Technical Report The effect of pancuronium on the solubility of aqueous thiopentone

Abstract

In this study we identified the precipitate formed when pancuronium bromide (.oH 3.9) and sodium thiopentone (pH 10.6) potency, pulmonary vascular tone or the incidence of peripheral thrombophlebitis are unclear.Since a number of reaction products could result from combining solutions of thiopentone and pancuronium, we determined the composition of the precipitate and supernatant when these two drugs are combined. MethodsA commercial preparation (Abbott Laboratories) of 1 g of sodium thiopentone with 60 mg sodium carbonate was diluted with 40 ml of double-distilled water immediately before each study. Commercially supplied ampoules of pancuronium bromide in a 0.1 per cent solution (Organon) were warmed to room temperature for all experiments.To determine the effect of pH on the solubility of thiopentone, 10ml of thiopentone (2.5 per cent) was stirred continuously at room temperature while the pH was monitored using a Radiometer pH meter. The pH ranter was calibrated with three standard solutions of pH 4.01, 7.00, and 9.18. Hydrochloric acid (HCI) (0.2 N) was titrated slowly into the thiopentone solution. When a persistent white suspension was observed, the pH was recorded. The study was then repeated with pancuronium 0.1 per cent substituted for the 0.2 N HC1. All titrations were repeated in triplicate.Ultraviolet (UV) light is strongly absorbed by covalent chemical bonds. A given arrangement of bonds (for example, a benzene ring) will absorb a specific range of UV frequencies within the UV spectrum. As a result, a complex molecule such as pancurunium or thiopentone will have a pattern of UV absorption which reflects its unique chemical structure, The UV absorption spectrum of thiopentone was detcrrnined by acidifying 2.5 per cent thiopentone with 0. l N HCI. The resultant precipitate was washed; redissolved in NaOH solution, and analyzed. The UV absorption spectrum of pancuronium was determined after dilution to a 0.01 per cent solution.In the final study, we analyzed the precipitate. A high-speed centrifuge tube was filled with 50/a,l of 2.5 per cent thiopentone and 4.5 cc of 0. I per cent pancuronium. CAN J ANAESTH 1987 ,' 34:1 r pp87-9

Precipitation of thiopental with muscle relaxants: a potential hazard

“…Mivacurium, closest in pH to thiopentone shows the least precipitation compared with the other more acidic muscle relaxants. The precipitate for the reaction has been shown by UV spectrophotometry to be thiopentone acid, 4 and subsequent studies have shown that it is highly insoluble in human plasma (<0.1 mg mL −1 ), especially when compared with thiopental (700 mg mLl −1 ). 3 …”

Anaphylactic reactions during induction of anaesthesia using rocuronium for muscle relaxation: A report including 3 cases

“…We would like to draw attention to the precipitation in the iv line that may occur when muscle relaxants are injected (36). When thiopental (pH 11) is mixed with a nondepolarizing muscle relaxant (pH 4) a precipitation of insoluble thiopental crystals occurs (41,42). Animal studies have shown that these thiopental crystals cause lung emboli (41), which may cause bronchospasm due to the release of bronchoconstrictive mediators in the lung capillaries (2,36).…”

De‐mystifying the “Mixifusor”

“…Trial and error (lots of errors…) showed that precipitation may follow in any number of unlicensed drug mixtures with succeeding generations repeating the mistakes of their predecessors. 1,2 Naïvely, anesthetists may assume that the absence of crystals or of any other changes visible to the naked eye implies compatibility but this is not necessarily the case. Ever since it first became available for use in clinical practice, anesthetists have experimented with the addition of diluents and other drugs to the propofol formulation.…”

“…Older anesthetists may remember the crunch of precipitating thiopental caused by injecting succinylcholine into an un‐flushed cannula. Trial and error (lots of errors…) showed that precipitation may follow in any number of unlicensed drug mixtures with succeeding generations repeating the mistakes of their predecessors 1,2 . Naïvely, anesthetists may assume that the absence of crystals or of any other changes visible to the naked eye implies compatibility but this is not necessarily the case.…”