IV Drug Administration Considerations

Terminology

Admin Method

IV push: an IV “push” or “bolus” is an injection of medication through a needleless port on an existing IV line. A syringe is inserted into the catheter to send a one-time dose of drug into the bloodstream. The use of terms IV bolus or IV push can mistakenly be interpreted as meaning the drugs are to be administered quickly. This is not the case as medications administered by direct IV injection are given slowly, over at least 1 minute and often for even longer (e.g. 2 to 5 minutes).

IV infusion: an IV infusion is a controlled administration of medication into the bloodstream over time. The two main methods of IV infusion use either gravity or a pump to send medication into the catheter:

Pump infusion. A pump infusion is the most common method used. The pump is attached to the IV line and sends medication and a solution, such as sterile saline, into the catheter in a slow, steady manner. Pumps may be used when the medication dosage must be precise and controlled.
Drip infusion. This method uses gravity to deliver a constant amount of medication over a set period of time. With a drip, the medication and solution drip from a bag through a tube and into the catheter.

Types of IV Infusions:

Continuous infusion – the uninterrupted infusion of a parenteral drug over several hours (continuous drip) to days. It involves adding medication to sterile IV solution (100 to 1,000 mL bag), and then hanging the IV solution as a primary infusion. Most IV continuous infusions are given for a short duration.
Intermittent infusion – an infusion of a volume of fluid/medication over a set period of time (e.g., 30, 60, or 120 minutes) at prescribed intervals (e.g. every 4, 6, 8, 12, or 24 hours) and then stopped until the next dose is required. An intermittent IV medication may be called a piggyback medication, a secondary medication, or a mini bag medication. IV medications may be given in small volumes of sterile IV solution (25 to 250 mL) and infused over a desired amount of time (given for 30 minutes every 4 hours) or as a single dose. Many medications must be given slowly to prevent harm to the patient, and this method of administration reduces the risk of rapid infusion. A piggyback medication is given through an established IV line that is kept patent by a continuous IV solution or by flushing a short venous access device (saline lock).

pH Range

Blood plasma has a pH between 7.35 and 7.45. The incidence of phlebitis increases if the pH of the intravenous solution differs from that of plasma. Fluids with with acidic or alkaline pH cause irritation and endothelial damage, leading to phlebitis and even thrombus formation in severe cases.

pH does not vary in a clinically significant way based on common dilution volumes, but may differ between different drug manufacturers or the temperature of the solution.

A 2011 Infusion Nursing Standards of Practice stated that infusions with a pH less than 5 or greater than 9, should be given via a central venous catheter (CVC). However, in 2016, the updated Infusion Therapy Standards of Practice removed pH less than 5 as a sole criterion for requirement of central venous access.

Osmolarity Range

Normal osmolarity of blood or serum is about 300-310 mOsm/L. The tonicity of an IV fluid dictates whether the solution should be delivered via the peripheral or central venous route. Hypotonic and hypertonic solutions may be infused in small volumes and into large vessels, where dilution and distribution are rapid.

Solutions differing greatly from the normal range may cause tissue irritation, pain on injection, and electrolyte shifts. When solutions with extremes of tonicity are infused, fluids shift into or out of cells, including endothelial cells of the tunica intima near the catheter tip and blood cells. The resulting changes in the cell size of the vein wall causes the inflammatory and clotting processes to occur, leading to phlebitis and thrombophlebitis.

The generally accepted upper limit for a peripheral IV is 900 mOsm/L. When the osmolality exceeds 900 mOsm/L, the ability of the peripheral veins to dilute parenteral infusions sufficiently is compromised, and chemical irritation of the vein intima occurs. As osmolarity increases over 600 mOsm/L there develops a dramatic increase in phlebitis and as such, consideration should be given to administering those solutions via a central line (CVC or PICC).

