scholarly journals Filling Gaps on Stability Data: Development, Validation and Application of a Multianalyte UHPLC-DAD Method to Determine the Stability of Commonly Administered Drugs in Different Carrier Solutions Used in Palliative Care

Analytica ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 33-43
Author(s):  
Christian Steuer ◽  
Ursina Müller ◽  
Fiona Haller ◽  
Peter Wiedemeier

In palliative care, continuous subcutaneous infusion (CSCI) is common practice for drug administration when oral application of drugs is not feasible or not reliable anymore. However, use of CSCI is limited to chemical stability of drugs and their combination in carrier solution. To determine the stability of different mixtures of commonly used drugs in palliative care, a multi-analyte UHPLC-DAD method controlled by an internal standard was successfully developed. The method was validated in terms of specificity, accuracy, precision, and linearity across the calibration range. Seven analytes could be separated within 10 min by C18-reversed phase chromatography. The method was successfully applied to close gaps in stability data and complete missing data for decision makers in health care units. Our results indicated the stability of binary mixtures and one ternary mixture in 0.9% saline and 5% glucose as carrier solutions. The obtained data will support pharmacists in palliative care for the preparation of parenteral drug solutions in the future.

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Per Fürst ◽  
Staffan Lundström ◽  
Pål Klepstad ◽  
Peter Strang

Abstract Background Continuous subcutaneous infusion (CSCI) via ambulatory infusion pump (AIP) is a valuable method of pain control in palliative care. When using CSCI, low-dose methadone as add-on to other opioids might be an option in complex pain situations. This study aimed to investigate the effects, and adverse effects, of CSCI for pain control in dying patients, with particular interest in methadone use. Methods This was an observational cohort study. Imminently dying patients with pain, admitted to specialized palliative inpatient wards and introduced on CSCI, were monitored daily by staff for symptoms (Integrated Palliative Care Outcome Scale - IPOS), sedation (Richmond Agitation and Sedation Scale – RASS), performance status (Eastern Cooperative Oncology Group - ECOG) and delirium (Confusion Assessment Method - CAM). Results Ninety-three patients with a median survival of 4 days were included. Of the 47 patients who survived ≥3 days, the proportion of patients with severe/overwhelming pain decreased from 45 to 19% (p < 0.001) after starting CSCI, with only a moderate increase in morphine equivalent daily dose of opioids (MEDD). Alertness was marginally decreased (1 point on the 10-point RASS scale, p = 0.001), whereas performance status and prevalence of delirium, regardless of age, remained unchanged. Both patients with methadone as add-on (MET, n = 13) and patients with only other opioids (NMET, n = 34), improved in pain control (p < 0.05 and 0.001, respectively), despite that MET patients had higher pain scores at baseline (p < 0.05) and were on a higher MEDD (240 mg vs.133 mg). No serious adverse effects demanding treatment stop were reported. Conclusions CSCI via AIP is an effective way to reduce pain in dying patients without increased adverse effects. Add-on methadone may be beneficial in patients with severe complex pain.


2021 ◽  
pp. 026921632110132
Author(s):  
Laura Heath ◽  
Matthew Carey ◽  
Aoife C Lowney ◽  
Eli Harriss ◽  
Mary Miller

Background: COVID-19 has tragically resulted in over 2.5 million deaths globally. Despite this, there is a lack of research on how to care for patients dying of COVID-19, specifically pharmacological management of symptoms. Aim: The aim was to determine the dose ranges of pharmacological interventions commonly used to manage symptoms in adult patients dying of COVID-19, establish how effectiveness of these interventions was measured, and whether the pharmacological interventions were effective. Design: This was a rapid systematic review with narrative synthesis of evidence, prospectively registered on PROSPERO (ID: CRD42020210892). Data sources: We searched MEDLINE, EMBASE, CINAHL via the NICE Evidence Health Databases Advanced Search interface; medRxiv; the Cochrane COVID-19 Study Register; and Google Scholar with no date limits. We included primary studies which documented care of patients dying of COVID-19 under the care of a specialist palliative care team. Results: Seven studies, documenting the care of 493 patients met the inclusion criteria. Approximately two thirds of patients required a continuous subcutaneous infusion with median doses of 15 mg morphine and 10 mg midazolam in the last 24 h of life. Four studies described effectiveness by retrospective review of documentation. One study detailed the effectiveness of individual medications. Conclusions: A higher proportion of patients required continuous subcutaneous infusion than is typically encountered in palliative care. Doses of medications required to manage symptoms were generally modest. There was no evidence of a standardised yet holistic approach to measure effectiveness of these medications and this needs to be urgently addressed.


