Physical compatibility of sulbactam/durlobactam with select intravenous drugs during simulated Y-site administration.

PURPOSE: Sulbactam/durlobactam is a combination antibiotic designed to target Acinetobacter baumannii, including carbapenem-resistant and multidrug-resistant strains. The objective of this study was to determine the physical compatibility of sulbactam/durlobactam solution during simulated Y-site administration with 95 intravenous (IV) drugs. METHODS: Vials of sulbactam/durlobactam solution were diluted in 0.9% sodium chloride injection to a volume of 100 mL (the final concentration of both drugs was 15 mg/mL). All other IV drugs were reconstituted according to the manufacturer's recommendations and diluted with 0.9% sodium chloride injection to the upper range of concentrations used clinically or tested undiluted as intended for administration. Y-site conditions were simulated by mixing 5 mL of sulbactam/durlobactam with 5 mL of the tested drug solutions in a 1:1 ratio. Solutions were inspected for physical characteristics (clarity, color, and Tyndall effect), turbidity, and pH changes before admixture, immediately post admixture, and over 4 hours. Incompatibility was defined as any observed precipitation, significant color change, positive Tyndall test, or turbidity change of ≥0.5 nephelometric turbidity unit during the observation period. RESULTS: Sulbactam/durlobactam was physically compatible with 38 out of 42 antimicrobials tested (90.5%) and compatible overall with 86 of 95 drugs tested (90.5%). Incompatibility was observed with albumin, amiodarone hydrochloride, ceftaroline fosamil, ciprofloxacin, daptomycin, levofloxacin, phenytoin sodium, vecuronium, and propofol. CONCLUSION: The Y-site compatibility of sulbactam/durlobactam with 95 IV drugs was described. These compatibility data will assist pharmacists and nurses to safely coordinate administration of IV medications with sulbactam/durlobactam.

Compatibility of calcium chloride with milrinone, epinephrine, vasopressin, and heparin via in vitro testing and simulated Y-site administration.

PURPOSE: The purpose of this study is to evaluate calcium chloride (CaCl) compatibility with commercially available and extemporaneously compounded milrinone, vasopressin, epinephrine, and heparin. This report describes 2 clinical scenarios in which patients experienced intravenous catheter precipitation when receiving multiple continuous infusions, including CaCl, and the results of an in vitro simulation of those scenarios. The hypothesis was that one or a combination of the medications would precipitate with CaCl. METHODS: CaCl compatibility was tested in 3 stages to simulate clinical situations where line precipitation occurred. Multiple tests were conducted in each stage to determine if precipitation had occurred, including visual assessment, absorbance measurement at 650 nm, and pH measurement. First, milrinone, vasopressin, epinephrine, and heparin were mixed pairwise with CaCl in a test tube. Second, the medications were mixed in different combinations deemed likely to precipitate. Finally, 5 medications were infused via simulated Y-site administration. Incompatibility was defined as observed crystals, haziness, or turbidity upon visual inspection or absorbance of greater than 0.01 absorbance unit (AU). All solutions were tested at time 0 and at 20, 60, 240, and 1,440 minutes. RESULTS: Across all tests, only a commercially available formulation of heparin 2 units/mL in 0.9% sodium chloride injection precipitated with CaCl, alone or in combination with other medications. Upon further review, it was found that this specific formulation of heparin contained a monohydrate and dibasic sodium phosphate buffer. CONCLUSION: CaCl only precipitated with a commercially available heparin formulation that contained a phosphate buffer. CaCl was deemed to be compatible with all other medications and formulations tested.

Physical compatibility of remimazolam with opioid analgesics, sedatives, and muscle relaxants during simulated Y-site administration.

