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9 Pediatric Trauma Resuscitation

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Table 9.2 Common emergency medication doses in children

Medication Dose Adenosine 0.1mg/kg IV rst dose (max 6mg)

Amiodarone (VF/VT arrest)

Atropine sulfate 0.02mg/kg IV (min 0.1mg, max

Calcium chloride (10%) 10–20mg/kg IV Calcium gluconate (10%) 15–60mg/kg IV Diazepam 0.5–1.0mg/kg IV Dobutamine 2–20mcg/kg/min IV Dopamine 2–5mcg/kg/min IV (>15mcg/kg/min

Epinephrine (asystole/ PEA arrest)

Epinephrine infusion 0.1mcg/kg/min IV, then titrate (range:

Lidocaine 1mg/kg IV push

Magnesium sulfate 25–50mcg/kg IV over 10–20min

Morphine sulfate 0.1mg/kg IV Midazolam 0.1mg/kg IV (max 5mg) Naloxone 0.1mg/kg IV (if less than 5years old

Pancuronium 0.1–0.2mg/kg IV Sodium bicarbonate 1–4mEq/kg IV Succinylcholine 2.0mg/kg (if<10kg)

Thiopental 4–6mg/kg IV Vecuronium 0.2mg/kg IV

VF ventricular brillation, VT ventricular tachycardia, PEA pulseless electrical activity

rapid push

0.2mg/kg IV second dose (max 12mg)

5mg/kg IV (max 15mg/kg/day)

0.5mg)

0.04mg/kg IV for second dose

for alpha effect)

0.01mg/kg IV rst dose (repeat Q3–5min during CPR)

0.1–1mcg/kg/min)

20–50mcg/kg/min IV

(max 2g)

or 20kg) 2mg IV (if greater than 5years or

20kg)

1.0–1.5mg/kg (if>10kg)

which should be rapidly treated with needle decompression at the second intercostal space at the mid-clavicular line versus emergency thoracostomy tube placement. Children are diaphragmatic breathers, and therefore, gastric distension can be an unrecognized contributor to respiratory distress, especially in the young child who is distended from swallowing air while crying. If concerned about gastric distension, a nasogastric tube (or orogastric tube in very young children who are obligate nose-breathers) should be placed to decompress the stomach.

9.4.5 C=Circulation (Hemorrhage Control)

Hemorrhage is the most common etiology of shock in trauma, but do not overlook obstructive etiologies (cardiac tamponade and tension pneumothorax) and distributive etiologies (neurogenic shock).

Assessment of volume status and shock is difcult in the child. Children have impressive physiologic reserve and can maintain SBP until late-stage hypovolemic shock (>30% blood loss). As in adults, tachycardia, tachypnea, altered level of consciousness, and poor peripheral perfusion (mottled cool extremities, weak thready pulses, narrowed pulse pressure, delayed capillary rell) are early and important signs of hypotensive shock.

Establishing vascular access in an injured child is a priority and can be challenging. Peripheral IVs are ideal, but after two unsuccessful attempts, an intraosseous line (IO) should be considered. IO lines offer a quick and reliable alternative for high-volume infusion of any uid (crystalloid, blood products), and medications, including pressors. An IO line is placed in the anteromedial tibia, 2–3cm distal to the tibial tuberosity after a quick skin prep for sterility (Fig. 9.2), avoiding wounds, fractures, or infected/burned skin. IO lines

Fig. 9.2 (a) Intraosseous line placement. (b) EZ-IO drive

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M. L. Hennessy and P. T. Masiakos

Table 9.3 Fluid management in children

Resuscitation uids (NS or LR) If hypotension or signs

of shock

Daily maintenance uid requirements (D5 1/2NS or D10 1/2NS)

Weight<10kg 100mL/kg/day Weight 11–20kg 1000mL+50mL/kg/day (for every kg

Weight>20kg 1500mL+20mL/kg/day (for every kg

Bolus 20mL/kg. Then switch to blood product transfusions (10mL/kg)

over 10)

over 20)

should be placed with a single attempt—multiple holes can lead to leakage of uids and resultant compartment syndrome. Denitive IV access can also be obtained with a central line in the femoral vein (the preferred location in a pediatric patient, under US guidance if available) or a peripheral vein cutdown (i.e., saphenous vein).

