Reader response

Myron Yaster MD

From Aidan Tait, MD, MS, Clinical Assistant Professor, Department of Anesthesia, Division of Pediatric Anesthesia -- Stanford on Valuing Undervalued Anesthesiology Teachers

Another factor at play here is that pediatric anesthesia and pediatric surgery are increasingly practiced at subspecialty children's hospitals often affiliated with academic medical centers. That is, to become a pediatric anesthesiologist, and to participate in a high-volume pediatric practice, often requires that one work for an academic institution. There are notable exceptions to this, but the trend -- particularly for medically complex children and more complex pediatric surgical care -- is for this kind of work to be centralized in large academic children's hospitals. As such, many budding pediatric anesthesiologists have aligned themselves with a career in academia without necessarily knowing what that means. I became a pediatric anesthesiologist because I absolutely love taking care of children and families during some of the most intense moments of their lives. I also love teaching residents and fellows and prioritize that as much as I can. I identify strongly as a "clinician educator," and most of the best anesthesiologists I learned from in training were clinician educators as well. I have genuine academic interests that I pursue because I believe in them -- and they come out of memorable clinical experiences I have had taking care of sick, vulnerable children in the operating room. All of my non-clinical work emanates from what I love most: being a dedicated and skilled pediatric anesthesiologist. That has always been primary for me, even in different academic and non-academic practice environments. What has changed over the last few decades is that outstanding clinical pediatric anesthesiologists increasingly look around and find that the best jobs for them are at academic institutions that often have traditional academic priorities, even if they themselves might not. 

From Rita Agarwal MD, FAAP, FASA, Clinical Professor of Anesthesiology, Stanford University, Department of Anesthesiology, Perioperative and Pain Medicine, Past President Society for Pediatric Pain Medicine on Valuing Undervalued Anesthesiology Teachers

I read this PAAD with great interest. I have been blessed in that I have been successful at 2 institutions, despite not being a researcher. I agree with the premise of the paper that it is harder to advance and be successful at many institutions in the clinician educator track and often these tracks are considered 2^nd tier, but it is still possible. Part of the issue is that it is often less clear what constitutes promotable activity. The concept of  core competencies is intriguing, if it indeed helps simplify the process for faculty to get promoted (or advance in other ways). For me the key to my success was early, enthusiastic and persistent involvement with our national societies including the SPA, SPPM, and the AAP, willingness to volunteer and speak up and eagerness to look for opportunities. I was also lucky in that I had a some supporters at my home institutions  (3  Robert M Smith Award winners, Charlie Lockhart and Rob Friesen from Children’s Colorado and Nancy Glass form Texas Children’s) who introduced me to other great mentors on the national stage (Jay Deshpande, Joe Tobin , you, Chuck Berde, and so many other great people).

My advice for clinical educators is stay open minded and look for opportunities everywhere to establish a national or regional reputation ( that seems to be a consistent requirement for many promotions committees) , advocate  for yourself and colleagues, and be creative.

From Lisa Isaac, MD, FRCPC Pediatric Anesthesiologist and Pain Physician, Associate Professor, Director of Equity, Diversity and Inclusion, Department of Anesthesiology and Pain Medicine,, University of Toronto, Pediatric Pain Fellow Coordinator, Medical Director, Transitional Pain Service, Department of Anesthesia and Pain Medicine, Hospital for Sick Children

I read with interest your review of Veranda-Alerrama et al's article of ESP block with cryoablation for thoracotomy and Nuss procedure(1). This demonstrates a tremendous improvement in pain management for an extremely painful surgery.

Our group also recently found excellent results with respect to reduced length of stay and likely a reduction of opioid use using a 5 point ERAS protocol (2) in our institution. Patients are seen preoperatively in the transitional pain clinic (pTPS) following their surgical visits to identify risk factors for persistent pain, opioid misuse and to provide education on multimodal pharmacological (constipation prevention and management, bilateral serratus anterior blocks with bupivicaine and dexmedetomidine, cryoablation T4-8, gabapentin, methocarbamol or diazepam, NSAIDs, acetaminophen and opioid in hospital and for home) and nonpharmacological pain management. We begin gabapentin 3 days preop, and serratus anterior (SA) blocks are done with dexmedetomidine to prolong the duration. They have IV PCA to oral morphine or hydromorphone on POD 1 and discharged day 1 or 2  with outpatient pTPS followup within the week, which allows minimal opioid prescribing for discharge. They are usually on low dose opioids for less than a week. The advantage of the serratus anterior block, used in our institution since its use for coarctation repair(4), is its ease of positioning, as it is done while the patient is supine. 

With this ERAS protocol, we have reduced the hospital length of stay by 3 days to 1.86 days, as with Aranda-Valderrama et al, and seem to have reduced overall opioid use but with high patient satisfaction. It would be very interesting to compare the serratus anterior block to the ESP block for feasibility and opioid use, but in the context of an ERAS protocol for multiple sites. Thank you for highlighting important innovations in perioperative pain management. 

1. Aranda-Valderrama P, Greenberg RS, Vecchione TM, et alCombined erector spinae plane block with surgical intercostal nerve cryoablation for Nuss procedure is associated with decreased opioid use and length of stayRegional Anesthesia & Pain Medicine 2024;49:248-253.

