Constant Infusion Research Articles

Prophylactic use of a lidocaine constant rate infusion versus saline in dogs undergoing balloon valvuloplasty for management of pulmonic stenosis: A randomized control trial

ObjectiveTo evaluate the effect of a prophylactic lidocaine constant rate infusion (CRI) on the incidence and malignancy of catheter-induced ventricular ectopic complexes (VECs) during balloon valvuloplasty for management of pulmonic stenosis in dogs. Study designSingle-centre, prospective, randomized study. AnimalsClient-owned dogs (n = 70) with pulmonic stenosis. MethodsDogs were randomly assigned to one of two anaesthetic protocols: administration of lidocaine 2 mg kg–1 bolus followed by a CRI (50 μg kg–1 minute–1; group LD) or a saline placebo (group SL) during balloon valvuloplasty. All dogs were premedicated with methadone (0.3 mg kg–1) intramuscularly and a digital three-lead Holter monitor was applied. Anaesthetic co-induction was performed with administration of alfaxalone (2 mg kg–1) and diazepam (0.4 mg kg–1), and anaesthesia was maintained with isoflurane vaporised in 100% oxygen. CRIs were started on positioning of the dog in theatre and discontinued as the last vascular catheter was removed from the heart. All dogs recovered well and were discharged 24 hours postoperatively. Blinded Holter analysis was performed by an external veterinary cardiologist using commercially available dedicated analysis software; p < 0.05. ResultsOf the 70 dogs enrolled in the study, 61 were included in the final analysis: 31 in group LD and 30 in group SL.There was no significant difference between sinus beats (p = 0.227) or VECs (p = 0.519) between groups. In group LD, 19/31 (61.3%) dogs had a maximum ventricular rate ≥250 units and 20/30 (66.7%) dogs in group SL (p = 0.791). Conclusion and clinical relevanceIn this study, the use of a prophylactic lidocaine bolus followed by CRI in dogs undergoing balloon valvuloplasty for management of pulmonic stenosis did not significantly decrease the incidence nor the malignancy of VECs during right heart catheterization compared with a saline CRI.

Increased Perirolandic Cortical Excitability May Facilitate Sensory Motor Mapping in Children (P13-1.003)

<h3>Objective:</h3> We are hereby describing a case of refractory pediatric epilepsy where resection of perirolandic seizure foci was performed successfully under neurophysiologic guidance. <h3>Background:</h3> Pediatric neurophysiologic sensory-motor mapping is frequently unsuccessful, due to inability to localize central sulcus (CS) and primary motor cortex (M1). These shortcomings result from poor somatosensory evoked potentials (SSEP) and high M1 depolarization thresholds respectively, both reflections of the immaturity of the central nervous system. <h3>Design/Methods:</h3> Case report <h3>Results:</h3> An 8-year-old boy with developmental delay, debilitating focal epilepsy and epileptic encephalopathy underwent phase 2 video EEG monitoring. The recordings showed seizures with early involvement of several depth electrodes located within the right parieto-frontal regions, and an early motor semiology involving the left arm. The patient underwent neurophysiologically guided resection of the seizure foci under general anesthesia. Pre-resection electrocorticography (ECoG) via a 64 contact grid showed abundant perirolandic epileptiform discharges (ED), maximal postcentrally. Cortical recordings of high amplitude median SSEP and a low depolarization threshold led to successful CS localization and identification of M1, respectively. A subdural strip electrode placed over the precentral gyrus and secured in position, allowed simultaneous ECoG and motor monitoring during the resection of the postcentral foci. Initially, ECoG showed near continuous runs of ED, unchanged by cortical electrical stimulation. Under steady state anesthesia, at a constant propofol infusion rate, this activity decreased in frequency and stopped altogether towards the end stages of the resection, as the M1 threshold increased by 7 mA. Post-resection fronto-parietal ECoG recordings were quiet. Post-operatively, the patient became seizure free, showed cognitive improvement and no motor deficits. <h3>Conclusions:</h3> Increased cortical excitability may lead to successful functional mapping in children. Under steady anesthetic conditions, increases in the M1 threshold during resection of nearby epileptic foci may be an early sign of decrease in the abnormal regional cortical excitability. <b>Disclosure:</b> Dr. Alzahrany has nothing to disclose. Dr. Simon has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Risk Management Foundation of the Harvard Institutions Incorporated. Dr. Simon has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for MCIC Vermont. Dr. Simon has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Aaronson, Rappaport, Feinstein&amp; Deutch. Dr. Simon has received publishing royalties from a publication relating to health care. Dr. Simon has received personal compensation in the range of $0-$499 for serving as a Speaker with American Clinical Neurophysiology Society . Dr. Simon has a non-compensated relationship as a Speaker with International Society of Intraoperative Neurophysiology that is relevant to AAN interests or activities. Dr. Simon has a non-compensated relationship as a Speaker with Brazilian Congress of Neurology that is relevant to AAN interests or activities.

