Bran Stark, a 10-year-old boy, was exploring Winterfell during King Robert Baratheon’s visit to Winterfell. This patient is the son of Ned Stark, Lord of the North, and heir of the powerful House Stark. As a curious young boy, he wanted to watch the festivities from the view of a tower. This was not unusual for Bran, who “had known ever stone of those buildings, inside and out; he had climbed them all, scampering up walls as easily as other boys ran downstairs”. He started climbing a decrepit tower with Summer, his direwolf, watching him eagerly from below. Little by little Bran, made his way to the top of the tower where he was met with an unusual scene- Jaime and Cersei Lannister, twin siblings, were engaging in incestuous intimacy.
When Bran reached the window to the Lannister’s room, Jamie walked over to Bran and pushed him off the window opening. He plunged an approximated 100+ feet to the ground, landing on his back. Detailed exam was not performed on scene, but Bran did not cry out upon impact, instead, he laid there without movement even after help had arrived.
Bran was comatose and unresponsive throughout his resuscitation. Once deemed stable by the Maesters at Winterfell, he was transferred to his bed to be watched by his loved ones. One evening, an assassin suddenly appeared in his room while his mother, Catelyn Stark was at his bed side. She confronted the intruder who tried to take her life with a dagger. Throwing her to the side, it became clear that the assassin had his sights set on the comatose Bran. Fortunately, Summer, Bran’s direwolf, jumped on the man and ripped out his throat, and Bran did not suffer any further injuries. A few weeks later, Bran woke suddenly just as his sister’s direwolf, Lady, was murdered. Whether this is a causal or coincidental event is controversial.
While a detailed medical examination was not performed on Bran, it could be assumed that he had significant injuries given the mechanism of injury and presenting GCS. Had it been invented at the time, the Maesters should have followed ATLS principles focusing on primary and secondary survey. For severely injured trauma patients, key principles in Damage Control resuscitation should be followed.
What is pediatric Damage Control Resuscitation?
Originally conceived by the US Navy during World War I, damage control strategy focused on prioritizing repairs to optimize the survival of a ship whereby a complete repair would detract from performing life-saving procedures first.1 This concept, when translated to trauma, led to improvements in mortality and morbidity in penetrating abdominal trauma in 1979.2 This concept was expanded from penetrating abdominal trauma surgery to general trauma surgery and became what is now known as damage control surgery (DCS). Damage control resuscitation (DCR) refers to a set of principles aimed at preventing death due to traumatic hemorrhage that includes but is not limited to DCS. In trauma these principles include early hemorrhage control, restoration of blood volume, and correcting physiological derangements.2 DCR works synergistically with DCS to rapidly restore homeostasis in trauma patients.
Patients with hemorrhagic shock secondary to trauma often have the “lethal triad” of metabolic acidosis, coagulopathy, and hypothermia known (as discussed in the case on Bran’s half-brother, Jon Snow). The lethal triad, if untreated, leads to worsening hemorrhage, hypoperfusion, coagulopathy, and eventual death. DCR combats these cascading events through early hemorrhage control, antifibrinolytics, limiting crystalloids, balanced transfusions, and permissive hypotension.3 It is important to note that metabolic derangements in severe trauma are not limited to the traditional “lethal triad” (e.g. inflammatory events, hypocalcemia, etc), and are beyond the scope of this article.
Despite strong evidence in the literature for the use of DCR in adults, there is limited evidence in the pediatric patient, and the physiological and epidemiological differences between adults and pediatric populations raises significant considerations for its implementation. In this article, we will explore three main concepts in damage control resuscitation and how they relate to the pediatric population:
- Permissive Hypotension
- Massive Transfusion
- Triggers for Massive Transfusion
Permissive hypotension refers to fluid-limited resuscitation in hemorrhagic shock with a goal to target a lower systolic blood pressure and MAP than physiologic normal. It is thought that permissive hypotension exerts protective effects through limiting hemorrhage and dilutional coagulopathy. Aggressive fluid resuscitation may increase cardiac output and thus leads to increase MAP and peripheral vasodilation. Peripheral dilation along with destabilization of clot may result in increased uncontrolled hemorrhage in the trauma patient. Neither crystalloid fluids, nor packed red blood cells alone, contain the platelets or coagulation factors that deplete rapidly during hemorrhage. Aggressive resuscitation with crystalloids or packed cells alone can therefore lead to a dilutional coagulopathy.4
A systematic review in 2018 found permissive hypotension may confer survival benefit in adult trauma resuscitation though studies were all of poor to moderate quality. Permissive hypotension in adult trauma typically targets a systolic blood pressure (SBP) of 80-90 mmHg, mean arterial pressure of 50 mmHg, or a palpable radial pulse (4) (although this varies by studies, institutions, blunt versus penetrating trauma, and whether traumatic brain injury is suspected). Notably, the American College of Surgeons (ACS) defines hypotension as systolic blood pressure of 70 + 2 x Age (years) in mmHg for children aged 1-10 and <90mmHg for children >10 years old.5