Initial uid resuscitation is indicated when there are signs of hypovolemic shock. Initial bolus consists of 20mL/kg of warmed normal saline or lactated Ringer’s solution. Updated 2019 ATLS guidelines now recommend all further resuscitation be via balanced 10–20mL/kg boluses of pRBC, FFP, and platelets. Balanced resuscitation, though demonstrating survival advantage in adults, has yet to be supported by the limited available data in pediatric populations. If crossmatched, type-specic blood is not immediately available, O-negative blood is indicated. Once resuscitated, maintenance uid requirements (Table9.3) can be estimated using the “4–2–1” rule and should be administered as D5 1/2NS (or D10 1/2NS for neonates). The “4–2–1” rule estimates hourly uid requirements and is calculated=4mL/kg/h (for the rst 10kg)+2mL/kg/h (second 10kg)+1mL/kg/h (all subsequent kg).

As in adults, hemodynamic instability in a trauma patient is considered hemorrhagic shock in a child until proven otherwise and must be controlled expeditiously. Notably, extended focused abdominal sonography in trauma (eFAST) is less reliable in pediatric populations and thus a negative eFAST exam should not dissuade the provider from obtaining further cross-sectional imaging if concern for injury is present. In contrast to adults with closed head injuries, in an infant, prior to suture closure of the skull, intracranial hemorrhage may produce hemodynamic instability. Adjunctive treatment with antibrinolytics such as tranexamic acid (TXA) has come into routine use in the adult trauma population. Data now suggests that TXA may have similar hemostatic benets in pediatric trauma patients with hemorrhagic shock, likely with a low-risk prole, though more pediatricspecic data is needed and routine pre-hospital administration, such as is often done in adult patients, is not recommended at this time. Dosing for children over the age of 12 is the same as adults (1g loading dose, then an additional 1 g given over 8 h), while younger children should

Table 9.4

Eye opening

4 Spontaneous Spontaneous 3 To verbal stimuli To verbal stimuli 2 To pain only To pain only 1 None None

Verbal response

5 Coos and babbles Oriented, appropriate 4 Irritable cries Confused 3 Cries to pain Inappropriate words 2 Moans to pain Incomprehensible

1 None None

Motor response

6 Moves spontaneously and

5 Withdraws to touch Localizes painful stimuli 4 Withdraws in response to pain Withdraws in response to

3 Abnormal exion posture in

2 Abnormal extension posture in

1 None None

If a patient is intubated, unconscious, or preverbal, the most important

part of this scale is motor response and should be closely evaluated

Modied Glasgow coma scale in children

Infant Child

sounds

purposefully

response to pain

Obeys commands

pain Flexion in response to

pain Extension in response to

pain

receive a weight-based dose (15mg/kg loading dose, and infusion of 2mg/kg/h for 8h).

9.4.6 D=Disability (Neurologic Assessment)

Head injury accounts for the highest degree of morbidity and mortality in children and is the principal determinant of patient outcomes. However, on the whole, children have more frequent and robust recovery from even serious head injury, when compared to similar injuries in adults. Therefore, careful attention to preventing secondary injury and maximizing tissue perfusion to the brain can greatly improve outcome. These secondary insults include ischemia, hypoxia, hypotension, hyperthermia, hypercapnia, acidosis, and increased intracranial pressure. The Glasgow Coma Scale is modied in young children who are preverbal to measure neurologic function and prognosis. The motor response scale tends to provide the most reliable assessment of function in a preverbal or intubated child (Table9.4).

9.4.7 E=Exposure forSecondary Survey

In preparation for the secondary survey, the child must be exposed completely for a complete head-to-toe physical examination. Keep in mind pediatric patients have a larger

9 Pediatric Trauma Resuscitation

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body surface area to volume ratio and therefore lose heat quickly. The prudent use of warm uids, forced-air warming blankets, warming lights, and warm ambient room temperature can prevent heat loss in a child.

9.5 Secondary Survey

Children are more prone to multisystem trauma due to their small body size and more compliant body (less protective bones, muscle, and fat of the torso). They can sustain internal injuries without signicant external signs of trauma. Careful attention to a bruise on the abdominal wall resulting from a bicycle handlebar should lead to a more thorough investigation of the abdomen—a classic mechanism for pancreatic injury. A lap belt mark across the abdomen may raise concerns of lumbar spine fracture (Chance fracture), with an associated risk of small bowel injury.

9.6 Diagnostic Modalities

Physical examination in a child can be technically challenging, and adjunct diagnostic modalities and imaging may be used to provide additional information in the evaluation of a pediatric trauma patient. Screening C-spine and AP chest radiographs can help diagnose fractures, dislocations, hemo-/ pneumothorax, and mediastinal injury. AP pelvic lms are of limited utility in the pediatric population but can be considered in select circumstances, though if suspicion for pelvic injury is high, CT imaging should be obtained. Extended focused assessment with sonography in trauma (e-FAST) exam can be performed quickly and exposes the patient to no potential harm from delay or ionizing radiation. However, the higher incidence of solid organ injury without free uid in pediatric populations renders e-FAST a less sensitive modality in children than in adults, and should not be used in isolation to rule out intra-abdominal injury when there is a clinical suspicion of signicant injury. Sensitivity of e-FAST in pediatric populations is reported as 40–90% and specicity of 79–100%. Of course, a standard battery of laboratory tests, including a type & cross, liver function tests, blood gas, complete blood count and metabolic panel, is useful in the diagnosis and treatment of the injured child.