PURPOSE: There is a lack of information on the compatibility of remimazolam with opioid analgesics, muscle relaxants, and other sedatives. This study aimed to evaluate the physical compatibility of remimazolam with these drug classes. METHODS: Remimazolam was combined with 1 or 2 target drugs (remifentanil, fentanyl, rocuronium, vecuronium, dexmedetomidine, and midazolam). Ten physical compatibility tests were conducted, including four 3-drug compatibility tests. Remimazolam was dissolved in 0.9% sodium chloride injection to a final concentration of 5 mg/mL. Other medications were diluted in 0.9% sodium chloride injection to obtain clinically relevant concentrations. Compatibility tests were conducted with 3 test solutions, wherein remimazolam and the target drugs were compounded at equal volume ratios (1:1 or 1:1:1). Visual appearance was assessed and testing of Tyndall effect, turbidity, and pH was performed immediately after mixing and then again 1 hour and 4 hours after mixing. Appearance and turbidity were evaluated by comparison with the control solution of each target drug diluted with 0.9% sodium chloride injection to the same concentration as the test solution. RESULTS: All drugs tested were determined to be compatible with remimazolam. The drug combination with the highest change of turbidity was remimazolam and vecuronium (a mean increase of 0.16 NTU relative to the remimazolam control solution), 4 hours after mixing. The combination with the highest pH was remimazolam, fentanyl, and vecuronium (mean [SD], 3.76 [0.01]), 4 hours after mixing. The combination of remimazolam and fentanyl showed a larger change in pH at 4 hours after mixing (a mean increase of 2.6%) than immediately after mixing. CONCLUSION: Remifentanil, fentanyl, rocuronium, vecuronium, dexmedetomidine, and midazolam are physically compatible with remimazolam during simulated Y-site administration.

Construção e validação de ferramenta preventiva sobre incompatibilidade medicamentosa em via Y / Construction and validation of a preventive tool on drug incompatibility in the Y-route / Construcción y validación de una herramienta preventiva de incompatibilidad de medicamentos en la ruta Y

Introdução: A terapia com medicamentos endovenosos é muito utilizada nas unidades hospitalares, porém, possui uma elevada chance de incidentes, principalmente quando os medicamentos são administrados simultaneamente em via Y. Essa prática pode resultar em incompatibilidades medicamentosas classificadas em reações físicas e químicas. Objetivo: Construir e validar uma ferramenta preventiva de incompatibilidade medicamentosa em via Y. Método: Estudo metodológico com abordagem quantitativa. Foi desenvolvido em três etapas: Levantamento bibliográfico, construção e diagramação do material e por fim, a validação da ferramenta preventiva. Para validação, a ferramenta preventiva foi submetida ao processo de validação de face e conteúdo por juízes com expertise na temática. Resultados: Construiu-se e validou-se uma ferramenta preventiva através da busca de dados na literatura com a participação de sete juízes especialistas na temática. Os itens avaliativos referentes a tabela de incompatibilidade medicamentosa quanto aos objetivos, estrutura, apresentação e relevância da ferramenta preventiva foi considerada válida, pois foram julgados como adequado pelos especialistas. Conclusão: A validação de conteúdo, foi considerada válida pelos juízes, portanto, espera-se que o material alcance o seu objetivo ao ser aplicado durante a prática clínica. Dessa forma, será disponibilizado à instituição para que seja utilizado, favorecendo a prevenção de danos e contribuindo para a segurança dos pacientes, bem como melhorando a qualidade da assistência e educação em saúde.

Introduction: Intravenous drug therapy is widely used in hospital units, however, it has a high chance of incidents, especially when drugs are administered simultaneously in a Y route. This practice can result in drug incompatibilities classified into physical and chemical reactions. Objective: To build and validate a preventive tool for drug incompatibility in the Y pathway. Method: Methodological study with a quantitative approach. It was developed in three stages: bibliographic survey, construction and layout of the material and finally, the validation of the preventive tool. For validation, the preventive tool was submitted to the face and content validation process by judges with expertise in the subject. Results: A preventive tool was built and validated through the search for data in the literature with the participation of seven expert judges on the subject. The evaluative items referring to the medication incompatibility table regarding the objectives, structure, presentation and relevance of the preventive tool were considered valid, as they were judged as adequate by the specialists. Conclusion: The content validation was considered valid by the judges, therefore, it is expected that the material reaches its objective when applied during clinical practice. In this way, it will be made available to the institution for use, favoring the prevention of damage and contributing to patient safety, as well as improving the quality of health care and education.

