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Physical Incompatibility of Injection Diclofenac Sodium with Isolyte P

Sinha, Prabhat Kumar MD; Neema, Praveen Kumar MD; Manikandan, Sethuraman MD; Unnikrishnan, K. P. MD

doi: 10.1213/01.ANE.0000106968.93476.DD
LETTERS TO THE EDITOR: Letters & Announcements

Department of Anesthesiology

Sree Chitra Tirunal Institute for Medical Sciences and Technology

Trivandrum, India

To the Editor:

Diclofenac sodium, a nonsteroidal antiinflammatory drug, is commonly used to provide analgesia in perioperative settings. Its physical incompatibility with IV fluid is unknown. However, we wish to report an incident of its physical incompatibility with Isolyte P used during elective neurosurgery.

A 7-yr-old, 18-kg boy, diagnosed to have an intracranial mass with the features of obstructive hydrocephalus, was scheduled for endoscopic third ventriculostomy under endotracheal anesthesia. During the surgical procedure, Isolyte P, a pediatric maintenance fluid, through a three-way connector connected to a 10-cm extension tube, was run to one of the patient’s arm veins. As soon as we started injecting diclofenac sodium (Voveran® Novartis India Limited, Thane, India), 25 mg, diluted in 10 mL 0.9% normal saline via three-way connector through which Isolyte P was also running, we noticed white precipitation along the tubing distal to the three-way connector. The injection was stopped immediately before the precipitate could enter the circulation.

This observation was reproduced in vitro after mixing 1 mL of the diclofenac injection with 25 mL of the Isolyte P in a test tube. A thin film of the solution was prepared on the slide and viewed under microscope that confirmed that mixing the two solutions indeed produce precipitate. Furthermore, we sent the drug (Voveran®) for the analytical examination by the gas chromatographic method and found that 22.83% propylene glycol was present in the solution. We believe that the preservative present in the diclofenac injection (propylene glycol) must have interacted with one of the constituents of Isolyte P. Isolyte P contains, apart from salts of potassium and sodium, the sodium metabisulphite. In vitro, potassium and sodium salts do not precipitate upon mixing with the diclofenac sodium injection. To prove our point further, we mixed diazepam injection (Tablets [India] Ltd, Chennai) (which also contains propylene glycol) with Isolyte P and noticed similar white precipitates. Moreover, preservative free diclofenac injection (Troika, Gujarat, India) (that does not contain propylene glycol) when mixed with Isolyte P did not precipitate. Therefore, it is certain that the propylene glycol and sodium metabisulphite, constituents in the diclofenac sodium injection and in the Isolyte P, respectively, have interacted and caused physical incompatibility.

The recommendation of the manufacturer of the diclofenac sodium is to buffer the drug with sodium bicarbonate before its use; however, we routinely mix diclofenac injection in 100 mL of either lactated Ringer’s or normal saline (0.9%) without buffering with sodium bicarbonate and use it as an IV infusion over a half-hour period in perioperative settings. We never had this problem before. Hence, in the present case also, we did not buffer it with sodium bicarbonate before injection.

The clinical significance of this physical incompatibility is uncertain. However, it is known that the particles larger than 6 μm in diameter, as might occur with physical incompatibility, have a potential for embolization, especially in lungs (1). Furthermore, physical incompatibility may also result in altered drug potency. However, we do not know the exact level of decreased potency of diclofenac in this context.

Our observation suggests that the diclofenac injection and Isolyte P combination should be added to the list of drugs known to cause physical incompatibility. Furthermore, we recommend injection diclofenac should be administered in dedicated IV lines.

Prabhat Kumar Sinha, MD

Praveen Kumar Neema, MD

Sethuraman Manikandan, MD

K. P. Unnikrishnan, MD

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Reference

1. Levene MI, Wigglesworth JS, Desai R. Pulmonary fat accumulation after intralipid infusion in the preterm infant. Lancet 1980; 2: 815–8.
© 2004 International Anesthesia Research Society