Constant Infusion Research Articles

Use of Spinal Anaesthesia with Anaesthetic Block of Intercostal Nerves Compared to a Continuous Infusion of Sufentanyl to Improve Analgesia in Cats Undergoing Unilateral Mastectomy.

Simple SummaryPostoperative analgesia is very important because pain causes various negative effects that prevent patient recovery. Our study aimed to evaluate the analgesic efficacy of subarachnoid anaesthesia combined with intercostal nerve block compared with a constant-rate infusion of sufentanyl citrate in cats undergoing unilateral mastectomy. This study demonstrated that the use of spinal anaesthesia with anaesthetic block of intercostal nerves, using levobupivacaine, guarantees long-lasting and high-quality analgesic coverage and minimises the post-surgical pain inevitably associated with invasive surgical procedures such as radical mastectomy. This study stemmed from a general trend towards increasing attention on postoperative pain after spaying procedures in cats. Since veterinarians are becoming more focused on relieving surgical pain, anaesthetists are expected to use better protocols that can minimise pain and therefore optimise surgical results. This method, considering the relative simplicity of its execution, can be used in daily clinical practice.Unilateral mastectomy is a common surgical procedure in feline species and requires postoperative pain management. Our study aimed to evaluate the analgesic efficacy of subarachnoid anaesthesia combined with an intercostal nerve block, in comparison with the use of sufentanyl citrate administered as a constant-rate infusion (CRI). Twenty cats were randomly divided into two groups (n = 10/group) based on the analgesic protocol used: the first received loco-regional anaesthesia with levobupivacaine (LR group), and the second received a CRI of sufentanyl (SUF group). The evaluation criteria during surgery were the need for a bolus of fentanyl in the event of an increased heart rate or increased blood pressure. In the postoperative period, the levels of comfort/discomfort and pain were used to obtain a score according to the UNESP-Botucatu multimodal scale. Subjects who scored above seven received analgesic drug supplementation. Intraoperative analgesia was satisfactory, with good haemodynamic stability in both groups. Four patients in the LR group required an extra dose of methadone after they achieved the sternal decubitus position, whereas those in the SUF group required many more doses. The analgesia achieved in the LR group was more satisfactory than that in the SUF group.

Optimization of dose and route of administration of the P‐glycoprotein inhibitor, valspodar (PSC‐833) and the P‐glycoprotein and breast cancer resistance protein dual‐inhibitor, elacridar (GF120918) as dual infusion in rats

Transporters can play a key role in the absorption, distribution, metabolism, and excretion of drugs. Understanding these contributions early in drug discovery allows for more accurate projection of the clinical pharmacokinetics. One method to assess the impact of transporters in vivo involves co‐dosing specific inhibitors. The objective of the present study was to optimize the dose and route of administration of a P‐glycoprotein (P‐gp) inhibitor, valspodar (PSC833), and a dual P‐gp/breast cancer resistance protein (BCRP) inhibitor, elacridar (GF120918), by assessing the transporters’ impact on brain penetration and absorption. A dual‐infusion strategy was implemented to allow for flexibility with dose formulation. The chemical inhibitor was dosed intravenously via the femoral artery, and a cassette of known substrates was infused via the jugular vein. Valspodar or elacridar was administered as 4.5‐hour constant infusions over a range of doses. To assess the degree of inhibition, the resulting ratios of brain and plasma concentrations, Kp's, of the known substrates were compared to the vehicle control. These data demonstrated that doses greater than 0.9 mg/hr/kg valspodar and 8.9 mg/hr/kg elacridar were sufficient to inhibit P‐gp‐ and BCRP‐mediated efflux at the blood‐brain barrier in rats without any tolerability issues. Confirmation of BBB restriction by efflux transporters in preclinical species allows for subsequent prediction in humans based upon the proteomic expression at rodent and human BBB. Overall, the approach can also be applied to inhibition of efflux at other tissues (gut absorption, liver clearance) or can be extended to other transporters of interest using alternate inhibitors.

Constant infusion case of one compartment pharmacokinetic model with simultaneous first-order and Michaelis-Menten elimination: analytical solution and drug exposure formula.

