Physico‐chemical stability of Plasma‐Lyte 148® and Plasma‐Lyte 148® + 5% Glucose with eight common intravenous medications

Abstract

Summary Background Plasma‐Lyte 148® is a balanced, crystalloid intravenous (IV) fluid which is both calcium‐free and isotonic. It prevents the hyperchloremic metabolic acidosis and iatrogenic hyponatremia seen with use of 0.9% sodium chloride and hypotonic solutions, respectively. However, data on compatibility with commonly used drugs are lacking. Aims To investigate the stability of Plasma‐Lyte 148® and Plasma‐Lyte 148® + 5% Glucose with eight commonly used therapeutic agents when compared with 5% glucose and 0.9% sodium chloride as diluents. We aimed to provide vital data which may facilitate the introduction of what appears to be a safer and more economic fluid. Methods Plasma‐Lyte 148® and Plasma‐Lyte 148® + 5% Glucose were mixed with morphine, midazolam, fentanyl, ketamine, clonidine, aminophylline, salbutamol, and furosemide at set concentrations. Comparisons were made to 0.9% sodium chloride and 5% glucose fluid controls. Six repeats of each IV fluid and drug admixture were analyzed through high‐performance liquid chromatography at three time points: 0, 2, and 24 hours. A concentration change of <5% was defined as chemically stable. Physical stability was assessed by observation of precipitate formation or color change. pH changes were measured using a Fisherbrand Hydrus 300 pH meter. Results Relative to starting concentration, all drugs except midazolam were stable to ±3%. All examined therapeutic agents were chemically stable at 2 and 24 hours relative to control solutions. No precipitate formed in any of the samples. All Plasma‐Lyte 148® and Plasma‐Lyte 148® + 5% Glucose drug admixtures remained in a safe, peripheral administration pH range of 5‐9 and were closer to the pH of blood than standard fluid‐drug admixtures. Conclusion Morphine, fentanyl, ketamine, salbutamol, aminophylline, and clonidine are stable for 24 hours when mixed with Plasma‐Lyte 148® and Plasma‐Lyte 148®+5% Glucose for administration at concentrations equivalent to those found at a typical Y‐site with maintenance fluid. Furosemide is stable at lower concentrations than those seen at a Y‐site, but midazolam displayed instability.

Exploring a case of incompatibility in a complex regimen containing Plasma‐Lyte 148 in the pediatric intensive care

“…Dawson et al studied the compatibility of ketamine 0.2 mg/ml (1 + 30) with the buffered electrolyte solution and concluded that the mix was physically compatible in the mixing ratio of 1 + 30 18 . Baxter Medical concluded that equal parts of ketamine 2 mg/ml and the buffered electrolyte solution to be physically compatible 19 .…”

“…Three studies investigating the intravenous compatibility of the same buffered electrolyte solution and the buffered electrolyte‐glucose solution with one‐drug‐at‐a‐time have been published. These studies reported concentration dependent compatibility between midazolam and the two buffered electrolytes, irrespective of whether glucose was present 17–19 . Hammond et al 17 investigated physical compatibility by visual inspection and reported that precipitation formed immediately when mixing three parts of midazolam 3 mg/ml with two parts of the buffered electrolyte solution or the buffered electrolyte‐glucose solution.…”

“…These studies reported concentration dependent compatibility between midazolam and the two buffered electrolytes, irrespective of whether glucose was present. 17 , 18 , 19 Hammond et al 17 investigated physical compatibility by visual inspection and reported that precipitation formed immediately when mixing three parts of midazolam 3 mg/ml with two parts of the buffered electrolyte solution or the buffered electrolyte‐glucose solution. Dawson et al 18 did not see any precipitation when investigating compatibility of midazolam 0.25 mg/ml with the buffered electrolyte solution.…”

“… 17 , 18 , 19 Hammond et al 17 investigated physical compatibility by visual inspection and reported that precipitation formed immediately when mixing three parts of midazolam 3 mg/ml with two parts of the buffered electrolyte solution or the buffered electrolyte‐glucose solution. Dawson et al 18 did not see any precipitation when investigating compatibility of midazolam 0.25 mg/ml with the buffered electrolyte solution. On the contrary, the manufacturer Baxter Medical reported that midazolam 1 mg/ml was compatible with the buffered electrolyte solution.…”

“…Dawson et al studied the compatibility of ketamine 0.2 mg/ml (1 + 30) with the buffered electrolyte solution and concluded that the mix was physically compatible in the mixing ratio of 1 + 30. 18 Baxter Medical concluded that equal parts of ketamine 2 mg/ml and the buffered electrolyte solution to be physically compatible. 19 It should be noted that the ketamine concentration in the mixtures of both these studies were lower than in our studies (=6.5 μg/ml and 1 mg/ml, respectively), compared with our clinical case and study using 10 mg/ml for 1 + 1 (=5 mg/ml) and 1 + 3 (=2.5 mg/ml).…”