Although many factors are involved in the development of phlebitis, including patient-related factors (e.g., advanced age, female sex, fragility, and immunosuppression) as well as use-related factors (e.g., poor catheter placement or catheter device management) and device-related factors (e.g., improper catheter size and failure to properly secure the IV catheter), physiochemical properties of the IV solution may also play a major role. IV solutions can have direct cytotoxic effects on veins, cause vasoconstriction, and produce damage by exposing cells to osmotic stress or nonphysiological pHs.

In order to further clarify the role of physiochemical properties of IV solutions in the development of adverse events (AEs), researchers undertook a three-phase project to standardize the dilutions of IV drugs most commonly used in hospitalized adult patients and to characterize the pH, osmolarity, and cytotoxic nature of these solutions.

Using a modified double-round Delphi method, 29 clinicians from multiple disciplines, including members of an Expert Advisory Group, developed a list of IV solutions (drugs and concentrations) intended for continuous or intermittent infusion in hospitalized patients. Drugs for direct IV administration, oncologic and radiologic drugs, and drugs for pediatric patients were excluded. All study drugs used either sodium chloride 0.9% (i.e., normal saline [NS]) or dextrose 5% in water [D5W] as the diluents based on their drug-diluent compatibility. For a drug to be included in the study, at least 70% of participating clinicians had to agree on a specific drug-concentration pair based on the pair's utility in various clinical situations.

A total of 106 drugs corresponding to 183 different concentrations and 307 different admixtures were included in the final analysis. Of these IV solutions, 36.6% were administered by continuous infusion and 63.4% were given by intermittent administration. These drugs were analyzed for pH, osmolarity, and vesicant nature. Vesicants were identified by a drug's prescribing information and the published literature.  

Drugs were categorized as having high risk, moderate risk, or low risk for AEs based on these three properties as determined by the medical literature and expert opinion. High-risk drugs were those with an osmolarity >600 milliosmoles (mOsm)/L or pH <4 or >9 or were known vesicants based on the literature. Moderate-risk drugs were those with an osmolarity between 450 and 600 mOsm/L or pH between 4 and 5 or 7.5 and 9 or were not known vesicants. Low-risk drugs were medications with an osmolarity <450 mOsm/L or a pH between 5 and 7.5 or were not known vesicants.

With respect to osmolarity, most admixtures (91.5%, which represented 101 drugs), had an osmolarity <600 mOsm/L and therefore had a moderate to low risk for AEs. However, 26 admixtures (which corresponded to 15 drugs) had an osmolarity >600 mOsm/L, which is considered high-risk for AEs. Admixtures that used D5W as a diluent tended to have a slightly higher osmolarity and slightly lower pH compared with NS. For a drug with high osmolarity, modifying the infusion rate or diluting the drug further may reduce the risk of phlebitis.

As to pH, 46.3% of admixtures (which corresponded to 60 drugs) had a pH between 5 and 7.5, indicating the lowest risk of AEs, but over one-fifth (20.1%) of admixtures (representing 29 drugs) had extremes of pH, (i.e., either <4 for 18 drugs or >9 for nine drugs), which put them at high risk for AEs.

A total of 19 drugs were deemed to be vesicants.

In total, 123 admixtures (40%), which involved 45 drugs (40%), were considered to be at high risk for AEs. Conversely, 99 (32.2%) of admixtures, which represented 47 (44.3%) of drugs, were deemed to be at low risk for complications.

Based on this information, the investigators proposed an algorithm for the selection of venous access to minimize AEs.

This article provides pharmacists and prescribers with useful information on identifying IV solutions that are most problematic based on their physiochemical properties. It also offers mitigation strategies to prevent AEs.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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