The main objective of this article is to propose the closed-form solution of one-compartment pharmacokinetic model with simultaneous first-order and Michaelis-Menten elimination for the case of constant infusion. For the case of bolus administration, we have previously established a closed-form solution of the model through introducing a transcendent X function. In the same vein, we found here a closed-form solution of constant infusion could be realized through introducing another transcendent Y function. For the general case of constant infusion of limited duration, the closed-form solution is then fully expressed using both X and Y functions. As direct results, several important pharmacokinetic surrogates, such as peak concentration [Formula: see text] and total drug exposure AUC[Formula: see text], are found the closed-form expressions and ready to be analyzed. The new pharmacokinetic knowledge we have gained on these parameters, which largely exhibits in a nonlinear feature, is in clear contrast to that of the linear case. Finally, with a pharmacokinetic model adapted from that formerly reported on phenytoin, we numerically analyzed and illustrated the roles of different model parameters and discussed their influence on drug exposure. To conclude, the present findings elucidate the intrinsic quantitative structural properties of such pharmacokinetic model and provide a new avenue for future modelling and rational drug designs.

In horses undergoing volatile anaesthesia, does intraoperative alpha-2-agonist infusion improve recovery?

PICO question
 In horses undergoing volatile anaesthesia with isoflurane or sevoflurane, does administration of an alpha-2 agonist as a CRI compared to anaesthetic maintenance with volatile alone improve recovery quality?
 
 Clinical bottom line
 Category of research question
 Treatment
 The number and type of study designs reviewed
 Eight papers were critically appraised. All prospective, randomised clinical trials. 7/8 papers were blinded and 4/8 were crossover design
 Strength of evidence
 Moderate
 Outcomes reported
 One paper investigating detomidine and one on romifidine showed no improvement in recovery quality. 3/3 medetomidine papers and 2/3 dexmedetomidine papers showed a significant improvement in recovery quality in the alpha-2 agonist CRI group
 Conclusion
 In a healthy horse undergoing general anaesthesia with isoflurane or sevoflurane maintenance, an intra-operative constant rate of infusion (CRI) of medetomidine and dexmedetomidine can lead to better recovery quality when compared to horses who are maintained on isoflurane or sevoflurane alone
 
 How to apply this evidence in practice
 The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources.
 Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.
 

Retrospective evaluation of the use of hydrocortisone for treatment of suspected critical illness-related corticosteroid insufficiency (CIRCI) in dogs with septic shock (2010-2017): 47 cases.

To evaluate characteristics of septic shock patients treated with hydrocortisone (HC) due to suspicion of critical illness-related corticosteroid insufficiency (CIRCI) as compared to septic shock patients without suspicion of CIRCI. Retrospective study between February 2010 and October 2017. University teaching hospital ICU. Data were collected for 47 dogs with septic shock. Twenty-one dogs were treated with HC (HC-treated) due to suspicion of CIRCI. Twenty-six dogs did not receive HC (non-HC-treated). HC was administered either as an intermittent IV bolus or as a constant rate infusion (CRI) to those patients with suspected CIRCI. Significantly higher baseline APPLEfull scores and predicted mortality were detected in the HC-treated patients compared to non-HC-treated patients (0.87vs 0.44 for predicted mortality, P=0.039). Patients in the HC-treated group were on more vasopressors and cardiotonics than those in the non-HC-treated group (2.5vs 1.5, P<0.001). All patients initially responded to vasopressor administration, with average time to resolution of hypotension being 90 minutes for the HC-treated group compared to 60 minutes for the non-HC-treated group (P=0.640). However, HC-treated patients took significantly longer to have a sustained resolution (a systolic blood pressure>90mm Hg or a mean blood pressure>65mm Hg for at least 4h) of their hypotension after starting vasopressors, as compared to their non-HC-treated counterparts (8.5vs 4h, P=0.001). Three (14.3%) HC-treated patients survived to discharge compared to 9 (34.6%) non-HC-treated patients, but this was not statistically significant. HC-treated patients had a higher baseline risk of mortality than non-HC-treated patients. There was no significant difference in survival between the HC-treated and non-HC-treated septic shock patients. Further studies are needed to evaluate the use of HC in patients with suspected CIRCI.

Comparison of Propofol or Isoflurane Anesthesia Maintenance, Combined with a Fentanyl-Lidocaine-Ketamine Constant-Rate Infusion in Goats Undergoing Abomasotomy.