Clearance and production of ammonia quantified in humans by constant ammonia infusion – the effects of cirrhosis and ammonia-targeting treatments

Hyperammonaemia is a key pathological feature of liver disease and the primary driver of hepatic encephalopathy (HE). However, the relative roles of increased ammonia production and reduced clearance are poorly understood as is the action of ammonia-targeting drugs for HE. We aimed to quantify whole-body ammonia metabolism in healthy persons and patients with cirrhosis and to validate our method by examining the effects of glycerol phenylbutyrate and lactulose+ rifaximin treatment. Ten healthy men and ten male patients with cirrhosis were investigated by 90-minute constant ammonia infusion to achieve steady-state plasma ammonia. Whole-body ammonia clearance was calculated as infusion rate divided by steady-state concentration increase and ammonia production was calculated as clearance multiplied by baseline ammonia concentration. Participants were re-investigated after the ammonia-targeting interventions. In healthy persons, ammonia clearance was 3.5 (3.1-3.9) L/min and ammonia production was 49 (35-63) μmol/min. Phenylbutyrate increased clearance by 11% (4-19%, p= 0.009). In patients with cirrhosis, ammonia clearance was 20% lower at 2.7 (2.1-3.3) L/min (p= 0.02) and production was nearly threefold higher at 131 (102-159) μmol/min (p <0.0001). Lactulose+ rifaximin reduced production by 20% (2-37%, p= 0.03). The infusion was generally well-tolerated apart from in one hyperammonaemic patient, with cirrhosis and possible bleeding unrelated to the infusion, who developed clinical HE that reverted when infusion was discontinued. Whole-body ammonia clearance and production may be measured separately using the described technique. This technique identified a lower clearance and a higher production of ammonia in patients with cirrhosis, and showed that phenylbutyrate increases clearance, whereas lactulose+ rifaximin reduces production. High blood ammonia plays a key role in cirrhosis-related brain dysfunction. However, the relative roles of reduced ammonia clearance and increased ammonia production are poorly understood as is the action of ammonia-targeting treatments. This study presents a relatively simple test to measure ammonia metabolism. By using this test, it was possible to show that patients with cirrhosis exhibit decreased ammonia clearance and increased ammonia production compared to healthy persons, and to quantify the unique effects of different ammonia-targeting treatments. The test described herein may be used to examine a range of questions related to normal physiology, pathophysiology and the mechanisms of action of ammonia-targeting treatments. ClinicalTrials.gov (1-16-02-297-20).

Comparison of Hemodynamic Effects of Dobutamine and Ephedrine Infusions in Isoflurane-Anesthetized Horses.

The objective of this study was to compare the hemodynamic effects of dobutamine and ephedrine during the management of anesthesia-related hypotension in healthy horses. Thirteen horses underwent general anesthesia with isoflurane and were randomly divided into two different groups, one of which received a dobutamine constant rate infusion (CRI) (1 µg/kg bwt/min) and the other received an ephedrine CRI (20 µg/kg bwt/min) when hypotension (<60 mmHg) was identified, following up to 15 min after the blood pressure reached 70 mmHg. All horses were equipped with a pulmonary artery catheter and a peripheral artery catheter, and multiparameter monitoring commenced as soon as they were under mechanical ventilation. Hemodynamic parameters were recorded, while tissue perfusion markers (peripheral oxygen saturation, arterial oxygen partial pressure, arterial carbon dioxide partial pressure, arterial pH, arterial plasma bicarbonate concentration, arterial oxygen saturation, mixed venous oxygen saturation, mixed venous oxygen content, arterial oxygen content, arteriovenous oxygen difference, oxygen delivery index, oxygen consumption index, and oxygen extraction ratio), serum lactate concentration, and troponin I concentrations were analyzed before the start of infusions (T0), when the blood pressure reached 70 mmHg (T1), and 15 min after T1 (T2). The time to restore the arterial pressure was similar in both groups (p > 0.05); however, the heart rate was higher in the ephedrine group (p = 0.0098), and sinus bradyarrhythmia occurred in the dobutamine group. Furthermore, both experimental protocols increased cardiac output (p = 0.0012), cardiac index (p = 0.0013), systemic vascular resistance (p = 0.008), systemic vascular resistance index (p < 0.001), and ameliorated perfusion markers. In the dobutamine group, the pulmonary artery wedge pressure (p < 0.001) and systolic index (p = 0.003) were elevated, while the arteriovenous oxygen difference was reduced in the ephedrine group (p = 0.02). Troponin I was used as a myocardial injury indicator, and did not differ between moments or between groups (p > 0.05). We concluded that both drugs were effective and safe to treat anesthetic hypotension under the conditions of this study.