capability; injuries of different chronological age (bruises or fractures at different stages of healing); delay in seeking medical care; sharply demarcated burns (scald); injuries related to bite marks, cigarette burns, rope marks, or involving perineal/genital region; multiple subdural, subarachnoid, or retinal hemorrhages without external signs of trauma (shaken baby syndrome); or multiple rib fractures (especially of different stages of healing). Specialty consultations should be initiated, including skeletal survey and ophthalmologic exams, when suspicion for non-accidental trauma is present.

Important Points

• ATLS is similar in adults and children, but there are some key physiologic and anatomic differences in children that are important to remember.

• Blunt trauma (i.e., handlebar) can produce injuries that resemble penetrating injuries (i.e., bowel perforation) in children with compliant abdominal walls.

• Broselow Pediatric Resuscitation Tape helps estimate a child’s weight to determine device size and medication doses.

• Cardiac arrest is often of respiratory etiology in a child. Use a Miller blade for intubation and an ETT the size of the child’s pinkie nger.

• Gastric distension can cause respiratory distress in children who swallow air while crying, because they are diaphragmatic breathers. Place nasogastric tube (orogastric in infants who are obligate nose-breathers) to decompress.

• Children have impressive physiologic reserve and maintain BP until severe blood loss (>30%). Lowest acceptable SBP=(Age×2)+70mmHg.

• Intraosseous line may be placed for emergency vascular access if peripheral IVs are not possible.

• Crystalloid bolus = 20 mL/kg. Blood transfusion “unit”=10mL/kg.

• e-FAST exam has limited value in a pediatric trauma patient.

• Many solid organ injuries in children can safely be managed nonoperatively.

• Suspect non-accidental trauma when the story does not add up.

9.7 Non-accidental Trauma

Non-accidental trauma is the leading cause of trauma in children and often goes unrecognized. Suspect non-accidental trauma in certain specialized circumstances: discrepancy between the reported history and physical exam ndings; injuries are not consistent with an infant’s developmental

Evaluation and treatment of the pediatric trauma patient

have some key differences from the adult patient. Blunt trauma is the most common mechanism of injury, but because of abdominal wall compliance, it can produce injuries that resemble penetrating mechanisms (i.e., handlebar injury producing small bowel perforation). Cardiac arrest is most often respiratory in etiology, and Miller blade and cufess endotracheal tube (the size of a child’s fth digit) are used for

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M. L. Hennessy and P. T. Masiakos

rapid sequence intubation. Nasogastric tube decompression can relieve respiratory distress from gastric distension in a crying child who has swallowed air. Children have impressive physiologic reserve and can maintain SBP until severe blood loss (>30%), so providers should not be falsely reassured by normal blood pressure. Intraosseous line is an excellent source of vascular access when peripheral IVs cannot be established. If there are signs of hypovolemia, a bolus of crystalloid (20 mL/kg) may be administered while assessing response. According to 2019 guidelines, subsequent volume resuscitation should be with blood products (10mL/kg). Many solid organ injuries in children can safely be managed nonoperatively. A high index of suspicion for non-accidental trauma must be maintained by any practitioner caring for pediatric trauma patients.

Suggested Reading

Committee on the Future of Emergency Care in the United States

Health System. Emergency Care for Children: Growing Pains. The National Academies Press; 2007.

Daley BJ, Lee S, Raju R, Geibel J. Emedicine. In: Considerations

in pediatric trauma; 2013. http://emedicine.medscape.com/

article/435031-overview#a1. On 9 Sept 2015.

Drucker NA, Keisin Wang S, Newton C.Pediatric trauma-related coag-

ulopathy: balanced resuscitation, goal-directed therapy and viscoelastic assays. Semin Pediatr Surg. 2019;28(1):61–6.

Eckert MJ, Wertin TM, Tyner SD, Nelson DW, Izenberg S, Martin

MJ.Tranexamic acid administration to pediatric trauma patients in a combat setting: the pediatric trauma and tranexamic acid study (PED-TRAX). J Trauma Acute Care Surg. 2014;77(6):852–8.

Galvagno SM, Nahmias JT, Young DA.Advanced trauma life support

update 2019. Anesthesiol Clin. 2019;37(1):13–32.

