Plasma morphine and glucuronide (M3G and M6G) concentrations in hospice inpatients

Abstract

Plasma morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) concentrations were quantified by high performance liquid chromatography (HPLC) in 36 hospice inpatients receiving morphine orally or subcutaneously. The data were analyzed in relation to dose, serum creatinine, serum gamma glutamyl transferase, and presence or absence of opioid-induced adverse effects. There were significant associations (P < 0.05) between plasma morphine, M3G (subcutaneous route only), and M6G concentrations and dose for both routes of administration. The mean dose-corrected plasma morphine concentration for the subcutaneous group was three times that of the oral group, confirming present oral to subcutaneous dose conversion practices. Nineteen patients experienced symptoms attributed to morphine: nausea and vomiting in ten and acute delirium in nine. Serum creatinine was elevated in patients with adverse effects (P = 0.031), as were the dose-corrected plasma M3G (P = 0.029) and M6G (P = 0.043) concentrations. All seven patients with serum creatinine concentrations above the normal range had symptoms attributed to opioid-induced adverse effects. Plasma M3G, M6G, and dose-corrected plasma M3G and M6G concentrations were significantly (P < 0.001) higher in these patients than in those with normal serum creatinine concentrations. The data indicate that accumulation of M3G and M6G may be a causal or aggravating factor in the nausea and vomiting and cognitive function profile of palliative and terminal care patients with significant renal function impairment.

Delirium and dehydration: some fluid for thought?

“…A study of cancer patients found no correlation between cognitive impairment and the morphine-6-glucuronide-to-morphine ratio [101]. In a small case series of hospice patients with morphine-related side effects, including cognitive impairment and nausea, morphine metabolite levels were elevated compared with controls, but it was not possible to establish the relative contribution of renal impairment and elevated metabolite levels to these side effects [4]. Although the plasma concentration of opioid metabolites has not been studied in relation to dehydration or volume deficit states, it is logical to assume that opioid metabolite levels would be elevated in these states, owing to their increased concentration in a reduced intravascular volume, and possibly also because of their reduced renal excretion.…”

The panorama of opioid‐related cognitive dysfunction in patients with cancer

“…These studies have consistently demonstrated elevated metabolite levels 88,89,92,[101][102][103][104][105][106] when measured in renal impairment. They also have suggested a frequent association between renal impairment and opioid toxicity.…”

Randomized Clinical Trial of Efficacy and Safety of a Single 2‐mg Intravenous Dose of Hydromorphone Versus Usual Care in the Management of Acute Pain

“…We speculate that the lack of a clear, linear inversely proportionate relationship between amount of opioid administered and need for additional analgesia when asked reflects the tremendous amount of interpatient variability in opioid requirement. 16,28,29 This is presumably driven, at least in part, by substantial differences in the "objective" magnitude of the painful stimulus; its subjective perception; and the poorly understood Values are n (%) unless otherwise noted. NRS = numeric rating scale.…”