Today’s “reader response” would be better entitled author response. As you all know, the goal of the PAADs is to be short 5-7 minute reads including the Friday reader responses. Lately several reader/author responses have pushed these limits. Please keep this in mind when sending me your comments. Going forward I may be unable to post responses that are too long…Myron Yaster MD
From Lynn D. Martin, MD, MBA, Professor Emeritus, Seattle Children’s / University of Washington, Department of Anesthesiology and Pain Medicine, CMO, Pediatric and Academic Services, AdaptX® in response to the PAAD Anonymous on 8/30/2024
I would like to thank Anonymous for his/her/their reply in the PAAD reader response from 8/30/24. I know that there are likely other pediatric anesthesiologists that feel similarly, so thank you for bringing your collective voices to the PAAD. I am compelled to reply for several reasons, but first I need to make it clear that I am not speaking for the PAAD editorial board of which I am a member, but rather as the senior author of the Hansen et al1 reference under review.
Use of a commercial software company in healthcare occurs in every hospital daily and is not a sin. All hospitals routinely utilize and pay for these services. I have found AdaptX® to be a unique commercial software solution that has been created by clinicians to expressly help clinical providers get real-time, self-serve access to their EMR data to learn and improve individual and/or group performance (clinical processes and outcomes). This commercial company filled a critical need (the lack of TIMELY data) during my tenure as the Chief of Anesthesiology and medical director for our ASC in Seattle. To take full advantage of the wonderful faculty and staff we had at Seattle Children’s, I needed to obtain and monitor routine clinical care measures in a manner that allowed us to share, learn from, and improve our clinical outcomes. I personally was not smart enough to get the necessary data I needed directly from either common EMR (Cerner - P2Sentinal or Epic - Slicer Dicer) as we used both during this time. Furthermore, when I asked for institutional IT support to find my answers, it would take months to get back reports and on occasion, nothing at all.
To illustrate this point, ask yourself “how did my patient from yesterday or even last week do?” How long did they stay in the PACU? What was their pain scores? Was the pain bad enough to require opioids? Did they receive treatment for PONV? How do my patients compare to patients from other anesthesiologists having the same procedures? You likely do not know the answer to these simple questions despite the answers living in your EMR. How can you improve your practice not knowing how you did? You are flying blind, without instruments, and risking a rare near-miss or worse a crash. You could read the literature and try the latest and greatest new medication, tool, or process to reduce this risk, but you are still blind to the results of your trial without the real time clinical outcome data. As I did, you could ask your well-intentioned, but overburdened IT team for the data and you may get a report back in days (if you are lucky), weeks (slow but maybe ok), or most commonly months later (not helpful) or never (an unusable outcome). How frequently do you get your data from alternative data sources like WUS, PRAN, MPOG, or ASC NSQIP (typically reports arrive once or twice a year for which your institution pays to participate)? Anonymous suggested that these “less expensive, more traditional (non-commercial) data sharing/quality efforts” are viable alternatives. I agree there have been good quality improvement publications using these alternative sources of data (some on my own CV). An example from that same PAAD reader response was another study from Seattle by Feldman et al.2 Studies like this one along with two separate meta analyze showing no increased risk of postoperative hemorrhage was not sufficient to convince our surgeons to change. Only when we showed them are (at the time) new capability to monitor in real time for postoperative reoperation did the group of surgeons hesitantly agree to our trial of ketorolac at the end of the surgical procedure. We knew with a reasonable degree of confidence at 6 months that the risk of reoperations was unchanged. Six years and >5000 patients later we know that the reoperation rate was not changed and this practice is safe.3 Typically for QI work, you decide to change your practice in one or more ways on a specific date, so you gather a year’s worth of data before (baseline) and after this change (test of change). You end up with 1 test over the year and hope your outcome is positive, only finding out after you get your data more than 1 year later.
Having been a paying customer for many of these alternative sources, none of them are structured and formatted into the widely recognized gold standard for quality improvement methodology, the statistical process control (SPC) format. In addition, they can’t deliver the information for learning from yesterdays or last week’s cases. Using this format in real time allows you to monitor and rapidly distinguish true signals from random system noise. For example, we ended one T&A QI trial for an obvious failure signal at 3 days. Using AdaptX®, we have been able to accelerate PDSA cycles to 3 months.3 Can any of these alternatives do this? The simple honest answer is no.