Regardless, these resuscitation targets do not apply to children for multiple reasons:
- Traumatic Brain Injury (TBI): TBI is the leading cause of mortality and morbidity in children.6 A single episode of hypotension in the brain injured child is related to statistically significant increased rate of mortality.7 The mechanism is thought to be due to decreased cerebral blood flow in the face of hypotension, leading to worsening secondary injury. A retrospective study of 10473 children from the National Trauma Database with isolated severe TBI found that a SBP of <75th percentile was associated with higher in-hospital mortality.8 Furthermore, in a retrospective cohort 93 children under 14 years old with severe TBI, pre-hospital and ED hypotension of SBP <5th percentile was associated with poor neurological outcomes.9 TBI is the rule, and not the exception, in pediatric blunt trauma. It is also the leading cause of death and disability due pediatric trauma. Given the high likelihood of TBI in blunt pediatric trauma, and the demonstrated poor outcomes with a single episode of hypotension in the brain injured child, permissive hypotension should not be employed in blunt pediatric trauma.8,9
- Compensatory Mechanisms: Pediatric patients can maintain normal blood pressures in face of significant hypovolemia. Hypovolemia can be an exceedingly late finding after the loss of upwards of 45% of the circulating volume.10 Cardiac output is robustly maintained in children through tachycardia with fixed stroke volume and peripheral vasoconstriction.10 Further hemorrhage leads to decompensated shock (shock with hypotension), which is associated with a further decrease in perfusion, and hypoxia. This may eventually result in bradycardia and arrest. Thus, once a child becomes hypotensive, they have already lost a significant blood volume, and any further blood loss further worsens morbidity and mortality. The overall mortality rate of 64344 pediatric patients from the Pennsylvania Trauma Outcome Study registry was 2.0% compared with 46% mortality in hypotensive patients (OR 12.8, 95%CI, 10.7-15.4) after controlling for injury severity, age, and admission neurological status.11 Despite the limitations of this analysis, these findings highlight the significant mortality of pediatric trauma patients with hypotension.
Volume Resuscitation Strategies and Pediatric Massive Transfusion
Massive blood transfusion refers to the replacement of large amounts of blood products in response to massive hemorrhage. The infusion of excessive crystalloid or pack red blood cells (PRBC) alone leads to dilutional coagulopathy as they do not contain clotting factors which are consumed during hemorrhage. Recent trauma literature and guidelines have shifted towards judicious use of crystalloids in pediatric trauma.
• ATLS 10th edition recommends 20 ml/kg for pediatric patients and removed a suggestion of giving 3 boluses of 20 ml/kg prior to blood products.
• US military hospitals from 2002 to 2012 in Afghanistan and Iraq found increased crystalloid administration was associated with increased ICU days, ventilator days and hospital stay after adjusting for ISS and age.12 It did not show an association with mortality.
• Similarly, an EAST multicenter prospective observational study showed crystalloid bolus after first 20cc/kg was associated with increased odds of ventilator, ICU and hospital days.13 It did not show an association with mortality.
The activation of massive transfusion protocols in pediatric trauma is rare. Of 356,583 patients in the National Trauma Data Bank, 13523 (4%) received a transfusion of which 173 were massive transfusions (0.04%) defined as >40cc/kg of blood products within first 24 hours.14 There is no set definition of what is classified as a massive transfusion in pediatric trauma or when to consider activating a massive transfusion protocol. Various definitions have been proposed for what constitutes massive blood transfusion. In the pediatric population massive transfusion have been suggested as one of the following:15
- Transfusion of total blood volume (TBV) >50% in 3h
- Transfusion of >100% TBV in 24h
- Ongoing blood loss of >10% TBV/min
- Other definitions can vary significantly as estimated need of 40cc/kg of any blood product within 2h to 24h, or >50% TBV in 24h.14
Massive transfusion protocols are based on a ratio of packed red blood cells, fresh frozen plasma, and platelets. Adjuncts often included in these protocols include calcium, TXA, PCC, fibrinogen etc. Evidence for ratio-based resuscitation is adapted from adult literature, though pediatric specific evidence is lacking. Various pediatric studies have resulted in mixed results with low quality of evidence.4 Recently, a large retrospective study of 465 children with massive transfusion activation showed better survival (p=0.02) with plasma to PRBC ratio equal or greater than 1.16 2 small prospective studies failed to show improvement in mortality outcomes in pediatric patients when a ratio-based pediatric massive transfusion was administered compared to a non-MTP cohort.17,18 Nevertheless, given the theoretical benefits, balanced pediatric massive transfusion protocols have been implemented in major sites though further research needs elucidate optimal protocol.