Probing the mechanism of reduced in vivo potency of insulin detemir

ABSTRACT Background Insulin detemir (IDet) is an insulin analog used to treat diabetes. IDet shows full efficacy but reduced potency compared to human insulin (HI) in both man and rat. In contrast, in pigs and dogs, IDet appears to have full in vivo potency. Non-receptor mediated degradation (NRMD) has previously been suggested as an explanation for the low potency of IDet, but this hypothesis has not been investigated further until now. Bacitracin is a nonspecific protease inhibitor which we hypothesized could inhibit NRMD of IDet in rats. Research design and methods Healthy male rats instrumented with permanent catheters underwent euglycemic clamp during constant infusion of either HI or IDet at effect-matched doses with co-infusion of vehicle or bacitracin. Results Plasma concentrations of IDet increased significantly (p < 0.005) during bacitracin compared to vehicle co-infusion and the concomitant increase in glucose infusion rate (GIR, p < 0.001) required to maintain euglycemic clamp indicates that the IDet rescued from NRMD indeed was active. No significant differences were detected with co-infusions of HI with either bacitracin or vehicle. Conclusions A large proportion of NRMD of IDet which can be inhibited by bacitracin may partly explain the reduced potency of IDet observed in rats and likely also in man.

Standard versus no post-filter ionized calcium monitoring in regional citrate anticoagulation for continuous renal replacement therapy (NPC trial).

Current guidelines recommend monitoring of post-filter ionized calcium (pfCa) when using regional citrate anticoagulation during continuous renal replacement therapy (RCA-CRRT) to determine citrate efficiency for the prevention of filter clotting. However, the reliability of pfCa raises the question of whether routine monitoring is required. Reducing the frequency of pfCa monitoring could potentially reduce costs and workload. Our objective was to test the efficacy and safety of no pfCa monitoring among critically ill patients receiving RCA-CRRT. This study was a non-inferiority randomized controlled trial conducted between January 2021 and October 2021 at King Chulalongkorn Memorial Hospital, Thailand. Critically ill patients who were treated with RCA-CRRT were randomized to receive either standard pfCa monitoring (aiming pfCa level of 0.25-0.35mmol/L), or no pfCa monitoring, in which a constant rate of citrate infusion was maintained at pre-determined citrate concentrations of 4mmol/L with blinding of pfCa levels to treating clinicians. The primary outcome was the filter lifespan. Non-inferiority would be demonstrated if the upper limit of the 95% confidence interval (CI) for the difference in filter lifespan between the groups was less than 20 h. Fifty patients were randomized to the standard pfCa monitoring group (n=25) or no pfCa monitoring group (n=25). The mean filter lifespan was 54±20 h in the standard pfCa monitoring group and 47±23 h in the no pfCa monitoring group (absolute difference 7.1 h; 95% CI -5.3, 19.5, P=.25). When restricting the analysis to circuits reaching the maximum duration of circuit lifespan at 72 h and clotted filters, the filter lifespan was 61±17 h in the standard pfCa group vs 60±19 h in the no pfCa monitoring group (absolute difference 0.9 h; 95% CI -11.5, 13.4, P=.88). Compared with the no pfCa monitoring group, the standard pfCa monitoring group had a significantly higher mean citrate concentrations (4.43±0.32 vs 4mmol/L, P<.001) and a higher rate of severe hypocalcemia (44% vs 20%, P=.13). No statistical differences were found in filter clotting, citrate accumulation, citrate overload and mortality between the two groups. Among critically ill patients receiving RCA-CRRT, no pfCa monitoring by maintaining the citrate concentrations of 4mmol/L is feasible. Larger randomized controlled trials should be conducted to ensure the efficacy, safety and cost-effectiveness of this strategy. ClinicalTrials.gov: NCT04792424 (registered 11 March 2021).