Even though I was trained by Myron and others at Johns Hopkins in the use of the scientific method, I have personally lost my zeal for scientific evidence from well controlled retrospective or prospective (and artificially constrained from my perspective) studies and replaced it with the use of real-world clinical data to make changes that improve actual clinical outcomes in months, and not the 17 years it is reported take research findings to slowly diffuse into routine clinical practice.4 Call me impatient, but I am old enough that I don’t have enough years left to be patient and wait for this slow diffusion of evidence to get into routine practice.
Lastly, I need to inform Anonymous that I initially held equity interest in AdaptX® during my clinical tenure in Seattle. However, I personally liquidated this equity after a very short period as I realized that AdaptX® data was a growing opportunity for scholarly projects and I wanted to have no potential conflict of interest throughout the remainder of my academic career. All the data described in the Hansen et al1 paper were collected prior to my retirement from clinical practice and current part-time employment with AdaptX®. Thus, there was no conflict present.
Why did I decide to work for AdaptX®? It is not for the money (my wife would gladly confirm this, although she questions if I have ‘really retired’). My retirement funds from 33 years of pediatric anesthesiology practice are more than sufficient to meet our needs. I chose to work with this company as a previously satisfied consumer who recognized that putting timely access to data directly into the hand of colleagues like you is a key NEW METHOD to unlocking continuous, RAPID, and sustained improvements in pediatric perioperative clinical outcomes. These improvements have been and continue to be my professional passion. We can and will do better, truly improving our practices for children, when we utilize all the tools available to us. This is my crusade! I want to continue sharing this passion and experience with others, so all children can and do receive better care.
References
Hansen EE, Chiem JL, Low DK, Rampersad SE, Martin LD. Enhancing Outcomes in Clinical Practice: Lessons Learned in the Quality Improvement Trenches. Anesth Analg. 2024;139:439-45. Doi:10.1213/ANE.0000000000006713. (PMID: 38446706).
2. Feldman RM, O’Reilly-Shah V, Dahl JP, Siu J, Newby M, Sutherland TN, Parikh SR, Jiang T, Franz A. Impact of Ketolorlac on Reoperation for Hemorrhage After Pediatric Tonsillectomy: A Single-Center Retrospecitve Propensity-Match Study. Otolaryngol Head Neck Surg. 2024;170:928-36. Doi:10.1002/ohn.577 Epub 2023 Nov 5. PMID 37925621.
3. Chiem JL, Franz AM, Hansen EE, Verma ST, Stanzione TF, Bezzo LK, Richards MJ, Parikh SR, Dahl JP, Low DK, Martin LD. Optimizing pediatric tonsillectomy outcomes with an opioid sparing anesthesia protocol: Learning and continuously improving with real-world data. Pediatr Anesth. Doi.org/10.1111/pan.14979. Epub 2024 Aug 30.
4. Morris ZS, Wooding S, Grant J. The answer is 17 years, what is the question: understanding time lags in translational research. Journal of the Royal Society of Medicine. 2011; 104(12):510–520. [PMID: 22179294]
From Lisa Einhorn, MD, FAAP, Associate Professor of Anesthesiology, Pediatric Division, Duke University School of Medicine is the first author of the paper on the use of single-dose methadone for pediatric tonsillectomy (PAAD Sept 11, 2024)
We recognize that the use of a long-acting opioid in the setting of a largely outpatient surgery like tonsillectomy is novel and might even be considered controversial by some. However, we believe there is a strong need to improve and investigate available therapeutic agents in children and adolescents that may extend analgesia beyond the early postoperative period. Methadone, with its rapid onset, well described pharmacokinetics, inactive metabolite, and long elimination half-life fulfills these therapeutic goals to better match the duration of anesthesia to the duration of pain after this common procedure.1,2 Our objectives are aligned with other investigations that propose interventions to reduce or completely eliminate the need for opioids in the postoperative period
.Figure. Visual representation of the number of US cases per year and total number of published trials on pain management since 1972 in Total Knee Arthroplasty (Adults) vs. Pediatric Tonsillectomy
As many readers of PAAD are undoubtedly aware, despite the frequency of tonsillectomy (approximately 500,000 children/year in the US alone), the optimal management of pain after this surgery remains elusive. This is partially due to the lack of high quality prospective clinical trials in this population. The figure shows the glaring disparity in the number of publications on pain management following tonsillectomy in children compared with, for example, total knee replacement in adults, despite relatively similar number of operations yearly. A recent scoping review on randomized controlled trials after tonsillectomy3 (highlighted in a prior PAAD) reported that only 12% of studies examined any postoperative medication use and only 24% of studies examined pain intensity beyond the first 24 hours after surgery. How can we judge the efficacy of our perioperative interventions without looking at outcomes beyond the PACU and early postoperative period? The “finish line” (so to speak) is clinically meaningful patient recovery after surgery, not the period between the entrance to the PACU and exit from the hospital.
