EDITORIAL Hyperkalemic cardiac arrest in pediatric patients undergoing massive transfusion: unplanned emergencies

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t is well known that the older the age of blood, the higher the supernatant potassium concentration (K+) of red blood cell (RBC) units. Other factors known to increase potassium during RBC transfusions, such as rate of transfusion, irradiation, and type of additive used, are well-described risk factors for hyperkalemia. When patients experience an increase in K+ concentration, the increase is often transient due to the redistribution of the potassium load. However, if a massive amount of blood is transfused, the stored RBC units may contain a sufficient amount of potassium to result in hyperkalemia. In this clinical scenario, transfusion-associated hyperkalemic cardiac arrest (TAHCA) may occur. The recent attention surrounding these reactions resulted in an advisory from the Society of Pediatric Anesthesia and its patient safety organization, Wake up Safe.1 In this issue of TRANSFUSION, a review article by Lee and colleagues2 identifies those risk factors and potential preventive measures by reviewing the published literature on TAHCA in a pediatric population. There is wide variation of RBC transfusion practice for both neonatal and pediatric populations. Spinella and colleagues3 conducted a survey in 2008 and 2009 to determine current practices in US and Canadian hospitals. Policies developed to prevent hyperkalemic reactions involve using fresher blood, RBC washing policies, and RBC irradiation. Based on the survey, the use of fresh blood was largely based on patient condition, such as cardiac surgery patients of all ages (46.5%), as opposed to the anticipation of massive transfusion (11.6%). Aside from neonatal exchange, the most common patient conditions for washing blood were patients undergoing neonatal cardiac surgery or cardiac surgery patients of all ages. Again, massive transfusion was not the most common indication for washing. The majority of the centers responded that blood was irradiated at the time of issue (64.5%), thus mitigating some of the concerns for the increase of potassium in an irradiated unit. In the current TRANSFUSION review, the authors take on the ambitious task of reviewing the prospective and retrospective published literature in the area of TAHCA associated with massive transfusion and find that the literature is quite limited. As an alternative to a metaanalysis, they conducted a review and detailed analysis of © 2014 AABB TRANSFUSION 2014;54:4-7. 4

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case reports and clinical studies of pediatric transfusion– associated hyperkalemia. Lee and colleagues reviewed 15 articles, nine case reports, and 13 clinical trials, although not all the clinical trials involved massive transfusions and five of the trials were routine and small-volume transfusions. Of the remaining eight that were not registries, six clinical studies that involved massive transfusions are described. Of interest, the authors note that some patients received smaller-volume transfusions that resulted in TAHCA. In one study, the common factors for TAHCA in patients who received rapid transfusion included acidosis, hyperglycemia, hypocalcemia, and hypothermia at the time of arrest. One important finding of this review is the identification of these metabolic abnormalities and methods of transfusion leading to TAHCA, which are just as important as developing blood bank protocols for product modification and age of units. For many transfusion services, procedures and protocols are set up for patient-specific conditions, but may not include specific measures to mitigate all risks. It is convenient to refer to these situations as “planned emergencies.” An example of this process may be a massive transfusion protocol. However, this type of protocol may even require more detail to identify subpopulations with unique factors for additional complications, such as TAHCA. Where we struggle in transfusion services is the identification and preparation for these “unplanned emergencies,” where complications such as hyperkalemia are potential problems during transfusion, but have not been previously anticipated. In these cases, there may not be time for processing steps, such as washing blood, so other strategies would be required. Lee and colleagues provide a summary of these measures to reduce TAHCA in pediatric patients. The first measure identified, “anticipate and replace blood loss before significant hemodynamic compromise occurs,” is an excellent example of the planned emergency. If clinicians can identify surgical procedures with known complication rates for massive transfusion and TAHCA, it may be possible to keep “fresher” units reserved for a patient. In our institution, craniofacial surgical patients were identified as a high risk for massive transfusions, so those patients have been placed preemptively on a fresher RBC unit protocol. In addition, recent publications examining real-time maximum order blood schedules, using computerized anesthesia records as a tool to identify trends in transfusion based on diagnostic

