Effect of remifentanil hydrochloride administered via constant rate infusion on the minimum alveolar concentration of isoflurane in cats

Objective - To evaluate the effects of increasing doses of remifentanil hydrochloride administered via constant rate infusion (CRI) on the minimum alveolar concentration (MAC) of isoflurane in cats. Animals - 6 healthy adult cats. Procedures - For each cat, 2 experiments were performed (2-week interval). On each study day, anesthesia was induced and maintained with isoflurane; a catheter was placed in a cephalic vein for the administration of lactated Ringer's solution or remifentanil CRIs, and a catheter was placed in the jugular vein for collection of blood samples for blood gas analyses. On the first study day, individual basal MAC (MAC Basal) was determined for each cat. On the second study day, 3 remifentanil CRIs (0.25, 0.5, and 1.0 μg/kg/min) were administered (in ascending order); for each infusion, at least 30 minutes elapsed before determination of MAC (designated as MAC R0.25, MAC R0.5, and MAC R1.0, respectively). A 15-minute washout period was allowed between CRIs. A control MAC (MAC Control) was determined after the last remifentanil infusion. Results - Mean ± SD MAC Basal and MAC Control values at sea level did not differ significantly (1.66 ± 0.08% and 1.52 ± 0.21%, respectively). The MAC values determined for each remifentanil CRI did not differ significantly. However, MAC R0.25, MAC R0.5, and MAC R1.0, were significantly decreased, compared with MAC Basal, by 23.4 ± 79%, 29.8 ± 8.3%, and 26.0 ± 9.4%, respectively. Conclusions and Clinical Relevance - The 3 doses of remifentanil administered via CRI resulted in a similar degree of isoflurane MAC reduction in adult cats, indicating that a ceiling effect was achieved following administration of the lowest dose.

Anatomical features of the urethra and urinary bladder catheterization in female mice and rats. An essential translational tool

PURPOSE: To present fundamental anatomical aspects and technical skills necessary to urethra and urinary bladder catheterization in female mice and rats. METHODS: Urethral and bladder catheterization has been widely utilized for carcinogenesis and cancer research and still remains very useful in several applications: from toxicological purposes as well as inflammatory and infectious conditions to functional aspects as bladder dynamics and vesicoureteral reflux, among many others. RESULTS: Animal models are in the center of translational research and those involving rodents are the most important nowadays due to several advantages including human reproducibility, easy handling and low cost. CONCLUSIONS: Although technical and anatomical pearls for rodent urethral and bladder access are presented as tackles to the advancement of lower urinary tract preclinical investigation in a broaden sight, restriction to female animals hampers the male microenvironment, demanding future advances.

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

Objective To describe simultaneous pharmacokinetics (PK) and thermal antinociception after intravenous (IV), intramuscular (IM) and subcutaneous (SC) buprenorphine in cats. Study design Randomized, prospective, blinded, three period crossover experiment. Animals Six healthy adult cats weighing 4.1±0.5kg. Methods Buprenorphine (0.02mgkg-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 24hours 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. Results TT increased above baseline from 15 to 480minutes and at 30 and 60minutes after IV and IM administration, respectively (p<0.05). Maximum increase in TT (mean±SD) was 9.3±4.9°C at 60minutes (IV), 4.6±2.8°C at 45minutes (IM) and 1.9±1.9°C at 60minutes (SC). TT was significantly higher at 15, 60, 120 and 180minutes, and at 15, 30, 45, 60 and 120minutes 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 (t1/2ke0=47.4minutes) and receptor binding (kon=0.011mL ng-1minute-1). Persistence of thermal antinociception was due to slow receptor dissociation (t1/2koff=18.2minutes). Conclusions and clinical relevance IV 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. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Intravenous Tramadol Injection has no Antinociceptive Effect in Horses Undergoing Electrical and Thermal Stimuli

Tramadol combines an μ opiate and nonopiate analgesic mechanism and might be a useful opioid in horses. This study evaluated the effect of IV tramadol on spontaneous locomotor activity (SLA), head height, and hoof withdrawal reflex (HWR) after thermal or electrical nociceptive stimuli in horses. Doses of 2 and 3 mg/kg tramadol did not affect HWR after electrical and thermal nociception, respectively. Head height and SLA were not modified by 2, 3, or 5 mg/kg tramadol. All horses treated with 5 mg/kg tramadol developed trembling in pectoral triceps, and gluteal muscles and adopted a base-wide stance. In conclusion, 2 and 3 mg/kg tramadol IV neither induced sedation nor prolonged HWR after thermal or electrical stimuli in conscious horses. The dose of 5 mg/kg tramadol IV produced excitement, and it is apparently unsuitable for clinical use. © 2013 Elsevier Inc. All rights reserved.