Simple SummaryGeneral anesthesia in small ruminants is still a challenge under field conditions. Propofol is an injectable short-acting anesthetic used to provide induction and/or anesthesia maintenance. Isoflurane is the inhaled anesthetic more widely used for providing general anesthesia; however, it requires an expensive equipment for its administration, and high doses may produce environmental pollution. Both anesthetics produce dose-related cardiovascular depressant effects. This study aimed to compare the effects of propofol or isoflurane, combined with a constant-rate infusion of fentanyl–lidocaine–ketamine (total [total intravenous anesthesia (TIVA)] and partial intravenous anesthesia [PIVA], respectively) in goats undergoing abomasotomy. Our results showed that both TIVA and PIVA protocols produced a satisfactory quality of anesthesia during surgery, with minimal changes in cardiopulmonary parameters. However, recovery from anesthesia induced by propofol fentanyl–lidocaine–ketamine might be of poor quality.This study aimed to compare, first, the anesthetic and cardiopulmonary effects of propofol or isoflurane anesthetic maintenance in goats receiving a fentanyl–lidocaine–ketamine infusion undergoing abomasotomy and, secondly, to compare the quality of the recovery from anesthesia. Two groups were used: propofol (TIVA) and isoflurane (PIVA). Goats were premedicated with fentanyl (10 μg/kg intravenously [IV]), lidocaine (2 mg/kg, IV), and ketamine (1.5 mg/kg, IV). Anesthesia was induced with propofol and maintenance consisted of fentanyl (10 μg/kg/h, IV), lidocaine (50 μg/kg/min, IV), and ketamine (50 μg/kg/min, IV) as constant-rate infusions (CRIs), combined with either CRI of propofol at initial dose of 0.3 mg/kg/min, IV (TIVA), or isoflurane with initial end-tidal (FE’Iso) concentration of 1.2% partial intravenous anesthesia (PIVA). The mean effective propofol dose for maintenance was 0.44 ± 0.07 mg/kg/min, while the mean FE’Iso was 0.81 ± 0.2%. Higher systolic arterial pressure (SAP) values were observed in total intravenous anesthesia (TIVA) during some time points. Recovery was smooth in PIVA, while restlessness, vocalizations, and paddling were observed in TIVA. Both protocols produced a satisfactory quality of anesthesia during surgery, with minimal impact on cardiopulmonary function. Nevertheless, recovery after anesthesia in TIVA might be of poor quality.

Evaluation of the analgesic effect of fentanyl–ketamine and fentanyl–lidocaine constant rate infusions in isoflurane-anesthetized dogs undergoing thoracolumbar hemilaminectomy

ObjectiveTo evaluate anesthetic conditions and postoperative analgesia with the use of intraoperative constant rate infusions (CRIs) of fentanyl–lidocaine or fentanyl–ketamine in dogs undergoing thoracolumbar hemilaminectomy. Study designProspective, randomized, blinded, clinical study. AnimalsA total of 32 client-owned dogs. MethodsDogs were premedicated with fentanyl (5 μg kg–1) administered intravenously (IV), anesthesia was induced with IV alfaxalone and maintained with isoflurane. Fentanyl (0.083 μg kg–1 minute–1) was infused IV with either ketamine (0.5 mg kg–1; then 40 μg kg–1 minute–1; group KF) or lidocaine (2 mg kg–1; then 200 μg kg–1 minute–1; group LF) assigned randomly. Heart rate, noninvasive arterial pressures, respiratory rate, esophageal temperature, end-tidal partial pressure of carbon dioxide and isoflurane concentration were recorded throughout anesthesia. Maintenance of anesthesia, recovery and postoperative pain (Glasgow Composite Pain Scale) were scored. Cardiopulmonary data were analyzed using a two-way anova with repeated measures, demographics of the two groups with a t test, and scores with Mann–Whitney U test, with p < 0.05. ResultsAll dogs recovered from anesthesia without complications. No significant difference was found between groups for cardiopulmonary variables, total anesthesia time, sedation score and requirement for postoperative sedation or for rescue analgesia. Anesthetic maintenance score was of lower quality in KF than in LF [median (interquartile range): 0 (0–0.5) versus 0 (0–0); p = 0.032)], but still considered ideal. Recovery score was higher and indicative of less sedation in LF than in KF [1 (1–1.5) versus 0.5 (0–1); p < 0.0001]. Pain score was higher in KF than in LF [2 (1–3) versus 1 (1–2); p = 0.0009]. Conclusions and clinical relevanceBoth CRIs of KF and LF provided adequate anesthetic conditions in dogs undergoing thoracolumbar hemilaminectomy. Based on requirement for rescue analgesia, postoperative analgesia was adequate in both groups.