Introducción: La farmacoterapia intravenosa es ampliamente utilizada en las unidades hospitalarias, sin embargo, tiene una alta probabilidad de incidencias, especialmente cuando los fármacos se administran simultáneamente en una vía Y. Esta práctica puede dar lugar a incompatibilidades medicamentosas clasificadas en reacciones físicas y químicas. Objetivo: Construir y validar una herramienta preventiva de incompatibilidad de medicamentos en la vía Y. Método: Estudio metodológico con enfoque cuantitativo. Se desarrolló en tres etapas: relevamiento bibliográfico, construcción y diagramación del material y finalmente, la validación de la herramienta preventiva. Para la validación, la herramienta preventiva fue sometida al proceso de validación facial y de contenido por jueces expertos en el tema. Resultados: Se construyó y validó una herramienta preventiva a través de la búsqueda de datos en la literatura con la participación de siete jueces expertos en el tema. Los ítems evaluativos referentes a la tabla de incompatibilidad de medicamentos en relación a los objetivos, estructura, presentación y relevancia de la herramienta preventiva fueron considerados válidos, pues fueron juzgados como adecuados por los especialistas. Conclusiones: La validación del contenido fue considerada válida por los jueces, por lo tanto, se espera que el material alcance su objetivo al ser aplicado durante la práctica clínica. De esta forma, se pondrá a disposición de la institución para su uso, favoreciendo la prevención de daños y contribuyendo a la seguridad del paciente, además de mejorar la calidad de la atención y educación en salud.

Simultaneous infusion of two incompatible antibiotics: Impact of the choice of infusion device and concomitant simulated fluid volume support on the particulate load and the drug mass flow rates.

Vancomycin and piperacillin/tazobactam are known to be incompatible. The objectives of the present study were to evaluate the impact of their simultaneous infusion on mass flow rates and particulate load and identify preventive strategies. We assessed both static conditions and a reproduction of an infusion line used in a hospital's critical care unit. A high-performance liquid chromatography/UV diode array system and static and dynamic laser diffraction particle counters were used. The mass flow rates were primarily influenced by the choice of the infusion device and the presence of simulated fluid volume support. Drug incompatibility also appeared to affect vancomycin's mass flow rate, and the dynamic particulate load increased during flow rate changes - especially in the infusion set with a large common volume line and no concomitant simulated fluid volume support. Only discontinuation of the piperacillin/tazobactam infusion was associated with a higher particulate load in the infusion set with a large common volume line and no concomitant simulated fluid volume support. A low common volume line and the use of simulated fluid volume support were associated with smaller fluctuations in the mass flow rate. The clinical risk associated with a higher particulate load must now be assessed.

Frequently acquired drugs in neonatal intensive care and their physical compatibility.

AIM: Incompatibility of intravenous drugs is dangerous and therefore undesirable. The aim of this study was to identify the most commonly acquired intravenous drugs in five neonatal intensive care units and test these for compatibility. METHODS: The most frequently acquired drugs in five key hospitals in the South-Eastern district of Norway for 2019 and 2020 served as a proxy for the prevalence of use. Representatives were selected from the three most prevalent groups based on the Anatomical Therapeutic Chemical classification system. Co-administration of drug pairs was simulated using clinically relevant concentrations and infusion rates representing mixing ratios in the catheter. Particle formation was assessed by particle counting and size measurement, by visual examination using Tyndall beam, by turbidity and by measuring pH of mixed samples. RESULTS: The most frequently acquired drug groups were anti-infectives, neurological agents and cardiovascular drugs. Compatibility testing revealed that both ampicillin and benzylpenicillin were incompatible with morphine. Flecainide and fluconazole showed no signs of incompatibility with morphine. No information on these combinations in a neonatal-relevant setting is available. CONCLUSION: We recommend to abstain from co-administering ampicillin and benzylpenicillin with morphine in neonatal intensive settings. Morphine co-administered with flecainide and fluconazole in neonatal patients were evaluated as safe.

Simulated Y-site compatibility of atosiban acetate with selected intravenous drugs.

