Real-Time Analytical Solutions as Series Formulas and Heaviside off/on Switch Functions for Multiple Intermittent Intravenous Infusions in One- and Two-Compartment Models

Pharmacokinetic compartment models are the only models that can extract pharmacokinetic parameters from data collected in clinical studies but their estimates lack accuracy, explanations and physiological significance. The objective of this work was to develop particular solutions to drug concentration and AUC in the form of mathematical series and Heaviside functions for repetitive intermittent infusions in the one- and two-compartment models, as a function of dose number and total time using differential calculus. It was demonstrated that the central and peripheral compartment volumes determined from regression analysis of the aminoglycoside antibiotic Sisomicin concentration in plasma represent the actual physiological body fluid volumes accessible by the drug. The drug peak time and peak concentration in the peripheral compartment were also calculated as a function of dose number. It is also shown that the time of intercompartmental momentary distribution equilibrium can be used to determine the drug’s apparent volume of distribution within any dosing interval in multi-compartment models. These estimates were used to carry out simulations of plasma drug concentration with time in the one-compartment model. In conclusion, the two-compartment open mammillary pharmacokinetic model was fully explained for the aminoglycoside antibiotic sisomicin through the new concept of the apparent volume of distribution.

Application of Patient Simulators Combined with Internet plus Scenario Simulation Teaching Models on Intravenous Infusion Nursing Education in China

Objective: To explore the effectiveness of applying patient simulators combined with Internet Plus scenario simulation teaching models on intravenous (IV) infusion nursing education, and to provide scientific evidence for the implementation of advanced teaching models in future nursing education. Methods: Enrolled 60 nurses who took the IV infusion therapy training program in our hospital from January 2022 to December 2023 for research. 30 nurses who were trained in traditional teaching models from January to December 2022 were selected as the control group, and 30 nurses who were trained with simulation-based teaching models with methods including simulated patients, internet, online meetings which can be replayed and scenario simulation, etc. from January to December 2023 were selected as the experimental group. Evaluated the learning outcomes based on the Competency Inventory for Nursing Students (CINS), Problem-Solving Inventory (PSI), comprehensive learning ability, scientific research ability, and proficiency in the theoretical knowledge and practical skills of IV infusion therapy. Nursing quality, the incidence of IV infusion therapy complications and nurse satisfaction with different teaching models were also measured. Results: The scientific research ability, PSI scores, CINS scores, and comprehensive learning ability of the experimental group were better than those of the control group (P 0.05), and their assessment results of practical skills, nursing quality of IV infusion therapy during training, and satisfaction with teaching models were all better than those of the control group with statistical significance (P < 0.05). The incidence of IV infusion therapy complications in the experimental group was lower than that in the control group, indicating statistical significance (P < 0.05). Conclusions: Teaching models based on patient simulators combined with Internet Plus scenario simulation enable nursing students to learn more directly and practice at any time and in any place, and can improve their proficiency in IV infusion theoretical knowledge and skills (e.g. PICC catheterization), core competencies, problem-solving ability, comprehensive learning ability, scientific research ability and the ability to deal with complicated cases. Also, it helps provide high-quality nursing education, improve the nursing quality of IV therapy, reduce the incidence of related complications, and ensure the safety of patients with IV therapy.

Research on the Causes and Nursing Interventions of Extravasation During Intravenous Infusion

Intravenous infusion,a common clinical drug treatment method,is widely used in the treatment of various diseases.Due to the invasive nature of puncture during intravenous infusion,patients may inevitably experience resistance and tension when facing nursing staff performing infusion procedures.Additionally,the complexity of the nursing staff’s work and the impact of the infusion therapy environment can exacerbate the tension between nurses and patients,leading to risks such as drug leakage and needlestick injuries.This article focuses on the factors influencing extravasation during intravenous infusion and elaborates on how high-quality nursing interventions can reduce the incidence of adverse events during intravenous infusion.These interventions aim to improve patient satisfaction with intravenous infusion nursing care and ensure the safety of intravenous infusion procedures.

An iterative Approach to Deriving Drug Infusions

A simple iterative process can be used to generate intravenous drug infusion profiles. It overcomes limitations in deriving compartmental pharmacokinetic models and has application to evaluation of new drugs and to clinical practice.