Renal and intraglomerular haemodynamics in chronic heart failure with preserved and reduced ejection fraction.

AimsCongestive heart failure (CHF) and impaired renal function are two often co‐existing medical conditions and associated with adverse cardiovascular outcome. The aim of the current study was to assess renal and intraglomerular haemodynamics by constant infusion input clearance technique in subjects with CHF.Methods and resultsThe group of subjects with CHF consisted of 27 individuals with HFpEF and 27 individuals with HFrEF and were compared with 31 healthy controls. Subjects underwent renal clearance examination to measure glomerular filtration rate (GFR) and renal blood and plasma flow (RBF and RPF) and to calculate intraglomerular haemodynamics such as resistances of the afferent (RA) and efferent arterioles (RE) as well as intraglomerular pressure (P glom). Measured GFR was lower in CHF subjects (68.1 ± 10.1 mL/min/1.73 m2) compared with controls (83.6 ± 13.4 mL/min/1.73 m2, P adj < 0.001) as was P glom (P adj < 0.001). Total renal vascular resistance (RVR) was higher in CHF subjects (87.3 ± 20.1 vs. 73.8 ± 17.1 dyn × s/cm5, P adj < 0.001) mediated by an increased resistance at the afferent site (3201 ± 1084 vs. 2181 ± 796 dyn × s/cm5, P adj < 0.001). Comparing HFpEF and HFrEF subjects, RA was higher in HFrEF subjects. The severity of CHF assessed by NT‐proBNP revealed an inverse association with renal perfusion (RPF r = −0.421, P = 0.002, RBF r = −0.414, P = 0.002) and a positive relation with RVR (r = 0.346, P = 0.012) at the post‐glomerular site (RE: r = 0.318, P = 0.022).ConclusionsRenal function assessed by measured GFR is reduced and renal vascular resistance at the preglomerular, afferent site is increased in HFpEF and, to greater extent, in HFrEF. Our data indicate a close cardiorenal interaction in CHF.

Metabolic and Hemodynamic Resting-State Connectivity of the Human Brain: A High-Temporal Resolution Simultaneous BOLD-fMRI and FDG-fPET Multimodality Study.

Simultaneous [18F]-fluorodeoxyglucose positron emission tomography functional magnetic resonance imaging (FDG-PET/fMRI) provides the capacity to image 2 sources of energetic dynamics in the brain-glucose metabolism and the hemodynamic response. fMRI connectivity has been enormously useful for characterizing interactions between distributed brain networks in humans. Metabolic connectivity based on static FDG-PET has been proposed as a biomarker for neurological disease, but FDG-sPET cannot be used to estimate subject-level measures of "connectivity," only across-subject "covariance." Here, we applied high-temporal resolution constant infusion functional positron emission tomography (fPET) to measure subject-level metabolic connectivity simultaneously with fMRI connectivity. fPET metabolic connectivity was characterized by frontoparietal connectivity within and between hemispheres. fPET metabolic connectivity showed moderate similarity with fMRI primarily in superior cortex and frontoparietal regions. Significantly, fPET metabolic connectivity showed little similarity with FDG-sPET metabolic covariance, indicating that metabolic brain connectivity is a nonergodic process whereby individual brain connectivity cannot be inferred from group-level metabolic covariance. Our results highlight the complementary strengths of fPET and fMRI in measuring the intrinsic connectivity of the brain and open up the opportunity for novel fundamental studies of human brain connectivity as well as multimodality biomarkers of neurological diseases.