OBJECTIVE: The physical compatibility of atosiban and selected drugs during simulated Y-site administration was evaluated. We also searched for any compatibility predictions regarding its physicochemical properties. STUDY DESIGN: Test admixtures were prepared by mixing 5 mL of each study drug solution with 5 mL of atosiban solution in a 1:1 ratio to simulate Y-site infusion. Assessments were made immediately after mixing (baseline), and at 0.5, 1, and 3 h. Visual incompatibility was defined as a presence of haze or any visible particulate matter, gas formation, or colour change. Turbidity and pH variation of the admixtures were also assessed using instrumental methods. RESULTS: None of the admixtures used with atosiban exhibited visual changes and no incompatibility regarding instrumental methods were observed, because no admixture had an increase of 0.5 nephelometric turbidity units, and no pH change was above one unit when compared to baseline. However, the pH of ampicillin and omeprazole admixtures fell outside of the atosiban stability range. CONCLUSIONS: Our study showed no physical incompatibility between atosiban and the test drugs in terms of visual changes or nephelometric and pH measurements. However, we recommend against atosiban and ampicillin or omeprazole coadministration until complementary compatibility studies are performed.

Utility of a Compatibility Chart for Continuous Infusions in the Intensive Care Unit.

BACKGROUND: In the intensive care unit (ICU), multiple intravenous drugs are often administered through the same catheter line, greatly increasing the risk of drug incompatibility. We previously developed a compatibility chart including 27 drugs and have used it to avoid drug incompatibilities in the ICU. This retrospective study evaluated the utility of this chart by analyzing prescriptions and incidents of incompatibilities in an ICU. METHODS: We analyzed 257 ICU prescriptions of two or more continuous infusions on the same day during the period between March 2016 and February 2017 and investigated the rate of compliance with the compatibility chart. Drug combinations were classified as "compatible," "tolerable compatible," "incompatible," and "no data." For all combinations, the compliance rate was defined as the ratio of compatible and tolerable compatible combinations. Additionally, using our hospital incident report database, we analyzed 27,117 injections administered in the ICU between March 2016 and February 2017 and investigated incidents related to incompatibility. RESULTS: Three hundred infusion combinations were identified in the prescriptions. The compliance rate was 97% (n = 293). Of the 113 combinations judged to be tolerable compatible, 98% (n = 111) consisted of three or more continuous medications injected through the same intravenous line. Of the two incidents related to incompatibility in the incident report database, the combination "nicardipine and furosemide" was defined as incompatible in the compatibility chart. CONCLUSIONS: The high rate of compliance with the compatibility chart suggested it was useful in preventing drug incompatibility.

Review of binary, ternary and quaternary mixtures for induction and maintenance of opioid free anesthesia.

OBJECTIVE: To describe and organize the current information available on  binary, ternary and/or quaternary mixtures used in opioid-free anesthesia (OFA), as well as their physicochemical stability, in order to  facilitate its correct administration, optimize its use, and prevent potential  effectiveness and safety issues. METHOD: A systematic review of the literature on OFA was conducted in  PubMed/Medline, Trissel, Micromedex, Lexicomp,  ww.ahfsdruginformation.com, ASHP's Extended Stability for Parenteral Drugs, and www.stabilis.org. Only articles published in English or Spanish until May 2020 and with  access to full text were considered. MeSH terms used included: "drug  incompatibility" AND "opioid-free anesthesia" AND "administration, intravenous" AND "dexmedetomidine" AND "lidocaine"  AND "ketamine" AND "magnesium sulphate" OR "infusions, intravenous. A  first search was carried out in PubMed/Medline that included OFA clinical cases. The results obtained were collected in a database. A second search  was carried out on the incompatibilities of intravenous mixtures.  Information was compiled on mutually-compatible/incompatible drugs,  reference concentrations, stability time at room temperature (23 ± 2 °C)  and under refrigeration (4 ± 2 ºC), type of administration recommended,  and relevant results and conclusions. Two two-dimensional tables on the  compatibility of each drug combination were created for administration as  Y-site infusion or as a mixture in a single solution. RESULTS: Seven hundred and eighty articles were identified, with the full  text of 203 being accessed. A total of 4,762 cases treated with OFA  protocols were chronologically collected from 32 different publications. Administration of two concomitant drugs was the most usual  regimen (42.4%). The most frequently drugs were dexmedetomidine (25  studies), ketamine hydrochloride (25 studies) and lidocaine (14 studies).  Compatibility/incompatibility data was collected for 11 drugs, associated to  7 pharmacological groups; compatibility with Y-site administration was  found in 43 of 55 combinations (78.18%) and with integration into one  single solution in 13 of 55 drug combinations (23.63%). None of the  sources reviewed reported any adverse results related to potential  pharmacological incompatibilities. CONCLUSIONS: Despite the availability of multiple OFA protocols, few studies analyze the compatibility between binary drug mixtures. No  information exists as yet regarding compatibilities in the context of ternary and quaternary mixtures.  Despite the availability of multiple OFA  protocols, few studies analyze the compatibility between binary drug  mixtures. No information exists as yet regarding compatibilities in the  context of ternary and quaternary mixtures.

