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Purpose: To elucidate the clinical impact of the novel oxytocin protocol using a syringe pump with a stratified dose compared with the conventional practice of putting oxytocin into the bag., Methods: This is a retrospective cohort study. We collected the data of the patients who underwent elective cesarean delivery under neuraxial anesthesia between June 2019 and May 2020. The patients were allocated to two groups according to oxytocin administration methods; the control group (the attending anesthesiologist put oxytocin 5-10 units in the infusion bag and adjusted manually after childbirth) and the protocol group (the oxytocin protocol gave oxytocin bolus 1 or 3 units depending on the PPH risk, followed by 5 or 10 unit h -1 via a syringe pump). We compared the total amount of oxytocin within 24 h postpartum, estimated blood loss, and adverse clinical events within 24 h postpartum between the two groups., Results: During the study period, 262 parturients were included. Oxytocin doses of intraoperative and postoperative were significantly lower in the protocol group (9.7 vs. 11.7 units, intraoperative, 15.9 vs. 18 units, postoperative). The subgroup analyses showed that the impact was more remarkable in the low PPH risk than in the high PPH risk. The multivariate linear regression analyses also confirmed the difference. The groups had no significant difference in blood loss, requirement of additional uterotonics, and other adverse events., Conclusions: Our oxytocin infusion protocol significantly reduced oxytocin requirements in elective cesarean delivery under neuraxial anesthesia without increasing blood loss. However, we could not find other clinical benefits of the novel protocol., (© 2024. The Author(s).)

Rationale and Key Points: This article explains how to prepare and administer an intravenous (IV) infusion using a gravity administration (giving) set or a volumetric pump in a safe, effective manner. Nurses undertaking this procedure must ensure they have the knowledge and skills to do so and work within the limits of their competence. This article serves as a revision of best practice in administering IV infusions of fluids and medicines. • IV infusions are delivered directly into the bloodstream, so care must be taken to protect the patient from harm by following the appropriate policies and protocols and monitoring the patient carefully for adverse reactions. • There is a risk of administering large volumes of IV fluid to the patient when using a gravity administration set, so a burette or volumetric pump should be used in patients who may not tolerate this. • Volumetric pumps vary, so it is essential that the nurse is familiar with the device, uses the specific administration set required and follows the manufacturer's instructions. REFLECTIVE ACTIVITY: 'How to' articles can help to update your practice and ensure it remains evidence-based. Apply this article to your practice. Reflect on and write a short account of: • How this article might improve your practice when preparing and administering an IV infusion. • How you could use this information to educate nursing students or your colleagues on the appropriate methods for preparing and administering an IV infusion., Competing Interests: None declared, (© 2024 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

Background: Safe and efficient provision of intravenous lipid emulsion (ILE) requires a strategy to individualize infusion rates. Estimating the maximum acceptable infusion rate (MaxInfRate) of soybean oil-based ILE (SO-ILE) in individuals by using a triglyceride (TG) kinetic model was reported to be feasible. In this study, we aimed to externally validate and, if needed, update the MaxInfRate estimation., Methods: The maximum TG concentration (TG max ) in patients receiving SO-ILE at MaxInfRate was evaluated to determine if it met the definition of being <400 mg/dl for 90th percentile of patients. The TG kinetic model was evaluated through prediction performance checks and was subsequently updated using the data set of both the previous model development and present validation studies., Results: Out of 83 patients, 74 had TG max <400 mg/dl, corresponding to a probability of 89.2% (95% CI, 81.9%-95.2%), and the 90th percentile of TG max was 400 mg/dl (95% CI, 328-490 mg/dl), closely aligned with the theoretical values. However, the individual TG max values were biased by the infusion rate because the covariate effects were overestimated in the TG kinetic model, requiring a minor revision. The updated MaxInfRate with the combined data set showed unbiased and more accurate predictions., Conclusion: The MaxInfRate was validated in external inpatients and updated with all available data. MaxInfRate estimation for individuals could be an option for the safe and efficient provision of SO-ILE., (© 2024 The Authors. Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Objectives: Intravenous medication errors continue to significantly impact patient safety and outcomes. This study sought to clarify the complexity and risks of the intravenous administration process., Design: A qualitative focus group interview study., Setting: Focused interviews were conducted using process mapping with frontline nurses responsible for medication administration in September 2020., Participants: Front line experiened nurses from a Japanese tertiary teaching hospital., Primary and Secondary Outcome Measures: The primary outcome measure was to identify the mental models frontline nurses used during intravenous medication administration, which influence their interactions with patients, and secondarily, to examine the medication process gaps between the mental models nurses perceive and the actual defined medication administration process., Results: We found gaps between the perceived clinical administration process and the real process challenges with an emphasis on the importance of verifying to see if the drug was ordered for the patient immediately before its administration., Conclusions: This novel and applied improvement approach can help nurses and managers better understand the process vulnerability of the infusion process and develop a deeper understanding of the administration steps useful for reliably improving the safety of intravenous medications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Dose banding (DB) was used to optimise the individualisation of patient treatments with gemcitabine (Gem) in order to improve workload planning at the pharmacy of the University Hospital Centre of Besançon (UHCB). A new simple and fast high-performance liquid chromatographic (HPLC) method was also developed for the quantification of Gem without dilution of the infusion bags., Methods: Individual doses of Gem preparations were retrospectively analysed over a 1-year period to determine the frequency of prepared doses. Using a maximum gap of 7.5% around the doses chosen, the selected Gem standard doses were 1400 mg, 1600 mg, 1800 mg and 2000 mg. Following the DB scheme, the frequency of prescription of standard and individualised Gem doses was analysed over a period of 10 months. The four selected Gem standard doses were aseptically prepared in polyolefin infusion bags. Each series of 20 bags was stocked under refrigerated storage conditions (4°C) for up to 84 days. The quantification of Gem without dilution of the infusion bags was obtained by the development of a HPLC method coupled to a diode array detector (DAD) or an evaporative light scattering detector (ELSD)., Results: During the 10-month period following implementation of the DB, 75.6% of the 1266 prescribed doses were covered by the four standardised preparations. The number of different Gem doses was reduced from 183 to 55. Concerning the Gem quantification, both heteroscedasticity and non-linearity were observed with DAD. Using an ELSD, the trueness values were between 98.59% and 101.52% with excellent repeatability values between 0.66% and 1.42%., Conclusion: A new HPLC method has been developed for the quantification of Gem without dilution of the infusion bags prepared in advance as a result of a target DB scheme successfully implemented in our pharmacy department., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The aim of this project was to investigate whether opioid pain scores, postoperative opioid requirements, and postanesthesia care unit (PACU) length of stay were impacted when comparing a 24-hour intravenous lidocaine infusion versus postoperative discontinuation of the lidocaine infusion., Design: A retrospective chart review was used both before and after the discontinuation of postoperative lidocaine infusions for a quality improvement project., Methods: The project was carried out in the adult surgery PACU setting at a level 1 trauma center between April 2021 and September 2021. The sample included 100 adult patients who fell under surgical specialties that used enhanced recovery after surgery protocol. After approval was obtained, data was collected via an electronic chart review using an evaluation tool created by the project team., Findings: Between the five surgical specialties used for this review, the PACU length of stay variable was reduced only in the gynecology oncology service (P= .041). Additionally, the postoperative opioid requirements were significantly reduced in the surgical oncology service (P = .02). Comparing the groups as a whole, 50 participants who had a 24-hour continuous lidocaine infusion and 50 participants whose lidocaine infusion was discontinued before PACU admission had no statistically significant values with pain scores, postoperative opioid requirements, and PACU length of stay., Conclusions: Results indicate that a 24-hour lidocaine infusion did not impact this patient population's pain scores, postoperative opioid requirements, or PACU length of stay., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