Double pigtail catheter reduction for seriously displaced intravenous infusion port catheter:A case report

BACKGROUND Implanted intravenous infusion port(TIAP)is mainly used for patients who need central venous infusion and poor peripheral vascular conditions.With the advantages of easy to carry,long maintenance cycle,few complications and excellent quality of life,it has been widely used in the fields of malignant tumor chemotherapy,parenteral nutrition support and repeated blood collection.Implanted intravenous infusion port(IVAP)dislocation can have significant complications if not recognised and reinstated immediately.CASE SUMMARY A 24-year-old man was treated with adjuvant chemotherapy for osteosarcoma.Severe displacement of IVAP catheter was found by chest X-ray examination.The IVAP cannot be used normally.Therefore,we conducted an emergency procedure to reset the catheter through double pigtail catheters,the operation was successful and the infusion port was restored.CONCLUSION When IVAP catheter displacement cannot be reset by conventional techniques,two pigtail catheters can be successfully used instead.

Optimization of the intravenous infusion workflow in the isolation ward for patients with coronavirus disease 2019

Objective:This study aimed to evaluate the effect of optimization of the intravenous infusion workflow in isolation wards for patients with coronavirus disease 2019.Methods:The infusion management group optimized the intravenous infusion workflow based on Hamer's Process Reengineering Theory and applied it to the treatment of patients with coronavirus disease 2019.The work efficiency,patients'satisfaction and economic indicators before and after optimization were compared.Results:After the infusion workflow was optimized,average times for preparation drugs and intravenous admixture,and patients'waiting time decreased from 4.84 min,4.03 min,and 34.33 min to 3.50 min,2.60 min,and 30.87 min,respectively,patients'satisfaction increased from 66.7%to 93.3%,and the cost of personal protective equipment(PPE)decreased from 46.67 sets and 186.6 CNY per day to 36.17 sets and 144.6 CNY,with statistical significance.Conclusion:The optimization of the intravenous infusion workflow can effectively decrease the cost of PPE while improving the efficiency of infusion and patients'satisfaction.

BLOOD PRESSURE CHANGES OF ELDERLY HYPERTENSIVE PATIENTS DURING DENTAL EXTRACTION UNDER SEDATION WITH CONTINUOUS INTRAVENOUS INFUSION OF MIDAZOLAM

Objective To evaluate the changes in blood pressure (BP) of elderly hypertensive patients having dental extraction under sedation with continuous intravenous infusion of midazolam. Methods One hundred elderly hypertensive patients undergoing dental extraction were recruited for this single-blind, randomized, controlled study. Patients in intervention group (n=50) were given midazolam dissolved in glucose solution and patients in control group (n=50) were given glucose solution only with communication technique. Systolic BP (SBP) and diastolic BP (DBP) were recorded in five time points. Results Under basal conditions, intervention group did not show significant difference in BP compared with control group. Before sedation, mean values of SBP and DBP (especially SBP) significantly increased compared with basal conditions in both groups (P<0.05). During dental extraction sessions, mean values of BP in intervention group significantly decreased than control group (P<0.05), but coefficient of variation did show significant difference in both groups. Conclusion Continuous intravenous infusion of midazolam has been proved to be very successful in controlling BP of elderly patients having dental extraction.

The Optimum Dosage Regimen of Intravenous Infusion for Drugs Obeying Parallel First-order and Michaelis-Menten Elimination Kinetics

For drugs obeying parallel first-order and Michaelis-Menten elimination kinetics,mathematical analysis concerning the optimum dosage regimen of intravenous infusion is conducted and following equations are derived:where Xo is the intravenous loading dose,Cb the plasma concentration level desired in clinical therapy,V the apparent distribution volume,k0 the rate constant of intravenouns infusion,K the first－order elimination rate constant,Vm the theoretical maximum rate of the Michaelis－Menten elimination process,Km the Michaelis constant.From this dosage regimen,plasma level maintains a constant Cb during the administration period.When K=0 the dosage regimen above is also suitable for drugs obeying Michaelis-Menten elimination kinetics.

Continuous intravenous infusion of recombinant human endostatin using infusion pump plus chemotherapy in non-small cell lung cancer