Objetivo: Describir y estructurar la información actual disponible sobre mezclas binarias, ternarias y/o cuaternarias empleadas en una  "anestesia libre de opiáceos", así como su estabilidad fisicoquímica, para  facilitar su correcta administración, optimizar su uso y prevenir posibles  problemas de efectividad o seguridad.Método: Revisión sistemática de la literatura sobre anestesia libre de opiáceos en PubMed/Medline, Trissel, Micromedex, Lexicomp, AHFS  Drug Information, Extended Stability for Parenteral Drugs y Stabilis Web.  Artículos publicados en inglés o español hasta mayo de 2020 y con acceso  a texto completo. Se emplearon los términos MeSH: "Drug Incompatibility" AND "Opioid Free Anesthesia" AND "Administration,  Intravenous" AND "Dexmedetomidine" AND "Lidocaine" AND "Ketamine"  AND "Sulphate Magnesium" OR "Infusions, Intravenous". Se realizó una  primera búsqueda en PubMed/Medline incluyendo casos clínicos de  anestesia general tipo anestesia libre de opiáceos. Los resultados  obtenidos se estructuraron en una base de datos. La segunda búsqueda  fue sobre incompatibilidades de las mezclas intravenosas. Se recogieron  medicamentos compatibles/ incompatibles; concentraciones de referencia; tiempo de estabilidad a temperatura ambiente (23 ± 2 °C) y en  refrigeración (4 ± 2 °C); tipo de administración recomendada y resultados  y conclusiones relevantes. Se crearon phardos tablas bidimensionales de la compatibilidad de cada combinación de fármacos para la administración en Y o en mezcla en una sola solución.Resultados: Se identificaron 780 artículos; se accedió al texto completo de 203. Se recogieron de forma cronológica los 4.762 casos  tratados en 32 diferentes publicaciones con protocolos de anestesia libre de opiáceos. El uso de dos fármacos fue la asociación más frecuente (42,4%). Los fármacos más empleados fueron dexmedetomidina (25 trabajos), clorhidrato de ketamina (25 trabajos) y lidocaína (14  trabajos). Se recopiló información de compatibilidad/incompatibilidad de  11 medicamentos, asociados a 7 grupos farmacológicos, encontrándose  compatibilidad en Y en 43 de 55 combinaciones (78,18%) y en mezcla en  una sola solución en 13 de 55 combinaciones de fármacos (23,63%). En  ningún trabajo publicado se expone algún tipo de evento adverso en  relación con una posible incompatibilidad farmacológica.Conclusiones: Existen múltiples protocolos de anestesia libre de  piáceos, pero los estudios de compatibilidad entre las diferentes mezclas  de fármacos empleadas son muy limitados cuando se trata de mezclas  binarias, y no existe información en el caso de mezclas ternarias y  cuaternarias.

Assessment of the physical compatibility of injectable enrofloxacin with commonly used intravenous fluids and drugs during simulated Y-port administration.