In 2017, a severe shortage of infusion bags resulted in a paradigm change in medication administration practice from intermittent infusion to intravenous push. The Institute for Safe Medication Practices proposed safe practice guidelines for adult intravenous push medications. A different study showed that ready-to-administer medication prepared in the sterile area of a pharmacy reduces the risk of harm, nurses' time for medication administration and the cost of medications. Based on the recommendation of the Institute for Safe Medication Practices, we decided to conduct a pilot study on the implementation of sterile compounding and administration of intravenous push medication in adult patients admitted to the hospital. In the study, the stability of five intravenous push antibiotic syringes was also determined in the syringes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Managing intravenous (IV) access is a standard proficiency for UK nurses, enabling them to administer IV injections and IV infusions and to manage injection equipment and infusion pumps and devices. In this article the author describes various types of venous access devices that are commonly seen in practice and details the preparation, checking and administration of IV fluids and medicines, including some complications that may arise. The author also discusses the calculation of fluid requirements, types of IV fluids, displacement values and ongoing care of venous access devices., Competing Interests: None declared, (© 2023 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

Intravenous infusion is an important route of drug therapy, and infusion safety is an important issue for medical staff. Long-term and multiple infusion routes at the same time bring inconvenience to patients. Multiple three-way switches in parallel infusion may lead to interruption of the liquid route, which can seriously endanger the life of patients. To address these clinical issues, medical staff from the School of Basic Medical Sciences of Hebei Medical University and the Emergency Department of the Second Hospital of Hebei Medical University designed a multiple combination portable infusion assistance device and obtained the National Utility Model Patent of China (ZL 2022 2 0226073.2). The device is mainly composed of adhesive tape sticker, fixed slots and pipelines, and also includes a three-way valve and a mixing chamber, and different modes of infusion assist devices can be selected according to clinical needs. The device is simple and convenient to operate, solves the problem of multiple liquid infusion blockages, improves the safety and comfort of infusion, and can meet the needs of liquid infusion in various clinical situations.

Introduction: Major depressive disorder is a serious, recurrent, and disabling psychiatric illness. Despite many proven treatments with multiple medications or therapies, approximately 30% of patients fail to achieve remission and are considered to have treatment-refractory depression (TRD). Recently, there has been a growing interest in the use of intravenous (IV) ketamine for the treatment of TRD. There is limited yet increasing evidence to support the use of ketamine, a glutamate receptor antagonist, in the management of depression; however, the lack of data regarding the safety and tolerability of therapy has limited its clinical use. By analyzing a cohort of veterans with TRD and comorbid psychiatric conditions treated with IV ketamine infusions for a 24-month study period, we aim to provide critical information about ketamine's clinical effectiveness and safety., Materials and Methods: Based on a retrospective chart review, we identified eight veterans with TRD receiving treatment with repeated-dose IV ketamine from 2018 to 2020. The magnitude of clinical response was based on the Beck Depression Inventory self-report scale and the Patient Health Questionnaire-9, both measured at the initial patient consultation and before the beginning of each ketamine infusion treatment. Safety analysis included changes to pre- and post-ketamine infusion on vital signs, effects on alertness and sedation, and potential psychosis-like effects. For all outcomes, we estimated a linear mixed-effects model that allowed heterogeneous residual variances for each veteran. The effect of continuous predictor variables was estimated using restricted cubic splines with knot points specified at the 5th, 35th, 65th, and 95th percentiles. All the analyses were conducted using SAS v.9.4, with P < .05 indicating the statistical significance. This study had institutional review board approval: 1220., Results: During the study period, the median number of ketamine infusions was 15 across a median of 164 days of treatment follow-up with a median time between ketamine infusions of 4 days. For both Beck Depression Inventory and Patient Health Questionnaire-9 scores, there was a statistically significant reduction across infusions (both P < .001), but the strongest reduction occurred before day 40. The change was statistically significant for decreased heart rate (P = .019) but not for systolic blood pressure (P = .612), diastolic blood pressure (P = .942), respiratory rate (P = .822), oxygen saturation (P = .070), and temperature (P = .943). Side effects were reported in six patients (75%); however, the only side effect reported was excessive sedation or dizziness immediately after infusion., Conclusions: In this study, repeated-dose IV ketamine infusions over a 24-month study period resulted in a significant reduction in depression scores in a group of veterans with TRD. The rapid onset of significant response, absence of psychosis-like effects or dissociative symptoms despite psychiatric comorbidities, and minimal effects on vital signs support the clinical efficacy and safety of this exciting new treatment option for patients with TRD. Limitations include a 2-year study period, lack of information on long-term effects, and the retrospective nature of the study. Prospective studies of longer duration are needed to assess the long-term efficacy and safety of IV ketamine for TRD., (© The Association of Military Surgeons of the United States 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Prevention of hypotension during the intra- and postoperative period is an important goal. Peripheral administration of low-concentration norepinephrine may be a safe and effective strategy to reduce the risk of hypotension., Methods: We conducted a 2-center, randomized pilot feasibility trial, with a target of 60 adult patients undergoing major noncardiac surgery. We randomized patients to receive a peripheral low-concentration (10 µg/mL) norepinephrine or placebo (saline 0.9%) infusion. The study drug infusion was titrated to achieve a minimum systolic blood pressure target, preselected within 10% of baseline value and within the range limit 100 to 120 mm Hg during surgery and for up to 4 or 24 hours postoperatively., Results: We achieved a high consent rate (84%), successful study drug administration throughout surgery (98% of patients) and absence of unblinding. There were no important study drug-related adverse events. The average intraoperative systolic blood pressure was 120 ± 12.6 mm Hg in the norepinephrine group and 115 ± 14.9 mm Hg in the placebo group. The mean difference between the intraoperative systolic blood pressure achieved less the preselected minimum systolic blood pressure target was 10.0 ± 12.7 mm Hg in the norepinephrine group and 2.9 ± 14.7 mm Hg in the placebo group; difference in means, 7.1 (95% confidence interval, 0.2-14.0) mm Hg., Conclusions: A future large trial evaluating the effectiveness and safety of peripheral administration of low-concentration norepinephrine during the perioperative period is feasible, and likely to achieve a minimum systolic blood pressure threshold., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