Murphy R, Ghosh A. Towards evidence based emergency medi-

cine: best BETs from the Manchester Royal Inrmary. The accuracy of abdominal ultrasound in paediatric trauma. Emerg Med J. 2001;18(3):208–9.

Scaife ER, Rollins MD, Barnhart DC, Downey EC, Black RE, Meyers

RL, Stevens MH, Gordon S, Prince JS, Battaglia D, Fenton SJ, Plumb J, Metzger RR.The role of focused abdominal sonography for trauma (FAST) in pediatric trauma evaluation. J Pediatr Surg. 2013;48(6):1377–83.

Tepas JJ III, Schinco MA.Chapter 45: Pediatric trauma. In: Moore

EE, Feliciano DV, Mattox KL, editors. Trauma. 5th ed. NewYork: McGraw-Hill Companies; 2004. p.1021–39.

Fluids, Blood Substitutes, andNew

Total body water

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Tools

SophiaTam, LaraSenekjian, andRamNirula

10.1 Physiology

10.1.1 Fluid Compartments

The amount of total body water differs with age and gender. The “average” 70-kg male is approximately 60% or 42L (since 1kg=1L of water) of water. Two-thirds of that water is intracellular and one-third is extracellular. Of the 14L of extracellular uid, about one-third of this volume, or 4.7L, is intravascular volume. It is this uid that is referred to as the circulating blood volume. Most of the oxygen-carrying capacity is within erythrocytes rather than in the uid itself, but without sufcient volume to distribute this red cell mass, effective delivery of oxygen ceases. As a result, appropriate volume resuscitation after hemorrhage is necessary to ensure adequate oxygen delivery (Fig.10.1).

10.1.2 Response toAcute Hemorrhage

Each of these uid volumes, the intravascular, the interstitial, and the intracellular, is in equilibrium; however, disturbances such as acute blood loss result in uid shifts in attempt to maintain effective circulating volume. Compensatory mechanisms, such as vasoconstriction and increased heart rate, are the physiologic responses to blood loss in order to maintain cardiac output. Catecholamine release immediately stimu- lates increase in the peripheral vascular resistance, leading to

S. Tam (*) Department of Surgery, University of Utah, Salt Lake City, UT, USA e-mail: sophia.tam@hsc.utah.edu

L. Senekjian Division of Trauma and Critical Care, University of California San Francisco—East Bay, Oakland, CA, USA e-mail: lsenekjian@alamedahealthsystem.org

R. Nirula Section of Burns/Trauma/Critical Care, University of Utah, Salt Lake City, UT, USA e-mail: r.nirula@hsc.utah.edu

Fig. 10.1 Body uid compartments. Distribution of total body water

increased diastolic pressure and reduced pulse pressure while simultaneously increasing heart rate. Histamine, bradykinin, β-endorphins, prostanoids, and cytokines directly impact vascular permeability and increase vasoconstriction. Intravascular uid is preferentially shunted to the heart, brain, and kidneys and away from the viscera and muscle. At the cellular level, inadequate oxygen due to poor tissue perfusion changes energy production to anaerobic metabolism which initially leads to metabolic acidosis and end-organ damage. End-organ damage causes a systemic inammatory response syndrome (SIRS), increasing vascular permeability, which causes uid leak and increased hypotension.

60% water

70 kg male

_ 3

ECF

ICF

Interstitial fluid

Intravascular fluid

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S. Tam et al.

Hypoperfusion also leads to increased thrombomodulin which complexes with thrombin, leading to protein C activation. Decreased available thrombin leads to less brinogen cleavage and platelet activation, contributing to traumainduced coagulopathy (TIC) potentiating hemorrhage.

Compensatory vasoconstriction of renal afferent arterioles results in decreased capillary hydrostatic forces, reducing uid loss from the intravascular space into the interstitial space. Increases in plasma oncotic pressure secondary to reduced renal ltration increase the amount of water that diffuses from the interstitial to the intravascular space. Activation of the renin-angiotensin-aldosterone axis increases sodium retention, which facilitates renal uid retention. Angiotensin also increases systemic vascular tone, which contributes to the reduced capillary hydrostatic forces. Decreased pressure in the atria and increased plasma oncotic pressure stimulate the release of antidiuretic hormone (ADH) from the posterior pituitary. ADH acts to increase renal distal tubule permeability to water through the production and placement of aquaporins in the luminal membrane, resulting in increased water retention.