BACKGROUND Lung cancer is one of the deadliest cancers in the world with the highest incidence and mortality rate among all cancers.Non-small cell lung cancer(NSCLC)accounts for approximately 80%of primary lung cancer.However,efficacy and safety of the current regimens for NSCLC is unsatisfactory.Therefore,there has been an increasing urgency for development of potential therapeutic therapies for NSCLC.AIM To investigate the therapeutic outcomes and safety of continuous intravenous infusion of recombinant human endostatin(Rh-endostain)using an infusion pump in retreated advanced NSCLC.METHODS Patients with retreated advanced NSCLC who were admitted to Zhejiang Provincial People's Hospital from October 2017 to April 2019 were recruited.These patients received continuous intravenous infusion of Rh-endostain using an infusion pump.Objective response rate(ORR),clinical benefit rate(CBR),median progression-free survival(mPFS),and incidences of adverse events(AEs)were analyzed after treatment.RESULTS A total of 45 patients with retreated advanced NSCLC were included,and all of them were evaluated.In these patients,ORR was 22.2%,CBR was 84.4%,and mPFS was 5.3 mo.The following AEs were observed,decreased hemoglobin(34 cases,75.6%),nausea/vomiting(32 cases,71.1%),elevated transaminase(24 cases,53.3%),leukopenia(16 cases,35.6%),thrombocytopenia(14 cases,31.1%),and constipation(1 case,3.4%).None of the patients had leukopenia,nausea/vomiting,and constipation of grade III and above.CONCLUSION The patients showed improved adherence to 5-d continuous intravenous infusion of Rh-endostain using an infusion pump.Favorable efficacy and safety of this treatment regimen were achieved in retreated advanced NSCLC.

The research progress in external application of physic liquor exosmosis in mannitol intravenous infusion

Mannitol is the first choice of clinical dehydrating agent, which can alleviate brain edema and reduce intracranial pressure. As a hypertonic solution, it has strong vascular irritation. Moreover, fast infusion speed is required, which can be related to pain, physic liquor exomosis and some other side effects. Regarding of the physic liquor exosmosis in mannitol intravenous infusion, this paper reviewed the research progress of different external application treatment, and provided references for clinical treatment of physic liquor exosmosis in mannitol intravenous infusion.

Intravenous Suitability Studies of Commonly Used Oxacillin Sodium Solutions in the Accufuser^(■) Infusion Device

Our study compares two commonly used solutions of oxacillin sodium, 5.0 mg/mL in either 0.9% sodium chloride (NS) or 5% dextrose water (D5W), for their continued suitability for IV usage, and stability of active compound over time, when stored at two different controlled temperatures for six weeks. Both solutions were stored in an intravenous infusion device commercially available as Accufuser? and kept at a continuously maintained temperature of either 4 ± 2?C (CT) or 25 ± 2?C (RT). Suitability for IV administration was assessed by measuring changes in macrographical transparency and pH over time, and drug stability was assessed by measuring changes in oxacillin concentration over time using high-performance liquid chromatography (HPLC). After 6 weeks, concentrations of oxacillin were unchanged in the CT solutions, while both RT solutions showed significant decreases in the concentration of oxacillin after only two weeks. Final concentration compared to starting concentrations after 6 weeks at RT, were 36.57% in NS, while virtually no oxacillin was detectable in D5W. Also pH measurements showed a slight decrement at 2 weeks with RT, and at 6 weeks, there was a significant change in pH in both NS and D5W at RT. There was no significant change in color, transparency or appearance after 6 weeks in any of the oxacillin solutions stored in the Accufuser? infusion device. In summary, two commonly used IV solutions for oxacillin administration(5 mg/mL in NS or D5W) stored ready to use in the Accufuser? showed significant changes over time when maintained at RT, that would make the solutions inappropriate for therapeutic use. Both solutions when maintained in CT were not significantly altered and continued to be appropriate in pH and drug concentration for IV therapy. This suggests that ready-to-use solutions of oxacillin sodium in the Accufuser? infusion device can be kept at CT for up to 6 weeks safely but should not be stored at RT due to loss of potency and changes in pH.

Study of concentration of vancomycin in serum during continuous intravenous infusion

Objective Pharmacokinetics/pharmacodynamics of vancomycin in serum were studied after continuous infusion. Methods Twelve neurosurgical postoperative patients with ventricular drainage were enrolled in this study. In each patient,a loading dose of vancomycin of 0. 5 g was administered for 1 h followed

Intravenous administration of glutathione protects parenchymal and non-parenchymal liver cells against reperfusion injury following rat liver transplantation