2. Downing L, Ramjist JK, Tyrrell A, Tsang M, Isaac L, Fecteau A. Development of a five point enhanced recovery protocol for pectus excavatum surgery. J Pediatr Surg. 2023 May;58(5):822-827. doi: 10.1016/j.jpedsurg.2023.01.028. Epub 2023 Jan 18. PMID: 36788057.

3. Biswas A, Luginbuehl I, Szabo E, Caldeira-Kulbakas M, Crawford MW, Everett T. Use of Serratus Plane Block for Repair of Coarctation of Aorta: A Report of 3 Cases. Reg Anesth Pain Med. 2018 Aug;43(6):641-643. doi: 10.1097/AAP.0000000000000801. PMID: 29794944

From Randy Flick MD, MPH, Mayo Clinic

Thanks for the great discussion of the FDA's accelerated approval of drugs intended to benefit patients with Duchene’s Muscular Dystrophy.  Your article presents an opportunity to clarify the role of the FDA (aka The Agency), it’s more typical approval process and the role of the advisory committee (AC) in the that process.  Although my comments will only tangentially touch on this particular approval, I hope to provide some useful insight based on my past experience on two different advisory committees.  Although not the AC that convened for this approval, the Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) is the AC addressing many or most of the approvals we are most concerned with.  SPA members have for at least the past 20 years had an outsized influence on AADPAC with multiple members serving as advisors or chairs of the committee including our late friend and colleague Ron Litman.   My comments should not be taken as defense of the Agency with regard to this or any other approval as, not infrequently, I found myself in disagreement with the actions or decisions flowing from committee meetings.  Notwithstanding, those disagreements, I believe now as I did when serving as an advisor, that the men and women of the FDA are passionate, dedicated public servants who care deeply about the important role they play in drug safety and public health.  They deserve our thanks and respect. 

The actions of the agency occasionally are at odds with the consensus of the AC as was the case in the approval of the DMD therapies.  In my experience on AADPAC, the committee differed with the FDA on only 2 or 3 important occasions one of which best highlights an important concept in the drug approval process that is not always apparent.  In 2014 Zohydro, an extended release long-acting opioid was approved over the objections of the AC causing a significant amount of controversy including congressional hearings and threats by some state governors to refuse to allow the drug to be dispensed in their state believing it would add to the ongoing opioid crisis.  What is instructive in this case can be found in the transcripts and in the subsequent letters to JAMA. 

During the discussion the Agency division director, Bob Rappaport, was asked questions by the committee that went something like this.  First, what is the standard that the manufacturer (sponsor) must meet for approval?  Answer; the drug must be safe an effective as labeled.    Second, what is the responsibility of the Agency with regard to the sponsor?  Answer; under the law, the agency must provide a level playing field for all sponsors such that they can expect to be treated equally with regard to safety, efficacy and labelling.  So, it does not matter if there is already one or one hundred safe effective drugs for pain or any other condition, if a new drug meets the aforementioned standard is must be approved.  Third, what is the role of the committee with regard to the level playing field?  Answer; the AC is free to do whatever it chooses and may disregard the wishes of the Agency, Congress, the sponsor or anyone else.  In the case of Zohydro, the AC chose to state clearly that despite being safe and effective as labelled (keep in mind the "as labelled" part) an additional non-abuse deterrent opioid was not needed and represented an additional threat to public health.  The vote was overwhelmingly against approval, but the agency subsequently overruled the committee and approved the drug anyway.  Because…it met the standard established by Congress.   

The take home is; although the actions of the Agency are sometimes unfathomable, they are usually rooted in complex regulation and or law that is frustrating to us as outsiders and is also often just as frustrating to the FDA and its leadership. 

Very briefly let me add that neither the agency nor the AC typically take into account the development or patient cost of the drug as a part of the approval process although the committee can and may have in this case.  Again...Safe and Effective as Labelled.  Nothing about cost effectiveness in the process. 

Good discussion.  The drug approval process might make a good session at a future Winter meeting.

From Myron and Mark Schreiner MD the accelerated approval process was something I thought all pediatric anesthesiologists should know something about. From this morning’s paper

“Pfizer’s phase 3 Duchenne muscular dystrophy (DMD) gene therapy failure has blown a $230 million hole in the New York pharma's second quarter financials (PDF). The drugmaker disclosed the discontinuation of the candidate—and the financial fallout—alongside the axing of a respiratory syncytial virus (RSV) combination vaccine.

The Big Pharma reported the failure of a phase 3 clinical trial for the DMD gene therapy fordadistrogene movaparvovec in June. At that time, Pfizer was still evaluating the next steps for the program. Six weeks later, the company has confirmed there will be no significant next steps, jettisoning the candidate from its pipeline and taking a $230 million charge in the process.

Pfizer’s decision brings a troubled program to an end. One month before the phase 3 fail, Pfizer paused dosing in the crossover portion of the phase 3 trial after a young boy in another study of the candidate died. The company also laid off 150 workers in North Carolina due to the gene therapy's failure. 

Sarepta Therapeutics’ DMD gene therapy Elevidys has also suffered setbacks, notably when it failed to hit the primary goal of a pivotal study, but the biotech has continued to grow sales and push to reach more patients. The FDA expanded Elevidys’ label in June.”