Background and Objectives: Status epilepticus as a pediatric emergency requires rapid seizure control in order to prevent subsequent disabilities. Therefore, the present study was conducted to compare the efficacy and side effects of continuous intravenous infusion of sodium valproate versus midazolam as a third-line treatment of status epilepticus in children., Methodology: This randomized clinical trial study included all children with convulsive and non-convulsive status epilepticus admitted to the pediatric intensive care unit (PICU) of the Bu-Ali Sina Hospital in Sari City (Mazandaran Province, Iran) who had not responded to first-line treatment with diazepam and second-line treatment with phenytoin or phenobarbital. They were consequently treated with continuous intravenous infusion of sodium valproate or midazolam to control persistent seizures., Results: The study comprised 70 patients who were randomly assigned to two equal groups of sodium valproate or midazolam treatment. The mean age of patients in group A (sodium valproate) and group B (midazolam) was 3.97 ± 3.33 and 3.84 ± 2.93 years, respectively. In the present study, the most common etiology of status epilepticus was remote symptomatic, accounting for 35% of cases in the two groups. Sodium valproate was effective in controlling status epilepticus in 91.4% of patients, while midazolam was found to be effective in 85.7% of patients (p > 0.05). Patients who received sodium valproate had shorter seizure duration after administration of the drug compared to those who received midazolam (p = 0.01). Eight patients in the midazolam group and two patients in the sodium valproate group were intubated (p = 0.023). The mean duration of stay in the PICU was 3.2 ± 1.4 and 5.6 ± 2.8 days in groups A and B, respectively, showing a significant difference (p = 0.001)., Conclusion: According to our findings, intravenous infusion of sodium valproate can be used as an effective and relatively safe treatment in children with all types of status epilepticus, especially in challenging situations such as lack of intensive care units or respiratory problems., Competing Interests: Declaration of Competing Interest None, (Copyright © 2021 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Background and Objectives: As a chiral drug, oxiracetam (ORT) can exist in two different isomeric forms: S-oxiracetam (S-ORT) and R-oxiracetam (R-ORT). S-ORT has emerged as a promising nootropic drug with the potential to treat brain injury and the resulting loss of neural function, memory and mental impairment as assessed by studies in various animal models. However, limited data are available on the pharmacokinetics of S-ORT in humans, so the present study was designed to evaluate the safety and pharmacokinetic profile of S-ORT in healthy volunteers., Methods: In part 1, subjects were intravenously administered single ascending dose (2.0, 4.0 and 8.0 g) S-ORT. In part 2, subjects were treated at a single intravenous infusion dose of 3.0 g S-ORT or 6.0 g racemic ORT using a two-sequence, two-period crossover design. In part 3, subjects were intravenously injected with 4.0 g S-ORT once a day for 7 days. Blood and urine samples were collected to evaluate the pharmacokinetic parameters and urine excretion rate. The safety profile of the drug was also evaluated throughout the study., Results: Fifty-two subjects (30 in part 1, 12 in part 2, 10 in part 3) completed the study; only one subject displayed a mild adverse event, which possibly was treatment related, and no serious adverse event occurred. In part 1 for a single dose of 2.0, 4.0 and 8.0 g, the maximum concentration (C max ) values were 111.28 ± 18.99, 230.76 ± 29.16 and 352.67 ± 42.94 μg/ml, respectively; the values of area under the plasma concentration-time curve (AUC) from time zero to the time of last quantifiable concentration (AUC 0-t ) were 267.09 ± 59.66, 524.50  ± 72.87 and 822.68 ± 95.21 μg·h/ml, respectively; the AUC from 0 h to infinity (AUC 0-∞ ) values were 274.72 ± 61.65, 536.06 ± 78.13 and 832.07 ± 96.91 μg·h/ml, respectively. The urine excretion rate of the unchanged drug was approximately 60%. After consecutive administration of S-ORT for 7 days, the accumulation index was 1.05 ± 0.08. The plasma drug concentration-time curves for both S-ORT and R-oxiracetam (R-ORT) were almost identical., Conclusions: S-ORT was well tolerated, and no serious adverse events occurred in 2.0, 4.0 and 8.0 g in single- and 4.0 g in multiple-dose studies. S-ORT showed dose linearity with increasing doses and no drug accumulation after 7 days of continuous administration was observed., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Limited research regarding administration of timed medication infusions in the prehospital environment has identified wide variability with accuracy, timing, and overall feasibility. This study was a quality improvement project that utilized a randomized, controlled, crossover study design to compare two different educational techniques for medication infusion administration. We hypothesized that the use of a metronome-based technique would decrease medication dosage errors and reduce time to administration for intravenous medication infusions., Methods: Forty-two nationally registered paramedics were randomized to either a metronome-based technique versus a standard stopwatch-based technique. Each subject served as a control. Subjects were asked to establish an infusion of amiodarone at a dose of 150 mg administered over 10 min, simulating treatment of a hemodynamically stable patient with sustained monomorphic ventricular tachycardia. Descriptive statistics and a repeated measures mixed linear regression model were used for data analysis., Results: When compared to a standard stopwatch-based technique, a metronome-based technique was associated with faster time to goal (median 34 s [IQR, 22-54] vs 50 s; [IQR 38-61 s], P = 0.006) and fewer mid-infusion adjustments. Ease of use was reported to be significantly higher for the metronome group (median ranking 5, IQR 4-5) compared to the standard group (median ranking 2, IQR 2-3; P < 0.001)., Conclusions: Knowledge regarding a metronome technique may help EMS clinicians provide safe and effective IV infusions. Such a technique may be beneficial for learners and educators alike., (© 2021. The Author(s).)

