Sedative Pharmacodynamics in Patients Supported With Extracorporeal Membrane Oxygenation
Bibliographic record
Abstract
Introduction: In patients supported with venovenous extracorporeal membrane oxygenation (VV ECMO), sedation is used to blunt respiratory drive. However, previous studies have shown a poor correlation between sedation scores and respiratory effort. This study evaluated the pharmacodynamic (PD) effects of commonly used sedatives (propofol and fentanyl) in sedation scores and respiratory effort of patients receiving VV ECMO support. Methods: This was a prospective, single-center, open-label PD study of propofol and fentanyl in patients with VV ECMO at the Toronto General Hospital. Sedative plasma concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. Patients’ sedation profile was measured with processed electroencephalography [patient state index (PSI)]; Riker-sedation agitation scale (SAS) was used to calculate the PSI area under the curve for deep sedation (SAS 1-2) prediction. Respiratory effort was measured using airway occlusion pressure (Pocc) and occlusion pressure during the first 0.1 seconds (P0.1). The primary outcome was the association of sedative concentrations with PSI, P0.1 and Pocc. Results: One hundred six evaluations were performed in 11 patients supported with VV ECMO. Mean (SD) age was 43 (±13) years, and 55% were female. Patients were followed for a median (IQR) of 146 (116-146) hours, all patients were sedated with propofol and fentanyl before ECMO cannulation, ten patients (91%) were paralyzed at the time of cannulation, and no patient was paralyzed beyond day one post-cannulation. The area under the curve for detecting deep sedation with PSI was 0.97 (95% CI 0.94-0.97), with an optimal PSI cut-off point of 62. However, oversedation with PSI <40 was encountered in 74% of the observations. PSI strongly correlated with propofol concentrations (correlation coefficient R= -0.7, p<0.001) but weakly correlated with fentanyl concentrations (R= -0.17, p= 0.02). Regarding respiratory effort, 34 observations were excluded due to neuromuscular blockade use, P0.1 and Pocc ranged between -14 to 0 [median (IQR) 0 (-1.5 to 0)] and -45 to 0 [median (IQR) 0 (-6.0 to 0)] cm H2O, respectively. Multiple linear regression showed a weak correlation between propofol concentrations and P0.1 (R= 0.3, p=0.01) andPocc (R= 0.35, p=0.01), and no significant association with fentanyl concentrations (p=0.4), sweep gas (p=0.4), or PaCO2 (p=0.2). Conclusion: There was a strong correlation between propofol concentrations and PSI but a weak correlation between propofol concentrations and respiratory effort, with variable respiratory drive observed across the range of sedative plasma concentrations. No significant correlation was found for fentanyl with PSI or respiratory effort.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".