Antinociceptive effects of levomethadone in standing horses sedated with romifidine

ObjectiveTo evaluate the antinociceptive effect of a bolus of intravenous levomethadone administered to horses during romifidine constant rate infusion (CRI). Study designProspective, randomized, masked, crossover experimental study. AnimalsA group of eight adult Warmblood horses (seven geldings, one mare) aged 6.6 ± 4.4 years, weighing 548 ± 52 kg [mean ± standard deviation (SD)]. MethodsLevomethadone 0.1 mg kg–1 or an equivalent volume of saline (control) was administered intravenously to standing horses 60 minutes after starting a romifidine CRI. Blood samples to quantify romifidine and levomethadone plasma concentrations by capillary electrophoresis were collected up to 150 minutes after levomethadone administration. The nociceptive withdrawal reflex threshold (NWRT) was determined continuously using an automated threshold tracking device. Sedation and cardiopulmonary variables were assessed at regular intervals. A pharmacokinetic-pharmacodynamic (PK-PD) model was elaborated. Data are presented as mean ± SD or median (interquartile range, 25%–75%) where appropriate. Differences between groups were considered statistically significant for p < 0.05. ResultsHorses exhibited higher NWRTs after levomethadone administration than after saline (123 ± 9% versus 101 ± 9% relative to baseline, p < 0.05). The PK-PD model identified a contribution of levomethadone to the NWRT increase. Effect size was variable among individuals. No adverse reactions to levomethadone administration were observed. A slight effect of levomethadone on sedation scores was evident for the 60 minutes following its administration. Conclusions and Clinical RelevanceA single injection of levomethadone has the potential to increase the NWRT during romifidine CRI in horses and can be administered in combination with α2-adrencoceptor agonists to enhance antinociception in horses. However, individual variation is marked.

Mathematical modelling of the dynamics of prostate cancer with a curative vaccine

A mathematical model for prostate cancer treatment using a curative vaccine is developed to determine the efficacy of constant drug infusion into the body tissues. It describes the interaction of prostate tumour cells, immune response, and treatment using the curative vaccine, commonly known as the Sipuleucel-T vaccine. Stability analysis of the model shows that, without treatment, prostate tumour cells would grow to the maximum carrying capacity. It is also demonstrated that the vaccine could clear prostate tumour cells from the body tissues if the curative vaccine efficacy is less than the ratio of the product of death of dendritic cells and its decay rate to the activation rate of the therapy. Global sensitivity analysis is investigated to establish critical factors that promote prostate cancer recurrence during treatment. Further analysis suggests that the recruitment rate of effector cells by dendritic cells, which leads to an increase in lysis of prostate tumour cells determines the curative vaccine’s success. Numerical simulations show that when the curative vaccine is administered at minimum doses, androgen-independent cancer cells take a long time to be eliminated from the body tissue. At the same time, they can be cleared in a short period when a standard or higher dose is administered. The use of a standard dose is preferable as it lowers the side effects, although the treatment period would be relatively long.

Unraveling the Contribution of Fluid Therapy to the Development of Augmented Renal Clearance in a Piglet Model.

Augmented renal clearance (ARC) observed in the critically ill pediatric population has received an increased attention over the last years due to its major impact on the disposition and pharmacokinetics of mainly renally excreted drugs. Apart from an important inflammatory trigger, fluid administration has been suggested to contribute to the development of ARC. Therefore, the primary objective of this study was to evaluate the effect of continuous intravenous fluid administration on renal function using a conventional piglet animal model and to quantify the impact of fluid administration on the pharmacokinetics of renally excreted drugs. At baseline, twenty-four piglets (12 treatment/12 control; 7 weeks old, all ♂) received the marker drugs iohexol (64.7 mg/kg body weight (BW)) and para-aminohippuric acid (10 mg/kg BW) to quantify glomerular filtration rate and effective renal plasma flow, respectively. In addition, the hydrophilic antibiotic amikacin (7.5 mg/kg BW) was administered. Following this baseline measurement, the treatment group received fluid therapy as a constant rate infusion of 0.9% saline at 6 mL/kg/h over 36 h. After 24 h of fluid administration, the marker drugs and amikacin were administered again. When comparing both groups, a significant effect of fluid administration on the total body clearances of iohexol (p = 0.032) and amikacin (p = 0.0014) was observed. Clearances of iohexol and amikacin increased with on average 15 and 14%, although large interindividual variability was observed. This led to decreased systemic exposure to amikacin, which was manifested as decrease in area under the plasma concentration-time curve from time 0 h to infinity from 34,807 to 30,804 ng.h/mL. These results suggest that fluid therapy is a key factor involved in the development of ARC and should be taken into account when administering mainly renally excreted drugs. However, further research is necessary to confirm these results in children.

