A Push for a (first-dose) Push

Why don’t we give more medications through peripheral IV push? Two concepts to consider are the medications osmolarity and its pharmacodynamics.

Medications with osmolarity greater than 600-900 mOsm/L have been associated with phlebitis, local irritation, and infiltration during peripheral administration. Because of this, the 2016 Infusion Nurses Society Infusion Therapy Standards of Practice state that solutions with osmolarity greater than 900 mOsm/L should be administered via central line. ^{1, 2} In recent years, institutions have sought to challenge or describe adverse events associated with peripheral administration of medications that exceed 900 mOsm/L. For example Dillon and colleagues at NYU Langone Medical Center reviewed the use of 3% hypertonic saline via peripheral administration and learned that the rate of infusion-related adverse events was low and administration was well tolerated despite its osmolarity of 1,027 mOsm/L.³  Additionally, 20% and 25% mannitol have been described previously and may be safely administered peripherally through IV push method despite having osmolarities of 1,098 mOsm/L, and 1,372 mOsm/L respectively. ⁴

Most recently, two articles were published providing additional safety data for the administration of first dose antibiotics as intravenous push utilizing 0.9% sodium chloride. Generally sterile water for injection (SWIF) is used due to its osmolarity of 0 mOsm/L, however limited supplies of SWFI have led to use of 0.9% NaCl which has 308 mOsm/L.^5,6  Marsh and colleagues evaluated 1000 patients who received aztreonam 1 or 2 grams, ceftriaxone 1 or 2 grams, cefepime 1 or 2 grams, or meropenam 500 mg or 1 gram. Administration occurred over 5 minutes and patients were monitored for 1 hour after administration.  In total only 10 patients experienced an adverse drug event of which 5 were adverse drug reactions due to allergy. Of the remaining 5 events, 4 were related to cefepime and 1 from ceftriaxone. The Naranjo adverse drug reaction score tool was utilized to determine that of the 4 cefepime events, only 1 was probably cefepime related and the 3 remaining were possibly related.⁷ 

Hays and Flack described their findings on the administration of piperacillin-tazobactam via intravenous push in an article that evaluated 300 patients. 299/300 patients tolerated IVP piperacillin tazobactam and one patient experienced an adverse drug reaction due to allergy. No infusion reactions were noted.⁴

From a pharmacodynamics standpoint, antibiotics are known to be concentration dependent or time dependent. Concentration dependent medications need to maximize the area under the curve (AUC) per unit of time in relation to the bacterial minimum inhibitory concentration (MIC) in order to increase bacterial killing. In these cases, utilizing intravenous push over 5 minutes vs a standard 30 minute infusion theoretically shouldn’t impact the AUC. Time dependent medications benefit from increasing infusion duration in order to maximize the time the concentration of the medication remains above the MIC. While beta lactams are known to be time dependent killers, there is at least one study that was able to determine that a 3-5 minute infusion produced similar time above the MIC as compared to a 30 minute infusion.²