The effect of orally administered nitrate on renal function and blood pressure in a randomized, placebo-controlled, crossover study in healthy subjects

BackgroundSeveral studies have shown inorganic nitrate/nitrite to reduce blood pressure in both healthy subjects and hypertensive patients. An effect presumably caused through bioconversion to nitric oxide. However, studies on inorganic nitrate/nitrite have shown inconsistent results on renal functions such as GFR and sodium excretion. The current study investigated whether orally administered nitrate would decrease blood pressure and increase GFR and urinary sodium excretion. MethodsIn a randomized, placebo-controlled, double-blinded, crossover study, 18 healthy subjects received a daily dose of 24 mmol potassium nitrate and placebo (potassium chloride) during 4 days in a randomized order. Subjects also ingested a standardized diet and completed a 24-h urine collection. GFR was determined by the constant infusion technique and during GFR measurement, brachial blood pressure (BP) and central blood pressure (cBP), heart rate, and arterial stiffness were measured every half hour using the Mobil-O-Graph®. Blood samples was analyzed for nitrate, nitrite, cGMP, vasoactive hormones and electrolytes. Urine was analyzed for nitrate, nitrite, cGMP, electrolytes, ENaCγ, NCC, CrCl, CH2O and UO. ResultsNo differences in GFR, blood pressure or sodium excretion were found between the treatments with potassium nitrate and placebo. However, both nitrate and nitrite levels in plasma and urine were significantly increased by potassium nitrate intake and the 24-h urinary excretion of sodium and potassium were stable, showing adherence to the standardized diet and the study medication. ConclusionWe found no decrease in blood pressure or increase in GFR and sodium excretion of 24 mmol potassium nitrate capsules as compared to placebo after 4 days of treatment.Healthy subjects may be able to compensate the effects of nitrate supplementation during steady state conditions. Future research should focus on long-term studies on the difference in response between healthy subjects and patients with cardiac or renal disease.

Effects of remifentanil on the noxiously stimulated somatosensory evoked potentials recorded at the spinal cord in dogs and cats

This study assessed the somatosensory evoked potentials (SEPs) in dogs and cats to compare the effect of remifentanil on the action potentials evoked by peripheral noxious stimulation in the spinal cord. Five healthy dogs and five healthy cats underwent general anaesthesia induced with propofol and maintained with isoflurane. Each animals received all dosage of a constant-rate infusion of remifentanil at 0 (control), 0.25, 0.5, 1.0 or 2.0 μg/kg/min. The hair of the dorsal foot of a hind limb was clipped and an intraepidermal stimulation electrode that could selectively stimulate the nociceptive Aδ and C fibres was attached. An electrical stimulus was generated by a portable peripheral nerve testing device. The evoked potentials were recorded by two needle electrodes inserted subcutaneously in the dorsal midline between the lumbar vertebra: L3-L4 and L4-L5. Bimodal waveforms were obtained by electrical stimulation in control dogs and cats. The inhibitory effect of remifentanil was evaluated by comparing the changes in the N1P2 and P2N2 amplitudes. The N1P2 amplitude was depressed by remifentanil in a dose-dependent manner in dogs, but it showed no remifentanil-induced changes in cats. While the P2N2 amplitude was also depressed in a dose-dependent manner in dogs, it showed milder remifentanil-induced effects in cats. The N1P2 and P2N2 amplitudes observed herein are assumed to represent the evoked potentials derived from the Aδ and C fibres, respectively. Thus, the inhibitory effect of remifentanil on nociceptive transmission at the spinal cord was much weaker in cats, especially for transmissions possibly derived from Aδ fibres.

In Vivo Threonine Oxidation Rate Is Dependent on Threonine Dietary Supply in Growing Pigs Fed Low to Adequate Levels

Threonine oxidation was examined in 12 growing pigs fed a well-balanced control diet or a threonine-deficient diet supplemented (Glu) or not (LT) with glutamic acid during constant infusion of L-[1-13C]-threonine, [1-14C]glycine and [1-14C]α-ketobutyrate for 10 h. During these infusions, liver glycine enrichment was significantly lower than plasma enrichment. Moreover, the pancreas to plasma glycine enrichment ratio was higher than the liver to plasma ratio (70–89%), showing that an important part of glycine de novo synthesis in pancreas occurred through the threonine dehydrogenase (TDG) pathway. These results imply that calculation of threonine oxidation into glycine should be made with the assumption of both hepatic and extrahepatic oxidation. Plateau values of plasma threonine, glycine and α-ketobutyrate enrichments and specific radio activities allowed estimations of threonine oxidation through the TDG and threonine dehydratase (TDH) pathways. Threonine oxidation into glycine was 12.16 ± 2.06, 2.89 ± 0.61 and 2.13 ± 0.44 µmol/(kg·h), respectively, in pigs fed the control, LT and Glu diets, and threonine oxidation into α-ketobutyrate was 1.80 ± 0.31, 0.88 ± 0.02 and 0.55 ± 0.06 µmol/(kg·h) for the control, LT and Glu groups, respectively. Total threonine oxidation rates were 75 and 81% lower in the LT and Glu groups, respectively, than in the control group. Liver TDG and TDH activity measured in vitro were not affected by either the level of dietary threonine supply the addition of glutamic acid. On the basis of plasma data, it may be concluded that the addition of glutamic acid to a threonine-deficient diet had no significant effect on threonine oxidation but did reduce the rate of threonine release from protein breakdown. Oxidation appears to be related to plasma threonine concentration.