Objectives: To apply therapeutic drug monitoring and dose-individualization of intravenous Busulfan to paediatric patients and evaluate the impact of syringe-pump induced Busulfan infusion lag-time after in vitro estimation., Methods: 76 children and adolescents were administered 2 h intravenous Busulfan infusion every 6 h (16 doses). Busulfan plasma levels, withdrawn by an optimized sampling scheme and measured by a validated HPLC-PDA method, were used to estimate basic PK parameters, AUC, Cmax, kel, t1/2, applying Non-Compartmental Analysis. In vivo infusion lag-time was simulated in vitro and used to evaluate its impact on AUC estimation., Key Findings: Mean (%CV) Busulfan AUC, Cmax, clearance and t1/2 for pediatric population were found 962.3 μm × min (33.1), 0.95 mg/L (41.4), 0.27 L/h/kg (33.3), 2.2 h (27.8), respectively. TDM applied to 76 children revealed 6 (7.9%) being above and 25 (32.9%) below therapeutic-range (AUC: 900-1350 μm × min). After dose correction, all patients were measured below toxic levels (AUC < 1500 μm × min), no patient below 900 μm × min. Incorporation of infusion lag-time revealed lower AUCs with 17.1% more patients and 23.1% more younger patients, with body weight <16 kg, being below the therapeutic-range., Conclusions: TDM, applied successfully to 76 children, confirmed the need for Busulfan dose-individualization in paediatric patients. Infusion lag-time was proved clinically significant for younger, low body-weight patients and those close to the lower therapeutic-range limit., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The formation of particulates in post-manufacture biopharmaceuticals continues to be a major concern in medical treatment. This study was designed to evaluate the content of micro-sized particles using flow imaging of antibodies in intravenous infusion bags. Intravenous immunoglobulin (IVIG) and Avastin® were selected as model drugs and plastic syringes with and without silicone oil (SO) were used to transfer the drugs into the bags (0.9% saline or 5% dextrose). Antibodies exposed to SO had significantly increased levels of microparticles in both diluents, suggesting SO accelerates particle formation, especially at a higher antibody concentration. Even before the drop stress, their count exceeded the USP guideline. Dropping the bags in the presence of SO produced larger microparticles. Meanwhile, air bubbles were retained longer in saline suggesting more protein film formation on its air-water interface. Overall, both drugs were conformationally stable and produced less particles in dextrose than in saline., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Decongestion is a primary goal during hospitalizations for decompensated heart failure (HF). However, data surrounding the preferred route and strategy of diuretic administration are limited with varying results in prior studies., Methods: This is a retrospective analysis using patients from ASCEND-HF with a stable diuretic strategy in the first 24 hours following randomization. Patients were divided into three groups: intravenous (IV) continuous, IV bolus and oral strategy. Baseline characteristics, in-hospital outcomes, 30-day composite cardiovascular mortality or HF rehospitalization and 180-day all-cause mortality were compared across groups. Inverse propensity weighted modeling was used for adjustment., Results: Among 5,738 patients with a stable diuretic regimen in the first 24 hours (80% of overall ASCEND trial), 3,944 (68.7%) patients received IV intermittent bolus administration of diuretics, 799 (13.9%) patients received IV continuous therapy and 995 (17.3%) patients with oral administration. Patients in the IV continuous group had a higher baseline creatinine (IV continuous 1.4 [1.1-1.7]; intermittent bolus 1.2 [1.0-1.6]; oral 1.2 [1.0-1.4] mg/dL; P <0.001) and high NTproBNP (IV continuous 5,216 [2,599-11,603]; intermittent bolus 4,944 [2,339-9,970]; oral 3,344 [1,570-7,077] pg/mL; P <0.001). There was no difference between IV continuous and intermittent bolus group in weight change, total urine output and change in renal function till 10 days/discharge (adjusted P >0.05 for all). There was no difference in 30 day mortality and HF readmission (adjusted OR 1.08 [95%CI: 0.74, 1.57]; P = 0.701) and 180 days mortality (adjusted OR 1.04 [95%CI: 0.75, 1.43]; P = 0.832)., Conclusion: In a large cohort of patients with decompensated HF, there were no significant differences in diuretic-related in-hospital, or post-discharge outcomes between IV continuous and intermittent bolus administration. Tailoring appropriate diuretic strategy to different states of acute HF and congestion phenotypes needs to be further investigated., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Drug protocols in intensive care units may require the concomitant administration of many drugs as patients' venous accesses are often limited. A major challenge for clinicians is to limit the risk of simultaneously infusing incompatible drugs. Incompatibilities can lead to the formation of particles and inactivation of drugs, whose consequences on the body have already been indicated. Our objective was to assess current strategies to counter the risk of incompatible infusions and control the resulting clinical consequences., Methods: This review was independently conducted by three investigators in respect of the PRISMA statement. Three online databases were consulted. Full-text articles, notes, or letters written in English or French, published or in press between the 1990s and the end of February 2020, with clinical study design, were eligible. Parameters of interest were mainly number and size of particles, and a number of observed/avoided incompatibilities., Results: All in all, 382 articles were screened, 17 meeting all the acceptance criteria. The strategies outlined and assessed were filtration, the use of multi-lumen devices, the purging of infusion lines, incompatibility tables and databases, and the use of standard operating procedures., Conclusion: Although many strategies have been developed in recent years to address drug incompatibility risks, clinical data is still lacking. All studies with in vitro design were excluded although some current innovative strategies, like niosomes, should be considered and studied by means of clinical data in the future., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Artificial pancreas system (APS) is an emerging new treatment for type 1 diabetes mellitus. The aim of this study was to develop a rat APS as a research tool and demonstrate its application. We established a rat APS using Medtronic Minimed Pump 722, Medtronic Enlite sensor, and the open artificial pancreas system as a controller. We tested different dilutions of Humalog (100 units/ml) in saline ranged from 1:3 to 1:20 and determined that 1:7 dilution works well for rats with ~500g bodyweight. Blood glucose levels (BGL) of diabetic rats fed with chow diet (58% carbohydrate) whose BGL was managed by the closed-loop APS for the total duration of 207h were in euglycemic range (70-180 mg/dl) for 94.5% of the time with 2.1% and 3.4% for hyperglycemia (>180mg/dl) and hypoglycemia (<70 mg/dl), respectively. Diabetic rats fed with Sucrose pellets (94.8% carbohydrate) for the experimental duration of 175h were in euglycemic range for 61% of the time with 35% and 4% for hyperglycemia and hypoglycemia, respectively. Heathy rats fed with chow diet showed almost a straight line of BGL ~ 95 mg/dl (average 94.8 mg/dl) during the entire experimental period (281h), which was minimally altered by food intake. In the healthy rats, feeding sucrose pellets caused greater range of BGL in high and low levels but still within euglycemic range (99.9%). Next, to study how healthy and diabetic rats handle supra-physiological concentrations of glucose, we intraperitoneally injected various amounts of 50% dextrose (2, 3, 4g/kg) and monitored BGL. Duration of hyperglycemia after injection of 50% dextrose at all three different concentrations was significantly greater for healthy rats than diabetic rats, suggesting that insulin infusion by APS was superior in reducing BGL as compared to natural insulin released from pancreatic β-cells. Ex vivo studies showed that islets isolated from diabetic rats were almost completely devoid of pancreatic β-cells but with intact α-cells as expected. Lipid droplet deposition in the liver of diabetic rats was significantly lower with higher levels of triacylglyceride in the blood as compared to those of healthy rats, suggesting lipid metabolism was altered in diabetic rats. However, glycogen storage in the liver determined by Periodic acid-Schiff staining was not altered in diabetic rats as compared to healthy rats. A rat APS may be used as a powerful tool not only to study alterations of glucose and insulin homeostasis in real-time caused by diet, exercise, hormones, or antidiabetic agents, but also to test mathematical and engineering models of blood glucose prediction or new algorithms for closed-loop APS., Competing Interests: The authors have declared that no competing interests exist.

Background: High-dose intravenous immunoglobulin (IVIG) is the mainstay of treatment for Kawasaki disease (KD). Usually, 2 g/kg of IVIG is administered over 10-24 h, depending on the institution or physician, but the association between infusion speed and effectiveness has not been reported. In this study, we evaluated the differences in efficacy and safety between two different IVIG administration speeds., Methods: This was a multicenter, unblinded, randomized controlled study. Patients newly diagnosed with KD were randomized into two groups: one who received IVIG over 12 h (12H group, double speed), and one that received IVIG over 24 h (24H group, reference speed). The endpoints included the duration of fever, incidence of coronary artery abnormalities (CAAs) and of adverse events. Laboratory data were evaluated before and after IVIG administration., Results: A total of 39 patients were enrolled. There was no difference between groups in fever duration after the initiation of IVIG (21 h vs. 21.5 h, p = 0.325), and no patient experienced CAAs. Two adverse events were observed in the 12H group (elevation of aspartate aminotransferase and vomiting), however no severe adverse events requiring treatments or extension of hospital stay were observed in either group. After initial IVIG administration, the change ratio of inflammatory markers, such as white blood cell counts, neutrophils, C-reactive protein, and albumin, did not show significant differences between the two groups. On the other hand, a greater increase of serum immunoglobulin G from its baseline level was observed in the 24H group compared to the 12H group (3037 ± 648 mg/dl vs. 2414 ± 248 mg/dl, p < 0.01)., Conclusion: The efficacy and safety of IVIG administered over 12 h (double speed) were similar to those administered over 24 h (reference speed)., Trial Registration: University Hospital Medical Information Network ( UMIN000014665 ). Registered 27 July 2014 - Prospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr&#95;view.cgi?recptno=R000017058.

