 9.3 ± 4.9 °C at 60 minutes (IV), 4.6 ± 2.8 °C at 45 minutes (IM) and 1.9 ± 1.9 °C at 60 minutes (SC). TT was significantly higher at 15, 60, 120 and 180 minutes, and at 15, 30, 45, 60 and 120 minutes after IV administration compared to IM and SC, respectively. IV and IM buprenorphine concentration-time data decreased curvilinearly. SC PK could not be modeled due to erratic absorption and disposition. IV buprenorphine disposition was similar to published data. The PK-PD model showed an onset delay mainly attributable to slow biophase equilibration (t_1/2k_e0 = 47.4 minutes) and receptor binding (k_on = 0.011 mL ng^?1 minute^?1). Persistence of thermal antinociception was due to slow receptor dissociation (t_1/2k_off = 18.2 minutes).Conclusions and clinical relevanceIV and IM data followed classical disposition and elimination in most cats. Plasma concentrations after IV administration were associated with antinociceptive effect in a PK-PD model including negative hysteresis. At the doses administered, the IV route should be preferred over the IM and SC routes when buprenorphine is administered to cats.     

High natural aerosol loading over boreal forests

Aerosols play a key role in the radiation balance of the atmosphere. Here, we present evidence that the European boreal region is a substantial source of both aerosol mass and aerosol number. The investigation supplies a straightforward relation between emissions of monoterpenes and gas-to-particle formation over regions substantially lacking in anthropogenic aerosol sources. Our results show that the forest provides an aerosol population of 1000 to 2000 particles of climatically active sizes per cubic centimeter during the late spring to early fall period. This has important implications for radiation budget estimates and relevancy for the evaluation of feedback loops believed to determine our future climate.     

The persistence of foot-and-mouth disease virus on wool

SUMMARY Five Suffolk sheep, held in a high-security isolation room, were exposed for 2 hours to the aerosol of 3 mature pigs that had been infected with foot-and-mouth disease virus (FMDV), strain O₁-BFS. The fleeces of 3 of the sheep were contaminated with FMDV at 2 days post exposure (dpe), while at 5 dpe the fleeces of all 5 sheep were more extensively, and more heavily, contaminated. The persistence of FMDV on contaminated wool was examined in vitro using multiple 0.5 g samples of Merino wool that were each contaminated with one of 3 strains of FMDV in tissue-culture medium: O₁-BFS, O-Morocco (O-MOR 9/91) or an Asia 1 strain (TAI 1/90). Wool samples were held at either 4°C, 18°C or 37°C, and decay curves were established for each virus at each temperature. These curves predicted that O₁-BFS, O-MOR 9/91 and TAI 1/90 would fall below detect-able levels at 72, 70 and 48 days post contamination (pc), respectively, for wool stored at 4°C; at 11, 12 and 12 days pc, respectively, for wool stored at 18°C; and at 57, 68 and 33 hours pc, respectively, for wool stored at 37°C. For wool contaminated with O₁-BFS-infected sheep faeces, urine or blood, or with O₁-BFS-infected cattle saliva, decay curves predicted virus to persist for 5 to 11 days pc at 18°C. We demonstrated that the simulated scouring of FMDV-contaminated wool at 60° to 70°C would usually reduce virus to below detectable levels. The detergent component of the scouring process had little, if any, antiviral activity, and scouring at 20°C or 50°C had limited impact on FMDV titres . We recommend that either (1) simple storage of FMDV-contaminated wool for 4 weeks at temperatures of 18°C or higher, or (2) scouring of contaminated wool at 60° to 70°C would be sufficient to remove the threat of FMDV-contaminated wool being infectious to other animals .     

Aerosol particles in the developing world; a comparison between New Delhi in India and Beijing in China

In developing countries, aerosol particles damage the health of hundreds of millions of people. Migration from the country side to megacities increases emissions and exposure to particles. Some countries have started to limit emissions based on particulate mass, but this may increase particle number concentrations. In this study we discuss some earlier measurements carried out in the developing world and compare results from one-week measurement campaigns concerning the particle number size distribution and PM₁₀ mass concentrations in New Delhi, India and Beijing, China. Our results show that submicron particle concentrations are high in both places. The average PM₁₀ concentration was 360 μg/m³ in New Delhi and 120 μg/m³ in Beijing. The corresponding total particle number concentrations in the size range 3–800 nm were 63 000 cm^?3 and 35 000 cm^?3. Number and mass concentrations and their characteristics showed significantly different behaviour between these two locations, which stresses the importance of long-term simultaneous measurements of both quantities in different types of megacities.     

