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Philip C. Spinella (ed.)Damage Control Resuscitationhttps://doi.org/10.1007/978-3-030-20820-2_17

17. DCR for Non-trauma Patients

Ryan P. Dumas^{1, 2} and Jeremy W. Cannon^{3, 4}

(1)

Division of General and Acute Care Surgery, UT Southwestern Medical Center, Dallas, TX, USA

(2)

Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

(3)

Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

(4)

Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA

Jeremy W. Cannon

Email: jeremy.cannon@uphs.upenn.edu

Keywords

Massive transfusionDamage control resuscitationPediatric hemorrhageGeriatric hemorrhageObstetric hemorrhageBlood componentsWhole bloodTranexamic acidFactor VIIaProthrombin complex concentrate

Introduction

Since the introduction of the truncated laparotomy in 1983 [1] and subsequent popularization of damage control surgery (DCS) by Rotondo et al. in 1993 [2], similar concepts have been applied to resuscitation, termed damage control resuscitation (DCR) [3, 4]. DCR combats the “lethal triad” of trauma coagulopathy and has become the standard of care for severely injured trauma victims with exsanguinating hemorrhage [4–8]. When combined with DCS, this approach has been associated with improved patient outcomes [9]. The fundamental importance of hemostatic resuscitation was underscored by the PROPPR trial in which patients in the 1:1:1 group achieved hemostasis sooner and had decreased mortality from hemorrhage within the first 24 hours [10].

Despite these potential benefits, the application of DCR principles remains variable [11, 12]. Evidence-based clinical recommendations for the application of DCR are the subject of a new Eastern Association for the Surgery of Trauma (EAST) guideline [13]. The emphasis on trauma applications is understandable given the demographics of hemorrhage-related deaths in the United States; however, peptic ulcer disease, ruptured abdominal aortic aneurysm, and maternal hemorrhage also claim numerous lives every year (Fig. 17.1). In addition , some studies estimate that perioperative hemorrhage in cardiac, vascular, oncologic surgery, and other operations for benign conditions are responsible for between 60% and 70% of patients undergoing massive transfusions [14, 15]. Thus, it is very important to consider how the principles of DCR may apply in these non-trauma populations [16]. This chapter will review the use of DCR principles in various nontraditional patient populations including pediatric patients, geriatric patients, and non-trauma patients.

../images/453814_1_En_17_Chapter/453814_1_En_17_Fig1_HTML.png — Fig. 17.1

Annual deaths and years of life lost (YLL) from hemorrhage in the United States. Each entity is shown as a relative percent, and the absolute numbers of deaths and YLL are shown above each bar (K denotes 1,000, M denotes 1,000,000). Perioperative deaths in the United States from other entities are not known and thus are not shown on this figure. AAA Abdominal Aortic Aneurysm, PUD Peptic Ulcer Disease. (Data from Cannon JW. Hemorrhagic shock. N Engl J Med 2018. 378:370–9)

Pediatrics

The principles of DCR should be in the forefront of every practitioner’s mind taking care of a bleeding pediatric patient. The core tenets of DCR in this population remain the same: hemostatic resuscitation while limiting crystalloid administration, recognizing and treating causes of hypothermia, coagulopathy and acidosis, and rapid definitive hemostasis [17]. There are, however, multiple unique elements of pediatric morphology and physiology that make DCR in this population particularly challenging. Pediatric patients are thinner, have less subcutaneous fat, and have an increased surface area to body mass ratio and are thus vulnerable to hypothermia [18]. Furthermore, although pediatric patients have relatively more circulating volume (10% body weight vs. 7% in adults), the absolute pediatric blood volume is quite small [19, 20]. Thus, even seemingly small volumes of blood loss can represent a catastrophic hemorrhage in a child. Finally, although pediatric patients have increased cardiac reserve and are able to compensate for up to nearly 50% of blood loss before developing hypotension, once this reserve is spent, they tend to progress quickly to cardiac arrest [21]. Evidence suggests that pediatric patients may also respond differently to inflammation as compared to adults [22] and that children less than 12 months of age have immature hemostatic systems and may have different blood transfusion requirements [23]. Additionally, procoagulant factor levels are reportedly low in pediatric patients until 6 months of age although the functional significance of these differences remains unclear [24]. Similarly, difference in platelet function, aggregation, and adhesion are also described [25].

With these important differences in mind, the following paragraphs summarize our current understanding of the application of adult DCR principles to pediatric patients. Historically, DCR has been used in pediatric patients undergoing burn resection and reconstruction for craniosynostosis [26]. More recently, data from combat operations in Iraq and Afghanistan have shed more light on the application of DCR in injured children [27, 28] while the ongoing MAssive Transfusion In Children (MATIC) study promises to illuminate modern pediatric resuscitation in civilian practice for both trauma and non-trauma patients (http://pediatrics.wustl.edu/matic/AboutMATIC).