AIM:To investigate the effects of intravenous administration of the antioxidant glutathione (GSH) on reperfusion injury following liver transplantation. METHODS:Livers of male Lewis rats were transplanted after 24 h of hypothermic preservation in University of Wisconsin solution in a syngeneic setting.During a 2-h reperfusion period either saline (controls,n=8) or GSH (50 or 100 μmol/(h·kg),n=5 each) was continuously administered via the jugular vein. RESULTS:Two hours after starting reperfusion plasma ALT increased to 1 457±281 U/L (mean±SE) in controls but to only 908±187 U/L (P<0.05) in animals treated with 100 μmol GSH/(h·kg).No protection was conveyed by 50μmol GSH/(h·kg).Cytoprotection was confirmed by morphological findings on electron microscopy:GSH treatment prevented detachment of sinusoidal endothelial cells (SECs) as well as loss of microvilli and mitochondrial swelling of hepatocytes.Accordingly,postischemic bile flow increased 2-fold.Intravital fluorescence microscopy revealed a nearly complete restoration of sinusoidal blood flow and a significant reduction of leukocyte adherence to sinusoids and postsinusoidal venules.Following infusion of 50μmol and 100 μmol GSH/(h·kg),plasma GSH increased to 65±7 mol/L and 97±18 mol/L,but to only 20±3 mol/L in untreated recipients. Furthermore,plasma glutathione disulfide (GSSG) increased to 7.5±1.0 mol/L in animals treated with 100μmol/(h·kg) GSH but infusion of 50μmol GSH/(h·kg) did not raise levels of untreated controls (1.8±0.5 mol/L vs 2.2±0.2 mol/L). CONCLUSION:Plasma GSH levels above a critical level may act as a “sink” for ROS produced in the hepatic vasculature during reperfusion of liver grafts.Therefore,GSH can be considered a candidate antioxidant for the Drevention of reperfusion injury after liver transplantation,in particular since it has a low toxicity in humans.

Drop Factor and Infusion Dose Calculation Discrepancies among Nurses in Southern Nigeria: A Cross-Sectional Study

Nurses must deliver infusions as prescribed since too slow or fast a dose could be deleterious to patients. Nurses experience challenges with infusion dose calculations, making them vulnerable to errors. The research team examined drop factor and infusion dose calculation discrepancies among nurses in southern Nigeria. Five university teaching hospitals were involved in this cross-sectional study conducted in 2019. To establish the drop factor of commonly available macro drip sets, the team randomly sourced 25 macro drip sets from the hospitals’ pharmacies. A sample of 291 nurses was selected using a proportionate random sampling technique. The team collected data using the Adult Infusion Dose Calculation Quiz and analyzed it at a 5% significance level. Twenty (80%) of the sampled macro drip sets displayed a drop factor value of 20 drops per milliliter (gtt/ml) on their packaging. When measured experimentally, 25 (100%) of the macro drip sets delivered exactly 20 gtt/ml. Only 36 (12.4%) respondents calculated macro drip infusion doses using the correct drop factor of 20 gtt/ml. Non-attendance of infusion administration training updates significantly increased the risk of error by 38% (p ≤ 0.001). In conclusion, the drop factor of macro drip sets used in southern Nigeria is 20 gtt/ml;nurses were prone to infusing patients at a lower dose than prescribed. Special training in infusion therapy might remedy this concern.

Therapeutic methods for diarrhea in children

DEFINITIONAcute diarrhoea is defined as passage of loose or waterystools at least three times in a 24 h period.When loosestools contain blood,it is called bloody diarrhoea(dysentery).It is the consistency of the stools which ismost important rather than the frequency.Breast-fed babiesoften pass'pasty'stools frequently which is not diarrhoea.The raother can often tell accurately whether child hasdiarrhoea or not.

Cerebrospinal Fluid Pharmacokinetics of Intravenous High Dose-Methotrexate

Objective： To study the cerebrospinal fluid pharmacokinetics of intravenously administered high dose-methotrexate （HD-MTX） and provide a solid fundament for clinical practice. Methods： MTX at a high dose ranging from 1.0 to 3.0 g per course was intravenously administered to 30 patients with malignant tumors. Blood and CSF samples were consecutively collected up to 36 h after the initiation of infusion （6 h）. MTX concentrations were measured by using a reversed phase high-performance liquid chromatography （RP-HPLC） assay. Results： CSF MTX concentrations were （1.65±1.52）×10^-6, （4.3±3.34）× 10^-7, （1.46±1.10）×10^-7 and （3.19±4.38）×10^-8 mol/L, respectively, at 0, 6, 12 and 24 h post infusion, and became undetectable at 36 h post infusion. The concentration-time curve of CSF MTX closely resembled that of the plasma MTX and fitted with the following linear regression equation： Y=0.057 97＋0.010 82X （Y： CSF MTX concentration, X： Plasma MTX concentration, r=0.8357）. Conclusion： CSF MTX was metabolized in a linear two-compartment model. Additionally, pharmacokinetic analysis of MTX levels indicated a positive correlation between CSF MTX and plasma MTX levels.