Cardiorespiratory and antinociceptive effects of two different doses of lidocaine administered to horses during a constant intravenous infusion of xylazine and ketamine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Intravenous versus inhalation anaesthesia for one-lung ventilation

BackgroundThis is an update of a Cochrane Review first published in The Cochrane Library, Issue 2, 2008.The technique called one-lung ventilation can confine bleeding or infection to one lung, prevent rupture of a lung cyst or, more commonly, facilitate surgical exposure of the unventilated lung. During one-lung ventilation, anaesthesia is maintained either by delivering an inhalation anaesthetic to the ventilated lung or by infusing an intravenous anaesthetic. It is possible that the method chosen to maintain anaesthesia may affect patient outcomes. Inhalation anaesthetics may impair hypoxic pulmonary vasoconstriction (HPV) and increase intrapulmonary shunt and hypoxaemia.ObjectivesThe objective of this review was to evaluate the effectiveness and safety of intravenous versus inhalation anaesthesia for one-lung ventilation.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL); The Cochrane Library (2012, Issue 11); MEDLINE (1966 to November 2012); EMBASE (1980 to November 2012); Literatura Latino-Americana e do Caribe em Ciencias da Saude (LILACS, 1982 to November 2012) and ISI web of Science (1945 to November 2012), reference lists of identified trials and bibliographies of published reviews. We also contacted researchers in the field. No language restrictions were applied. The date of the most recent search was 19 November 2012. The original search was performed in June 2006.Selection criteriaWe included randomized controlled trials and quasi-randomized controlled trials of intravenous (e. g. propofol) versus inhalation (e. g. isoflurane, sevoflurane, desflurane) anaesthesia for one-lung ventilation in both surgical and intensive care participants. We excluded studies of participants who had only one lung (i.e. pneumonectomy or congenital absence of one lung).Data collection and analysisTwo review authors independently assessed trial quality and extracted data. We contacted study authors for additional information.Main resultsWe included in this updated review 20 studies that enrolled 850 participants, all of which assessed surgical participants no studies investigated one-lung ventilation performed outside the operating theatre. No evidence indicated that the drug used to maintain anaesthesia during one-lung ventilation affected participant outcomes. The methodological quality of the included studies was difficult to assess as it was reported poorly, so the predominant classification of bias was 'unclear'.Authors' conclusionsVery little evidence from randomized controlled trials suggests differences in participant outcomes with anaesthesia maintained by intravenous versus inhalational anaesthesia during one-lung ventilation. If researchers believe that the type of drug used to maintain anaesthesia during one-lung ventilation is important, they should design randomized controlled trials with appropriate participant outcomes, rather than report temporary fluctuations in physiological variables.

Comparison of oxidative stress in ASA physical status I patients scheduled for minimally invasive surgery under balanced or intravenous anesthesia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Ultrasound analysis of a canine patient with renal disease and chronic liver disease undergoing treatment with intravenous stem cells

With the improvement in quality of life of animals, it is increasingly frequent clinical care of elderly patients, which present renal disorders, including chronic renal failure. Recent studies report the use of stem cells to treat renal failure, which would improve the levels of urea and creatinine, and in renal ultrasound evaluation. With the present work, the idea is to report a case of ultrasonographic evaluation in a patient with chronic renal failure, liver disease and splenic nodule, which underwent stem cell therapy, where there was an improvement in the sonographic evaluation of part of the liver.

Cumulative long-term safety, efficacy and patient-reported outcomes in children with juvenile idiopathic arthritis treated with intravenous abatacept: up to 7 years of treatment