Triggers for Pediatric Massive Transfusion Protocols (P-MTP)
The decision to initiate massive transfusion by a clinician depends on clinical judgement, response to resuscitation, and decision tools. Validated scores for adult trauma exist in including shock index, ABC, and RABT, which are used for prognosticating the need for massive transfusion. Unfortunately, no such validated prognostic scoring system exist for children. Furthermore a restrospective study showed adult scoring systems were not sensitive for predicting P-MTP. For example, the ABC score was only 29% sensitive. The conclusion of the study was that adult scoring systems should not be used to predict the need for P-MTP.19 Most clinicians activate massive transfusion based on clinical judgement. Given that massive transfusion is a rare occurrence in children, activation of MTP using clinician’s discretion leads to inconsistent and possibly ineffective utilization.20 The following studies provide insight into possible scores for identifying high-risk patients requiring MTP.
- The pediatric BIG score was developed from the Joint Theater Trauma Registry of 707 patients from combat-support hospitals in Iraq and Afghanistan by Borgman et al. 2011.21 INR, admission base deficit, and GCS were found to be associated with mortality. The score derived from this study: Base Deficit + 2.5 x INR + (15 – GCS), where higher scores are associated with increased mortality. The authors found AUC of 0.89 (95% CI, 0.83-0.95) and validated the score on dataset from a German Trauma registry. A prospective study in 2016 of 50 multi-trauma pediatric patients found a BIG score of >12.7 has a sensitivity and specificity of 86.7% and 71.4% respectively.22 Overall, the BIG score can be useful in prognosticating pediatric trauma in terms of mortality, however it requires laboratory results (decreasing its utility in acute resuscitation) and does not specifically indicate when massive transfusion protocol should be considered.
- Shock index is another potential scoring system that can be used, however must be adjusted to account for differences in pediatric physiology. SIPA (shock index pediatric-adjusted) separates children into:
4-6yo = 1.2
6-12yo = 1
>12 = 0.9
Zhu et al. analyzed a cohort of 2035 pediatric patients of which 39 received P-MTP of which they found shock index >1.4 and SBP <100 mmHg to be highly specific (94.3%) for the need of massive transfusion with a sensitivity of 45%. They also compared SIPA which had a sensitivity of specificity of 97% and sensitivity of 31%. Authors suggest SI >1.4 with SBP <100mmHg as a potential trigger for massive transfusion.23
- ABC score is defined as one point for each of the following: penetrating mechanism, positive FAST, SBP<90, HR>120 where >2 score has been used for activating MTP. ABC is poorly sensitive in predicting P-MTP as shown be previous studies; pediatric trauma patients are less likely to involve penetrating mechanisms and less likely to have a positive FAST despite solid organ injury which decreases sensitivity of the score. Phillips et al. in 2020, sought to develop the ABCD score which is defined as one point for each:24
- Penetrating Mechanism
- Positive FAST
- Lactate > 3.5
- Base Deficit > -8.8
They found that even a score of 1 or higher had a sensitivity of 97.9% with a specificity of 40.4%, and a score of 3 or higher had a sensitivity 77.4% and specificity of 78.8% for activation of P-MTP. This study was limited in its small sample size of 211 children and retrospective nature. It also relies on laboratory data. Despite this, the ABCD score shows promise as a possible score in P-MTP activation.
Back to Bran’s Case
Despite the significant mechanism of injury, Bran woke up several weeks later with paraplegia. Had the knowledge of DCR been discovered by the Maesters, it may have improved his resuscitation, and thus facilitated and early operation to his spine. The multiple techniques and equipment stated in this article was not available to the Maesters; there may not have been the availability of various blood products. Interestingly, whole blood transfusion (WB) could have been a viable option for Bran if the Maesters could acquire the appropriate tools and had knowledge of tests for donor compatibility.
Whole blood transfusion was the predominant blood product available for patients’ requiring transfusion for centuries. Unfortunately, early transfusions were fraught with adverse reaction. Recently, there has been a resurgence of interest in the use of whole blood transfusion in trauma patients, particularly by the military. Whole blood can minimize coagulopathy present in trauma resuscitation, particularly in massive transfusions. In fact, massive transfusion approximates the ratios of blood components to that of whole blood,25 which can be transfused within 24h or up to 35 days after cold storage. Small studies have indicated the safety of whole blood in transfusion of pediatric patients. However, there is a paucity of evidence for it compared to conventional modern resuscitation techniques.25 Despite this, if it were available during the rule of the Seven Kingdoms, the authors of this paper would advocate this treatment for Bran in the presence of significant hemorrhage.
We are glad to see Bran’s rise through the years in the world of Game of Thrones. The authors also speculate that it could have been fate that led to Bran’s injury and recovery. We acknowledge that even if modern techniques and knowledge was applied to Bran, he may very well have had the same outcome. Bran, himself, said it best “What if I fell from that tower for a reason”.
This post was copyedited & edited by Brent Thoma.
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