Intravenous drug self-administration remains the 'gold standard' for assessing abuse liability. Failure of a drug to maintain self-administration might indicate the absence of positive reinforcing effects but might also indicate the presence of aversive effects. Sensitivity to aversive and punishing effects of drugs (as well as nondrug stimuli) might collectively determine the likelihood of use, abuse and relapse. Using a choice procedure, this study compared the effects of remifentanil (mu opioid receptor agonist; 0.001-0.01 mg/kg/infusion) and histamine (H1-4 receptor agonist; 0.32-3.2 mg/kg/infusion), alone and in mixtures, to test the hypothesis that remifentanil/histamine mixtures are less reinforcing compared with remifentanil alone and less punishing compared with histamine alone. Male Sprague-Dawley rats (n = 10) chose between an intravenous infusion + a pellet and a pellet alone. Rats were indifferent to saline, chose remifentanil + a pellet over a pellet alone, and chose a pellet alone over histamine + a pellet. The effects of remifentanil/histamine mixtures generally were different from the constituent doses of histamine alone but not from remifentanil alone. A mixture containing 3.2 mg/kg/infusion histamine and either 0.001 or 0.0032 mg/kg/infusion remifentanil was not different from saline but was different from the effects of the constituent dose, insofar as choice increased compared with 3.2 mg/kg/infusion histamine alone and decreased compared with 0.001 or 0.0032 mg/kg/infusion remifentanil alone. Reinforcing doses of remifentanil combined with punishing doses of histamine can yield mixtures that are neither preferred nor avoided, offering 'proof-of-principle' for using drug mixtures to avoid adverse effects of opioid receptor agonists., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Gut microbe-derived metabolites influence human physiology and disease. However, establishing mechanistic links between gut microbial metabolites and disease pathogenesis in animal models remains challenging. The major route of absorption for microbe-derived small molecules is venous drainage via the portal vein to the liver. In the event of presystemic hepatic metabolism, the route of metabolite administration becomes critical. To our knowledge, we describe here a novel portal vein cannulation technique using a s.c. implanted osmotic pump to achieve continuous portal vein infusion in mice. We first administered the microbial metabolite trimethylamine (TMA) over 4 weeks, during which increased peripheral plasma levels of TMA and its host liver-derived cometabolite, trimethylamine-N-oxide, were observed when compared with a vehicle control. Next, 4-hydroxyphenylacetic acid (4-HPAA), a microbial metabolite that undergoes extensive presystemic hepatic metabolism, was administered intraportally to examine effects on hepatic gene expression. As expected, hepatic levels of 4-HPAA were elevated when compared with the control group while peripheral plasma 4-HPAA levels remained the same. Moreover, significant changes in the hepatic transcriptome were revealed by an unbiased RNA-Seq approach. Collectively, to our knowledge this work describes a novel method for administering gut microbe-derived metabolites via the portal vein, mimicking their physiologic delivery in vivo.

Background: Although enzyme replacement therapy with agalsidase beta resulted in a variety of clinical benefits, life-long biweekly intravenous infusion may impact on patients' quality of life. Moreover, regular infusions are time-consuming: although a stepwise shortening of infusion duration is allowed up to a minimum of 1.5 hr, in most centers it remains ≥3 hr, and no data exists about the safety and tolerability of agalsidase beta administration at maximum tolerated infusion rate., Methods: In this study, we reported our experience with a stepwise infusion rate escalation protocol developed in our center in a cohort of 53 Fabry patients (both already receiving and treatment-naΪve), and explored factors predictive for the infusion rate increase tolerability., Results: Fifty-two patients (98%) reduced infusion duration ≤3 hr; of these, 38 (72%) even reached a duration ≤2 hr. We found a significant difference between the mean duration reached by already treated and naΪve patients (p < .01). More severely affected patients (male patients and those with lower enzyme activity) received longer infusions for higher risk of infusion-associated reactions (IARs). A significant correlation between anti-agalsidase antibodies and IARs was found., Conclusion: Our infusion rate escalation protocol is safe and could improve patient compliance, satisfaction and quality of life., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

The aim of this study was to evaluate the efficacy and safety of outpatient antimicrobial therapy with piperacillin-tazobactam in continuous infusion using elastomeric pumps and to evaluate the economic impact compared with conventional hospital treatment in patients with Pseudomonas aeruginosa (PA) infections. This is an observational study. Patients with PA infection treated with continuous piperacillin-tazobactam infusion using elastomeric pumps in our hospital between January 2015 and December 2017 were included. Primary outcomes were mortality during antibiotic treatment and mortality at 30 days. Secondary outcomes were reinfection or relapse at 30 days and clinical cure rate. The cost of each episode was compared with theoretical cost of the same treatment using conventional hospitalization. 35 patients were included. One patient (2.9%) died during the treatment. Overall 30-day mortality was 5.7%. No death was related to infection by PA. One patient (2.9%) had a reinfection at 30 days. Cure was achieved in 93% of patients at the end of treatment. There were no severe complications related to elastomeric pumps. Treatment cost with outpatient antimicrobial therapy was 67% lower than theoretical cost with conventional hospital treatment. Oupatient antimicrobial therapy with piperacillin-tazobactam in continuous infusion using elastomeric pumps in patients with PA infections is safe and effective with lower costs.

ALS is a devastating neurodegenerative disease with few curative strategies. Both sporadic and familial ALS display common clinical features that show progressive paralysis. The pathogenesis remains unclear, but disruption of the blood-spinal cord barrier (BSCB) may contribute to the degeneration of motor neurons. Thus, restoration of the disrupted BSCB and neuroprotection for degenerating motor neurons could be therapeutic targets. We tested the hypothesis that an intravenous infusion of MSCs would delay disease progression through the preservation of BSCB function and increased expression of a neurotrophic factor, neurturin, in SOD1 G93A ALS rats. When the open-field locomotor function was under 16 on the Basso, Beattie, and Bresnahan (BBB) scoring scale, the rats were randomized into two groups; one received an intravenous infusion of MSCs, while the other received vehicle alone. Locomotor function was recorded using BBB scoring and rotarod testing. Histological analyses, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), were performed. The MSC group exhibited reduced deterioration of locomotor activity compared to the vehicle group, which displayed progressive deterioration of hind limb function. We observed the protection of motor neuron loss and preservation of microvasculature using Evans blue leakage and immunohistochemical analyses in the MSC group. Confocal microscopy revealed infused green fluorescent protein + (GFP + ) MSCs in the spinal cord, and the GFP gene was detected by nested PCR. Neurturin expression levels were significantly higher in the MSC group. Thus, restoration of the BSCB and the protection of motor neurons might be contributing mechanisms to delay disease progression in SOD1 G93A ALS rats., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Intracranial pressure (ICP) has to be maintained quite constant, because increased ICP caused by cerebrovascular disease and head trauma is fatal. Although controlling ICP is clinically critical, only few therapeutic methods are currently available. Barbiturates, a group of sedative-hypnotic drugs, are recognized as secondary treatment for controlling ICP. We proposed a novel "step-down infusion" method, administrating barbiturate (thiamylal) after different time point from the start of treatment under normothermia, at doses of 3.0 (0-24 h), 2.0 (24-48 h), 1.5 (48-72 h), and 1.0 mg/kg/h (72-96 h), and evaluated its safety and effectiveness in clinical. In 22 patients with severe traumatic brain injury or severe cerebrovascular disease (Glasgow coma scale ≤8), thiamylal concentrations and ICP were monitored. The step-down infusion method under normothermia maintained stable thiamylal concentrations (<26.1 µg/ml) without any abnormal accumulation/elevation, and could successfully keep ICP <20 mmHg (targeted management value: ICP <20 mmHg) in all patients. Moreover the mean value of cerebral perfusion pressure (CPP) was also maintained over 65 mmHg during all time course (targeted management value: CPP >65 mmHg), and no threatening changes in serum potassium or any hemodynamic instability were observed. Our novel "step-down infusion" method under normothermia enabled to maintain stable, safe thiamylal concentrations to ensure both ICP reduction and CPP maintenance without any serious side effects, may provide a novel and clinically effective treatment option for patients with increased ICP., (© 2021 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

