I am concerned about what Larry Mellick, MD, and Ravi Garg, MD, have written on guidelines for bronchiolitis and thrombolytic therapy for stroke, respectively. (“The Nihilistic Guidelines for AAP Bronchiolitis.” REM. 2022;44:22; https://bityl.co/ESoJ; “It’s time to stop giving tPA for stroke.” REM. 2022;44:27; https://bityl.co/ESoN.)
They obviously don’t follow the long-established science of multiple peer-reviewed studies.
Can Dr. Mellick be so bold that he believes he knows better than well-established guidelines based on good-quality evidence that have resulted in solid recommendations from the American Academy of Pediatrics? The four concluding points of his article come dangerously close to denying the science.
And Dr. Garg insinuating that Genentech participates in scientific malfeasance? He appears to accuse the drug’s sponsor of manipulating the data to favor the use of tPA in stroke. If we can’t trust pharmaceutical companies to be honest and transparent with their data, then how can we take dissident doctors seriously who ask such questions whose answers have already been settled by science?
Dr. Garg goes on to imply that the FDA was aware of said data manipulation in 1996, the year it approved tPA for stroke. What possible motivation could the FDA and the pharmaceutical industry have for approving a drug whose “most certain finding…is excess risk in the form of intracerebral hemorrhage and mortality?”
I fully support a free exchange of ideas, but to question such long-standing peer-reviewed literature is reckless and unscientific, especially in the current climate of conspiracy theory and misinformation. Dr. Garg ends his article with a timely question: “Where else in medicine do we accept such biased evidence as justification for potentially dangerous treatment for patients?”
Kevin Schierling, MD
Dr. Mellick responds: I am grateful to Dr. Schierling for his sincere concern. I understand perfectly; it is never comfortable to have a minority opinion. It’s even more uncomfortable when those whose work you criticize far outnumber you and are exceptionally brilliant and well-meaning. I have studied this disease process for years. To avoid the risk of personal bias (and embarrassment), I asked a senior researcher working with the University of South Alabama to review the quality of the research paper notes on which I based my opinions. The result of this independent review has only made me more confident. I was also emboldened because I practice pediatric emergency medicine and see patients with bronchiolitis syndrome respond to off-limit therapies every shift.
I am currently working on an exciting paper with a senior bronchiolitis researcher and a pediatric emergency physician that, among other key elements, will provide strong evidence that guideline disimplementation recommendations for albuterol, epinephrine, and saline hypertonic are wrong. The AAP and the international editors of the bronchiolitis guidelines had laudable intentions and based their opinions and recommendations on the evidence available at the time the guidelines were written. Unfortunately, combining several small, low-quality studies in a systematic review and meta-analysis does not yield high-quality information and certainly does not support a strong recommendation.
Nevertheless, allow me to share with you some evidence-based references that support my criticisms. Below are four valuable references for each of the easier ones (Hypertonic Saline and Racemic Epinephrine). Based on these meta-analyses and other important ones published since 2014, the deletion of hypertonic saline and racemic epinephrine should be immediately reversed by the guideline writers.
References for hypertonic saline solution: Neonatal Pediatrician. 2014;55(6):431; J Pediatr Pharmacol Ther. 2016;21(1):7; Cochrane Database System Rev. 2017;12(12):CD006458; and Pediatric Pulmonol. 2018;53(8):1089.
References for racemic epinephrine: Cochrane Database System Rev. 2011;(6):CD003123; Medicine based on Evid. 2012;17(1):12; N English J med. 2009;360(20):2079; and Pediatrics. 2021;147(5):e2020040816.
Albuterol is more complex and obscured by low quality studies, and it requires additional explanations that easily support conducting an albuterol therapy trial. These two references provide arguments and evidence to undo the total suppression of albuterol: West J Emergency Med. 2015;16(1):85 and Acad Emergency Med. 2008;15(4):305.
We hope to have a much more detailed and in-depth publication in the near future which may well be the final blow to the 2014 AAP bronchiolitis guidelines.