The long-term efficacy and safety of intravenous abatacept in patients (pts) with juvenile idiopathic arthritis (JIA) have been reported previously from the Phase III AWAKEN trial ([1, 2]). Here, we report efficacy, safety and pt-reported outcomes from the open-label, long-term extension (LTE) of AWAKEN, with up to 7 years of follow-up. Pts entered the LTE if they were JIA ACR 30 non-responders (NR) at the end of the 4-month lead-in period (abatacept only), or if they received abatacept or placebo (pbo) in the 6-month double-blind (DB) period. The Child Health Questionnaire was used to evaluate health-related quality of life (HRQoL); physical (PhS) and psychosocial (PsS) summary and pain scores were analyzed. Pain was assessed by parent global assessment using a 100 mm visual analog scale. Efficacy and HRQoL evaluations are reported up to Day 1765 (~ Year 5.5). Safety is presented for the cumulative period (lead-in, DB and LTE), for all pts who received abatacept during the LTE. Of the 153 pts entering the LTE (58 from DB abatacept group, 59 from DB pbo group, 36 NR), 69 completed the trial (29 abatacept, 27 pbo, 13 NR). For pts treated in the LTE, mean (range) exposure to abatacept was 53.6 (5.6–85.6) months. During the LTE, incidence rates of AEs and serious AEs per 100 pt-years were 209.1 and 5.6. Thirty pts (19.6%) had serious AEs; most were unrelated and were musculoskeletal (8.5%) or infectious events (6.5%). No malignancy was reported. There was one death (accidental; unrelated). At Day 169, JIA ACR 50 and 70 response rates were 79.3% and 55.2% in the abatacept group, and 52.5% and 30.5% in the pbo group; 31.0% and 10.2% of pts in the abatacept and pbo groups, respectively, had inactive disease. By Day 1765, JIA ACR 50 and 70 response rates were 93.9% and 78.8% in the abatacept group, and 80.0% and 63.3% in the pbo group; 51.5% and 33.3% had inactive disease. In the NR group, 69.2% and 53.8% of pts achieved JIA ACR 50 and 70 responses at Day 1765, and 30.8% had inactive disease. In pts who entered the LTE, mean baseline PhS scores were below the range for healthy children (abatacept 30.2, pbo 31.0, NR 29.5). At Day 169, 38.3% of pts had reached a PhS score >50 ((1). By the end of the LTE, 43.5% of pts had reached a PhS score >50. At baseline, mean PsS scores for those who entered the LTE were slightly lower than the mean for healthy children (abatacept 43.5, pbo 44.2, NR 47.0). At Day 169, 54.9% of pts had a PsS score >50 (1). By Day 1765, 58.1% of pts had reached a PsS score >50. At baseline, the mean pain score was 42.9. By Day 169, 13.9% of pts were considered pain free (pain score = 0); this was maintained over the LTE (1).

Pharmacokinetics of tetracycline in plasma, synovial fluid and milk using single intravenous and single intravenous regional doses in dairy cattle with papillomatous digital dermatitis

The purpose of this study was to compare the pharmacokinetics of tetracycline in plasma, synovial fluid, and milk following either a single systemic intravenous (i.v.) injection or a single i.v. regional antibiosis (IVRA) administration of tetracycline hydrochloride to dairy cattle with papillomatous digital dermatitis (PDD). To this end, plasma and synovial fluid tetracycline concentrations were compared with the minimal inhibitory concentration (MIC) values of the major bacteria, which are known to cause digital diseases and thus assess its efficacy in PDD. Residual tetracycline concentrations in milk from cows treated by both methods were also determined. Twelve Holstein cows with various stages of PDD were randomly assigned to two groups of six animals. Group 1 received a single systemic i.v. injection of 10 mg/kg of tetracycline hydrochloride. Group 2 received 1000 mg of tetracycline hydrochloride by IVRA of the affected limb. Blood, synovial fluid and milk samples were taken prior to tetracycline administration (time 0 control), and then at 22, 45 and 82 min, and 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h following drug administration. Tetracycline concentrations were determined by high-performance liquid chromatography. Mean tetracycline plasma and milk concentrations in Group 1 were higher than Group 2. The opposite was observed for synovial fluid concentrations. Group 2 synovial fluid concentrations were higher than the MIC value over 24 h for the bacteria most frequently responsible for claw disease. Compared with i.v. administration, IVRA administration of tetracycline produced very high synovial fluid and low plasma and milk concentrations.

Intravenous procedural sedation: an alternative in the treatment of patients with intellectual disability

Conscious sedation has become established as an important alternative to general anesthesia (GA) in dental treatment of patients with intellectual disability (ID). Aim: to investigate dental patients undergoing sedation using a mean dose of 0.6 mg/kg intravenous midazolam and the adverse events of sedation in patients with ID. Methods: This study analyzed the records of 163 dental patients with ID aged between 2 and 76 years who had undergone conscious intravenous sedation (CIV) using a mean dose of 0.61 mg/kg of midazolam at Araçatuba Dental School, São Paulo State University, Brazil. The efficacy and complications induced by CIV were evaluated in each subject. Results: CIV was effective for dental treatment in 80% of the cases. A total of 626 dental procedures were performed. The mean treatment time was 33.9 minutes. There was statistically significant difference (p<0.05) between absence and presence of adverse reactions. Adverse reactions were observed in 21.47% of the cases. Conclusions: The results of this study showed that CIV is a useful method for dental treatment of patients with ID and these patients can need higher doses of sedative to reach an adequate level of sedation.