Permissive Hypotension

Permissive hypotension has historically been one of the core tenets of DCR but remains one of the most controversial. The evidence for permissive hypotension in adults is mixed [29, 30]; thus, its application remains unclear [17]. Despite two randomize controlled trials that support use of permissive hypotension [31, 32] in trauma patients, a 2014 Cochrane Review concluded that there was insufficient evidence to support the use of hypotensive resuscitation strategies [33]. The most recent analysis from 2018, however, suggests there may still be a role and benefit for hypotensive resuscitation but that the majority of the studies are underpowered to detect a difference [34]. From the original study by Bickell et al. [23], it appears that delayed resuscitation is likely best applied to patients with penetrating torso injuries in an urban environment with extremely short prehospital times. To date, there are no pediatric trials that have studied the use hypotensive resuscitation on pediatric patient outcomes and there is insufficient evidence to support the use of permissive hypotension. Thus, best practice in the perioperative period is likely to target age-adjusted normotension. Table 17.1 summarizes the normal vitals ranges in pediatric patients.

Table 17.1

Normal pediatric physiology [105, 106]

	Respiratory rate (breaths per minute)	Heart rate (beats per minute)	Systolic blood pressure (mm Hg)
0–9 months	32	136	75
10–24 months	26	124	90
2–4 years	24	114	97
4–8 years	23	103	102
8–12 years	20	94	107
12–16 years	20	85	115

Minimize Crystalloids

There is evidence , however, to support the deleterious effects of crystalloid infusions in pediatric patients. Prehospital IV fluid administration has been associated with increased transfusion requirements, abnormal laboratory coagulation parameters, as well as a trend toward increased mortality [35]. In a recent large study of over 1300 pediatric trauma patients in Iraq and Afghanistan, investigators identified an association between crystalloid volume and both increased length of stay and prolonged ventilator days [36].

Coagulopathy and Shock

There is general consensus that the acute coagulopathy of trauma present in adults is also present in pediatric trauma patients. In a recent retrospective review of over 800 pediatric patients, early coagulopathy was present approximately one-third of patients and was associated with a significant increase in mortality [37]. Similar results have been reported in pediatric patients treated during combat operations [38]. Not surprisingly, hypotension and injury severity score with associated with early coagulopathy in pediatric patients [37].

Transfusion

Similar to adult patient populations, a massive transfusion protocol (MTP) should be implemented in all pediatric tertiary care centers [18, 21]. In pediatric patients, massive transfusion is defined as one of the following: transfusion >100% of estimated blood volume in 24 hours, ongoing transfusion of >10% of blood volume per minute, or replacement of 50% of estimated blood volume in 3 hours or less [23]. Importantly, a threshold of 40 cc/kg of all blood product transfused during the first 24 hours identified children at risk for mortality [27].

Although the evidence for MTP use in pediatric patients is still emerging, developing and employing an MTP for bleeding pediatric patients are likely beneficial [24]. The optimal target ratios of packed red blood cells, plasma, and platelets for the empiric phase of an MTP have yet to be firmly defined. It seems, however, that in pediatric patients, there may be more latitude in the exact ratio than in adults [28, 39]. Likewise, the optimal order of blood product administration has yet to be precisely defined. So long as volume overload is avoided, it is likely safe to lead with plasma and platelets followed by red blood cells. In the absence of an established best practice, there remains a lot of variation in the implementation of pediatric MTPs [23]. Fortunately, MTP for trauma in pediatric patients remains a relatively uncommon event compared to adults [40]. There is some evidence to support the use of TXA in pediatric trauma [41]; however, a recent survey of pediatric hospitals found that only 15% use antifibrinolytic therapy routinely [42].

Geriatrics/Elderly

Elderly patients represent an ever-growing demographic in our society. Although the elderly represents one-eighth of the population, they consume one quarter of trauma and critical care expenditures [43]. Patients over the age of 65 undergo approximately two million operations annually [44]. Studies have shown worse outcomes for elderly patients undergoing emergency operations [45] and when compared with their younger peers, elderly trauma patients are characterized as having worse outcomes [46]. Likewise, for those patients aged 65–79 undergoing a massive transfusion (defined as ≥10 units packed red blood cells over 2 consecutive calendar days [as an approximation for 24 hours given the nature of the data collection format for the registry]) for any indication, 30-day mortality was 27.7% and for patients over the age of 80 was 36%, compared to a mortality of just over 10% in patients ages 18–39 in a recent epidemiologic analysis [15]. This association between massive transfusion, age and mortality was also confirmed by another recent study [14]. Thus, we believe there are some important considerations when applying DCR principles to this population although to date, no study has specifically evaluated DCR outcomes in the elderly [47].