10.2 Hemorrhagic Shock

Hemorrhagic shock is classied based on the volume of blood lost from the circulation and the resulting disturbances in hemodynamics observed. It is important to remember that hemorrhage may be more than what is easily appreciated as external blood loss. Blood loss into potential spaces such as the hemithorax, abdomen, and retroperitoneum can reach life-threatening levels without appreciable external loss. The degree of hemorrhagic shock correlates with clinical signs; however, these signs may not be readily apparent in the elderly due to blunted physiologic response or medications as well as other subpopulations such as athletes and children (Table10.1). These clinical signs can help estimate the volume of blood lost and resuscitative needs as a starting point, but the amount and type of volume resuscitation ultimately are dictated by the patient’s physiologic response. Identifying and controlling the source of hemorrhage through appropriate diagnostic means such as chest/pelvic radiographs and extended Focused Assessment with Sonography for Trauma (eFAST) while initiating resuscitation, is the cornerstone of traumatic hemorrhagic shock management.

Table 10.1 ATLS classication of hemorrhagic shock

Parameter Class I Class II Class III Class IV Volume of

blood loss % of total

blood volume

Heart rate >100 >100 >120

Systolic blood pressure

Pulse pressure

Capillary rell

Respirations per minute

Urine output

Mental status

≤750mL

≤15%

Normal Normal Decreased Decreased

Normal or increased

Normal Sluggish Delayed Delayed

14–20 20–30 30–40 >35

≥30mL/h Normal to

slightly anxious

750– 1500mL

15–30% 30–40%

Decreased Decreased Decreased

20–0mL/h 5–10mL/h Minimal

Mildly anxious

1500– 2000mL

Anxious and confused

≥2000mL

≥40%

≥140

Confused and lethargic

10.3 Fluids

The standard of care for prehospital resuscitation is evolving with a shift from crystalloid to blood product resuscitation. The previous dictum that hypotensive trauma patients should receive 2L of IV crystalloid as the initial resuscitation followed by blood if parameters fail to improve has been replaced by earlier blood product administration in those suspected of hemorrhagic shock when available. Additionally, patient response can identify those patients with ongoing blood loss who require prompt hemorrhage control and blood. Patients are classied as responders, transient responders, or nonresponders after initial uid or blood administration. Responders are those that have immediate and sustained return of vital signs to normal with the administration of crystalloid. The need for blood transfusion is low, and after initial bolus, the need for further crystalloid is low. Often 1 L is sufcient in these patients. Transient responders are those patients with moderate and ongoing blood loss (type II–III shock). They will initially regain normal vital signs but will deteriorate after uid is stopped. The need for immediate blood in these patients is moderate to high, and these patients will likely need operative intervention immediately. Nonresponders are those

10 Fluids, Blood Substitutes, andNew Tools

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patients that have lost greater than 40% of the blood volume. The vital signs do not respond to initial uid bolus. Patients need immediate blood products to maintain adequate blood pressure to facilitate denitive management of bleeding in the operating room. While earlier administration of blood products such as FFP is associated with improved outcomes, the majority of prehospital providers do not carry blood products and, therefore, an understanding of the most effective uid types and their physiologic consequences is still required.

10.3.1 Crystalloids

Typical crystalloids are lactated ringers (LR) and normal saline (NS 0.9%). Rapid infusion, either mechanically with a rapid infuser or through the use of a pressure bag, can quickly increase effective circulating volume. Fluids should be warmed to 39°C prior to infusion to reduce hypothermia and its negative coagulation effects. Despite their relative isotonicity, these solutions rapidly leak out into the interstitium, making their effect on circulating volume transient. Only about a quarter to one third of the volume will remain in the intravascular space. It is this principle that formed the basis for an initial 2L bolus since approximately 700 mL would remain intravascular and would be adequate to resuscitate a patient in class I shock who did not have ongoing bleeding, but those with more profound shock would require blood. Hyperchloremia is frequently observed with normal saline resuscitation and can lead to a hyperchloremic metabolic acidosis, which should not be mistaken for an acidosis secondary to decreased tissue perfusion. Regardless, the additional acidosis from hyperchloremia will be detrimental to coagulation and require increased ventilatory demands to compensate.

Controversy exists regarding which uid, lactated ringers versus normal saline, is the most effective for resuscitation. Animal models suggest that the same degree of resuscitation with normal saline will require more volume and cause more disturbances in coagulation and greater pulmonary edema than lactated ringers. Lactated ringers can cause an insignicant increase in the lactate level, which is of little clinical consequence.

Previous recommendations were to administer all trauma patients 2 L of crystalloid as initial IV uid; however, recent studies have questioned this practice and advocate “permissive hypotension” in penetrating trauma with a restrictive crystalloid resuscitation strategy. Immediately post-trauma there appears to be no worsening of outcomes with 1L of crystalloid; however current advanced trauma life support (ATLS) guidelines suggest crystalloid be reserved for the hypotensive patient only until blood products are available.

