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.

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.

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.

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.

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.

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.

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

Lidocaine in fibromyalgia:A systematic review

BACKGROUND Fibromyalgia(FM)patients are treated with antidepressants,and in most cases,these drugs lose efficacy or present side effects.Intravenous lidocaine(IL)is an anesthetic drug used in some FM trials.AIM To systematically review the safety and efficacy of IL in FM patients.METHODS To systematically search PubMed for articles in English,Spanish,and Japanese with English Abstracts on FM and lidocaine between 1966 and February 2021.This study was registered at PROSPERO.RESULTS We found only ten articles published in this field,with a total of 461 patients.Females predominated varying from 95%to 100%in the studies.Age varied from 40.9 to 55 years old.Disease duration varied from 1 mo to 6.4 years.Lidocaine dose varied from 2 to 7.5 mg/kg via intravenous infusion.Follow-up period varied from 65.7 to 90 days.Regarding outcomes,most studies used the visual analogue scale(VAS)for pain;before short-term lidocaine administration,VAS was between 6.1 and 8.1 and after treatment was between 1.7 and 4.5 mm.Concerning long term lidocaine,VAS varied from 30%to 35.4%after lidocaine infusion.Side effects were observed in 0%to 39.6%of cases,they were usually mild or moderate.CONCLUSION This study demonstrates the short-term effectiveness and safety of intravenous lidocaine in FM patients.However,more studies,including long-term follow-up,are still needed.

Removal of"ruptured"pulmonary artery infusion port catheter by pigtail catheter combined with gooseneck trap:A case report

BACKGROUND Implanted intravenous infusion port(IVAP)is indicated for patients undergoing chemotherapy,total parenteral nutrition and long-term antibiotic treatment.Among their complications,the rupture and migration of the catheter of an IVAP via internal jugular vein represents a very rare but potentially severe condition.CASE SUMMARY A 43-year-old woman was identified with a spontaneous fracture and migration of catheter of an IVAP via right internal jugular vein after adjuvant chemotherapy for left breast cancer.A computed tomography showed the fractured catheter of the IVAP in the pulmonary artery.Therefore,we conducted an emergency procedure to remove the catheter fragment by a pigtail catheter combined with a gooseneck trap.CONCLUSION When the fractured catheter of an IVAP was detected,the special shape of the pigtail catheter in combination with the gooseneck trap successfully facilitated the removal of the dislodged catheter.

A Clinical Investigation on Garlicin Injectio for Treatment of Unstable Angina Pectoris and Its Actions on Plasma Endothelin and Blood Sugar Levels

To investigate the therapeutic effects and mechanisms of garlicin for treatment of unstable angina pectoris (UAP), garlicin injectio was intravenously dripped 60 mg/day in 34 cases for 10 days. Nitroglycerine was used in 21 cases of the control group. The results showed that the total effective rates in improving symptoms and electrocardiogram after garlicin treatment were respectively 82% and 62%, and that the plasma endothelin and blood sugar levels were markedly lowered in cases with hyperglycemia.

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.

Prolonged Infusion of Low Dose Gemcitabine in Advanced Pancreatic Carcinoma

Background: Gemcitabine was established as a monotherapy or in combination for locally advanced or metastatic pancreatic carcinoma. Aim: This study aimed to evaluate the efficacy of the low-dose gemcitabine over 6-hour infusion in patients with advanced pancreatic adenocarcinoma. Methods: 26 patients with locally advanced or metastatic pancreatic carcinoma were recruited into the study from December 2013 to October 2014. Patients received the treatment in Clinical Oncology Department, Sohag University, and Medical Oncology Department, Assiut University. Patients received low-dose gemcitabine (250 mg/m2) over 6-hour infusion, weekly for seven weeks and then on days 1 and 8 every 3 weeks till unacceptable toxicity or progression of the disease. Results: Twenty-six patients were enrolled in this study. After starting 7 weeks of treatment, the disease control rate was 38.5% in the form of complete response in 3.8% of patients, partial response in 26.9%, and stationary response in 7.7%. However, disease progression occurred in 61.5%. Progression-free survivals were 65.38%, 23.07%, 7.69% and 3.84% after 3, 6, 9 and 12 months, respectively. Also, overall survivals at 3-month, 6-month, 9-month, and 12-month were 61.53%, 42.30%, 23.07%, and 7.69%, respectively. Conclusion: Prolonged infusion of low dose gemcitabine is a tolerable and a good option in locally advanced or metastatic pancreatic carcinoma. There may be a benefit of that protocol in patients with bad performance status. More clinical trials with a combination of other cytotoxic agents or target therapy are needed to get better survival and lesser toxicity.