Elderly patients undergoing DCR for any indication are generally unwell at baseline with more medical comorbidities [48] and more frequent use of anticoagulants and antiplatelet agents [49, 50]. Progressive loss of physiologic reserve in this population has been coined “homeostenosis” [51]. A number of physiologic changes have been described and quantified , such as decreased pulmonary reserve [52], cardiovascular changes [53], and worsening renal function (Table 17.2) [54]. Hypoperfusion in the elderly may occur despite normal appearing vital signs [47]. Demetriades et al. showed that the majority of severely injured elderly patients did not meet traditional definition for trauma team activations based on presenting vitals [55]. Furthermore, traditional vital sign ranges that may predict mortality in patients less than 65 years of age may not be as useful in the elderly [56]. Due to preexisting atherosclerosis, elderly patients have a blunted vasoconstrictive responses [47]. It is very important to highlight, however, that the degree of physiologic change varies widely from patient to patient [51]. Further complicating the clinical picture, traditional endpoints of resuscitation such as urine output may not be as reliable in the elderly. Elevated lactate and base deficit levels should prompt increased monitoring as these laboratory indicators can herald occult hypoperfusion in the elderly. In elderly blunt trauma patients, elevated lactate and base deficit are associated with a fourfold increase in mortality [57]. Finally, geriatric patients, like pediatric patients, are very susceptible to hypothermia. A recent study found that patients over the age of 55 were more likely to arrive to the ICU hypothermic and hypothermia was found to be an independent risk factor for mortality [58].

Table 17.2

Changes in geriatric physiology with aging [51]

Neurologic

Decreased brain mass

Impaired autoregulation

Cardiovascular

Decreased maximum HR

Decreased maximum CO

Large arteries decreased compliance

Increased peripheral vascular resistance

Increased systolic blood pressure

Pulmonary

Decreased FEV1 and FVC

Increased VQ mismatch

Decreased inspiratory and expiratory pressures

Decreased alveolar surface area

Renal

Decreased solute secretion

Decreased renal mass

Decreased response to ADH, renin, and aldosterone

Temperature regulation

Decreased shivering

Decreased vasoconstriction

Decreased sweat production

Permissive Hypotension

Because vital signs are not a useful indicator of hypoperfusion in the elderly, the practice of permissive hypotension in this population is controversial. Permissive hypotension in the elderly has been studied in a retrospective fashion and was not associated with increased survival [59, 60]. However, the quality of the evidence is low and randomized controlled trials are lacking.

Crystalloids

Like in adults and pediatrics, however, the evidence supporting limiting crystalloid infusions in geriatric patients is more robust. In elderly patients in hemorrhagic shock, attempts should be made to limit crystalloid to two liters during the emergency department phase of patient care [61, 62].

Transfusions

Elderly patients have different cardiac physiology including impaired ventricular filling, decreased maximal cardiac output, and a decreased maximal heart rate [63]. Additionally, geriatric patients have a smaller blood volume and blunted cardiovascular responses [64]. Some studies also support more aggressive transfusion thresholds in non-bleeding geriatric patient with myocardial infarction [63]. Whether or not these benefits extended to patients undergoing DCR remains unclear.

Other non-trauma indications for DCR in the elderly patient population includes aortic surgery, cardiac surgery, and gastrointestinal hemorrhage. Recent studies have attempted to mitigate bleeding risk and the need for transfusion in these patient populations. For example, a recent randomized controlled trial of elderly patients undergoing combined coronary artery bypass grafting and aortic valve surgery found that prophylactic tranexamic acid reduced blood transfusion requirements perioperatively [65].

Anticoagulant and antiplatelet therapy in the aging population is also an important consideration during DCR of the elderly patient. These medications are widely prescribed and carry a substantial bleeding risk [50]. Particularly, the use of these medications increases the risk of intracranial hemorrhage. Additionally, these patients are also at risk for delayed hemorrhage following a negative CT scan examination of the head. Studies have shown that anticoagulant use increases the risk of mortality by sixfold in patients with a traumatic brain injury [66]. Although it is beyond the scope of this chapter, prompt reversal of therapeutic anticoagulation should be part of DCR for bleeding -injured and non-injured patients alike.

Obstetrics

Despite common perception, in large epidemiologic studies in industrialized nations, massive transfusion due to obstetrical bleeding is low 1.8% [15], and obstetrics patients have the lowest mortality following MTP (2.8%) [14]. When maternal bleeding does occur, however, it can be very dramatic and acute care surgeons are likely to be consulted to aid in the multidisciplinary care of these patients [67].

Before discussing some of the considerations of DCR in obstetrics patients, like elderly and pediatric patients, it is important to highlight some physiologic differences in pregnant mothers (Table 17.3). Changes during pregnancy, both hormonal and physiologic, most significantly affect the cardiovascular system. Despite a large increase in circulating blood volume, the major contributor is plasma volume with a relatively smaller increase in red cell mass. This is important when considering the pathophysiology of hemorrhagic shock. Whereas hemodynamic changes may be evident in Class II and III shock in nonpregnant patients, in pregnant patients, hemodynamic changes may not become visible until 1500–2000 cc of blood loss. Like blood volume in pregnancy, maternal cardiac output and oxygen consumptions are similarly increased [68].

Table 17.3

Changes in maternal physiology during pregnancy [107]

Plasma volume	Increases
Red blood cell mass	Increases
White blood cell count	Increases
Peripheral vascular resistance	Decreases
Heart rate	Increases
Systolic blood pressure	Decreases
Cardiac output	Increases
Clotting factors	Increase
Respiratory rate	Increases
Glomerular filtration rate	Increases

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