Our study reported a few important additional findings that were not mentioned in the PAAD review. In addition to opioid sparing in the first week after surgery, participants in the methadone groups required less rescue dexmedetomidine, had clinically and statistically meaningful shorter PACU stays, and greater number of opioid free postoperative days than those in the control group. Despite extensive education on first line pain management and regular use of acetaminophen and ibuprofen, 70% of patients in our study required some amount of opioid in the postoperative period for pain. Tonsillectomy hurts. These findings differ substantially from that published in the 2021 American Academy of Otolaryngology – Head and Neck Surgeons guidelines, which recommends no postoperative opioids for children 5-12 years after adenotonsillectomy. Despite these guidelines, available evidence indicates that the currently recommended non-opioid regimen (alternating doses of acetaminophen and NSAID around the clock) may not be sufficient.4 Even if acetaminophen and NSAIDS are adequate for 90-95% (best case scenario) of patients, this still leaves 25,000-50,000 children in the US with insufficient and poorly treated pain after surgery. These are unacceptable numbers.
Finally, a quick comment on pilot studies and future directions. The sample size of a study does not determine whether it is a “pilot” vs a “definitive” clinical trial. In fact, if you can validly and reproducibly show a clinically meaningful intervention in only 60 patients, and do not need 600 to do so, it might be more meaningful. In that vein, our trial was adequately powered for efficacy but not safety. Safety is of course a major consideration for any intervention in a novel population. Despite well-meaning concerns about opioid induced respiratory depression, there is absolutely no evidence that a single dose of perioperative methadone is associated with increased fatalities or even more adverse events than other opioids, and to suggest so, is unfounded. Nonetheless, we appreciate that safety assessment does require larger numbers of patients. Fortunately, we have recently been awarded a 5-year R01 grant by The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) to complete a randomized controlled trial using IV methadone in almost 400 children undergoing tonsillectomy (PI: Einhorn, Co-I: Kharasch). This trial is fully powered to analyze both efficacy and safety outcomes with the goal to identify the optimal age-specific, weight-based dose of intraoperative methadone for pediatric tonsillectomy that decreases postoperative opioid use and improves pain control compared to current practice. Stay tuned!
We urge readers to pursue improvements in analgesia for pediatric tonsillectomy, download our full article in Anesthesiology, and tune into the 45-minute Featured Author Podcast in which Dr Berde and I discuss this work.
References
1. Kharasch ED: Intraoperative methadone: rediscovery, reappraisal, and reinvigoration? Anesth Analg 2011; 112: 13-6
2. Ward RM, Drover DR, Hammer GB, Stemland CJ, Kern S, Tristani-Firouzi M, Lugo RA, Satterfield K, Anderson BJ: The pharmacokinetics of methadone and its metabolites in neonates, infants, and children. Paediatr Anaesth 2014; 24: 591-601
3. Shih MC, Long BD, Pecha PP, White DR, Liu YC, Brennan E, Nguyen MI, Clemmens CS: A scoping review of randomized clinical trials for pain management in pediatric tonsillectomy and adenotonsillectomy. World J Otorhinolaryngol Head Neck Surg 2023; 9: 9-26
4. Liu C, Ulualp SO: Outcomes of an Alternating Ibuprofen and Acetaminophen Regimen for Pain Relief After Tonsillectomy in Children. Ann Otol Rhinol Laryngol 2015; 124: 777-81