Electroencephalographic and Cardiovascular Changes Associated with Propofol Constant Rate of Infusion Anesthesia in Young Healthy Dogs.

This study aimed to evaluate electroencephalography (EEG) and cardiovascular changes associated with propofol constant rate of infusion (CRI) anesthesia in dogs. Six dogs were each given propofol CRI to induce different anesthetic phases including induction (1 mg/kg/min for 10 min), and decremental maintenance doses of 2.4 mg per kg per min, 1.6 mg per kg per min, and 0.8 mg per kg per minute over 45 min. Processed EEG indices including patient state index (PSI), (burst) suppression ratio (SR), and spectral edge frequency (95%) were obtained continuously until the dogs recovered to sternal recumbency. The dogs were intubated and ventilated. Cardiovascular and EEG index values were compared between anesthetic phases. The PSI, SR, mean arterial blood pressure, and subjective anesthetic depth scores were highly correlated throughout anesthetic depth changes. The PSI decreased from 85.0 ± 17.3 at awake to 66.0 ± 29.0 at induction, and then sharply reduced to 19.7 ± 23.6 during maintenance and returned to 61.5 ± 19.2 at extubation. The SR increased from 15.4 ± 30.9% at induction to 70.9 ± 39.8% during maintenance and decreased to 3.4 ± 8.9% at extubation. We concluded that EEG indices can be used to aid in tracking ongoing brain state changes during propofol anesthesia in dogs.

Concentrations and kinetics of renal biomarkers in dogs with gastric dilatation-volvulus with and without 24-h intravenous lidocaine.

Gastric dilatation volvulus (GDV) can lead to organ failure including acute kidney injury (AKI). Due to its cytoprotective, antioxidant and anti-inflammatory effects, lidocaine has a potential to prevent AKI in dogs with GDV. Prospective, observational cohort study in client-owned dogs with GDV. To determine concentrations of renal biomarkers for AKI in dogs with GDV with and without intravenous (IV) lidocaine therapy. Thirty-two dogs were randomized to receive either IV lidocaine (2 mg/kg, followed by a lidocaine constant rate infusion at a dose of 50 μg/kg/min over 24 h; n = 17) or no lidocaine (n = 15). Blood and urine samples were taken at admission (T 0) (only blood), during or immediately after surgery (T 1), and 24 (T 24) and 48 (T 48) h after surgery. Plasma creatinine (pCr), plasma neutrophil gelatinase-associated lipocalin (pNGAL), urinary NGAL (uNGAL), uNGAL to creatinine ratio (UNCR), and urinary gamma-glutamyl transferase to creatinine ratio (uGGT/uCr) were evaluated. Biomarker concentrations were compared between dogs with and without IV lidocaine and the course of each marker was determined in comparison to its admission value. In the entire population, a significantly higher pCr at T 0 (median, 95 μmol/L, interquartile range, 82-105) compared with T 1 (69 μmol/L, 60-78), T 24 (63 μmol/L, 52-78), and T 48 (78 μmol/L, 65-87) (P < 0.001) was found. Plasma NGAL increased significantly between T 0 (5.66 ng/mL, 3.58-7.43) and T 24 (7.50 ng/mL, 4.01-11.89) (P = 0.006) and T 48 (9.86 ng/mL, 5.52-13.92) (P < 0.001), respectively. Urinary NGAL increased significantly between T 1 (0.61 ng/mL, 0.30-2.59) and T 24 (2.62 ng/mL, 1.86-10.92) (P = 0.001) and T 48 (4.79 ng/mL, 1.96-34.97 (P < 0.001), respectively. UNCR increased significantly between T 1 (0.15 μg/mmol, 0.09-0.54) and T 24 (1.14 μg/mmol, 0.41-3.58) (P = 0.0015) and T 48 (1.34 μg/mmol, 0.30-7.42) (P < 0.001), respectively. Concentrations of uGGT/uCr increased significantly from T 0 highest at T 24 (6.20 U/mmol, 3.90-9.90) and significantly decreased at T 48 (3.76 U/mmol, 2.84-6.22) (P < 0.001). No significant differences in any renal biomarker concentration were found between dogs with and without IV lidocaine therapy. Plasma NGAL, uNGAL and UNCR remained increased up to 48 h post-surgery. No evidence of lidocaine-associated renoprotection was found.