EDITORIAL

categories, may assist in identifying patients at higher risk.4 This knowledge will enable the physician to communicate concerns before surgery, so even if blood is not initially issued, a conversation can take place to know what is available, how long washing or plasma reduction would take, and the agreement to issue the fresher units first, with older units “on hold” in the event of a massive bleed. An example of this scenario is described in the review to illustrate how this measure may be achieved in practical terms. Lee and colleagues identified other measures to reduce TAHCA through their literature review, which included responsibilities of the clinician or anesthesiologist performing the transfusion. The size of the catheter, that is, larger bore, and peripheral transfusion over central lines may help mitigate the risk of TAHCA. At our institution, we also emphasize the rate of transfusion as a critical precaution that can be controlled even in patients with a central line. Along with this concept is the avoidance of rapid infusers in higher-risk patients. Pediatric transfusion medicine specialists, such as Strauss, have also described infusion rate as a critical factor in reducing the risk of the hyperkalemia in pediatric patients. In an earlier TRANSFUSION editorial, Strauss5 calculated potassium load based on different pediatric clinical scenarios. He recommended that if RBCs are required for unexpected massive bleeding, infusion rate be given at 0.5 mL/kg/min to avoid hyperkalemic reactions. Strauss also emphasized that guidelines should be developed to anticipate these situations. Other recommendations may include checking and treating electrolyte abnormalities frequently. Like any drug given in the operating room, RBC transfusions have the potential to change the patients’ electrolytes. These effects may be exacerbated by the use of drugs used to anesthetize the patient. Understanding the effects of different drugs given, along with careful monitoring of electrocardiogram (ECG) and electrolytes, will allow the anesthesia team to expeditiously intervene before the untoward outcome of a cardiac arrest. The majority of cases of TAHCA occur in the perioperative setting. To mitigate the risk of TAHCA, it is important for the anesthesiologist to identify at-risk patients, as well as prepare the perioperative team and blood bank for the possibility of massive transfusions. Individual hospitals should utilize their perioperative electronic health record to identify the types of cases that have historically required massive transfusion (more than 70 mL/kg blood within a 24-hr period or greater than 35 mL/kg within a 3-hr period), as defined by the review by Lee and coworkers. Preoperative labs including electrolytes and hemoglobin should be obtained for these higher-risk pediatric patients. A large-bore peripheral IV (greater than 23 gauge in pediatrics) should be started and utilized for

massive transfusion preferentially to central access. Ideally, the blood bank should select units that are fresh or washed (preferably within 6 hr of irradiation); however, this recommendation is often not easily accomplished in large-volume clinical centers. During massive transfusion, the anesthesia team has multiple patient care issues to identify and treat simultaneously, although care should be taken to check arterial blood gasses, electrolytes, and glucose to diminish the possibility of TAHCA. In addition, potassium levels can become rapidly elevated if the surgical procedure predisposes the patient to a period of hypoperfusion of a large vascular bed with subsequent reperfusion. Patients who are undergoing surgery and losing large amounts of blood are often hyperglycemic, hypovolemic, and acidotic, conditions that predispose to hyperkalemia. ECGs should be monitored for early signs of hyperkalemia including peaked T-waves, prolongation of the PR interval, and widening of the QRS complex. For these “unplanned emergencies” the anesthesia team should have treatments readily available, including dextrose-insulin and bicarbonate to shift potassium back into the cells and calcium as a physiologic antagonist and be mindful of hypovolemia and decreased cardiac output, which can both increase the possibility of hyperkalemia. It is prudent clinical practice to manage TAHCA not as an unanticipated complication, but as an expected complication that may occur with any given patient in highrisk situations. The case reports and literature surveyed in this review support that premise. There are patients who undergo TAHCA despite receiving fresher units, smallervolume transfusions, or transfusions through a peripheral line. Therefore, it is important to recognize that hyperkalemia may occur at any time during surgery so that physicians have proper training and preparation to handle these events. Much like we identify patients at risk for other transfusion reactions and attempt to provide pretransfusion medication or mitigating steps, identifying patients at risk for a hyperkalemic reaction and/or arrest is important. One way to identify these patients is through the preanesthesia evaluation. A recent Practice Advisory for Preanesthesia Evaluation reviews preoperative laboratory tests that should be performed before surgery.6 Of interest, in asymptomatic or nonselected patients, abnormal potassium concentrations were reported in 0.2% to 16% of patients. However, for selected high-risk patients, abnormal potassium concentrations were reported in 2.9% to 71% of patients. These data may suggest that the anticipated transfusion population is a selected population that requires special consideration, especially with abnormal potassium concentrations reported before surgery. The cited Anesthesia Advisory concludes that perioperative therapies, that is, transfusions, endocrine disorders, risk of renal and liver dysfunction, and use of certain Volume 54, January 2014 TRANSFUSION