Plasma levels of a methadone constant rate infusion and their corresponding effects on thermal and mechanical nociceptive thresholds in dogs

BackgroundThe present study aimed to collect pharmacokinetic data of a methadone continuous rate infusion (CRI) and to investigate its effect on mechanical and thermal nociceptive thresholds. Seven, 47 to 54 months old beagle dogs, weighing 9.8 to 21.2 kg, were used in this experimental, randomized, blinded, placebo-controlled crossover study. Each dog was treated twice with either a methadone bolus of 0.2 mg kg− 1 followed by a 0.1 mg kg− 1 h− 1 methadone CRI (group M) or an equivalent volume of isotonic saline solution (group P) for 72 h. Mechanical and thermal thresholds, as well as vital parameters and sedation were measured during CRI and for further 24 h. Blood samples for methadone plasma concentrations were collected during this 96 h period.ResultsPercentage thermal excursion (%TE) increased significantly from baseline (BL) until 3 h after discontinuation of CRI in M. Within P and between treatment groups differences were not significant. Mechanical threshold (MT) increased in M until 2 h after CRI discontinuation. Bradycardia and hypothermia occurred in M during drug administration and dogs were mildly sedated for the first 47 h. Decreased food intake and regurgitation were observed in M in five and four dogs, respectively. For methadone a volume of distribution of 10.26 l kg− 1 and a terminal half-life of 2.4 h were detected and a clearance of 51.44 ml kg− 1 min− 1 was calculated. Effective methadone plasma concentrations for thermal and mechanical antinociception were above 17 ng ml− 1.ConclusionA methadone CRI of 0.1 mg kg− 1 h− 1 for 3 days after a loading dose results in steady anti-nociceptive effects in an acute pain model in healthy dogs. Main side effects were related to gastrointestinal tract, hypothermia, bradycardia and sedation.

Development of Herbal Green Tea Bags with &lt;em&gt;Osbeckia octandra&lt;/em&gt; L.(DC.) (Heen bovitiya) and Evaluation of the Effect of InfusionTime and Temperature on Extracted Phytochemicals

Herbal tea or a tisane is a mixture of dried plant parts used for medicinal purposes. Present study was aimed to develop herbal green tea bags with Osbeckia octandra (Heen bovitiya) leaves predominantly and evaluate the effect of infusion time and temperature on their total phenolic (TP), total flavonoid (TF) contents and in vitro antioxidant activity. Six different tea bags (T1 to T6) were prepared by incorporating dried O. octandra (leaves), Camellia sinensis (leaves), Zingiber officinale (rhizomes), Vanilla planifolia (pods) and Allium sativum (bulbs) in different proportions. Each herbal tea bag was infused at a constant infusion temperature of 100 ⁰C for 3, 5 and 7 minutes and for a constant infusion time of 7 minutes at different temperatures; 100, 90 and 80 ⁰C. TP, TF contents, in vitro radical scavenging activity and ferric reducing antioxidant power of all tea extracts were determined by spectroscopic analysis. Data were analyzed with one sample t-test. All infusions were rich in phytochemicals; phenols, flavonoids, tannins, terpenes, triterpenoids, phytosterols, saponins, alkaloids, amino acids and carbohydrates. TP, TF contents and in vitro antioxidant activity of the formulated tea bags were significantly higher after the addition of O. octandra leaves and the values were different at different infusion conditions (p&lt;0.05). At constant infusion time of 7 minutes, TP, TF contents and antioxidant activity of O. octandra incorporated green tea bags were higher when infused at 80 ⁰C compared to 90 ⁰C and 100 ⁰C. At constant infusion temperature of 100 ⁰C, the values were higher for the formulated green tea bags when infused for 7 minutes compared to 3 and 5 minutes. Hence, it was concluded that the formulated tea bags with O. octandra leaves were rich with antioxidants and that they should be brewed for a long time period (7 minutes) at a low temperature (80 ⁰C).