Hypertonic saline has also been studied as a resuscitation uid to restore effective circulating volume. These hypertonic solutions require smaller volumes to expand the circulating volume as they draw interstitial and intracellular uid into vascular space. Hypertonic saline (3%, 7.5%) compared to isotonic crystalloids have yielded varying results in terms of 30-day mortality.

Wade etal. examined hypertonic saline and dextran-based resuscitation in a prospective, randomized sample of 230 victims of penetrating torso trauma. While no signicant mortality difference was found in the entire population, in the cohort that required surgical intervention for control of hemorrhage (about two-thirds), a signicant survival difference (84.5% compared with 67.1% in the control group (p=0.01)) was demonstrated. There were no signicant differences in coagulopathy or volume of resuscitation required between groups.

The Resuscitation Outcomes Consortium (ROC) trauma trial comparing hypertonic saline with isotonic saline in the United States and Canada was halted early due to futility. This study was stopped at a preplanned interim analysis for the lack of overall survival benet and poor enrollment. Interim analysis of patients in this study demonstrated no increased survival at 28days and a slightly higher mortality (12.2% compared to 10%) in the hypertonic saline population. Eastern Association for the Surgery of Trauma (EAST) guidelines currently state that small 250 mL boluses of hypertonic saline are equivalent to large volume (1L) of NS or LR.

10.3.2 Colloids

Two large reviews of the use of colloids in hemorrhagic shock found the relative risk of mortality to be increased at least 30% compared to crystalloid infusion; however, these reviews were not limited exclusively to trauma patients. There has been renewed interest in initial resuscitation of penetrating trauma victims with colloid following the war in Iraq. Difculties related to the transport of large volumes of isotonic crystalloid solution into austere combat environments make small resuscitation with colloid solutions more attractive. Combat medics are now using colloids such as HEXTEND™ (6% Hetastarch solution) as rst-line therapy for soldiers and other victims in shock with the rationale that it remains in the intravascular space longer, thus requiring less need for crystalloid, particularly when long prehospital transport times are required. However, research into the use of colloid solutions versus crystalloid solutions in civilian penetrating trauma is more controversial. A meta-analysis of colloid- versus crystalloid-based resuscitation trials in trauma patients demonstrated a trend toward improved survival in those receiving crystalloids.

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S. Tam et al.

10.4 Blood

Patients in hemorrhagic shock would, ideally, be resuscitated with blood in the prehospital setting; however, resuscitation with whole blood presents several challenges. Specically, whole blood does not preserve well; however, several centers use whole blood for their initial resuscitation challenging this notion. Separation into components improves the ability and duration of blood storage. Current ATLS guidelines recommend replacement of lost blood volume in a 1:1:1 ratio of packed red cells to fresh frozen plasma (FFP) to platelets. This recommendation is based on the results of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) clinical trial which showed no signicant difference in the all cause 30-day mortality between a 1:1:1 and. a 1:1:2 blood:platelet:FFP ratio. Importantly, fewer patients died of exsanguination in the 1:1:1 group in the rst 24h, and there was no increase in transfusion-related complications even with the high ratio of products given. “Typed” or patientmatched blood products are rapidly available in most trauma centers, but physicians are often faced with a symptomatic patient while the crossmatch is taking place. O negative blood is usually available for immediate release and should be used in symptomatic patients with massive blood loss until cross-matched blood is available.

Adverse events associated with any transfusion of blood products include transfusion reaction, transfusion-related acute lung injury, and immunosuppression that can contribute to multiple organ failure and infectious risks. While screening can reduce some of these risks, the risk is not zero. The most common infectious risks are with bacterial contamination of platelets, about 1in 3000. The risks of hepatitis C and human immunodeciency virus (HIV) are approximately 1in 2 million per unit transfused.

10.4.1 Massive Transfusion

Patients requiring massive transfusion are uncommon in civilian trauma centers, occurring in approximately 1–3% of admissions, but are associated with signicant morbidity and mortality.

The most feared complication of massive blood loss is the lethal triad of hypothermia, acidosis, and coagulopathy. The massive transfusion of component therapy can exacerbate this as stored products are refrigerated and therefore should be warmed through a uid warmer during resuscitation (except for platelets). In addition to the risk associated with blood therapy, massive transfusion requirements add the risk of hyperkalemia, hypocalcemia, and decreased effectiveness of oxygen delivery in tissues. Reduced effectiveness in the target tissues is related to depletion of 2,3- diphosphoglycerate in cells that reduces oxygen off-loading and membrane

defects that reduce the ability of the red cell to traverse smaller capillaries.

A critical review by Canadian National Advisory Committee on blood and blood products reviewed the 1:1:1 ratio in patients needing massive transfusion. They agree that there is limited level I evidence to support this practice but do suggest a “three-strategy approach.” This includes early tranexamic acid, the development of foundation ratio for the patient, and titrating this ratio based on clinical improvement and lab values.