Background: Acute ischemic stroke (AIS) is an important factor leading to adult death and disability globally. For AIS patients who meet certain conditions, recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis is an important method recommended by national guidelines to achieve vascular recanalization. However, complications such as hemorrhagic transformation and vascular reocclusion after thrombolysis are still unsolved problems in clinical. Several systematic reviews of clinical randomized controlled trials (RCTs) in the past have shown that Chinese herbal injections (CHIs) can improve the neurological function of patients, increase the tolerance of ischemic tissues to hypoxia, and inhibit platelet aggregation. Therefore, this study conducted a meta-analysis of AIS treatment with intravenous thrombolysis alone and compared it with the combined application of CHIs. To evaluate whether CHIs have a synergistic effect on thrombolytic therapy and provide a basis for clinical application., Methods: The following databases will be searched until September 2020: ①English databases: PubMed, Cochrane Library, Embase; ②Chinese databases: CNKI, Wanfang database, Weipu database, SinoMed. RCTs will be included to compare the efficacy of thrombolysis combined with CHIs and thrombolysis alone in the treatment of AIS. Data extraction and risk of bias assessments will be carried out by 2 verifiers independently. The risk of bias will be evaluated through the Cochrane risk of bias tool. Review Manager software 5.3 will be used for statistical analysis., Results: This study will provide comprehensive evidence for the treatment of AIS by CHIs combined with intravenous thrombolysis from multiple aspects., Conclusion: The conclusion of the meta-analysis will provide a basis for judging whether CHIs combined with intravenous thrombolysis is an effective measure for the treatment of AIS., Ethics and Dissemination: Ethical approval is not needed because this study will be based on data that already published. We will publish the findings of this study in a peer-reviewed journal and related conferences., Prospero Registration Number: CRD42020215546., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To identify modifiable and non-modifiable risk factors for peripheral intravenous catheter (PIV) failure among patients requiring intravenous treatment for oncology and haematology conditions., Methods: A single-centre prospective cohort study was conducted between October 2017 and February 2019. Adult in-patients requiring a PIV for therapy were prospectively recruited from two cancer units at a tertiary hospital in Queensland, Australia. The primary outcome was a composite of complications leading to PIV failure (local and bloodstream infection; occlusion; infiltration/extravasation; leakage; dislodgement; and/or phlebitis). Secondary outcomes were (i) PIV dwell time; (ii) insertion and (iii) failure of a CVAD; (iv) adverse events; (v) length of hospital stay. Outcomes were investigated using Bayesian multivariable linear regression modelling and survival analysis., Results: Of 200 participants, 396 PIVs were included. PIV failure incidence was 34.9%; the most common failure type was occlusion/infiltration (n = 74, 18.7%), then dislodgement (n = 33, 8.3%), and phlebitis (n = 30, 7.6%). While several patient and treatment risk factors were significant in univariable modelling, in the final multivariable model, only the use of non-sterile tape (external to the primary dressing) was significantly associated with decreased PIV dislodgement (hazard ratio 0.06, 95% confidence interval 0.01, 0.48; p = 0.008)., Conclusion: PIV failure rates among patients receiving cancer treatment are high, the sequelae of which may include delayed treatment and infection. Larger studies on risk factors and interventions to prevent PIV failure in this population are needed; however, the use of secondary securements (such as non-sterile tape) to provide further securement to the primary PIV dressing is particularly important., Trial Registration: Study methods were registered prospectively with the Australian New Zealand Clinical Trials Registry on the 27 th March 2017 (ACTRN12617000438358); https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372191&isReview=true.

Purpose of Review: While ketamine is an established anesthetic, its role in the management of acute surgical pain is less certain. Therefore, a literature review is warranted to examine the role of ketamine in acute pain management., Recent Findings: The use of ketamine appears to be most efficacious in larger procedures that lead to increased systemic inflammation or extensive tissue damage. In addition, ketamine seems to be most successful when administered consistently throughout a procedure, such as by an infusion instead of a single bolus, in order to have adequate dosing for an analgesic effect. Therefore, the focus of research should be on procedures that lead to moderate to severe pain using frequent dosing to determine the most effective role of ketamine. Most importantly, the current literature shows that ketamine can be used as a successful part of multimodal anesthesia with few side effects in patients undergoing major procedures associated with moderate to severe pain.

Obstructive sleep apnea (OSA) is defined by intermittent and recurrent episodes of partial or complete obstruction of the upper airway during sleep. Intermittent and recurrent hypoxia/reoxygenation is the main pathophysiological mechanism of OSA. Its consequences include systemic inflammation, activation of the sympathetic nervous system, and release of oxygen free radicals. Infusion of intravenous (IV) lidocaine has anti-inflammatory, antihyperalgesic, and analgesic properties, supporting its use as an anesthetic adjuvant. Lidocaine can reduce nociception and/or cardiovascular responses to surgical stress, as well as postoperative pain and/or analgesic requirements. Because of the high prevalence of OSA in obese patients, the use of opioids to manage postoperative pain in that population is often accompanied by the development of adverse respiratory events, such as hypoventilation and hypoxemia. IV infusion of lidocaine has been shown to enhance the quality of early recovery after laparoscopic bariatric and upper airway surgery. However, limited evidence exists regarding its use in patients undergoing surgery for OSA. In addition, whether IV infusion of lidocaine can improve postoperative early recovery in patients undergoing surgery for OSA remains unknown. Therefore, we hypothesized that IV infusion of lidocaine can improve postoperative early recovery in patients undergoing surgery for OSA. Perioperative infusion also may be a promising analgesic adjunct to enhanced recovery after surgery (ERAS) protocols.

