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.

Twenty-eight patients with severe pain due to cancer, who could no longer obtain acceptable pain relief from optimised doses of oral opioids, were entered into a study which compared pain relief, satisfaction with pain therapy and estimates of neuropsychological functioning during treatment with spinally administered (i.e., epidural and intrathecal) morphine as either repeated bolus doses or as a continuous infusion. These measures of efficacy and side effects were repeated every 2 weeks until either the patient died (82% of patients), withdrew from the study or were no longer able to complete the tests due to deterioration of their condition. The mean (range) duration of treatment was 169 (6-537) days for those patients receiving continuous infusion and 140 (28-378) days for those patients receiving repeated bolus doses. There was no significant difference in visual analogue pain scores, pain relief scores and satisfaction scores between the bolus and infusion groups. Furthermore, low pain scores and high pain relief scores indicated that both treatment modalities provided effective pain control. Similarly, there was no significant difference between the two groups in the various tests used to assess depression or neuropsychological function (i.e., memory, vigilance, attention and processing). There was a significantly greater degree of dose escalation in patients receiving continuous infusion compared to patients receiving repeated bolus doses. For 6 patients in the infusion group the catheter was sited in the intrathecal space, as the dose requirements by the epidural route exceeded the delivery capacity of the pump. For 4 patients in the bolus group the catheter was similarly sited, due to pain on injection and leakage/blockage.(ABSTRACT TRUNCATED AT 250 WORDS)

Eighteen inpatients receiving morphine for cancer pain in a palliative care unit were recruited to a study employing a range of neuropsychological tests to assess cognitive function. The tests employed were National Adult Reading Test, Williams Delayed Recall Test, Immediate Memory for Digits, Trailing Making Test, and the Digit Symbol Substitution Test. These data were correlated with biochemical tests of renal and hepatic function, morphine dose, route of administration, plasma morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) concentrations. Despite having no clinical evidence of impairment of cognitive function, the level of current intellectual functioning (Symbol Digit Substitution Test) was on average two standard deviations below normal. Immediate memory appeared to be well preserved, but Delayed Recall and Trailing Making Test scores were significantly above normal. There was no significant correlation between morphine dose, or plasma morphine and M3G and M6G concentrations, and the neuropsychological test results, although a weak correlation was found between plasma morphine concentration and digits forward (r = -0.47, p < 0.05) and Digit Symbol Substitution scores (r = -0.46, p < 0.05). Seven patients had some degree of nausea or vomiting, ascribed as an opioid adverse effect, and had higher serum creatinine concentrations, worse neuropsychological performance, and significantly higher plasma M3G concentrations (p < 0.05). These data provide some evidence to suggest that cognitive functioning in patients with advanced cancer receiving morphine may be significantly impaired despite apparent clinical normality. From these data it is not possible to determine what relative causal contribution the disease and the drug made to these observations, although renal function, plasma morphine, and M3G concentrations may be important. Future research should address a broad range of neuropsychological testing to assist in the modification of practices aimed at enhancement of quality of life, such as opioid substitution or rotation.

No abstract

A Barlow‐type electromechanical strain gauge and an indium/gallium‐in‐rubber strain gauge were compared for linearity of output, replicability, stability, and sensitivity to temperature changes. Distension of the strain gauges was achieved by placing them on standard size glass dilators, while temperature changes were produced and monitored in a controlled environment. Both gauges demonstrated comparable and very linear outputs and both had high test‐retest reliability. Variations in temperature affected the outputs for both gauges, although for neither did they affect the degree of linearity between pen deflection and circumference. The electromechanical strain gauge was marginally less sensitive to temperature changes than the indium/gallium gauge, although for neither was the degree of error introduced of great practical significance. Although the output from the electromechanical strain gauge was slightly less stable over time than that from the indium/gallium gauge, when all variables were considered, the former gauge was marginally preferred over the latter.