OBJECTIVE: To evaluate physical compatibility of small animal (SAE) and large animal (LAE) injectable formulations of enrofloxacin with select IV fluids and drugs. SAMPLE: 162 admixtures containing SAE or LAE with saline (0.9% NaCl) solution, lactated Ringer solution (LRS), Plasma-Lyte A (PLA), 6% hydroxyethylstarch 130/0.4 (HES), metoclopramide, or ampicillin-sulbactam. PROCEDURES: In the first of 2 simultaneously conducted experiments, admixtures containing enrofloxacin (10 mg/kg) and a volume of IV fluid that would be administered over a 20-minute period when dosed at the maintenance infusion rate (40 mL/kg/d for saline solution, LRS, and PLA and 20 mL/kg/d for HES) were created. In the second experiment, enrofloxacin (10 mg/kg) was admixed with saline solution (40 mL/kg/d) and metoclopramide (2 mg/kg/d) or ampicillin-sulbactam (30 mg/kg). In both experiments, admixture components were infused into a flask over 20 minutes assuming patient weights of 5, 10, and 20 kg. Admixtures were created by use of undiluted SAE and SAE diluted 1:1 with saline solution and undiluted LAE and LAE diluted 1:1 and 1:10 with saline solution. Admixtures were assessed for physical incompatibility at 0, 15, 30, and 60 minutes after completion of mixing. Physical incompatibility was defined as gross precipitation, cloudiness, Tyndall effect, or change in turbidity. RESULTS: Admixtures containing undiluted SAE or LAE were physically incompatible with saline solution, PLA, LRS, and HES. Because saline solution was used to dilute SAE and LAE, all admixtures containing diluted SAE or LAE were also physically incompatible. Physical compatibility of enrofloxacin with metoclopramide or ampicillin-sulbactam could not be assessed because those admixtures also contained saline solution. CONCLUSIONS AND CLINICAL RELEVANCE: Enrofloxacin was physically incompatible with all tested solutions.

Strategies to prevent drug incompatibility during simultaneous multi-drug infusion in intensive care units: a literature review.

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.

Physical Compatibility of Nafamostat with Analgesics, Sedatives, and Muscle Relaxants for Treatment of Coronavirus Disease 2019.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) may require continuous administration of analgesics, sedatives, and muscle relaxants. Nafamostat has recently been reported as a therapeutic agent for COVID-19. However, there is a lack of information on the compatibility of nafamostat with the aforementioned drug classes. This study evaluated the physical compatibility of nafamostat with these drug classes. METHODS: Nafamostat was combined with 1-3 target drugs (fentanyl, morphine, midazolam, dexmedetomidine, and rocuronium). Fifteen physical compatibility tests were conducted. Nafamostat was dissolved in 5% glucose solution; the final concentration was 10 mg/mL. All other medications were diluted in 0.9% sodium chloride to obtain clinically relevant concentrations. The power of hydrogen (pH) of all medications was measured during each test. Compatibility tests were conducted with 4 test solutions in which nafamostat and the target drugs were compounded at equal volume ratios (1:1, 1:1:1, or 1:1:1:1). Visual appearance, turbidity, and pH were evaluated immediately after mixing and at 1 and 3 hours. Physical incompatibilities were defined as gross precipitation, cloudiness, appearance of the Tyndall effect, or a turbidity change of ≥0.5 nephelometric turbidity units (NTU) based on nafamostat. RESULTS: The mean pH of nafamostat was 3.13 ± 0.03. The combination of nafamostat, fentanyl, and dexmedetomidine had the highest pH (3.39 ± 0.01; 3 hours after mixing). All drugs were compatible with nafamostat until 3 hours after admixture, with a mean turbidity value of ≤0.03 NTU. CONCLUSIONS: Infusions combining nafamostat with the tested sedatives, analgesics, and muscle relaxants could be safely administered.

Intestinal bacteria are involved in Radix Glycyrrhizae and Radix Euphorbiae Pekinensis incompatibility.

