Intrathecal administration of high-dose morphine solutions decreases the pH of cerebrospinal fluid

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Abstract
Terminally ill patients suffering from intractable cancer pain are treated in our hospital on an outpatient basis with a percutaneous intrathecal (i.t.) catherer and a portable pump delivering morphine continuously. In a patient showing an increased demand of morphine the dose was raised from 1.5 to 2 mg/h, but pain intensity did not decrease. Subsequently a 1.5 ml dose of 5% lidocaine was administered; however, no motor or sensory block was observed. After controlling the catheter position and passage through the catheter, a sample of cerebrospinal fluid (CSF) was taken and the pH was measured. It was found to be outside the physiological range of 7.19 (normal range: 7.27 – 7.37), possibly explaining the decreased activity of the local anesthetic. The purpose of this study was to determine the influence of morphine, with or without sodium metabisulfite, on pH in vitro, using artificial CSF (ACSF) and on pH in vivo during i.t. administration of morphine. An in vitro model was used to measure pH changes by adding a morphine solution (concentrations of 0.5, 2, 5 and 10 mg/ml) with and without sodium metabisulfite to ACSF solutions (Elliott B). Fourteen patients were consecutively selected for continuous administration of morphine. An i.t. catheter was inserted, tunnelled and connected with an external pump (Provider 5500, Abbott, Chicago, IL). CSF was aspirated and pH was measured with a blood-gas system (Ciba-Corning 288, Medfield, USA). In vitro, morphine solutions with or without sodium metabisulfite added to an Elliott B solution (pH = 7.47, 37°C) caused a concentration-related decrease in pH. In vivo, in 9 patients, the daily morphine dose was less than 24 mg and the range of the CSF pH was between 7.25 and 7.44. In 5 patients, the daily morphine dose was higher than 24 mg and the CSF pH ranged from 6.92 to 7.24. In 4 patients myoclonic seizures and an increase in pain were observed. Our study suggests that long-term i.t. administration of high-dose morphine solutions with or without sodium metabisulfite may decrease the pH of CSF outside the normal range of 7.27 – 7.37. This may explain the diminished effectiveness of i.t. administered local anesthetics and morphine due to the increase of the ionized part of the available drug. Buffer capacity of CSF is insufficient to maintain normal pH values in patients receiving high doses of morphine solutions. A more neutral morphine formulation may be necessary for i.t. use.