Background: Individuals meeting criteria for treatment-resistant depression (TRD) are differentially affected by high levels of anxiety symptoms., Aims: There is a need to identify the efficacy of novel rapid-onset treatments in adults with mood disorders and comorbid anxious-distress., Methods: This study included patients with treatment-resistant major depressive disorder (MDD) or bipolar disorder (BD) who were receiving intravenous (IV) ketamine treatment at a community-based clinic.Anxious-distress was proxied using items from the Quick Inventory of Depressive Symptomatology-Self Report 16-item (QIDS-SR 16 ) and Generalized Anxiety Disorder 7-item (GAD7) scales. The difference in QIDS-SR 16 total score, QIDS-SR 16 suicidal ideation (SI) item and GAD7 score were analyzed between groups., Results: A total of 209 adults with MDD ( n = 177) and BD ( n = 26) were included in this analysis. From this sample, 94 patients (mean = 45 ± 13.9 years) met the criteria for anxious-distress. Individuals meeting the criteria for anxious-distress exhibited a significantly greater reduction in QIDS-SR 16 total score following four infusions ( p = 0.02) when compared with patients not meeting the anxious-distress criteria. Both anxious-distressed and low-anxiety patients exhibited a significant reduction in SI ( p < 0.0001) following four infusions.Finally, there was a significantly greater reduction in anxiety symptoms in the anxious-distress group compared with the non-anxious distress group following three ( p = 0.02) and four infusions ( p < 0.001)., Conclusion: Patients with TRD and prominent anxiety receiving IV ketamine exhibited a significant reduction in depressive, SI and anxiety symptoms.

Chimpanzees are genetically and physiologically similar to humans. Several pharmacokinetic models of propofol are available and target controlled infusion (TCI) of propofol is established in humans, but not in chimpanzees. The purpose of this study was to investigate if human pharmacokinetic models can accurately predict propofol plasma concentration (Cp) in chimpanzees and if it is feasible to perform TCI in chimpanzees. Ten chimpanzees were anaesthetized for regular veterinary examinations. Propofol was used as an induction or maintenance agent. Blood samples were collected from a catheter in a cephalic vein at 3-7 time points between 1 and 100 min following the propofol bolus and/or infusion in five chimpanzees, or TCI in six chimpanzees. Cp was measured using high-performance liquid chromatography. The Marsh, Schnider and Eleveld human pharmacokinetic models were used to predict Cp for each case and we examined the predictive performances of these models using the Varvel criteria Median PE and Median APE. Median PE and Median APE for Marsh, Schnider and Eleveld models were within or close to the acceptable range. A human TCI pump was successfully maintained propofol Cp during general anesthesia in six chimpanzees. Human propofol pharmacokinetic models and TCI pumps can be applied in chimpanzees.

Background: The COVID-19 pandemic challenges multiple sclerosis services to be innovative in delivering infusible therapies. To reduce time in clinical settings, and potential staff or space losses, we implemented rapid infusion protocols for selected patients., Objective: To analyse the rate of infusion related reactions and patient experience of rapid infusions of natalizumab and ocrelizumab. To document time reduction patients spent in clinical settings during the COVID-19 pandemic., Methods: Patients with prior exposure to at least three natalizumab or two 300mg ocrelizumab infusions were approved for rapid protocols. A retrospective audit and survey were completed., Results: We analysed 269 rapid natalizumab infusions and 100 rapid ocrelizumab infusions. Infusion related reactions during the natalizumab or ocrelizumab infusions occurred in two patients (1.52%) and eight patients (8%), respectively. All infusion related reactions were mild to moderate and did not require infusion discontinuation. No infusion reactions occurred during the post-infusion observation. Patient experience was positive., Conclusion: Frequency or severity of infusion related reactions in rapid infusions were no different compared to published data. In the setting of COVID-19, pandemic rapid infusion protocols could potentially save hospital resources and limit patient exposure to a high-risk clinical setting while still maintaining ongoing treatment of multiple sclerosis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A totally implantable venous access port (TIVAP) is important in children who need intravenous infusion for a long time. A number of studies have shown methods for locating the tip of the TIVAP catheter. To explore whether transesophageal echocardiography (TEE) can be used to accurately locate the TIVAP catheter tip through a subclavian approach and to improve the rate of correct TIVAP catheter placement and reduce complications of TIVAP placement. In 36 children who needed TIVAP implantation surgery, we used real-time TEE guidance to place the catheter tip around the crista terminalis. In all children, chest X-rays were used to figure out whether the catheter tip as localized by TEE was within the T5-T7 segment. Then, we compared the length of the catheter calculated by the height formula and the actual catheter length applied under TEE guidance. The medical records, surgical details, nursing records, and recorded complications were collected during the follow-up. The success rate of TIVAP implantation was 100% in all enrolled patients and no hemopneumothorax or pinch-off syndrome occurred. Compared with TEE, chest X-ray showed a coincidence rate of 80.56% in correctly detecting the TIVAP catheter tip locate. The height-derived catheter length (11.0 [9.6, 11.8]) cm and the TEE-derived catheter length (10.0 [9.3, 10.8]) cm were significantly different (p < .001). TEE can be used to guide TIVAP catheter positioning through a left subclavian approach in children accurately and successfully and more accurate than chest X-ray and height calculation formula., (© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

The inability to maintain drug abstinence is often referred to as relapse and consists of a process by which an abstaining individual slips back into old behavioral patterns and substance use. Animal models of relapse have been developed over the last decades and significantly contributed to shed light on the neurobiological mechanisms underlying vulnerability to relapse. The most common procedure to study drug-seeking and relapse-like behavior in animals is the "extinction-reinstatement model." Originally elaborated by Pavlov and Skinner, the concepts of reinforced operant responding were applied to addiction research not before 1971 (Stretch et al., Can J Physiol Pharmacol 49:581-589, 1971), and the first report of a reinstatement animal model as it is now used worldwide was published only 10 years later (De Wit and Stewart, Psychopharmacology 75:134-143, 1981). According to the proposed model, opioids are typically self-administered intravenously, as humans do, and although rodents are most often employed in these studies, a variety of species including nonhuman primates, dogs, cats, and pigeons can be used. Several operant responses are available, depending on the species studied. For example, a lever press or a nose poke response typically is used for rodents, whereas a panel press response typically is used for nonhuman primates. In this chapter we describe a simple and easily reproducible protocol of heroin-seeking reinstatement in rats, which proved useful to study the neurobiological mechanisms underlying relapse to heroin and vulnerability factors enhancing the resumption of heroin-seeking behavior.

