Correspondence  |   March 2019
In Reply
Author Notes
  • Institute for Healthcare Delivery Science, Departments of Population Health Science and Policy/Orthopedics, Icahn School of Medicine at Mount Sinai, New York, New York (J.P.). jashvant.poeran@mountsinai.org
  • (Accepted for publication November 16, 2018.)
    (Accepted for publication November 16, 2018.)×
Article Information
Correspondence
Correspondence   |   March 2019
In Reply
Anesthesiology 3 2019, Vol.130, 515-516. doi:10.1097/ALN.0000000000002570
Anesthesiology 3 2019, Vol.130, 515-516. doi:10.1097/ALN.0000000000002570
We welcome the thoughtful comments by Dr. Steadman and Riou et al., in reply to our study.1  We aimed to evaluate the use of IV acetaminophen and its association with outcomes including opioid utilization, opioid-related adverse effects, and cost and length of hospitalization. Dr. Steadman mentioned several limitations of our study—some justified (and mentioned in our study’s Limitations section) and some less so—and observational research in general. Dr. Steadman states that “A better study would be a randomized double-blinded one in which the only variable would be the use of IV acetaminophen versus oral acetaminophen for 24 h in a cohort of patients that did not include chronic opiate users, and in which the multimodal regimen was standardized rather than determined by individual predilections.” We agree that this would be an ideal study situation to a certain extent. However, such a study would be difficult to conduct or would significantly lack generalizability, because common practice almost never is in alignment with the control group or intervention group. Indeed, multiple (nonopioid) modalities (e.g., nerve blocks, neuraxial analgesia, acetaminophen, and gabapentinoids, among others) are available for use in multimodal regimens; this results in an exponential increase in the number of potential combinations to use in practice.2  Therefore, there currently is no universally recognized standard regimen to be used in a trial desirous of generalizability, and identifying the optimal multimodal regimen in a trial setting would be impossible given the sheer number of combinations. A more practical approach would be to use observational data to identify combinations of nonopioid modalities and timing that may result in the most optimal outcomes. This will inform trials where a selected number of multimodal regimens may be compared. Particularly the “individual predilections” noted emphasizes the difference between trial and real-world settings that provided the most thought-provoking result from our study: IV acetaminophen is mostly used as a single-dose administration on the day of surgery, which is not likely to result in a clinically relevant reduction of opioid utilization. Indeed, real-world use of drugs often differs from use in controlled trial settings where they are deemed efficacious.3  We maintain that the value of this investigation is the demonstration of the real-world use of IV acetaminophen that was not associated with clinically significant reductions in opioid utilization. Importantly, we agree with Dr. Steadman that “Giving a single dose of IV acetaminophen and expecting a miraculous change in opiate use is unsophisticated at best” and that “IV acetaminophen is a tool like any other in our armamentarium. If we use a tool ineffectively, then we are the problem—not the tool,” and we reiterate our call for the identification of patient subgroups and IV acetaminophen administration schedules most likely to result in benefit.1  However, in all fairness and to stay true to generally accepted scientific principles, one has to consider the possibility that no benefit may be found at all.