Stability of Nafcillin Sodium Solutions in the Accufuser^(■) Elastomeric Infusion Device

The aim of this study was to investigate the stabilities of two kinds of solutions of nafcillin sodium (2.5 mg/mL) in 0.9% sodium chloride solution (NS, normal saline) and in injectable 5% dextrose water (D5W) in the intravenous elastomeric infusion device (Accufuser&#174) based on recommended solutions and storage periods. The injectable nafcillin solutions (NS- and D5W-nafcillin) in the Accufuser&#174?device were stored and evaluated at controlled temperatures (room temperature, RT, 5℃ ± 2℃ and cold temperature, CT, 4℃ ± 2℃) during 6 weeks. Effects of the periods of storage (from 0 to 6 weeks) and the temperatures of storage (RT and CT) on the physicochemical appearances and concentrations of active compounds were determined. The visual clarity, pH, and concentrations of nafcillin sodium were determined by stability-indicating high-performance liquid chromatography (HPLC)-ultraviolet (UV) detection. The results showed that in NS and D5W solutions, the amount of nafcillin slightly changed and remained 92.66% and 97.30% of their initial amounts at CT during 6 weeks, respectively. On the other hand, in NS and D5W solutions at RT, the amount significantly decreased with time and reached 27.66% and 31.97% of their initial amounts during 4 weeks, respectively. Slight decrement of pH was observed in CT storage while significant change was observed in the RT storage. Moreover, in CT, no significant changes in physical appearances and colors of the solutions were observed during the study. However, the solutions changed into yellowish color and some particles were detected in both kinds of nafcillin solutions (NS and D5W) after 1.5 weeks in RT conditions. To sum up, under CT two kinds of nafcillin sodium solutions (NS and D5W) were stable with time in Accufuser&#174?without any significant physical changes and retained almost all of the initial concentrations up to 6 weeks. However, the solutions were not stable in RT storage. We suggest that nafcillin sodium solutions in an Accufuser&#174?should be preferentially diluted in NS and D5W while storing in CT condition.

Influence of different intravenous injection containers on residual liquid volume and its economic impact

The objective of this study was to evaluate the influence of infusion container design on the volume of residual drug solution following use in a clinical setting. 0.9% （w/v） NaCl infusion solution containers （5 types, each of three capacities： 100 mL, 250 mL and 500 mL） following clinical use for in-patients at Peking University Third Hospital were collected during Sept. and Oct. 2007. The volume of residual drug solution was determined. Hospital pharmacy records were used to determine the potential economic implications of discarding residual drug solutions. The mean residual volumes ranged from 0.38 mL to 4.80 mL and, in general, residual volume increased with increasing container capacity. The residual volumes for one type of double-port soft bag were significantly lower than the residual volumes for all other containers of the same capacity （P〈0.05）, including glass and semi-rigid plastic bottles. Highest residual volumes were observed for the single-port soft bag. Estimates of the value of discarded residual drug solution ranged from approximately US $15,000 to US $150,000 per annum in our hospital. Infusion container design has a major influence on residual drug solution volumes following intravenous infusion. Appropriate choice of bag design remains an important consideration for the economics and efficacy of infusion treatment in Chinese hospitals.

Primary intracoronary stenting in comparison with intravenous rt-PA thrombolysis plus rescue intracoronary intervention in patients with acute myocardial infarction

OBJECTIVES: To compare primary stenting in the infarct-related coronary artery with intravenous rt-PA therapy plus rescue intracoronary stenting. METHODS: Ninety-eight patients with a first acute myocardial infarction (AMI) were randomly treated with primary intracoronary stenting (primary stenting group) or with intravenous rt-PA therapy plus rescue intracoronary stenting (thrombolysis plus stenting group). Thrombolysis in myocardial infarction (TIMI) flow grade was assessed by angiography in emergency, and cardiac function (left ventricular ejection fraction, LVEF) was calculated by echocardiography before discharge between the two groups. RESULTS: There were 47 patients (97.91%) in primary stenting group and 50 patients (100%) in thrombolysis plus stenting group had achieved TIMI grade 2 - 3 flow after the procedure. But the former had more cases (93.8%) of TIMI 3 flow than that of latter (60.0%, P = 0.0001). There was no difference between the two groups in cardiac events during hospitalization. But the patients in primary stenting group had better cardiac function (LVEF 0.62 +/- 0.14 vs. 0.50 +/- 0.12, respectively, P = 0.0001) between the two groups. CONCLUSIONS: Primary intracoronary stenting may improve myocardial reperfusion in emergency and inhibit the decline of cardiac function after AMI in comparison with intravenous rt-PA thrombolysis plus rescue intracoronary stenting.

Determination of ifenprodil by LC–MS/MS and its application to a pharmacokinetic study in healthy Chinese volunteers

This paper reports the development and validation of an assay for ifenprodil based on liquid chromatography–tandem mass spectrometry(LC–MS/MS)and its application to a pharmacokinetic study involving single and multiple intravenous infusions to healthy Chinese volunteers.After sample preparation of plasma by liquid–liquid extraction with ethyl acetate,the analyte and internal standard,urapidil,were separated by reversed phase chromatography in a run time of 4 min and detected by positive ion electrospray ionization followed by multiple reaction monitoring of the precursor-to-product ion transitions at m/z 326.2-308.1 for ifenprodil and m/z 388.4-205.3 for IS.The assay was linear in the concentration range 0.2–50.0 ng/mL with recovery 476.4%.In the pharmacokinetic study of single intravenous infusions of 5,10 and 15 mg ifenprodil,peak plasma concentrations and areas under the plasma concentration–time curve were both linearly related to dose.In the pharmacokinetic study of multiple once daily intravenous infusions of 10 mg ifenprodil for 7 days,pharmacokinetic parameters were similar to those after the single dose showing that ifenprodil does not accumulate on repeated administration.