Comparison of Hydromorphone versus Fentanyl‐based Sedation in Extracorporeal Membrane Oxygenation: A Propensity‐Matched Analysis

Landolf, Kaitlin; Rivosecchi, Ryan; Gómez, Hernando; Sciortino, Christopher M.; Murray, Holt; Padmanabhan, Rajagopala; Sánchez, Pablo G.; Harano, Takashi; Sappington, Penny L.

doi:10.1002/phar.2385

Cited by 19 publications

(20 citation statements)

References 30 publications

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“…The probable cause of relatively low recovery for the lipemic matrix was the selection of the extraction solvent and very high lipophilicity of the target compound. In the current study, 1-chlorobutyl and acetonitrile probably could not provide adequate lipid sequestration in the organic layer, as the dielectric constant of 1-chlorobutan is only 7.2 [51]. This resulted in visible, persisting milkiness of the plasma after the extraction.…”

Section: Discussionmentioning

confidence: 67%

Lipemia in the Plasma Sample Affects Fentanyl Measurements by Means of HPLC-MS2 after Liquid-Liquid Extraction

2021

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Examination of fentanyl levels is frequently performed in certain scientific evaluations and forensic toxicology. It often involves the collection of very variable blood samples, including lipemic plasma or serum. To date, many works have reported the methods for fentanyl detection, but none of them have provided information about the impact on the assay performance caused by an excessive amount of lipids. This aspect may be, however, very important for highly lipophilic drugs like fentanyl. To address this issue, we developed the liquid chromatography method with mass spectrometry detection and utilized it to investigate the impact of lipids presence in rabbit plasma on the analytical method performance and validation. The validation procedure, conducted for normal plasma and lipemic plasma separately, resulted in good selectivity, sensitivity and linearity. The limits of detection and quantification were comparable between the two matrices, being slightly lower in normal plasma (0.005 and 0.015 µg/L) than in lipemic plasma (0.008 and 0.020 µg/L). Liquid–liquid extraction provided a low matrix effect regardless of the lipid levels in the samples (<10%), but pronounced differences were found in the recovery and accuracy. In the normal plasma, this parameter was stable and high (around 100%), but in the lipemic matrix, much more variable and less efficient results were obtained. Nevertheless, this difference had no impact on repeatability and reproducibility. In the present work, we provided reliable, convenient and sensitive method for fentanyl detection in the normal and lipemic rabbit plasma. However, construction of two separate validation curves was necessary to provide adequate results since the liquid-liquid extraction was utilized. Therefore, special attention should be paid during fentanyl quantification that involves lipemic plasma samples purified by this technique.

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Section: Discussionmentioning

confidence: 67%

Lipemia in the Plasma Sample Affects Fentanyl Measurements by Means of HPLC-MS2 after Liquid-Liquid Extraction

2021

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“…This is consistent with Landolf and colleagues, who found higher delirium-free and coma-free days in the hydromorphone group, which was driven by coma-free days but not delirium-free days. 8 Although there were no differences in opioid or sedative (propofol and benzodiazepine) doses per ECMO day between groups, there was a significant decrease in propofol requirements on ECMO days three, four, and five for patients in the hydromorphone group. This finding requires more investigation as one may imply that hydromorphone patients may have reduced propofol requirements at the expense of greater benzodiazepine use.…”

Section: Discussionmentioning

confidence: 79%

“…To our knowledge, only two studies directly compare fentanyl to hydromorphone and their impact on patient-centered clinical outcomes. 8,9 Given the knowledge of pharmacokinetics, ex vivo data, and limited in vivo data, some institutions have established hydromorphone as the primary opioid used in ECMO patients. At our institution, fentanyl is most commonly utilized as the first-line opioid.…”