The safety and efficacy of remimazolam tosylate for induction and maintenance of general anesthesia in pediatric patients undergoing elective surgery: Study protocol for a multicenter, randomized, single-blind, positive-controlled clinical trial.

Introduction: Remimazolam is an ultra-short-acting benzodiazepine sedative agent commonly used in general anesthesia, procedural sedation, and intensive care unit (ICU) sedation. This study aimed to explore the efficacy and safety of remimazolam versus propofol for the induction and maintenance of general anesthesia in preschool-age children undergoing elective surgery. Methods and analysis: In this multicenter, randomized, single-blind, positive-controlled non-inferior clinical trial, one hundred ninety-two children aged 3-6years will be randomly allocated as a 3:1 ratio into two groups: Group R with an intravenous dose of remimazolam 0.3mg/kg for the induction of anesthesia followed by a constant infusion rate of remimazolam 1-3mg/kg/h to maintain anesthesia, and Group P with an intravenous dose of propofol 2.5mg/kg for the induction of anesthesia followed by a constant infusion rate of propofol 4-12mg/kg/h to maintain anesthesia. The primary outcome will be the rate of the successful induction and maintenance of anesthesia. The secondary outcomes will include the time to LoC, the Bispectral Index (BIS) value, awakening time, extubation time, post-anesthesia care unit (PACU) discharge time, usage of additional sedative drugs during the induction period, usage of remedial drugs in PACU, emergence delirium, pain in PACU, behavior scores at day 3 after surgery, parental and anesthesiologists' satisfaction, and adverse events. Ethics and dissemination: This study has been approved by the ethics review boards at all participating hospitals. The Ethics Committee of the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (Reference No. LCKY 2020-380, November 13, 2020) is the central ethics committee.

Effect on physiological parameters and anaesthetic dose requirement of isoflurane when tramadol given as a continuous rate infusion vs a single intravenous bolus injection during ovariohysterectomy in dogs.

Tramadol produces a significant reduction in both sevoflurane and isoflurane minimum alveolar concentrations in dogs under experimental conditions. This study aims to compare the effects of tramadol administered as a constant rate infusion (CRI) with those of tramadol administered as a single intravenous bolus on physiological parameters and isoflurane requirements in dogs undergoing ovariohysterectomy. In this study, forty female dogs undergoing ovariohysterectomy were enrolled. The bitches were anesthetized with 5 mg/kg of tiletamine/zolazepam combined with 0.05 mg/kg of acepromazine intravenously. Anesthesia was maintained with isoflurane delivered in 100% oxygen. The group A (n = 20) received tramadol 4 mg/kg in a single intravenous bolus, whereas the group B (n = 20) received tramadol 1.5 mg/kg in an intravenous bolus followed by tramadol 2.6 mg/kg/h as a CRI. The following parameters were recorded: heart rate, respiratory rate, non-invasive blood pressure, body temperature, EtCO2, SpO2 and inspired and expired concentrations of isoflurane. Parameter measurements were performed from pre-preedication (baseline) to skin suturing. The dogs were healthy subjects that demonstrated no abnormalities on laboratory investigations. Significant tachycardia was recorded after administration of tiletamine/zolazepam combined with acepromazine in both groups. Heart rate decreased after intubation but remained significantly higher compared to baseline values in both groups. Systolic blood pressure significantly decreased in both groups but the recorded values were within the physiological range. Mild reduction in body temperature was recorded in both groups. SpO2 and EtCO2 remained within the physiological range. Isoflurane requirement was significantly lower in the group B compared to the group A. Transient twitching was recorded in two dogs belonging to the group A after tramadol administration. Compared to tramadol given as a single intravenous bolus injection during ovariohysterectomy in dogs, tramadol administered as a CRI reduces isoflurane requirements in dogs anesthetized with tiletamine/zolazepam combined with acepromazine. Both tramadol given as a CRI and a single intravenous bolus injection, induce decrease in heart rate, respiratory rate and in body temperature but the values of these parameters remain within physiological range in dogs undergoing ovariohysterectomy.

Tumour growth control: analysis of alternative approaches

In this work we address the problem of tumour growth control by properly exploiting a low-dimensional model that grounds on the Chemical Reaction Network (CRN) formalism. Originally conceived to work both in deterministic and stochastic frameworks, it is shown that, except for the case of very low number of tumour cells, the deterministic approach is appropriate to characterize the system behaviour, especially for control planning purposes. Two alternative control approaches are here investigated. One trivially assumes a constant infusion of external drug administration, the other is designed according to a state-feedback control scheme, with complete or partial knowledge of the state. Pros and cons of both control laws are investigated, showing that the tumour size at the beginning of the therapy plays a role of paramount importance for fixed infusion therapies, whilst only state-feedback laws can eradicate arbitrarily large tumours.