Vesicant

Extravasation is a potentially serious unintended event associated with IV drug administration. Extravasation is defined as the leakage or inadvertent administration of a vesicant drug or solution from a vein into the extravascular space. Infiltration, often used in reference to extravasation, refers to leakage of a non-vesicant drug or solution. Initial symptoms of extravasation are similar to infiltration and include persistent pain, burning, stinging, swelling, and either blanching or erythema at the site of injection or along the course of the vein.

However, vesicants are differentiated from non-vesicants in that can cause tissue death and serious or life-threatening complications if they leak out of a vein. Vesicants can be acidic or basic, hyperosmolar, or vasoconstrictive. They can damage the subcutaneous tissue outside of the vein, including muscles, tendons, and bone, at the point of puncture or the catheter's tip and lead to tissue necrosis, blistering, and ulceration. Damage from extravasation can progress to a significant degree, causing permanent disability and disfigurement, and necessitating surgical debridement or skin grafting.

Many chemotherapy drugs are vesicants, but many other non-chemo drugs are also vesicants, including:

calcium salts: such as calcium chloride and calcium gluconate
potassium chloride: high concentrations of potassium chloride
dextrose solutions: solutions with a concentration greater than 10%
contrast agents: used in radiology
other drugs: such as acyclovir, nafcillin, vancomycin, and sodium bicarbonate.

In 2017, the Infusion Nurses Society (INS) published the results of a taskforce addressing vesicant medications; the following antimicrobials were removed from the INS vesicant list: amphotericin B, ampicillin, cloxacillin, doxycycline, gentamicin, metronidazole, oxacillin and penicillin. Retained on the vesicant list as having intermediate risk are acyclovir, nafcillin, and vancomycin.

Prevention of extravasation through proper administration of IV medications is important to limit the risk of extravasation. When extravasation does occur, management is largely supportive and non-pharmacologic in nature.

Preferred Vascular Access

A vascular access device (VAD) provides access to veins for the delivery of IV medications.

A peripheral venous catheter (PVC), peripheral venous line or peripheral venous access catheter is a catheter (small, flexible tube) placed into a peripheral vein for intravenous therapy such as administering medication and fluids. Upon insertion, the line can also be used to draw blood. A peripheral venous catheter is usually placed in a vein on the hand or arm. A standard IV line can typically be used for up to 4 days.

A central venous catheter (CVC) is a thin, flexible tube that is inserted into a vein, usually below the right collarbone, and guided (threaded) into a large vein above the right side of the heart called the superior vena cava. It is used to give intravenous fluids, blood transfusions, chemotherapy, and other drugs. The catheter is also used for taking blood samples. It may stay in place for weeks or months and helps avoid the need for repeated needle sticks.

Peripherally Inserted Central Catheter (PICC) is an external device placed in upper arm. A PICC line is a safe, stable, and effective way to deliver IV medications. They can stay in the body for weeks or months, alleviating the need to subject your veins to the numerous needle sticks necessary if the PICC was not there. Additionally, some medications are caustic to the vasculature; PICC lines allow these medications to be delivered to larger vessels that are less likely to be damaged. PICC lines are thus a very versatile choice for patients requiring long-term venous access for conditions such as nutritional deficiencies or IV antibiotics.

The 2011 Infusion Nurses Society Standards of Practice suggest that therapies appropriate for central venous catheters (CVC or PICC) include "… vesicant or known irritants, parenteral nutrition, a variety of antibiotics and any medications with a pH of less than 5 or greater than 9 and osmolarity of greater than 600 mOm/L."

However, in 2016, the updated standards removed pH < 5 as a sole criterion for requirement of central venous access. The guidelines recognized that a VAD choice should generally NOT be based necessarily on a SINGLE factor, be it pH, osmolality, or classification as a vesicant or irritant. Rather, it must be based on many factors, including anticipated duration of infusion therapy, type and number of infusates, location of the peripheral IV catheter, catheter size, condition of the patient’s veins, and patient preference.