Sedative and analgesic potentials of dexmedetomidine gluconate using constant rate infusion technique in rabbit

Rabbits are easily stressed. Stress can be caused by pain, disease, unfamiliar surroundings, transport, rough handling or proximity of potential predators. Thus, this study was conceived to evaluate the effective sedative and analgesic doses of dexmedetomide gluconate in rabbits using the constant rate infusion (CRI) technique. Eight healthy adult New Zealand White rabbits with an average weight of 1.93 ± 0.33kg were used for the study. They were starved of feed for three hours before the experiment but were supplied water sufficiently. The CRI infusion was prepared by adding 1mcgkg-1 into 500mL bags of lactated ringer's solution. Each rabbit received an initial dose of 20mcgkg-1 dexmedetomidine® intramuscularly at the thigh muscle. Venous access was secured fifteen minutes later and the fluid prepared for CRI was connected to the cannular, the fluid was set to flow at daily fluid maintenance rate of 90mlkgday-1 for one hour. The procedure was repeated replacing 20mcgkg-1 with 40mcgkg-1. Neither sedation nor analgesia was achieved with 20mcgkg-1 dexmedetomidine® while 40mcgkg-1 gave mild to moderate sedation, however, no analgesic effect was observed with the two dose regimes. In conclusion, sedation was achieved with 40mcgkg-1 but no analgesic effect was achieved in both doses used.

Effect of Constant Rate Infusion of Tramadol-Xylazine and Pentazocine Xylazine on Acute Pain Response in Xylazine-Pentobarbitone Anaesthetized Dogs Undergoing Digital Amputation

The study evaluated the effect of constant rate infusion of tramadol-xylazine and pentazocine-xylazine on pain in dogs undergoing digital amputation. Twelve mongrel used for the study were randomly assigned to four groups (n=3). Group 1 received loading dose (LD) Xylazine (1mg/kg IV) and Pentobarbitone sodium (Na) (30mg/kg IV) [LD-XP] prior to digital amputation (DA).Group 2 received LD-XP andXylazine (1mg/kg/hr) by constant rate infusion (CRI IV) prior to DA. Group 3 received LD Xylazine (1mg/kg IV), Pentobarbitone Na (30mg/kg IV), CRI Xylazine (1mg/kg/hr) and Tramadol (1mg/kg/hr) prior to DA. Group 4 received LD-XP, CRI Xylazine (1mg/kg/hr) and CRI Pentazocine (1mg/kg/hr) prior to DA. Results of the pain score evaluation showed that at 1, 3, 6 and 24 hours post-surgery (PS), group 4 had the lowest (p

Limited usefulness of the observation of eye bulb rotation and neuro-ophthalmic responses for assessing the depth of equine anesthesia: an observational study comparing three protocols

The observation of the neuro-ophthalmic responses is an established basic tool for monitoring the depth of anesthesia in horses. However, their usefulness during balanced anesthesia in the clinic is questionable. The aim of this study was to compare the usefulness of neuro-ophthalmic responses during 3 commonly used anesthetic protocols. An observational study was performed on 22 horses, 5 maintained only with isoflurane (ISO group), 12 maintained with isoflurane and a constant rate infusion of ketamine (ISO+KET group), and 5 maintained with isoflurane and a constant rate infusion of detomidine (ISO+DET group). The occurrence of all five responses was noted: spontaneous palpebral and provoked palpebral response, corneal response, nystagmus and eye bulb rotation. The most consistent with the literature and most useful for anesthetic depth assessment was the observation of spontaneous palpebral reflex in all of the groups (p = 0.788) and the most significant differences were visible for the observation of the provoked palpebral reflex (p = 0.015) for all groups. The reflexes in the group ISO+DET were less consistent with the literature than in other groups, making them least useful. The group ISO seemed to have the reflexes’ observations most consistent with the literature expectations. The corneal reflex was always present and nystagmus always absent which confirmed the observations from literature. The above results suggest that neuro-ophthalmic responses, especially eye bulb rotation and provoked palpebral reflexes, should not be the only indicators in assessing the depth of anesthesia during maintenance with ketamine or detomidine with concurrent isoflurane.