2021 ◽  
Vol 8 (7) ◽  
Author(s):  
Sutherland A ◽  
◽  
Carey M ◽  
Miller M ◽  
◽  
...  

We describe the case of a 68 year old with a transglottic squamous cell carcinoma, a tracheostomy and persistent blood stained tracheal secretions. Oral and intravenous Tranexamic Acid (TA) effectively controlled the bleeding. On losing both routes, we administered 2g of TA (20ml) by continuous subcutaneous infusion over 24 hours. Control of bleeding was maintained over 18 days until death. No site reactions were observed. A literature review was undertaken, however, none of the studies looked at the use of TA in an end of life or palliative care population. We identified 3 clinical palliative care guidelines relating to continuous subcutaneous administration of TA. Further use should be reported in the literature to build the evidence base surrounding this novel practice.


2013 ◽  
Author(s):  
Lise Fillion ◽  
◽  
Louise Saint-Laurent ◽  
Martine Fortier

1982 ◽  
Vol 47 (01) ◽  
pp. 001-002 ◽  
Author(s):  
Nenita Parrilla ◽  
Jack Ansell

SummaryA preliminary clinical trial was conducted to determine the feasibility of achieving and regulating therapeutic anticoagulation with heparin given by continuous subcutaneous infusion. Five patients with deep venous thrombosis confirmed by impedance plethysmography and/or venography were studied. All patients received an initial heparin dose of 5000 units by IV bolus. This was followed by a continuous subcutaneous heparin infusion at a dose of 15 to 25 units per kilogram per hour. Effective levels of anticoagulation were achieved in all five patients. Regulation and maintenance of therapeutic anticoagulation were no more difficult than with intravenous therapy. No major complications were encountered during therapy.Continuous subcutaneous infusion of heparin may have advantages over standard intravenous therapy or high dose intermittent subcutaneous therapy. However, more extensive clinical evaluation is warranted.


2021 ◽  
Vol 13 (3) ◽  
pp. 1326
Author(s):  
Hongfang Li ◽  
Huixiao Wang ◽  
Yaxue Yang ◽  
Ruxin Zhao

The interactions of water, energy, and food, which are essential resources for human survival, livelihoods, production, and development, constitute a water–energy–food (WEF) nexus. Applying symbiosis theory, the economic, social, and natural factors were considered at the same time in the WEF system, and we conducted a micro-level investigation focusing on the stability, coordination, and sustainability of the symbiotic units (water, energy, and food), and external environment of the WEF system in 36 prefecture-level cities across three northeastern provinces of China. Finally, we analyzed the synergistic safety and coupling coordination degree of the WEF system by the combination of stability, coordination, and sustainability, attending to the coordination relationship and influences of the external environment. The results indicated that the synergistic safety of the WEF system in three northeastern provinces need to equally pay attention to the stability, coordination, and sustainability of the WEF system, since their weights were 0.32, 0.36 and 0.32, respectively. During 2010–2016, the synergistic safety indexes of the WEF system ranged between 0.40 and 0.60, which was a state of boundary safety. In the current study, the coupling coordination degree of the WEF system fluctuated around a value of 0.6, maintaining a primary coordination level; while in the future of 2021–2026, it will decline to 0.57–0.60, dropping to a weak coordinated level. The conclusion could provide effective information for decision-makers to take suitable measures for the security development of a WEF system.


1971 ◽  
Vol 125 (4) ◽  
pp. 1009-1018 ◽  
Author(s):  
R. E. Chambers ◽  
J. R. Clamp

The stability of monosaccharides in methanolic hydrochloric acid of different strengths and at different temperatures was determined. They are generally stable for 24h in methanolic 1m- and 2m-hydrochloric acid at both 85°C and 100°C, but undergo considerable destruction in methanolic 4m- and 6m-hydrochloric acid at 100°C. Analysis of glycopeptides and oligosaccharides of known composition showed that release of carbohydrate was complete within 3h in methanolic 1m-hydrochloric acid at 85°C. Removal of methanolic hydrochloric acid by rotary evaporation resulted in considerable losses of monosaccharides, which could be prevented by prior neutralization. Methanolysis caused extensive de-N-acetylation of acetamidohexoses, so that a re-N-acetylation step is necessary in the analytical procedure. The addition of acetic anhydride for this purpose also prevented loss of internal standard by adsorption on the insoluble silver salts used in neutralization. Several trimethylsilylating agents were studied and suitable conditions are recommended. The effects on the analytical system of water and some common organic and inorganic contaminants are assessed.


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