Renal tubular transporter-mediated interactions between mirogabalin and cimetidine in rats

Cimetidine at a clinical dosage decreased the renal clearance (CLr) of mirogabalin in humans by inhibition of renal secretion. Mirogabalin is a substrate of human OAT1/3, OCT2, MATE1 and/or MATE2-K. To clarify the mechanism behind the above interaction, it was investigated whether cimetidine inhibits the process of mirogabalin uptake at the basolateral side or the process of its efflux at the apical side in rat kidney in vivo. Cimetidine was administered to rats by a constant infusion to achieve an unbound plasma concentration of 7.0 μM and examine its effect on the renal disposition of [14C]metformin, [3H]p-aminohippuric acid (PAH), and [14C]mirogabalin. Cimetidine significantly induced the intrarenal accumulation of radioactivity (Kp, kidney) and decreased the renal clearance (CLr) of [14C]mirogabalin. These effects resulted in significantly decreased total clearance (CLt). Kp, kidney, and CLr of [14C]metformin, except CLt, were also affected, but no parameters of [3H]PAH were affected by cimetidine. These findings clarified that an unbound plasma concentration of cimetidine of 7.0 μM inhibited the apical efflux not the basolateral uptake of [14C]mirogabalin in rat kidney, suggesting that mirogabalin/cimetidine interaction was caused by inhibiting the apical efflux transporter, human MATE1 and/or MATE2-K, not the basolateral uptake transporter, human OCT2, in the kidney.

Septal myocardial abscess in a Thoroughbred mare

SummaryAn 11‐year‐old multiparous Thoroughbred mare with a history of colic was referred for further evaluation. Clinical findings at the time of initial examination included arrhythmia, tachycardia, tachypnoea and hypothermia without marked signs of abdominal pain. Electrocardiography revealed ventricular tachycardia at a rate of 211 beats/min. Lidocaine was administered as a constant rate infusion to treat the arrhythmia, and the heart rate and rhythm were normalised. There were no abnormal findings on ultrasonography of the abdomen and thorax. An echocardiographic examination revealed a hypoechoic spherical area within the muscular part of the intraventricular septum. Unfortunately, the mare died suddenly 3 days after treatment. Post‐mortem examination confirmed the presence of an encapsulated abscess in the intraventricular septum. Staphylococcus aureus and Staphylococcus chromogenes were isolated from the lesion. It was thought to be responsible for the arrhythmia seen in this case. This is the first case of a septal myocardial abscess in a horse.

Evaluation of a constant rate intravenous infusion of dexmedetomidine on the duration of a femoral and sciatic nerve block using lidocaine in dogs.

This study investigated the effects of 1 μg/kg/h intravenous constant rate infusion (CRI) of dexmedetomidine on the sensory and motor blockade for femoral and sciatic nerve blocks in dogs undergoing stifle surgery. Client-owned dogs referred for stifle surgery were enrolled in this prospective, randomized, blinded study. Dogs were pre-medicated with acepromazine (0.005-0.01 mg/kg intramuscularly, IM); anesthesia was induced with propofol intravenously and maintained with isoflurane in a mixture of air and oxygen. Electrolocation-guided sciatic and femoral nerve blocks with lidocaine 2% (0.15 mL/kg) were performed using the parasacral and lateral pre-iliac approaches, respectively. After performing local block, a systemic infusion of saline solution (group C) or dexmedetomidine (group D) was started at a CRI at 1 ml/kg/h and continued until the end of surgery. Dexmedetomidine was infused at a dose of 1 μg/kg/h. Respiratory and hemodynamic variables were recorded during surgery. Sensory and motor blockade was evaluated by response to pinching the skin innervated by the sciatic/femoral nerves, with forceps and by observing the dogs' ability to walk and testing proprioception at 30, 60, 120, 180, and 240 min after extubation. Analgesia was monitored with SF-GCPS. Methadone IM was administered as rescue analgesia. Intraoperative data were analyzed by analysis of variance, while postoperative data were analyzed by the independent two-tailed t-test and a Kaplan-Meier test (p < 0.05). Twenty dogs were included in this study (10/group). A significant difference in the recovery of sensory nerve function was observed between the groups. The mean durations of the sensory blockade for femoral and sciatic nerves, respectively, was longer (p < 0.001) for group D [168 (146-191, 95% CI), 161 (143-179, 95% CI) min] than in group C [120 (96.1-144, 95% CI), 116 (90.9-142, 95% CI]. No differences in the recovery of patellar and tibial reflexes, proprioceptive function, and ability to walk were found among groups. The overall postoperative rescue analgesia requirement was significantly different (p = 0.019) between groups, with an incidence of 5/10 (50%) dogs in group D and 10/10 (100%) dogs in group C. Dexmedetomidine administered as a CRI (1 μg/kg/h) combined with local lidocaine increases the duration of the sensory component of the sciatic and femoral nerve blocks and reduces the requirement for additional analgesia during the immediate postoperative hours.

