From David Jobes MD Commenting on October 27th PAAD: Remembering the Classics: Support For The Use Of Fresh Whole Blood in Young Children Undergoing Complex Open Heart Surgery. Note in that PAAD I (Myron) made the point that blood banks treat blood products the way that grocery stores sell chicken…they make more money selling the parts than selling a whole chicken….
Commentary 1
This study is a classic in representing the divide between medical practice and the business of medicine. The usual progression of a therapy from efficacy (both demonstrated and replicated) to effective (as applied in clinical practice) along with safety leads to adoption by clinicians to better care for patients. Firstly, this is a study of efficacy of FWB which was replicated at Sick Kids Hospital in 2008. A subsequent retrospective study at CHOP in 2015 demonstrated effectiveness when FWB was adopted as a standard practice for 3836 patients over 15 yrs. However, since then my casual survey of pediatric cardiac surgeons and pediatric cardiac anesthesiologists from many centers produced a unanimous response regarding FWB “I would like to use FWB, but I can’t get it.” What is missing from this picture? Medical centers for the most part are dependent on a donor center from whom they annually or semiannually contract to purchase red blood cells, platelets, cryoprecipitate, and plasma. Often multiple hospitals (not the surgeons or anesthesiologists) negotiate contracts with the same donor center. The donor centers control nearly all blood availability and are configured to manufacture components. From a business point of view, they have little incentive to change practices which would interfere with flexibility in fulfilling multiple contractual commitments which are focused on component orders. Additionally, when the donor pool is diminished (e.g., Covid), manufacturing components is more efficient in fulfilling contracts. There is little to no competition between donor centers to use FWB as a bargaining point and hospitals would not look favorably on a price increase either. Could Dr. Yaster’s fowl (or foul!) allegory be correct?
Commentary 2
The background story. In the mid 1950’s the introduction of the refrigerated centrifuge and plastic collection bags, made it possible to separate whole blood components. This practice became increasingly used when in 1974 the FDA along with surgical societies endorsed the uniform use of component therapy essentially eliminating the use of whole blood. Cardiac surgery with CPB was introduced in 1953 and initially used for adult patients. A series of successful surgery in infants was not reported until 1980 at which time component use was the only option. These infants were a new surgical population and exhibited coagulopathic bleeding uniformly requiring multiple component transfusions unlike adults. Frustrated surgeons and anesthesiologists struggled to find the right combinations of components to reinstate normal coagulation and hemostasis. Two critical elements contributed to the problem – the obligatory disproportional dilutional effects of the CPB circuit as used in adults and a quantitatively immature coagulation system (not recognized until 1992). The lowest coagulation factor levels occur in newborns and are not equivalent to adults until adolescence. This may be viewed as a classic example of unrecognized population differences where “infants and children are not little adults”. The efficacy of whole blood as demonstrated in this paper and subsequent studies should have been adopted as the safest and most beneficial strategy for this population. Casual survey of pediatric cardiac surgeons and pediatric cardiac anesthesiologists from many centers produce a unanimous response regarding FWB “I would like to use FWB, but I can’t get it.” Could Dr. Yaster’s fowl (or foul!) allegory be correct?
Commentary 3
Why is this paper a classic? There are several reasons:
1. A clinical observation stimulating a well-designed study which validates the observation.
2. The evidence prompts multiple studies that have far reaching impact, e.g., the benefits of cold storage on short term platelet effectiveness, the benefit of whole blood in trauma resuscitation, prompting studies to define ”Fresh”, supporting longer storage of refrigerated WB in remote areas where fractionation is not possible.
3. It is disruptive – counters the current standard practice of room temperature storage of platelets for a specific purpose. Counters the standard practice of component manufacturing on behalf of a specific population. Blood center personnel are so ingrained by established practices that a common refrain when a change is requested is “…that can’t be because everybody knows…….” (Anecdote: CHOP has been supplied with FWB for many years because the donor center director at the time told me “If that’s what the evidence shows, we will provide it.”)
4. Illustrates again that “pediatric patients are not just little adults.”
5. Illustrates again the divide between the clinical practice of medicine and the business of medicine. Dr. Yaster’s fowl (or foul!) allegory may well be applicable.
From Monica S. Vavilala, MD, Professor, Anesthesiology and Pediatrics, Adjunct Professor, Health Systems and Population Health Director, Harborview Injury Prevention & Research Center University of Washington commenting on the series of PAADs on hypotension in infants.