ETHNOPHARMACOLOGICAL RELEVANCE: Eighteen Incompatible Medicaments (EIM) belongs to the category of incompatibility of Traditional Chinese medicine (TCM). This theory forbids concomitant using any one of the eighteen herbal pairs such as Radix Glycyrrhizae (RG)-Radix Euphorbiae Pekinensis (REP), Radix Aconiti-Bulbus Fritiliariae Cirrhosae, and Radix et Rhizoma Veratri Nigri-Radix Ginseng. Concomitant using RG and REP could result in more serious adverse effects on major organs such as kidney, heart, and liver. AIM OF THE STUDY: To investigate the effects of RG-REP decoctions on gut microbiota and short-chain fatty acids (SCFAs) for the purpose of elucidating the mechanism of RG-REP incompatibility. MATERIALS AND METHODS: Six groups of male SD rats were intragastrically administrated with distilled water, RG decoction, REP decoction, 1:1 RG-REP decoction, 2:1 RG-REP decoction and 3:1 RG-REP decoction, respectively, twice daily for 30 consecutive days, and the feces of each rat was separately sampled for gut microbiota analysis and SCFAs assay. 16S rDNA sequencing was employed to comparatively investigate the structure and abundance of intestinal bacteria in rat feces. Gas chromatography (GC) was used to quantitatively determine the contents of SCFAs in rat feces and in vitro samples. The correlation between bacteria and the production of SCFAs was analyzed by Spearman correlation analysis. An in vitro model of human intestinal bacteria was also constructed to simulate and validate the in vivo experiment. RESULTS: The contents of butyric acid in both rat feces and in vitro samples decreased in RG-REP groups. The general structure of gut microbiota in RG-REP groups was not significantly different from that in control group. However, RG alone increased the abundance of Lactobacillus while this effect was counteracted by concomitant using with REP. REP alone decreased the abundance of two interrelated species, Akkermansia and Butyricimonas, and this effect was strengthened by concomitant using REP with RG in the ratio of 1:1. In comparison with REP alone, RG-REP combination also significantly increased the abundance of Streptococcus and Prevotella. CONCLUSION: The incompatibility of RG-REP combination is associated with its negative effect against probiotic bacteria and positive effect on conditional pathogenic bacteria as well as its inhibition on butyric acid production.

Comparative Physicochemical Evaluation of Starch Extracted from Pearl millet seeds grown in Sudan as a Pharmaceutical Excipient against Maize and Potato Starch, using Paracetamol as a model drug.

OBJECTIVES: The aim of the current study was to compare the physicochemical and disintegrant properties of pearl millet starch with other starches using paracetamol as model drug. METHODOLOGY: Determination of percentage yield, Physicochemical, micrometrics characteristics of starch/granules, drug excipients compatibility studies and evaluation of prepared paracetamol tablets were measured using official techniques. RESULTS: The yield of the millet starch ranged from 30 to 40%. Moisture content 8.77%, pH 5.7, Swelling capacity 1.2, Hydration capacity 1.748, Moisture uptake 11.8%, Amylose 24.6%, with poor flowability and compressibility. No significant difference in hardness, friability% & disintegration times for formulations containing millet starch to that containing potato and maize starch (P>0.05). CONCLUSION: From the study, Millet seeds locally cultivated in Sudan gave a high yield of starch, has same physicochemical properties as maize and potato starch so can be used as an alternative to those starches.

Physical compatibility of alprostadil with selected drugs commonly used in the neonatal intensive care units.

