Stability, Compatibility, and Safety of Intrathecal Bupivacaine Administered Chronically via an Implantable Delivery System

Abstract

Bupivacaine is stable and compatible with a commonly used implantable drug infusion system. In this study, chronic supplementation of intrathecal opioids with bupivacaine was a safe method for providing continued management of chronic pain of cancer or noncancer origin.

Programmable Intrathecal Opioid Delivery Systems for Chronic Noncancer Pain: A Systematic Review of Effectiveness and Complications

“…Among these, 52 articles were excluded from both the effectiveness and complications review based on the same criterion: 26 because they were case reports ; 13 because they did not report data separately for patients with programmable IDDS, 39-51 9 because >10% of the sample had spasticity or a specific disease [52][53][54][55][56][57][58][59][60] ; and 4 because they focused only on patients who had not responded to their first IDDS drug. [61][62][63][64] (Where there was more than 1 reason for exclusion, we noted only the first reason identified.)…”

Stability and Tolerability of High Concentrations of Intrathecal Bupivacaine and Opioid Mixtures in Chronic Noncancer Pain: An Open-Label Pilot Study

“…Another simulated study using 7.5 mg/mL bupivacaine in aqueous hyperbaric dextrose (82.5 mg/mL) showed a similar bupivacaine stability with greater than 96% of the original concentration remaining at 12 weeks [18]. A recent in vitro study that examined mixtures of morphine sulphate or hydromorphone (both 50 mg/mL), bupivacaine hydrochloride (24 mg/mL), and clonidine hydrochloride (2 mg/mL) showed good stability over 90 days at 37°C [19].…”

Bupivacaine crystal deposits after long-term epidural infusion

“…At this point interventional pain therapy, such as epidural analgesia can be introduced with much greater efficacy [12]. Tissue toxicity to LA has been documented in animal studies particularly at higher concentrations [2,3,4,6,7,8,11,13,14,15,16,17,18,19,20,25,29,31,32,33,34,37,38] but seldom observed using the recommended clinical concentrations in humans [1,15,22,23,24,26,28,31].…”

“…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.…”