IV compatability of analgesics

Myron Yaster MD and Rita Agarwal MD

In today’s Pediatric Anesthesia Article of the Day, the authors, O’Loughlin et al., wanted to know if “Intravenous acetaminophen is compatible with multiple analgesics at a variety of concentrations that may or may not be applicable to pediatric setting?”1   

First, before getting to our review a conflict of interest disclaimer: I (MY) was on the drug safety monitoring board (DSMB) when IV acetaminophen was being studied and developed more than 20 years ago. Thus, I was a paid consultant to the sponsoring company (Cadence Pharmaceuticals). I don’t think this affected my review in today’s PAAD but to be completely transparent I am reporting it to you.

After its FDA approval, I wholeheartedly supported the release of IV acetaminophen into clinical practice because of its efficacy and safety profile.  However, over time as the original sponsor was bought by one than another pharmaceutical company the price per vial increased dramatically.  Indeed, it became so expensive compared to acetaminophen’s enteral formulations that I could no longer support its routine use.  However, there are many patients who cannot take enteral drugs, making the IV route the only practical way to give acetaminophen.  Thus, today’s article provides practitioners and pharmacists enormous guidance when multiple analgesics are used in treating pain.  Myron Yaster MD

Original article

Edmond O'Loughlin, Yan Ghee Peng, Angela Cheaib, Matthew T V Chan, Robin Williams. Compatibility of intravenous acetaminophen with morphine, fentanyl and ketamine in acute pediatric pain setting. Paediatr Anaesth. 2022 Jul;32(7):862-869. PMID: 35398962

For patients admitted to the hospital after surgery, the age-old dilemma facing us in the operating room is “how many IVs (or ports if a central line) will be needed by the nursing staff during postoperative care”? The short answer: No matter what you do, it’s never enough. If only one IV is placed, you will absolutely get the death stare by the bedside nurse.  And if it’s an ICU patient, don’t even ask…you’ll be lucky if the nurses or ICU staff don’t anonymously character assassinate you by writing you up for misconduct. (Myron will be discussing a series of articles on weaponized incident reporting from the ASA monitor in next week’s PAAD)

Have you ever asked yourself: “Why”? Although there are many reasons nurses require so many IVs or ports one stands out…if patients require more than one drug, particularly if one of them is infused by a continuous infusion, a second line or port is needed because of drug-drug (-drug) compatibility issues of the infusates.  Physically and chemically, non-compatible drugs may cause precipitation and affect a drug’s availability, stability, and/or duration of action.

Using multiple “binary mixtures of acetaminophen with morphine, fentanyl, or ketamine, the study was performed in two phases. Firstly, a colorimetric assessment was done to examine the preliminary feasibility and acetaminophen recovery. Subsequently, high-performance liquid chromatography/mass spectrometry were used to evaluate the recovery of all components in the mixture”.1  The great news: “The stability data presented demonstrates that intravenous acetaminophen can be safely combined with the potent analgesics in concentrations commonly used in acute pediatric pain setting. Furthermore, the duration (up to 60 min) of stability demonstrated, allows for the combination of these medications, particularly as intermittent co-administration with acetaminophen, to be used in children requiring analgesic infusions, over a range of clinical scenarios”.1  Further, because a previous study found2 that IV acetaminophen is physically compatible with two different three-in-one TPN formulations used for children of different age groups, maybe only one IV (or port) is necessary!

OK, there’s a catch.  Isn’t there always?  The study was performed in Australia and the IV acetaminophen used was Perfalgin™ and may not be chemically the same as the one we use in North America.  Thus, we suspect that this study will need to be repeated with the product used here.  Sounds to us that this is a “no-brainer” research project for one of you! This is also a great opportunity for those of you who work on the inpatient pain services to find out what your institutional practices are regarding co-administering 2 different IV analgesic medications.

References

1.           O'Loughlin E, Peng YG, Cheaib A, Chan MTV, Williams R: Compatibility of intravenous acetaminophen with morphine, fentanyl and ketamine in acute pediatric pain setting. Paediatr Anaesth 2022; 32: 862-869

2.           Staven V, Iqbal H, Wang S, Grønlie I, Tho I: Physical compatibility of total parenteral nutrition and drugs in Y-site administration to children from neonates to adolescents. J Pharm Pharmacol 2017; 69: 448-462