A Push for a (first-dose) Push

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Rachel Rafeq
Emergency medicine pharmacist and toxicology enthusiast. Trained in medication safety and I apply that to everything. I love photography and world schooling my kids.

The Pre-brief

While administration of antibiotics by intravenous push is a common concept, it may be an underutilized technique.

Traditionally, antibiotics are administered as intravenous piggyback infusions which may take up to an hour or more depending on the medication and its associated adverse effects. However, in recent years, availability of fluids has fluctuated and perhaps unintentionally paved the way to consider the feasibility of intravenous push delivery of antibiotics.

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

Benefits

There may be some added benefits to administering the first dose of antibiotic via intravenous push:

  • Medication compatibility becomes a non-issue. Let’s say patient JD arrives to the ED hemodynamically unstable and is quickly intubated and initiated on vasopressor support. You want to initiate cefepime and the nurse isn’t sure if the cefepime and norepinephrine can be run through the same line. The ED pharmacist confirms that the compatibility data is uncertain. 8 If the patient is limited in the number of lines they have, then it may be feasible to consider administration of cefepime IV push over 5 minutes to minimize delay of other therapies.
  • Increased practicality of medication storage: Intravenous piggyback infusions may need to come from pharmacy if space is limited to store infusion bags inclusive of medications that require refrigeration. These requirements will be determined by what product your institution purchases. Storage of vials for reconstitution and intravenous push delivery may be easier and expedite time to medication delivery.
  • Reduced medication cost: Cost will vary based on which products you purchase but in theory it may be cheaper to utilize the drug vial plus diluent vs a compounded intravenous infusion bag or alternatively, a pre-made bag by pharmacy which will require additional pharmacy resources.

Minimize delays: In sepsis, broad spectrum antibiotic administration should occur within 1 hour of presentation. Gregorowicz et al conducted a retrospective study in ED patients to evaluate the difference in time from sepsis diagnosis to completion of the first dose of antibiotics comparing two different administration strategies:  IVP administration over 3 minutes versus IV piggyback over 30 minutes. Medications administered through IVP aztreonam, cefepime, ceftriaxone, ertapenam, meropenam, and piperacillin/tazobactam. Additional medications administered in the IVPB group included ampicillin, ampicillin/sulbactam, cefoxitin, and ceftazidime. 274 patients were included in the analysis: 143 patients in IVPB group vs 131 in IVP group (notably 54 patients in the IVP group were ultimately excluded due to receipt of IVPB infusion instead of IVP). Median time from sepsis diagnosis to administration of first beta-lactam antibiotic was 48 minutes (19-96) in IVP group vs 72 minutes (8-180) in IVPB group. Median time to complete administration of the broad-spectrum sepsis regimen was 108 minutes (66-144) in IVP group vs 114 minutes (42-282) in IVPB group. The IVP group was less likely to fail the goal of beta lactam antibiotics within 1 hour (44.6% vs 57.3%) and 3 hours (7.6% vs 24.5%) of sepsis diagnosis compared to IVPB.  No adverse events noted in either group.9  

The Debrief

If the proper safety assessment has taken place, intravenous push may be a feasible option to expedite delivery of first dose antibiotics. This holds true for those medications that are concentration dependent and are less than 900 mOsm/L or have data to support peripheral administration.

The Institute for Safe Medication Practice Guidelines on Intravenous push administration should be followed. This includes ensuring appropriate labeling of the medication syringe, preparing the medication in a clean, uncluttered area, and ensuring that clear instructions are available for the correct reconstitution of the medication.10 

Examples for the preparation of intravenous push antibiotics to be administered over 3-5 minutes include4,7:

References

  1. Gandhi, R., Steiger, S., Elshaboury, R. and Lund, J., 2018. I.V. push administration of medications reconstituted with 0.9% sodium chloride injection. American Journal of Health-System Pharmacy, 75(12), pp.851-852.
  2. Spencer, S., Ipema, H., Hartke, P., Krueger, C., Rodriguez, R., Gross, A. and Gabay, M., 2018. Intravenous Push Administration of Antibiotics: Literature and Considerations. Hospital Pharmacy, 53(3), pp.157-169.
  3. Dillon, R., Merchan, C., Altshuler, D. and Papadopoulos, J., 2017. Incidence of Adverse Events During Peripheral Administration of Sodium Chloride 3%. Journal of Intensive Care Medicine, 33(1), pp.48-53.
  4. Hays, W. and Flack, T., 2020. Safety and tolerability of i.v. push piperacillin/tazobactam within an emergency department. American Journal of Health-System Pharmacy, 77(13), pp.1051-1053.
  5. Accessdata.fda.gov. 2020. [online] Available at: <https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018632s051lbl.pdf> [Accessed 11 August 2020].
  6. Accessdata.fda.gov. 2020. [online] Available at: <https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/016366s214lbl.pdf> [Accessed 11 August 2020].
  7. Marsh, K., Ahmed, N., Decano, A., Dubrovskaya, Y., Jen, S., Siegfried, J., Chen, X. and Merchan, C., 2020. Safety of intravenous push administration of beta-lactams within a healthcare system. American Journal of Health-System Pharmacy, 77(9), pp.701-708.
  8. Trissel, Lawrence A. (2009). Trissel’s stability of compounded formulations. Washington, D.C. :American Pharmacists Association,
  9. Gregorowicz, A., Costello, P., Gajdosik, D., Purakal, J., Pettit, N., Bastow, S. and Ward, M., 2020. Effect of IV Push Antibiotic Administration on Antibiotic Therapy Delays in Sepsis. Critical Care Medicine, 48(8), pp.1175-1179.
  10. Institute For Safe Medication Practices. 2020. Safe Practice Guidelines For Adult IV Push Medications. [online] Available at: <https://www.ismp.org/guidelines/iv-push>

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