Automatic Regulation of Basal Insulin Infusion in a Personalized Insulin Therapy System

A method and a system for automatic regulation of the basal insulin administration rate for maintenance of glycemia in the target range are proposed. The method is based on proportional regulation of the infusion rate using feedback. It suspends the insulin delivery when the glucose level falls below a threshold value. According to the modeling results, the proposed method can be used to compensate hyperglycemia of different etiologies with reduction of the settling time in comparison with constant rate insulin infusion.

Intravenous Infusion of the β3-Adrenergic Receptor Antagonist APD418 Improves Left Ventricular Systolic Function in Dogs With Systolic Heart Failure

BackgroundUnlike β1- and β2-adrenergic receptors (ARs), β3-AR stimulation inhibits cardiac contractility and relaxation. In the failing left ventricular (LV) myocardium, β3-ARs are upregulated, and can be maladaptive in the setting of decompensation by contributing to LV dysfunction. This study examined the effects of intravenous infusions of the β3-AR antagonist APD418 on cardiovascular function and safety in dogs with systolic heart failure (HF). Methods and ResultsThree separate studies were performed in 21 dogs with coronary microembolization-induced HF (LV ejection fraction [LVEF] of approximately 35%). Studies 1 and 2 (n = 7 dogs each) were APD418 dose escalation studies (dosing range, 0.35–15.00 mg/kg/h) designed to identify an effective dose of APD418 to be used in study 3. Study 3, the sustained efficacy study, (n = 7 dogs) was a 6-hour constant intravenous infusion of APD418 at a dose of 4.224 mg/kg (0.70 mg/kg/h) measuring key hemodynamic endpoints (e.g., EF, cardiac output, the time velocity integral of the mitral inflow velocity waveform representing early filling to time-velocity integral representing left atrial contraction [Ei/Ai]). Studies 1 and 2 showed a dose-dependent increase of LVEF and Ei/Ai, the latter being an index of LV diastolic function. In study 3, infusion of APD418 over 6 hours increased LVEF from 31 ± 1% to 38 ± 1% (P < .05) and increased Ei/Ai from 3.4 ± 0.4 to 4.9 ± 0.5 (P < .05). Vehicle had no effect on the LVEF or Ei/Ai. In study 3, APD418 had no significant effects on the HR or the systemic blood pressure. ConclusionsIntravenous infusions of APD418 in dogs with systolic HF elicit significant positive inotropic and lusitropic effects. These findings support the development of APD418 for the in-hospital treatment of patients with an acute exacerbation of chronic HF.

Use of intravenous lidocaine to treat dexmedetomidine-induced bradycardia in sedated and anesthetized dogs

ObjectiveTo assess cardiopulmonary function in sedated and anesthetized dogs administered intravenous (IV) dexmedetomidine and subsequently administered IV lidocaine to treat dexmedetomidine-induced bradycardia. Study designProspective, randomized, crossover experimental trial. AnimalsA total of six purpose-bred female Beagle dogs, weighing 9.1 ± 0.6 kg (mean ± standard deviation). MethodsDogs were randomly assigned to one of three treatments: dexmedetomidine (10 μg kg–1 IV) administered to conscious (treatments SED1 and SED2) or isoflurane-anesthetized dogs (end-tidal isoflurane concentration 1.19 ± 0.04%; treatment ISO). After 30 minutes, a lidocaine bolus (2 mg kg–1) IV was administered in treatments SED1 and ISO, followed 20 minutes later by a second bolus (2 mg kg–1) and a 30 minute lidocaine constant rate infusion (L-CRI) at 50 (SED1) or 100 μg kg–1 minute–1 (ISO). In SED2, lidocaine bolus and L-CRI (50 μg kg–1 minute–1) were administered 5 minutes after dexmedetomidine. Cardiopulmonary measurements were obtained after dexmedetomidine, after lidocaine bolus, during L-CRI and 30 minutes after discontinuing L-CRI. A mixed linear model was used for comparisons within treatments (p < 0.05). ResultsWhen administered after a bolus of dexmedetomidine, lidocaine bolus and L-CRI significantly increased heart rate and cardiac index, decreased mean blood pressure, systemic vascular resistance index and oxygen extraction ratio, and did not affect stroke volume index in all treatments. Conclusion and clinical relevanceLidocaine was an effective treatment for dexmedetomidine-induced bradycardia in healthy research dogs.