Plasma concentrations of midazolam during continuous subcutaneous administration in palliative ca re

Bleasel, Martin D.; Peterson, Gregory M.; Dunne, Paul

doi:10.1177/026921639400800307

Cited by 14 publications

(10 citation statements)

References 14 publications

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“…Moreover, in some studies the subcutaneous route was preferred because of lower complication risks. Only small and outdated prospective studies are available for midazolam, which all found subcutaneous administration of midazolam to be feasible and effective [ 39 , 43 , 44 ]. Regarding haloperidol, only retrospective descriptive studies or overview articles are available, even without addressing the administration route [ 45 – 48 ].…”

Section: Discussionmentioning

confidence: 99%

Medication use during end-of-life care in a palliative care centre

et al. 2015

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Background In end-of-life care, symptoms of discomfort are mainly managed by drug therapy, the guidelines for which are mainly based on expert opinions. A few papers have inventoried drug prescriptions in palliative care settings, but none has reported the frequency of use in combination with doses and route of administration. Objective To describe doses and routes of administration of the most frequently used drugs at admission and at day of death. Setting Palliative care centre in the Netherlands. Method In this retrospective cohort study, prescription data of deceased patients were extracted from the electronic medical records. Main outcome measure Doses, frequency and route of administration of prescribed drugs Results All regular medication prescriptions of 208 patients, 89 % of whom had advanced cancer, were reviewed. The three most prescribed drugs were morphine, midazolam and haloperidol, to 21, 11 and 23 % of patients at admission, respectively. At the day of death these percentages had increased to 87, 58 and 50 %, respectively. Doses of these three drugs at the day of death were statistically significantly higher than at admission. The oral route of administration was used in 89 % of patients at admission versus subcutaneous in 94 % at the day of death. Conclusions Nearing the end of life, patients in this palliative care centre receive discomfort-relieving drugs mainly via the subcutaneous route. However, most of these drugs are unlicensed for this specific application and guidelines are based on low level of evidence. Thus, there is every reason for more clinical research on drug use in palliative care.Electronic supplementary materialThe online version of this article (doi:10.1007/s11096-015-0094-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Medication use during end-of-life care in a palliative care centre

et al. 2015

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“…[107] In palliative patients, no correlation was found between midazolam concentrations and liver disease, probably because liver diseases in this population are not as severe as in ICU patients. [108] Finally, CYP3A metabolism can also be affected by the use of other drugs. In the palliative setting, there might be a relevant interaction with dexamethasone.…”

Section: Midazolammentioning

confidence: 99%

Pharmacokinetic considerations and recommendations in palliative care, with focus on morphine, midazolam and haloperidol

Franken

Winter

Esch

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

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The pharmacokinetics of drugs in terminally ill patients can be complex and limited evidence exists on guided drug use in this population. To improve the quality of life of these patients, more knowledge and more pharmacokinetic/pharmacodynamics studies in terminally ill patients are needed to develop individualised dosing guidelines. Until then knowledge of pharmacokinetics and the physiological changes that occur in the final days of life can provide a base for dosing adjustments that will improve the quality of life of terminally ill patients. As the interaction of drugs with the physiology of dying is complex, pharmacological treatment is probably best assessed in a multi-disciplinary setting and the advice of a pharmacist, or clinical pharmacologist, is highly recommended.

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“…Unfortunately the time it takes to reach adequate sedation varies widely between patients and awaking from a sedative state often occurs . A possible explanation for this might be large inter‐individual variability (IIV) in midazolam pharmacokinetics, which has already been shown in other populations . Large variability is also expected in terminally ill patients due to the heterogeneity of the population, including severe co‐morbidities (e.g.…”

Section: Introductionmentioning

confidence: 99%

Hypoalbuminaemia and decreased midazolam clearance in terminally ill adult patients, an inflammatory effect?

Franken

Masman

Winter

et al. 2017

Brit J Clinical Pharma

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Aims Midazolam is the drug of choice for palliative sedation and is titrated to achieve the desired level of sedation. Because of large inter‐individual variability (IIV), however, the time it takes to achieve adequate sedation varies widely. It would therefore greatly improve clinical care if an individualized dose could be determined beforehand. To find clinically relevant parameters for dose individualization, we performed a pharmacokinetic study on midazolam, 1OH‐midazolam (1‐OH‐M) and 1OH‐midazolam‐glucuronide (1‐OH‐MG) in terminally ill patients. Methods Using nonlinear mixed effects modelling (NONMEM 7.2), a population pharmacokinetic analysis was conducted with 192 samples from 45 terminally ill patients who received midazolam either orally or subcutaneously. The covariates analysed were patient characteristics, co‐medication and blood chemistry levels. Results The data were accurately described by a one compartment model for midazolam, 1‐OH‐M and 1‐OH‐MG. The population mean estimates for midazolam, 1‐OH‐M and 1‐OH‐MG clearance were 8.4 l h−1 (RSE 9%, IIV 49%), 45.4 l h−1 (RSE 12%, IIV 60.5%) and 5.1 l h−1 (RSE 11%, IIV 49.9%), respectively. 1‐OH‐MG clearance was correlated with the estimated glomular filtration rate (eGFR) explaining 28.4% of the IIV in 1‐OH‐MG clearance. In addition, low albumin levels were associated with decreased midazolam clearance, explaining 18.2% of the IIV. Conclusion Our study indicates albumin levels and eGFR as relevant clinical parameters to optimize midazolam dosing in terminally ill patients. The correlation between low albumin levels and decreased midazolam clearance is probably a result of inflammatory response as high CRP levels were correlated in a similar way.

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Plasma concentrations of midazolam during continuous subcutaneous administration in palliative ca re

Cited by 14 publications

References 14 publications

Medication use during end-of-life care in a palliative care centre

Medication use during end-of-life care in a palliative care centre

Pharmacokinetic considerations and recommendations in palliative care, with focus on morphine, midazolam and haloperidol

Hypoalbuminaemia and decreased midazolam clearance in terminally ill adult patients, an inflammatory effect?

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