10.4.2 Whole Blood

Until recently, whole blood was not widely available or used for the resuscitation of the civilian patient. Warm fresh whole blood is not approved by the Food and Drug Administration because it is transfused before transmitted disease tests are available. Partly due to these infectious disease testing concerns, the pendulum swung toward blood component therapy (BCT) for many years. The resurgence of whole blood occurred after the mortality benet of warm whole blood was described by Spinella etal. during the recent military conicts in the Middle East.

Cold whole blood (CWB) has emerged as a strategy that addresses many of the limitations of warm fresh whole blood in the civilian trauma patient. Studies have shown lower absolute 30-day mortality rates with CWB versus BCT; however, none have shown statistically signicant results. One recent multicenter study showed that patients who received CWB rather than standard BCT during their initial trauma resuscitation were less likely to die in the trauma bay; however, there was no signicant difference in 30-day mortality. In vitro studies have suggested that the hemostatic potential in whole blood is higher than that from blood component therapy and hemostatic capacity is maintained for at least 14days, although more clinical data is needed. Some trauma centers are now using CWB in conjunction with BCT for hemorrhagic shock with improved outcomes. The use of whole blood for trauma resuscitation continues to be an active area of research without a general consensus on its use in the civilian trauma patient.

10.4.3 Autotransfusion

Shed blood can be used for autotransfusion in those with signicant hemorrhage. Recovery of autologous blood lost either intraoperatively or through chest tubes can be processed and reinfused. Several commercial devices are available to process lost blood and remove excess cations, lipids, debris, and other supernatants, leaving washed autologous red cells in a weak anticoagulant buffer solution for reinfu-

10 Fluids, Blood Substitutes, andNew Tools

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sion. Generally, most physicians believe that the blood lost must be sterile, either in the operative eld or within a closed system such as a chest tube; however, that is controversial. Hollow viscus injury has been listed as a potential contraindication to the use of red cell salvage methods; however, two small studies concluded that autotransfusion of contaminated blood in trauma did not result in a signicant increase in the rate of infectious complications or death.

10.4.4 Coagulopathy Prevention andTreatment

Too much crystalloid infusion, particularly saline, can exacerbate coagulation defects through hemodilution of coagulation factors and platelets. It appears that hypertonic saline infusion may have more profound effects on coagulation when compared to isotonic uids. Furthermore, sodium citrate, one of the preservatives used in blood products, will bind calcium in circulation and lower levels of this cofactor for hemostasis. Colloids such as dextran and hydroxyethyl starch also impair normal coagulation, with hydroxyethyl starch impairing brin polymerization and dextran inhibiting platelet function.

Measuring the severity of trauma-induced coagulopathy has evolved. Endothelial injury that follows trauma, upregulation of tissue factor, and hyperbrinolysis all lead to a tenuous state of consumptive coagulopathy. This may be further complicated by direct oral anti-coagulants, warfarin, or antiplatelet agents in those with comorbidities. Given these factors, traditional means of monitoring activated partial thromboplastin time (APTT) and prothrombin time (PT) or even platelet function may not provide the entire picture of coagulopathy and the need for specic factors. Thromboelastography (TEG) evaluates the viscoelastic properties of whole blood as it clots. These tests give information about clot formation, strength, and dissolution. At least one randomized trial and several observational studies have identied lower mortality and lower need for transfusion with a TEG-directed approach to transfusion. Using TEG as a guide for resuscitation is gaining popularity, and many trauma centers have algorithms for interventions based on TEG results.

The role for agents aimed at reversing trauma induced coagulopathy has been unclear. Recombinant factor VII has yet to show clear mortality benet and its use is limited by cost. The data on the efcacy of prothrombin complex concentrates (PCC) is lacking for trauma-induced coagulopathy; however; a single-institution retrospective study has shown more rapid reversal of INR and decreased transfusion requirements with the addition of PCC to plasma compared to plasma alone.

Plasma has demonstrated logistical challenges regarding storage and reconstitution. Plasma is widely available in the United States in the form of frozen plasma, liquid plasma, and thawed plasma. Freeze-dried plasma has long been described in the military setting; however, it is an ongoing area of research in civilian trauma. To date there are no highquality studies that show statistically signicant differences in transfusion requirements or mortality compared to frozen plasma. Freeze-dried plasma does appear to be safe to use, easy to restore, and can be given faster than frozen plasma which must stored at −18°C and then thawed before use.