In-Line Filter Use

Filters are used with the intravenous administration of many medications. These filters may be contained within an IV line (in-line filter). In-line filters for IV lines can help prevent contaminants from entering a patient's bloodstream. In-line IV filters house a membrane that separates the whole unit into a patient side and an air-vent side. Proper priming techniques allow the fluid to fill the air-vent side first while saturating the membrane and then filling the patient side. The saturated membrane will prevent air from passing through to the patient side. Today, at least three different commercial in-line filter systems are available. The 5.0 μm in-line filter reduces rough particles (glass, rubber, plastic). The potential advantage of the finer positively charged 0.2 and 1.2 μm in-line filters is that they can hold back these larger particles but also particles from drug incompatibilities (precipitants), air, microorganisms (bacteria size 1-3 μm), and smaller endotoxins. There are currently no filters that remove viruses due to their extremely small size.

However, in-line filters can also have negative aspects, such as reducing infusion flow rates due to clogging and adding costs. Not all intravenous medications should be administered through a filter, and others may require filters of a specific size. The molecules of some medications may be too large to pass through a filter, or may otherwise bind to the filter and be removed. For these medications, it is essential to avoid using in-line filters.

Infusion Set Type

It is a common misconception that all intravenous administration lines are made of the same material. They are not. In some cases, choosing an incorrect administration line can cause deleterious changes to the medication being given. Not only is this potentially harmful to the patient, as chemical change may take place in the medication upon contact and interaction with administration set material, but there may also be a significant loss in the efficacy of the medication and degradation of its therapeutic effect.

Infusion sets made from PVC (polyvinyl chloride) may have adverse effects on some medications. The effects of PVC on these drugs happens due to two phenomena: adsorption and leaching.

Sorption describes the adsorption of a drug to the polymer surface and the absorption of a drug into the polymeric matrix. In other words, the PVC attracts the drug molecules to attach themselves to the IV set’s inner lining. Drug sorption to tubes in administration sets causes unpredictable drug loss and makes it difficult to control the delivered drug concentration. Drug sorption to polymeric tubes is therefore a major impediment to the precise transfer of injectable drugs into the body. Subsequently, the patient receives a lesser amount of the prescribed drug(s). Some drugs adsorbed to the IV sets are diazepam, lorazepam, insulin, nitroglycerin, and thiopental sodium.

The addition of bis(2-Ethylhexyl) phthalate (DEHP) to the PVC-based infusion devices provides flexibility to the finished materials. However, the chemical bonding between the DEHP and the PVC does not always happen completely. Consequently, leaching occurs. Leaching refers to the release of DEHP from the IV sets made of PVC. DEHP mixes with the drug in solution, and it causes a wide range of toxic effects. Examples of drugs that can leech DEHP include cyclosporine and paclitaxel.

Alternatives to PVC bottles, bags, and IV sets are available. Examples include glass bottles and polyolefin bags (VisIV) both of which are PVC-free and DEHP-free. Polyethylene-lined IV tubing can be used to prevent DEHP from leaching into meds during IV administration.

Protect From Light

Ultraviolet light from the sun and blue light from the sun and from fluorescent and incandescent light bulbs, as well as from light-emitting diode [LED] technology, can alter the pharmaceutical properties of several drugs, potentially leading to a lose of effectiveness due to decreased drug stability. These light sources can cause drug oxidation and/or hydrolysis leading to photodegradation. This degradation can lead to loss of potency, adverse side effects, and the formation of toxic degradation products.

Certain medications are especially sensitive to ultraviolet and blue light exposure, including biologics, chemotherapeutics, and protein-containing and protein-derived products (e.g., vaccines and immune globulins). Medications that require long IV infusion times are also vulnerable to pharmacological changes from light.

Several light-shielding methods can be used to protect the drug from light during IV administration. Foil wrapping can be used but doing so may be cumbersome and time consuming. The use of amber bags and amber lined infusion sets are effective alternatives. The light-proof infusion set also called the light-resistant infusion set protect their contents from the damaging effects of light. These infusion sets protect photo-sensitive drugs from photochemical degradation or destruction, like paclitaxel, cisplatin, aminophylline, and sodium nitroprusside.