Importance: Few high-quality studies have clarified whether hypertonic saline is best administered as slow continuous infusion (SCI) therapy or rapid intermittent bolus (RIB) therapy for symptomatic severe hyponatremia., Objective: To compare the risk of overcorrection in RIB and SCI with hypertonic saline in patients with symptomatic hyponatremia., Design, Setting, and Participants: This prospective, investigator-initiated, multicenter, open-label, randomized clinical trial enrolled 178 patients older than 18 years with moderately severe to severe hyponatremia and glucose-corrected serum sodium (sNa) levels of 125 mmol/L or less. Recruitment took place from August 24, 2016, until August 21, 2019, across emergency departments and wards of 3 general hospitals in the Republic of Korea., Interventions: Either RIB or SCI of hypertonic saline, 3%, for 24 to 48 hours stratified by the severity of clinical symptoms., Main Outcome and Measures: The primary outcome was overcorrection at any given period, defined as increase in the sNa level by greater than 12 or 18 mmol/L within 24 or 48 hours, respectively. Secondary and post hoc outcomes included efficacy and safety of the treatment approaches. The sNa concentrations were measured every 6 hours for 2 days., Results: The 178 patients (mean [SD] age, 73.1 [12.2] years; 80 (44.9%) male; mean [SD] sNa concentrations, 118.2 [5.0] mmol/L) were randomly assigned to the RIB group (n = 87) or the SCI group (n = 91). Overcorrection occurred in 15 of 87 (17.2%) and 22 of 91 (24.2%) patients in the RIB and SCI groups, respectively (absolute risk difference, -6.9% [95% CI, -18.8% to 4.9%]; P = .26). The RIB group showed lower incidence of relowering treatment than the SCI group (36 of 87 [41.4%] vs 52 of 91 [57.1%] patients, respectively; absolute risk difference, -15.8% [95% CI, -30.3% to -1.3%]; P = .04; number needed to treat, 6.3). Groups did not differ in terms of efficacy in increasing sNa concentrations nor improving symptoms, but RIB, when compared with SCI, showed better efficacy in achieving target correction rate within 1 hour (intention-to-treat analysis: 28 of 87 (32.2%) vs 16 of 91 (17.6%) patients, respectively; absolute risk difference, 14.6% [95% CI, 2%-27.2%]; P = .02; number needed to treat, 6.8; per-protocol analysis: 21 of 72 (29.2%) vs 12 of 73 (16.4%) patients, respectively; absolute risk difference, 12.7% [95% CI, -0.8% to 26.2%]; P = .07). The statistical significance of the intention-to-treat and per-protocol analyses were similar for all outcomes except for achieving the target correction rate within 1 hour., Conclusions and Relevance: This randomized clinical trial found that both RIB and SIC therapies of hypertonic saline for treating hyponatremia were effective and safe, with no difference in the overcorrection risk. However, RIB had a lower incidence of therapeutic relowering treatment and tended to have a better efficacy in achieving sNa within 1 hour than SCI. RIB could be suggested as the preferred treatment of symptomatic hyponatremia, which is consistent with the current consensus guidelines., Trial Registration: ClinicalTrials.org Identifier: NCT02887469.

At our institution, tacrolimus is used as a second-line agent for the prevention and treatment of graft-versus-host-disease in the allogeneic hematopoietic stem cell transplantation (HSCT) unit after patients have experienced a serious or intolerable adverse event to cyclosporine. As per our standard practice, tacrolimus is administered via 2-h intermittent IV infusions (IIVs) every 12 h rather than continuous IV infusion. Shorter infusion times are cautioned due to concerns of higher rates of nephrotoxicity, neurotoxicity and infusion-related reactions, although there is a paucity of data to support this claim. Our primary objective was to evaluate the safety of a 2-h IIV of tacrolimus in an adult HSCT population. We retrospectively reviewed the charts of 104 patients who received tacrolimus by IIV (3574 doses; median = 22, range 1-158, IQR = 28) from 2002 to 2016. Primary outcomes collected include rates of nephrotoxicity, neurotoxicity and infusion-related reactions. One (0.9%) grade 2 infusion-related reaction occurred and resolved without discontinuation of tacrolimus. Of 16 incidences (13.6%) of nephrotoxicity, all but 10 (8.5%) cases resolved. Precipitating factors for nephrotoxicity unrelated to tacrolimus were identified in all 10 cases. There were 41 incidences (35%) of neurotoxicity, of which, 8 (6.8%) were considered serious. All neurotoxicity reverted to baseline or resolved completely. We propose that a 2-h IIV of tacrolimus is a safe method of administration in the adult HSCT setting.

Background: To compare the utility of a targeted smartphone application (TSPA) with a non-programmable calculator (NPC) when calculating fluid drip rates (FDR) and constant rate infusions (CRIs)., Methods: In a prospective randomised clinical study, 48 fourth-year veterinary students entered one of four parallel groups involving two mock scenarios: fentanyl calculation using an NPC followed by lidocaine calculation using a TSPA, fentanyl (TSPA) followed by lidocaine (NPC), lidocaine (NPC) followed by fentanyl (TSPA) or lidocaine (TSPA) followed by fentanyl (NPC). Students calculated volume of drug added to maintenance fluids and drops/second that correctly administered the drug dose and FDR. Time to completion was assessed using an analysis of variance. A Fisher's exact test assessed the effect of study period, scenario and device in the proportion of correct/incorrect answers., Results: Participants took longer to complete the scenarios in period 1 and 2 with the NPC (380.7±195.6 seconds and 488±154.8 seconds, respectively) than the TSPA (247.5±88.8 seconds and 224±94.2 seconds, respectively) (P<0.0031 and P<0.0001). Participants were more likely to complete the scenarios incorrectly with the NPC (n=32) when compared with the TSPA (n=7) (P<0.0001)., Conclusions: TSPAs are more efficient and accurate when calculating CRIs and FDR compared with conventional methods. Medical mathematics must be emphasised during the veterinary curriculum., Competing Interests: Competing interests: None declared., (© British Veterinary Association 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Hepatorenal syndrome (HRS) is a fatal complication of renal dysfunction associated with ascites, liver failure and advanced cirrhosis. Although the best option for long-term survival is liver transplantation, in the critical acute phase, vasoconstrictors are considered first-line supportive agents. Terlipressin is the most widely used vasoconstrictor globally but owing to its short elimination half-life, it is usually administered six hourly by slow intravenous bolus injection. This requires patients to remain in hospital, increasing hospital bed costs and affecting their quality of life. An alternative option for administration of terlipressin is as a continuous infusion using an elastomeric infusor device in the patient's home. However, stability data on terlipressin in elastomeric infusor devices is lacking. This research aimed to evaluate the stability of terlipressin reconstituted in infusor devices for up to 7 days at 2-8 °C and subsequently at 22.5 °C for 24 h, to mimic home storage and administration temperatures. We report that terlipressin was physically and chemically stable under these conditions; all reconstituted infusor concentrations retained above 90% of the original concentration over the test conditions. No colour change or precipitation in the solutions were evident.

Target-controlled infusion systems are increasingly used to administer intravenous anaesthetic drugs to achieve a user-specified plasma or effect-site target concentration. While several studies have investigated the ability of the underlying pharmacokinetic-dynamic models to predict plasma concentrations, there are no data on their performance in predicting drug concentrations in the human brain. We assessed the predictive performance of the Marsh propofol model and Minto remifentanil model for plasma and brain tissue concentrations. Plasma samples were obtained during neurosurgery from 38 patients, and brain tissue samples from nine patients. Propofol and remifentanil concentrations were measured using gas chromatography mass spectrometry and liquid chromatography tandem mass spectrometry. Data were analysed from the nine patients in whom both plasma and brain samples were simultaneously obtained. For the Minto model (five patients), the median performance error was 72% for plasma and -14% for brain tissue concentration predictions. The model tended to underestimate plasma remifentanil concentrations, and to overestimate brain tissue remifentanil concentrations. For the Marsh model (five patients), the median prediction errors for plasma and brain tissue concentrations were 12% and 81%, respectively. However, when the data from all blood propofol assays (36 patients) were analysed, the median prediction error was 11%, with overprediction in 15 (42%) patients and underprediction in 21 (58%). These findings confirm earlier reports demonstrating inaccuracy for commonly used pharmacokinetic-dynamic models for plasma concentrations and extend these findings to the prediction of effect-site concentrations., (© 2020 Association of Anaesthetists.)