Section: Introductionmentioning

confidence: 99%

Opioid and sedative requirements in extracorporeal membrane oxygenation patients on hydromorphone versus fentanyl

et al. 2021

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Background:The extracorporeal membrane oxygenation (ECMO) circuit causes pharmacokinetic alterations of medications which impact drug selection and dosing. Although hydromorphone has a favorable pharmacokinetic profile, it is unclear whether hydromorphone provides better patient-centered benefits compared to fentanyl. The objective of this study is to compare opioid and sedative requirements in ECMO patients started on a fentanyl-versus hydromorphonebased analgesia regimen.Methods: This was a non-interventional retrospective cohort study. It was conducted at a single center in the cardiovascular intensive care units and cardiac intensive care units. We included venovenous (VV) or venoarterial ECMO patients. Patients who were started on a fentanyl continuous infusion within 24 h of cannulation were compared to patients started on a hydromorphone continuous infusion. Results:A linear mixed effects model was performed to compare doses of opioid, sedative, and propofol between groups over time. We included 28 hydromorphone patients and 53 fentanyl patients, with 85% on VV ECMO. There were no differences between hydromorphone and fentanyl groups in opioid or sedative (including propofol and benzodiazepine) doses for any ECMO day (p value for interaction .63 and .83, respectively). Propofol doses alone, however, were significantly higher in the fentanyl group on ECMO days three, four, and five.Conclusions: There appear to be no major differences in opioid or sedative requirements whether ECMO patients are initiated on a hydromorphone-or fentanyl-based regimen.

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“…17,25 A retrospective observational study evaluating fentanyl-versus hydromorphone-based sedation in adult patients on ECMO support demonstrated lower narcotic requirements and more delirium-free and coma-free days in the hydromorphone cohort. 26 However, in a similar study, fentanyl-based sedation was shown to have numerically lower requirements of nonanalgesic sedatives and a statistically significant reduction in benzodiazepine requirements when compared to alfentanil, which is a less lipophilic fentanyl derivative. Therefore, the lipophilicity concerns do not appear to fully explain benefits seen with non-fentanyl-based sedation.…”

Section: Parenteral Opioidsmentioning

confidence: 94%

Approach to Sedation and Analgesia in COVID-19 Patients on Venovenous Extracorporeal Membrane Oxygenation

et al. 2021

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Objective: To describe clinically pertinent challenges of managing sedation in COVID-19 patients on venovenous extracorporeal membrane oxygenation (VV-ECMO) and describe considerations for enhanced safety and efficacy of pharmacological agents used. Data Sources: A PubMed search was performed using the following search terms: ECMO, ARDS, sedation, COVID-19, coronavirus, opioids, analgesia, fentanyl, hydromorphone, morphine, oxycodone, methadone, ketamine, propofol, dexmedetomidine, clonidine, benzodiazepines, midazolam, lorazepam, and diazepam. Study Selection and Data Extraction: Relevant clinical and pharmacokinetic studies were considered. All studies included were published between January 1988 and March 2021. Data Synthesis: Patients with acute respiratory distress syndrome secondary to COVID-19 may progress to requiring VV-ECMO support. Agents frequently used for sedation and analgesia in these patients have been shown to have significant adsorption to ECMO circuitry, leading to possible diminished clinical efficacy. Use of hydromorphone-based analgesia has been associated with improved clinical outcomes in patients on VV-ECMO. However, safety and efficacy regarding use of other agents in this patient population remains an area of further research. Relevance to Patient Care and Clinical Practice: This review addresses clinical challenges associated with sedation management in COVID-19 patients requiring VV-ECMO support and provides potential strategies to overcome these challenges. Conclusions: Historically, sedation and analgesia management in patients requiring ECMO support have posed a challenge for bedside clinicians given the unique physiological and pharmacokinetic changes in this patient population. A multimodal strategy to managing analgesia and sedation should be used, and the use of enteral agents may play a role in reducing parenteral agent requirements.

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Comparison of Hydromorphone versus Fentanyl‐based Sedation in Extracorporeal Membrane Oxygenation: A Propensity‐Matched Analysis

Cited by 19 publications

References 30 publications

Lipemia in the Plasma Sample Affects Fentanyl Measurements by Means of HPLC-MS2 after Liquid-Liquid Extraction

Lipemia in the Plasma Sample Affects Fentanyl Measurements by Means of HPLC-MS2 after Liquid-Liquid Extraction

Opioid and sedative requirements in extracorporeal membrane oxygenation patients on hydromorphone versus fentanyl

Approach to Sedation and Analgesia in COVID-19 Patients on Venovenous Extracorporeal Membrane Oxygenation

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