This study aimed to determine the physical compatibility of alprostadil with 17 continuous infusion drugs commonly administered in neonatal intensive care units. Test samples were prepared in a laminar airflow hood. Alprostadil 20 mcg/ml was mixed with each drug in a 1:1 ratio, in two orders of mixing. Physical stability of the admixtures was assessed by visual examination and by measuring turbidity. Visual examination was conducted by two observers by two methods: visual examination against a black and white background under normal fluorescent light and using a high-intensity monodirectional light. pH was measured as chemical stability predictor. Evaluations were performed immediately and 4 h after mixing. An additional visual control was performed at 24 h. Visual examination was positive or doubtful for the four drug combinations not considered compatible. Turbidity values were under 0.5 NTU throughout the study in all samples. No modifications of one pH unit or more was detected in any drug pair over time.Conclusion: Alprostadil was considered physical compatible with 13 drugs (adrenalin, amiodarone, calcium gluconate, dobutamine, dopamine, fentanyl, flecainide, furosemide, heparin, ketamine, midazolam, milrinone and morphine). Incompatibility could not be ruled out for 3 drugs (cisatracurium, dexmedetomidine and noradrenalin), and insulin was considered incompatible with alprostadil. What is Known: • Y-site administration is common in neonatal intensive care units, and volume of diluents and rate of infusions in newborns were lower than in adults which might result in high concentrations and prolonged contact time at Y-site administration. • Available data about compatibility of alprostadil with other drugs was scarce. What is New: • Alprostadil was compatible with 13 drugs commonly used in neonatal intensive care units. • Insulin was considered incompatible with alprostadil, and incompatibility cannot be ruled out for cisatracurium, dexmedetomidine and noradrenalin with alprostadil.

Compatibility of medications with intravenous lipid emulsions: Effects of simulated Y-site mixing.

PURPOSE: To determine the physical intravenous Y-site compatibility of 19 commonly used medications at pediatric concentrations with 3 different types of lipid emulsion. METHODS: Medications at commonly used pediatric concentrations were mixed in a 1:1 ratio with lipid emulsions (Intralipid, Nutrilipid, and Smoflipid) and incubated at room temperature for 4 hours to simulate Y-site administration. Each sample was then diluted with particle-free water and analyzed using the analytical technique of light obscuration recommended in United States Pharmacopeia (USP) general information chapter 729 (USP <729>). Physical compatibility was determined by measuring the percentage of fat residing in globules larger than 5 µm (PFAT5) per USP <729> recommendations. RESULTS: Most combinations tested were physically compatible based on USP <729> regulations. Incompatibilities differed for the different brands of lipid emulsion. The two combinations that met USP <729> criteria for physical incompatibility were cisatracurium 2 mg/mL with Intralipid and gentamicin 2 mg/mL with Smoflipid. CONCLUSION: Three different lipid emulsions were physically compatible at the Y site with the majority of medications tested. Data regarding Y-site compatibility for one lipid emulsion product cannot be safely extrapolated to another without additional testing.

Towards more efficient use of intravenous lumens in multi-infusion settings: development and evaluation of a multiplex infusion scheduling algorithm.

BACKGROUND: Multi-drug intravenous (IV) therapy is one of the most common medical procedures used in intensive care units (ICUs), operating rooms, oncology wards and many other hospital departments worldwide. As drugs or their solvents are frequently chemically incompatible, many solutions must be administered through separate lumens. When the number of available lumens is too low to facilitate the safe administration of these solutions, additional (peripheral) IV catheters are often required, causing physical discomfort and increasing the risk for catheter related complications. Our objective was to develop and evaluate an algorithm designed to reduce the number of intravenous lumens required in multi-infusion settings by multiplexing the administration of various parenteral drugs and solutions. METHODS: A multiplex algorithm was developed that schedules the alternating IV administration of multiple incompatible IV solutions through a single lumen, taking compatibility-related, pharmacokinetic and pharmacodynamic constraints of the relevant drugs into account. The conventional scheduling procedure executed by ICU nurses was used for comparison. The number of lumens required by the conventional procedure (LCONV) and multiplex algorithm (LMX) were compared. RESULTS: We used data from 175,993 ICU drug combinations, with 2251 unique combinations received by 2715 consecutive ICU patients. The mean ± SD number of simultaneous IV solutions was 2.8 ± 1.6. In 27% of all drug combinations, and 61% of the unique combinations the multiplex algorithm required fewer lumens (p < 0.001). With increasing LCONV, the reduction in number of lumens by the multiplex algorithm further increased (p < 0.001). In only 1% of cases multiplexing required > 3 lm, versus 12% using the conventional procedure. CONCLUSION: The multiplex algorithm addresses a major issue that occurs in ICUs, operating rooms, oncology wards, and many other hospital departments where several incompatible drugs are infused through a restricted number of lumens. The multiplex algorithm allows for more efficient use of IV lumens compared to the conventional multi-infusion strategy.