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medications and alternative therapies, justifies careful perioperative serum chemistry monitoring. Lee and colleagues summarize the pediatric case reports and clinical studies of TAHCA in two convenient tables. The unrecorded data in many of the case reports and clinical trials lead to additional uncertainty about the contribution of the RBC units to the reactions in question. In attempts to underscore the importance of these types of reactions, the Society for Pediatric Anesthesia began collecting information about hyperkalemic reactions leading to arrests. After review of the case reports, the Pediatric Anesthesia Quality Improvement Initiative published an Advisory Report with recommendations for RBC products. Again, similar to the case reports and clinical trials in the current review by Lee and coworkers the collection of data was not standardized, making it difficult to evaluate each reaction to determine what role, if any, the RBC transfusions played. Overall, recommendations in the Advisory Report included the use of “fresh” blood in cases where massive transfusion is anticipated. The advisory defines fresh as 7 days or less, but that definition was not based on conclusive scientific evidence. Other recommendations include transfusing as soon as possible after irradiation and washing older or irradiated units before transfusion. Some challenges for meeting these requirements involve the fact that not every institution has an irradiator and/or cell washer on site, making the timing of these processing steps before transfusion less controllable. In response to the Wake up Safe Advisory, the AABB issued a statement addressing some concerns for the universality of some of the recommendations and precautions to developing guidance based on limited and inconclusive evidence.7 Evaluation of TAHCA reactions requires both input from the blood bank and clinical team to make the best decision moving forward for care of patients where major bleeding and hyperkalemic arrests may be predicted. Unilateral decisions made by either group, without discussion of the data and their implications for clinical practice, may lead to erroneous conclusions resulting in policy and procedures that are not medically indicated and/or adequate to mitigate these reactions. As one example, clinicians may begin to measure the K+ concentration in stored blood using nonvalidated instruments that are not approved for measuring K+ in stored RBCs. A further concern is that these erroneous K+ values may lead clinicians to label RBC units as either “good or bad,” thus potentially resulting in the unnecessary wastage of RBCs. Clear communication, in addition to procedures and policies, is required, so as not to delay care in an emergent situation in a massively bleeding patient, where concerns of TAHCA are one of many complications during lifesaving measures. It sounds cliché to state, “We need more studies and data” to understand the risk factors associated with 6

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TAHCA and pediatric patients undergoing massive transfusion. However, more complete information will assist with guidance for policies and procedures that are medically indicated and within expectations that can be met with the current blood supply in hospital transfusion services.8 We applaud the efforts of Lee and colleagues for a comprehensive attempt to summarize the current literature with regard to these reactions and to bring our attention not only to the K+ load in the stored blood, but the low cardiac output state contributing to these reactions. In summary, the following risk factors were identified as contributors for TAHCA: longer storage age of the RBC product, speed and volume of RBC products transfused, age and size of patient, method of transfusion, and presence of comorbidities. The authors conclude that newer guidance to reduce TAHCA should be developed for the small subset of pediatric patients identified at risk. However, they also emphasize that other pediatric patients, without the cited risk factors, may continue to safely receive routine blood components of any age without concern of TAHCA.

CONFLICT OF INTEREST None.

Deborah Sesok-Pizzini, MD, MBA Mark-Alan Pizzini, MD e-mail: [email protected] University of Pennsylvania Philadelphia, PA

REFERENCES 1. Tyler DC. The Pediatric Anesthesia Quality Improvement Initiative Wake Up Safe. Hyperkalemic Statement. 2011.

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[cited 2013 Sep 4]. Available from: http://wakeupsafe.org/ findings.iphtml Lee AC, Reduque LL, Luban NL, et al. Transfusionassociated hyperkalemic cardiac arrest in pediatric patients receiving massive transfusion. Transfusion 2014; 54:244-54. Spinella PC, Dresler A, Tucci M, et al.; for the Pediatric Acute Lung Injury and Sepsis Investigators Network. Survey of transfusion policies at US and Canadian children’s hospitals in 2008 and 2009. Transfusion 2010;50: 2328-35. Frank SM, Rothschild JA, Masear CG, et al. Optimizing preoperative blood ordering with data acquired from an anesthesia information management system. Anesthesiology 2013;118:1286-97. Strauss RG. Red blood cell storage and avoiding hyperkalemia from transfusions to neonates and infants. Transfusion 2010;50:1862-5.

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6. American Society of Anesthesiologists Task Force on Preanesthesia Evaluation. Practice advisory for preanesthesia evaluation. An updated report. Anesthesiology 2013;116:1-16. 7. American Association of Blood Banks. Hyperkalemia

pediatric surgery cases. Sep 14. 2011. [cited 2013 Sep 4]. Available from: http://www.aabb.org/pressroom/Pages/ hyperkalemia110914.aspx 8. Vraets A, Lin Y, Callum JL. Transfusion-associated hyperkalemia. Transfus Med Rev 2011;25:184-96.

concerns: potential changes in requests for blood for

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Hyperkalemic cardiac arrest in pediatric patients undergoing massive transfusion: unplanned emergencies.

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