Stability Test of Ampicillin Sodium Solutions in the Accufuser^(■) Elastomeric Infusion Device Using HPLC-UV Method

The stabilities of two kinds of solutions (30 mg/mL) of Ampicillin sodium in 0.9% NaCl in water (NS, normal saline) and in sterile water (SW) in the intravenous elastomeric infusion device (Accufuser&#174) were evaluated based on recommended solutions and storage periods. The injectable NS- and SW-Ampicillin solutions in the Accufuser&#174 device were stored and evaluated at controlled temperature (room temperature, 25℃ ± 2℃ and cold temperature, 4℃ ± 2℃) during 7 days. Effects of the periods of storage (from 0 to 7 days) and the temperatures of storage (RT and CT) on the physico-chemical appearances and concentrations of active compounds were determined. The visual clarity, pH, and concentrations of Ampicillin were determined by stability-indicating high-performance liquid chromatography (HPLC)-ultraviolet (UV) detection. The results showed that the amount of Ampicillin in studied solutions gradually decreased with time. The Ampicillin in NS, which was stored in CT, was relatively stable, retaining 94% of its original amount up to 7 days. The solution that showed least stability was Ampicillin in SW, which was stored in RT, retaining 80% of its original amount. Generally, solutions that were stored in CT were more stable than the solutions that were stored in RT. No significant changes in physical appearance or color of the solutions were observed during the study. Particles were not detected in any solution samples. In summary, two kinds of solutions of Ampicillin sodium, in NS and SW, showed different chemical stabilities with time in intravenous infusion device without any significant physical changes and retained about 94% vs 89% and 83% vs 80% of initial concentrations after 7 days in CT and RT, respectively. We suggest that 30 mg/mL of Ampicillin sodium in NS solution in an Accufuser&#174 infusion device which is stored in CT can be applicable for 7 days in clinical situations.

Simulation of the Resin Film Infusion Process Based on the Finite Element Method

A physically accurate and computationally effective pure finite element method （FEM） was developed to simulate the isothermal resin infusing process. The FEM was based on conservation of resin muss at and instant of time and was objective of resin film infusion （RFI） fiber impregnation and mold filling . The developed computer code was able to simulate the resin infusing visually. A numerical example presented here demonstrated that compared with traditional finite element/ control-volume （FE/CV）, and FEM was physically accurate and computationally efficient.

Efficacy of continuous gastric artery infusion chemotherapy in relieving digestive obstruction in advanced gastric cancer

BACKGROUND Obstruction or fullness after feeding is common in gastric cancer(GC)patients,affecting their nutritional status and quality of life.Patients with digestive obstruction are generally in a more advanced stage.Existing methods,including palliative gastrectomy,gastrojejunostomy,endoluminal stent,jejunal nutrition tube and intravenous chemotherapy,have limitations in treating these symptoms.AIM To analyze the efficacy of continuous gastric artery infusion chemotherapy(cGAIC)in relieving digestive obstruction in patients with advanced GC.METHODS This study was a retrospective study.Twenty-nine patients with digestive obstruction of advanced GC who underwent at least one cycle of treatment were reviewed at The Second Affiliated Hospital of Zhejiang University School of Medicine.The oxaliplatin-based intra-arterial infusion regimen was applied in all patients.Mild systemic chemotherapy was used in combination with local treatment.The clinical response was evaluated by contrast-enhanced computed tomography using Response Evaluation Criteria In Solid Tumors(RECIST)criteria.Digestive tract symptoms and toxic effects were analyzed regularly.A comparison of the Karnofsky Performance Status(KPS)score and Stooler’s Dysphagia Score before and after therapy was made.Univariate survival analysis and multivariate survival analysis were also performed to explore the key factors affecting patient survival.RESULTS All patients finished cGAIC successfully without microcatheter displacement,as confirmed by arteriography.The median follow-up time was 24 mo(95%CI:20.24-27.76 mo).The overall response rate was 89.7%after cGAIC according to the RECIST criteria.The postoperative Stooler’s Dysphagia Score was significantly improved.Twentytwo(75.9%)of the 29 patients experienced relief of digestive obstruction after the first two cycles,and 13(44.8%)initially unresectable patients were then considered radically resectable.The median overall survival time(mOS)was 16 mo(95%CI:9.32-22.68 mo).Patients who received radical surgery had a significantly longer mOS than other patients(P value<0.001).Multivariate Cox regression analysis indicated that radical resection after cGAIC,intravenous chemotherapy after cGAIC,and immunotherapy after cGAIC were independent predictors of mOS.None of the patients stopped treatment because of adverse events.CONCLUSION cGAIC was effective and safe in relieving digestive obstruction in advanced GC,and it could improve surgical conversion possibility and survival time.