The stability of mixtures of morphine hydrochloride, bupivacaine hydrochloride, and clonidine hydrochloride in portable pump reservoirs for the management of chronic pain syndromes

Abstract

The physical and chemical stability of a combination of drugs commonly administered into the epidural or intrathecal space for the treatment of chronic pain was investigated. The concentrations of bupivacaine hydrochloride, morphine hydrochloride, and clonidine hydrochloride were measured using high performance liquid chromatography. The solutions were stored in reservoir bags for up to 90 days. No macroscopic or microbiological signs of precipitation, change in color, or contamination were observed, and pH remained stable. None of the three drugs declined in concentration during the observation period. A small increase in concentration of all three drugs did occur over time, most probably due to evaporation processes. In conclusion, no problems in physical or chemical stability are to be expected when combining morphine, bupivacaine, and/or clonidine for long-term epidural or intrathecal administration. In the case of clinically apparent loss of analgesic efficacy, other mechanisms should be considered.

Endocrine Consequences of Long-Term Intrathecal Administration of Opioids

“…There are some indications that patients can obtain more effective pain control from intrathecal treatment, as morphine is supplied directly at the level of the spinal cord (6). Other medications, such as clonidine, nonsteroidal antiinflammatory drugs, neostigmine, ketamine, octreotide, and aspirin, can be added intrathecally to enhance the analgesic effects of morphine (7). By contrast, the hope that the intrathecal administration of opioids would substantially reduce the number of side-effects associated with oral morphine has not been fulfilled (8).…”

Bupivacaine crystal deposits after long-term epidural infusion

“…Morphine does not alter the pH or solubility of LA mixtures [5,16]. The stability and compatibility of such LA mixtures are proven to be safe in infusion systems [5,9,14,16,30] and safe when used clinically [14]. On the contrary this case and anoth- er case report [1] discovered bupivacaine deposits with unreactive necrosis in different human tissues (e.g.…”

Infusate Contamination in Regional Anesthesia: What Every Anesthesiologist Should Know

“…Wulf et al 43 examined mixtures of bupivacaine 0.3%, morphine 6.7 mg/mL, and clonidine 0.03 mg/mL from portable pump reservoirs intended for intrathecal infusion. They found that at room temperature, these mixtures were microbiologically stable over a period of 90 days.…”

“…Much attention has been given to the assessment of chemical stability of local anesthetics alone or in combination with epinephrine or opioids. [38][39][40][41][42][43] These admixtures have been studied in both polyvinylchloride bags and in portable infusion pumps. In general, compounds commonly used in regional anesthetic practice, including lidocaine, bupivacaine, ropivacaine, morphine, fentanyl, and hydromorphone, are chemically stable for periods of weeks to months and are not the limiting factor in determining hang-time.…”