Assessment of postoperative pain after unilateral mastectomy using two different surgical techniques in dogs

Background

There are few studies reporting pain and postoperative analgesia associated with mastectomy in dogs. The aim of this study was to evaluate postoperative pain after unilateral mastectomy using two different surgical techniques in the dog.

Findings

Twenty female dogs were assigned (n=10/group) to undergo unilateral mastectomy using either the combination of sharp and blunt dissection (SBD) or the modified SBD (mSBD) technique, in which the mammary chain is separated from the abdominal wall entirely by blunt (hand and finger) dissection except for a small area cranial to the first gland, in a prospective, randomized, clinical trial. All dogs were premedicated with intramuscular acepromazine (0.05 mg/kg) and morphine (0.3 mg/kg). Anesthesia was induced with intravenous ketamine (5 mg/kg) and diazepam (0.25 mg/kg), and maintained with isoflurane. Subcutaneous meloxicam (0.2 mg/kg) was administered before surgery. Postoperative pain was evaluated according to the University of Melbourne pain scale (UMPS) by an observer who was blinded to the surgical technique.. Rescue analgesia was provided by the administration of intramuscular morphine (0.5 mg/kg) if pain scores were >14 according to the UMPS. Data were analyzed using t-tests and ANOVA (P>0.05). There were no significant differences between the groups for age, weight, extubation time, and duration of surgery and anesthesia (P>0.05). There were no significant differences for postoperative pain scores between groups. Rescue analgesia was required in one dog in each group.

Conclusions

The two surgical techniques produced similar surgical times, incidence of perioperative complications and postoperative pain. Multimodal analgesia is recommended for treatment of postoperative pain in dogs undergoing unilateral mastectomy.     

Evaluation of the isoflurane‐sparing effects of fentanyl,lidocaine, ketamine,dexmedetomidine, or the combination lidocaine‐ketamine‐dexmedetomidine during ovariohysterectomy in dogs

ObjectiveTo evaluate the isoflurane‐sparing effects of an intravenous (IV) constant rate infusion (CRI) of fentanyl, lidocaine, ketamine, dexmedetomidine, or lidocaine‐ketamine‐dexmedetomidine (LKD) in dogs undergoing ovariohysterectomy.Study designRandomized, prospective, blinded, clinical study.AnimalsFifty four dogs.MethodsAnesthesia was induced with propofol and maintained with isoflurane with one of the following IV treatments: butorphanol/saline (butorphanol 0.4 mg kg^?1, saline 0.9% CRI, CONTROL/BUT); fentanyl (5 μg kg^?1, 10 μg kg^?1 hour^?1, FENT); ketamine (1 mg kg^?1, 40 μg kg^?1 minute^?1, KET), lidocaine (2 mg kg^?1, 100 μg kg^?1 minute^?1, LIDO); dexmedetomidine (1 μg kg^?1, 3 μg kg^?1 hour^?1, DEX); or a LKD combination. Positive pressure ventilation maintained eucapnia. An anesthetist unaware of treatment and end‐tidal isoflurane concentration (Fe′Iso) adjusted vaporizer settings to maintain surgical anesthetic depth. Cardiopulmonary variables and Fe′Iso concentrations were monitored. Data were analyzed using anova (p < 0.05).ResultsAt most time points, heart rate (HR) was lower in FENT than in other groups, except for DEX and LKD. Mean arterial blood pressure (MAP) was lower in FENT and CONTROL/BUT than in DEX. Overall mean ± SD Fe′Iso and % reduced isoflurane requirements were 1.01 ± 0.31/41.6% (range, 0.75 ± 0.31/56.6% to 1.12 ± 0.80/35.3%, FENT), 1.37 ± 0.19/20.8% (1.23 ± 0.14/28.9% to 1.51 ± 0.22/12.7%, KET), 1.34 ± 0.19/22.5% (1.24 ± 0.19/28.3% to 1.44 ± 0.21/16.8%, LIDO), 1.30 ± 0.28/24.8% (1.16 ± 0.18/32.9% to 1.43 ± 0.32/17.3%, DEX), 0.95 ± 0.19/54.9% (0.7 ± 0.16/59.5% to 1.12 ± 0.16/35.3%, LKD) and 1.73 ± 0.18/0.0% (1.64 ± 0.21 to 1.82 ± 0.14, CONTROL/BUT) during surgery. FENT and LKD significantly reduced Fe′Iso.Conclusions and clinical relevanceAt the doses administered, FENT and LKD had greater isoflurane‐sparing effect than LIDO, KET or CONTROL/BUT, but not at all times. Low HR during FENT may limit improvement in MAP expected with reduced Fe′Iso.