Acid-base and biochemical stabilization and quality of recovery in male cats with urethral obstruction and anesthetized with propofol or a combination of ketamine and diazepam

This study compared acid-base and biochemical changes and quality of recovery in male cats with experimentally induced urethral obstruction and anesthetized with either propofol or a combination of ketamine and diazepam for urethral catheterization. Ten male cats with urethral obstruction were enrolled for urethral catheterization and anesthetized with either ketamine-diazepam (KD) or propofol (P). Lactated Ringer's solution was administered by intravenous (IV) beginning 15 min before and continuing for 48 h after relief of urethral obstruction. Quality of recovery and time to standing were evaluated. The urethral catheter was maintained to measure urinary output. Hematocrit (Hct), total plasma protein (TPP), albumin, total protein (TP), blood urea nitrogen (BUN), creatinine, pH, bicarbonate (HCO3-), chloride, base excess, anion gap, sodium, potassium, and partial pressure of carbon dioxide in mixed venous blood (pvCO(2)) were measured before urethral obstruction, at start of fluid therapy (0 h), and at subsequent intervals. The quality of recovery and time to standing were respectively 4 and 75 min in the KD group and 5 and 16 min in the P group. The blood urea nitrogen values were increased at 0, 2, and 8 h in both groups. Serum creatinine increased at 0 and 2 h in cats administered KD and at 0, 2, and 8 h in cats receiving P, although the values were above the reference range in both groups until 8 h. Acidosis occurred for up to 2 h in both groups. Acid-base and biochemical stabilization were similar in cats anesthetized with propofol or with ketamine-diazepam. Cats that received propofol recovered much faster, but the ketamine-diazepam combination was shown to be more advantageous when treating uncooperative cats as it can be administered by intramuscular (IM) injection.

Relapse of Intravenous Drug Use Triggered by Enfuvirtide, a Parenteral Antiretroviral Medication

Fuzeon (R) (enfuvirtide; Hoffmann-LaRoche, Nutley, NJ) is a parenteral medication prescribed to antiretroviral-experienced HIV patients. Clinicians are frequently concerned when prescribing enfuvirtide to former drug addicts because of the risk of triggering relapse, however, no previous report has described this adverse event. We describe two HIV-infected patients, previously abstinent from injection drug use, who experienced relapse or near-relapse situations after starting treatment with enfuvirtide. Along with the concerns related to adherence and to injection site reactions, clinicians who prescribe enfuvirtide should consider and discuss the risk of triggering relapse among former or recovering drug addicts.

Multiple Intravenous Administrations of Human Umbilical Cord Blood Cells Benefit in a Mouse Model of ALS

Background: A promising therapeutic strategy for amyotrophic lateral sclerosis (ALS) is the use of cell-based therapies that can protect motor neurons and thereby retard disease progression. We recently showed that a single large dose (25x10(6) cells) of mononuclear cells from human umbilical cord blood (MNC hUCB) administered intravenously to pre-symptomatic G93A SOD1 mice is optimal in delaying disease progression and increasing lifespan. However, this single high cell dose is impractical for clinical use. The aim of the present pre-clinical translation study was therefore to evaluate the effects of multiple low dose systemic injections of MNC hUCB cell into G93A SOD1 mice at different disease stages. Methodology/Principal Findings: Mice received weekly intravenous injections of MNC hUCB or media. Symptomatic mice received 10(6) or 2.5x10(6) cells from 13 weeks of age. A third, pre-symptomatic, group received 10(6) cells from 9 weeks of age. Control groups were media-injected G93A and mice carrying the normal hSOD1 gene. Motor function tests and various assays determined cell effects. Administered cell distribution, motor neuron counts, and glial cell densities were analyzed in mouse spinal cords. Results showed that mice receiving 10(6) cells pre-symptomatically or 2.5x10(6) cells symptomatically significantly delayed functional deterioration, increased lifespan and had higher motor neuron counts than media mice. Astrocytes and microglia were significantly reduced in all cell-treated groups. Conclusions/Significance: These results demonstrate that multiple injections of MNC hUCB cells, even beginning at the symptomatic disease stage, could benefit disease outcomes by protecting motor neurons from inflammatory effectors. This multiple cell infusion approach may promote future clinical studies.