Stability and Compatibility of Hydromorphone and Ketamine in Normal Saline
Bibliographic record
Abstract
ABSTRACT Objectives: This report presents the results of a 2-part study of hydromorphone and ketamine. The objective of the first part of the study was to assess the physical compatibility over a 24-h period of 12 combinations of hydromorphone and ketamine prepared in syringes by direct mixing of the manufacturers’ solutions. The objective of the second part of the study was to evaluate the compatibility and chemical stability of 4 concentration combinations of hydromorphone and ketamine diluted in 0.9% sodium chloride (normal saline [NS]) after storage for 24 days at 4°C or 23°C. Methods: For the 24-h study, physical compatibility was assessed visually for mixtures of hydromorphone and ketamine at concentrations ranging from 1.0 to 47.5 mg/mL and from 0.5 to 49.0 mg/L, respectively. For the 24-day compatibility and chemical stability study, the following mixtures were assessed: hydromorphone 1.0 mg/mL and ketamine 0.5 mg/mL, hydromorphone 20.0 mg/mL and ketamine 0.5 mg/mL, hydromorphone 1.0 mg/mL and ketamine 20.0 mg/mL, and hydromorphone 20.0 mg/mL and ketamine 20.0 mg/mL. The mixtures were inspected visually, pH was determined, and the concentration of the 2 drugs in each mixture was determined by a stability-indicating liquid chromatographic method. Results: The concentrations of quality control samples and standards deviated less than 5% on average from known concentrations for both hydromorphone and ketamine. Mean analytical error for replicate samples between and within days was less than 5% for both drugs. For the 24-h physical compatibility study, the 12 mixtures of hydromorphone and ketamine were physically compatible for the duration of the study. For the 24-day chemical stability study, both hydromorphone and ketamine retained greater than 90% of their initial concentrations for the entire study period when stored at either 4°C or 23°C. The pH of all solutions changed by less than 0.2 pH unit over the study period. Conclusions: A 24-day expiration date is recommended for the following mixtures of hydromorphone and ketamine, diluted in NS and stored in glass at 4°C or 23°C: hydromorphone 1.0 mg/mL and ketamine 0.5 mg/mL, hydromorphone 20.0 mg/mL and ketamine 0.5 mg/mL, hydromorphone 1.0 mg/mL and ketamine 20.0 mg/mL, and hydromorphone 20.0 mg/mL and ketamine 20.0 mg/mL. Mixtures with a wider range of concentrations of the 2 drugs were physically compatible for 24 h, but expiry dates for mixtures of these drugs at any specific institution should take into account the known contamination rate within the institution’s IV additive program. RESUME Objectifs : Ce rapport presente les resultats d’une etude de deux parties sur l’hydromorphone et la ketamine. L’objectif de la premiere partie de l’etude etait d’evaluer la compatibilite physique, sur une periode de 24 heures, de 12 associations d’hydromorphone avec de la ketamine, preparees dans des seringues en melangeant directement les solutions du fabricant. L’objectif de la seconde partie etait d’evaluer la compatibilite et la stabilite chimique des associations hydromorphone–ketamine, a quatre concentrations differentes, diluees dans du chlorure de sodium a 0,9 % (solution salee [NS]) et entreposees pendant 24 jours a 4 °C ou a 23 °C. Methodes : Lors de l’etude de 24 heures, la compatibilite physique a ete evaluee par inspection visuelle des melanges hydromorphone–ketamine aux concentrations variant entre 1,0 et 47,5 mg/mL et entre 0,5 et 49,0 mg/L, respectivement. Lors de l’etude de compatibilite et de stabilite chimique sur 24 jours, les associations suivantes ont ete evaluees: hydromorphone 1,0 mg/mL-–ketamine 0,5 mg/mL, hydromorphone 20,0 mg/mL–ketamine 0,5 mg/mL, hydromorphone 1,0 mg/mL– ketamine 20,0 mg/mL, et hydromorphone 20,0 mg/mL– ketamine 20,0 mg/mL. Les melanges ont ete inspectes visuellement, le pH a ete mesure et les concentrations des deux medicaments dans chacun des melanges ont ete determinees au moyen d’une epreuve de stabilite par chromatographie liquide. Resultats : Les concentrations des etalons et des echantillons de controle de la qualite presentaient un ecart moyen inferieur a 5 % des concentrations connues pour l’hydromorphone et la ketamine. L’erreur analytique moyenne pour les sousechantillons entre chaque jour et d’un jour a l’autre etait inferieure a 5 % pour les deux medicaments. Pour l’etude de compatibilite physique de 24 heures, les 12 associations hydromorphone– ketamine se sont revelees physiquement compatibles pendant toute la duree de l’etude. Quant a l’etude de stabilite chimique sur 24 jours, l’hydromorphone et la ketamine ont toutes deux, entreposees a des temperatures de 4 °C ou de 23 °C, conserve plus de 90 % de leurs concentrations initiales pendant toute la duree de l’etude. Le pH de toutes les solutions a varie de moins de 0,2 unites de pH au cours de l’etude. Conclusions : Il est recommande de ne pas conserver pendant plus de 24 jours les melanges suivants d’hydromorphone et de ketamine, dilues dans du NS et entreposees dans des contenants de verre a 4 °C ou a 23 °C : hydromorphone 1,0 mg/mL– ketamine 0,5 mg/mL, hydromorphone 20,0 mg/mL–ketamine 0,5 mg/mL, hydromorphone 1,0 mg/mL–ketamine 20,0 mg/mL, et hydromorphone 20,0 mg/mL–ketamine 20,0 mg/mL. Les melanges des deux medicaments a des concentrations plus etendues etaient physiquement compatibles pendant 24 heures; les dates d’expiration des melanges de ces deux medicaments doivent tenir compte du taux de contamination bacterienne relatif au programme d’additifs aux solutes intraveineux de chaque etablissement.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| 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) | 0.000 | 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 teacher head, 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".