A clinically utilized intravenous continuous rate infusion of diltiazem does not significantly decrease systolic function in healthy dogs.

To determine if left ventricular systolic function on echocardiography, systemic blood pressure, and electrocardiography change with a clinically accepted intravenous (IV) diltiazem constant rate infusion (CRI) compared to a control. 10 healthy client-owned adult dogs. Prospective, masked, crossover study from May 27, 2021, to August 22, 2021. Dogs were randomized to receive diltiazem (loading dose of 240 μg/kg, IV followed by a CRI of 6 μg/kg/min for 300 minutes) or the same volume of 5% dextrose in water (D5W) administered IV followed by the opposite intervention after a 7-day washout. Blood pressure was monitored during each CRI, and echocardiographic and electrocardiographic studies were performed immediately before the CRI and during the last hour of the CRI. Postdiltiazem systolic time interval (STI) (median, 0.30; range, 0.16 to 0.34) was significantly lower than post-D5W STI (median, 0.32; range, 0.22 to 0.40; P = .046). All other echocardiographic parameters did not differ significantly between each of the groups after receiving diltiazem or D5W. Systemic blood pressure did not change significantly with either diltiazem (P = .450) or D5W (P = .940), and none of the dogs became hypotensive at any point in the study. Expectedly, negative dromotropy was observed with diltiazem. A significant decrease in left ventricular systolic function was not appreciated in healthy dogs receiving diltiazem at a clinically accepted intravenous infusion rate at this dosing regimen. Further studies are needed in dogs with cardiac disease.

Long-term Glucose Infusions had no Influence on Gonadotropins Hormone Secretion in Ovariectomized Goats

‌Background: It is reported that high nutritional supplementation treatment for seven days stimulated pulsatile LH secretion attended by increased in the plasma glucose and insulin concentrations in goat. The present study tested the hypothesis that whether providing peripheral glucose to goats associated with digestion of high nutrition supplementation increase gonadotropin secretion in ovariectomized goats. Materials and Methods: There was two experimental groups. The treatment animals from both experiences received glucose infusion. In the first experiment (constant glucose infusion; 50% glucose + saline at a rate of 7.5 ml/h for 7 days) and in the second experiment (progressive glucose infusion; 20% glucose + saline by increasing 5% glucose in 24hr intervals for 7 days at a rate of 15 ml/h for 7 days). The control animals from both experiences received saline infusion in the same manner. Findings: In the first experiment, there was no significant diversity in the concentrations of glucose and insulin among the treatment period as compared with mean pre-infusion period or compared to control groups except for Day 2 (p&lt;0.05). In the second experiment, concentrations of both the glucose and insulin started increasing significantly from Day 2 and remained with elevated levels until day 7 as compared with mean pre-infusion period or compared to control groups (p&lt;0.05). The mean Follicle stimulating hormone concentration in treatment group was not affected by glucose infusion as compared with pre-infusion periods or control group. The mean LH (concentration and pulse frequency) was not affected by glucose or saline infusion in both experiments. Conclusion: The present studies suggest that an increase in the glucose availability does not control the gonadotropin secretion as a stimulatory mediator in ovariectomized goats.

Eras outcomes based on perioperative pain modalities: A single institution study

Background: Enhanced Recovery After Surgery (ERAS) pathways are evidence-based protocols to expedite postoperative recovery and provide cost-effective care. Outcome goals for ERAS pathway include minimization of narcotic pain medication and goal-directed intravenous (IV) fluid use. Surgically placed wound catheters, ON-Q pumps, deliver a constant anesthetic infusion in the preperitoneal or transverse abdominus plane (TAP), and are not associated with hemodynamic changes. The role of ON-Q pumps as a perioperative main modality used in an ERAS pathway remains unknown. The aim of this study was to evaluate outcomes in patients undergoing pancreatic or hepatic resection on an ERAS pathway with ON-Q pumps at our institution.