Day-to-day variations during clinical drug monitoring of morphine, morphine-3-glucuronide and morphine-6-glucuronide serum concentrations in cancer patients. A prospective observational study.

BACKGROUND: The feasibility of drug monitoring of serum concentrations of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) during chronic morphine therapy is not established. One important factor relevant to drug monitoring is to what extent morphine, M6G and M3G serum concentrations fluctuate during stable morphine treatment. METHODS: We included twenty-nine patients admitted to a palliative care unit receiving oral morphine (n = 19) or continuous subcutaneous (sc) morphine infusions (n = 10). Serum concentrations of morphine, M6G and M3G were obtained at the same time on four consecutive days. If readmitted, the patients were followed for another trial period. Day-to-day variations in serum concentrations and ratios were determined by estimating the percent coefficient of variation (CV = (mean/SD) x100). RESULTS: The patients' median morphine doses were 90 (range; 20-1460) mg/24 h and 135 (range; 30-440) mg/24 h during oral and sc administration, respectively. Intraindividual fluctuations of serum concentrations estimated by median coefficients of day-to-day variation were in the oral group for morphine 46%, for M6G 25% and for M3G 18%. The median coefficients of variation were lower in patients receiving continuous sc morphine infusions (morphine 10%, M6G 13%, M3G 9%). CONCLUSION: These findings indicate that serum concentrations of morphine and morphine metabolites fluctuate. The fluctuations found in our study are not explained by changes in morphine doses, administration of other drugs or by time for collection of blood samples. As expected the day-to-day variation was lower in patients receiving continuous sc morphine infusions compared with patients receiving oral morphine.

Self-reports are not related to objective assessments of cognitive function and sedation in patients with cancer pain admitted to a palliative care unit.

Cancer patients often report complaints of cognitive impairment and sedation. It is not well known if subjective complaints reflect objective assessments of cognitive function (CF) and sedation. We obtained self-reports of sedation and CF from 29 patients admitted to a palliative care unit and receiving morphine treatment. Sedation was reported on a verbal rating scale (VRS) and CF was reported using the EORTC QLQ-C30 health-related quality-of-life questionnaire CF scale. The self-reports were compared with objective assessments of sedation and CF by applying the Observer's Assessment of Alertness/Sedation (OAA/S) scale and Mini Mental State Examination (MMS), respectively. The assessments were repeated for seven patients who were readmitted to the palliative care unit. The patient self-reports of memory, concentration and sedation were dichotomized into noncomplainers and complainers. The percentages of complainers were 54%, 46% and 37% for memory, concentration and sedation, respectively. Patients who complained from difficulties with concentration or memory did not score differently from noncomplainers on objective assessments of CF (MMS score), but had a significantly higher level of fatigue. Patients complaining from sedation did not score differently from noncomplainers on objective assessments of sedation (OAA/S score). We observed no significant correlations between EORTC QLQ-C30 CF scale scores and MMS scores, or between VRS sedation scores and OAA/S scores. The study demonstrates a lack of relationship between patient self-reports and objective methods for assessing sedation and cognitive failure. This finding illustrates the importance of differentiating between observations and patient self-reports. The results also question the validity of patient self-reports for measurements of cognitive failure and sedation.