“Studies of cerebral autoregulation in children, particularly infants, are rare. Assumptions about the lower limit of autoregulation (LLA) in healthy children and in pediatric critical illness are not objectively verified in research. Therefore clinical care relies on these assumptions or extrapolations from adult physiology. It has long been assumed that the LLA in infants and children is lower because resting MAP is lower and because there is some general sense that it “must be lower”. Yet studies from infants and young children show that the LLA is relatively similar to older adults. This means that the lower limit reserve is lower in infants and young children. Data from infants and young children provide evidence to this fact. Now,the significance of the LLA merits discussion and medications that reduce cerebral metabolic rate in may mitigate the theoretical “risk” that infants and young children may experience. And risks are not evenly distributed. what may be acceptable tolerance of blood pressure below the LLA in healthy patients may be an unacceptable risk in patients who are predisposed to cerebral ischemia such as from TBI or stroke or other conditions.
References
Patel ND, Batra M, Udomphorn Y, Wainwright M, Vavilala MS. Cerebral Autoregulation in Healthy Term Newborns: Brief Report. Pediatr Neurol. 2022 Oct;135:4-5. doi: 10.1016/j.pediatrneurol.2022.07.001. Epub 2022 Jul 7. PMID: 35961056.
Vavilala MS, Lee LA, Lam AM. The lower limit of cerebral autoregulation in children during sevoflurane anesthesia. J Neurosurg Anesthesiol. 2003 Oct;15(4):307-12. doi: 10.1097/00008506-200310000-00003. PMID: 14508171.
From Ben Walker MD Department of Anesthesiology UW School of Medicine and Public Health Madison in response to methadone PAAD. Ben was the senior author of the paper reviewed in the November 3, 2022 PAAD “methadone vs ivpca”
We really appreciate highlighting our retrospective study on methadone use and ERAS at our institution. I just wanted to respond to a few points made by Drs. Brockel and Yaster. First, to clarify our protocol, a night basal infusion was not used at all in the postop methadone group and only rarely (a few cases) in the pre-incisional methadone group. The PCA group (no methadone) was the only group to routinely receive a PCA. We ran a basal at night because meta-analysis show that the only benefit of a basal rate is improved sleep without a benefit in pain control and we believe this increases the overall safety profile of a PCA. We do not recommend using a basal rate on a patient receiving methadone. Regarding prn IV hydromorphone vs IV PCA, we agree that this introduces a "middle man" and can delay administration, but we feel this is justified because the postoperative methadone group (the only group without a PCA) used a median of 2 doses in their recovery period until taking po oxycodone on POD1-2 (at which time all groups would be reliant upon prn RN-administered po meds). Part of our rationale for eliminating the PCA was due to a nationwide IV opioid shortage a few years ago. The pharmacists noted significant amounts of PCA waste in patients who received pre-incisional methadone and approached us about switching to IV prn. Around the same time, Sophie Pestieau presented data at a SPA meeting about the postoperative methadone protocol at National Children's, which she shared with us. Our APS followed these patients for about 12 months after eliminating the PCA, but eventually stopped because we weren't making any changes to the protocol. A lower APS census can be advantageous to a smaller institution like ours that is supervised by an attending with OR duties, but may not be a good strategy for larger institutions with an APS staffed separately from the OR.
Regarding opioid side effects and LOS, Drs. Brockel and Yaster reported that these "were not part of the study". We reported on both of these and found no differences in sedation scores. As we mention in our limitations section, we could not report on nausea/vomiting because we began scheduling ondansetron in the postoperative methadone group due to nursing variability in administering prn ondansetron. Nalbuphine use was not reported because it was almost nonexistent in groups, again likely due to RN variability (and unfamiliarity) with that medication. We reported LOS in Table 2, and noted in the discussion regarding the early progress we made in LOS (from 5 to 3 days) with optimizing all aspects of postop care when we started the ERAS protocol, and could not demonstrate a further difference in LOS associated with our opioid reduction. Other aspects of postoperative care, such as PT, did not change over the study period.
We wholeheartedly agree with Drs. Brockel and Yaster that the best way to study this topic would be with a prospective trial. We do not have the volume to support this type of study at our institution (that was five years of spines at our institution), and our orthopedic and nursing colleagues were not receptive to withholding methadone in a control group based on their experiences. As the previous PAAD highlighted with data from Dr. Sadhasivam's group, others have published more widely on this topic and may have the capacity for an RCT. However, we believe our study is "positive" (based on criteria put forth by Chuck Berde - always right - in his article on peds analgesic trial design in Pediatrics) because we demonstrated a reduction in overall opioid use while maintaining analgesia with similar pain scores.