Direct oral anticoagulants (DOAC) have overtaken vitamin K antagonists as the most widely prescribed oral anticoagulants since its approval by the US FDA for the prevention of multiple thromboembolic events. Currently there are two specic DOAC reversal agents that have been approved by the US FDA: idarucizumab (specically for the reversal of dabigatran) and andexanet alfa (for reversal of apixaban and rivaroxaban). The major limitations of these adjuncts are availability, cost, and a lack of available data on the effectiveness of different reversal agents. PCC has been used in an off-label fashion for DOAC reversal and tends to be the most widely used option for reversal given its attainability and feasible cost.

10.4.5 Tranexamic Acid

Hyperbrinolysis is a key component that contributes to the acute coagulopathy of trauma, which is associated with increased mortality. Over the last decade, tranexamic acid (TXA) has emerged as a tool to address hyperbrinolysis in trauma patients. It acts by binding to plasminogen blocking its interaction with brin, thereby preventing dissolution of brin clot. CRASH-2 was the largest, international, randomized control trial that demonstrated a 28-day mortality benet in adult trauma patients that received TXA within 3h of initial injury without a difference in the incidence of vascular occlusive events. There was a signicant reduction in death caused by bleeding in patients with a SBP < 75 mmHg. However, patients that received TXA greater than 3h from injury had an increased risk of mortality. Since this landmark study, TXA has been increasingly adopted in the pre-hospital setting with literature showing decreased early mortality within 48h of injury but no benet in 30-day mortality.

10.4.6 Pre-hospital Plasma

The administration of plasma has demonstrated a mortality benet in the severely injured patient, part of the damage control resuscitation strategy. The Preshospital Air Medical Plasma (PAMPer) trial was a multicenter, cluster- randomized

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S. Tam et al.

trial that studied the efcacy and safety of the prehospital administration of thawed plasma in trauma patients at risk for hemorrhagic shock. Sperry etal. demonstrated almost a 30% reduction in mortality in the patients that received pre- hospital plasma compared to the standard care group. There was no increased incidence of inammatory-mediated or transfusion-related complications. A post hoc analysis of the PAMPer trial and another randomized control trial (COMBAT) conrmed this and furthermore demonstrated that pre-hospital plasma mitigated the risk of death associated with transport times longer than 20 min. While more institutions work to implement the use of pre-hospital plasma, there are many logistical and nancial barriers to overcome.

10.4.7 Blood Substitutes

Given the problems associated with the use of allogeneic blood products, there has been extensive research into other methods of oxygen delivery. Most of the research has been focused on solubilized-free hemoglobin or hemoglobin- based oxygen carriers (HBOC). In the United States, these products are only available on research protocols; however, Hemopure™ is available for use in South Africa. Recently, a meta-analysis of the available English language literature covering 16 separate trials, ve different products, and a total population of approximately 3700 patients was published. Their analysis found an increased rate of adverse events, particularly acute myocardial infarctions with 30% increased risk for mortality in patients treated with blood substitutes. One of the main criticisms of this meta-analysis is that it considered several different types of HBOCs rather than each type as a separate entity. A recent US multicenter trial of Polyheme™ (Northeld Laboratories) of 714 mostly young males whose mechanism was approximately 52% penetrating found no statistically signicant differences in 30-day mortality when compared to control groups but a slight increase in complications (93% versus 88% p=0.04), including myocardial infarctions (3% versus 1%). The authors had an independent review of the patients with myocardial infarctions that did not nd any appreciable difference between the groups. This study indicates that Polyheme™ was equally efcacious to the standard of careutilizing blood and that it had a reasonable safety prole. Therefore, in the absence of blood or during blood shortages, Polyheme™ may be a reasonable alternative for patients with an acute traumatic anemia.

down transport as mortality is increased when delay to denitive care occurs. As above, the administration of pre- hospital tranexamic acid and thawed plasma should be customized according to patient selection and regional feasibility.

10.5.2 Trauma Bay

The ATLS algorithm mandates the ABCDEs of trauma evaluation. As part of circulation, large bore intravenous (IV) access should be obtained immediately, if not accomplished in the eld. Ideally, two peripheral IVs will be placed in either antecubital vein. Poiseuille’s law regarding laminar ow shows that ow is inversely related to the length and the fourth power of the radius. Thus, a large bore (18 gauge or larger), short IV catheter allows the rapid delivery of uids and blood products if needed. If injuries and anatomy preclude IV placement, consider insertion of an interosseous (IO) line. IO catheters can be rapidly placed in one of several places with one of several commercially available devices and require minimal training and knowledge of anatomy. Any one of several commercially available products can be placed on the anterior surface of the tibia, the humeral head, and even the sternum with relative ease and minimal operator experience. Device studies have demonstrated rapid delivery of uids to the central circulation. Should peripheral access be unable to be obtained or should the need for central access arise, a central venous line can be placed quickly with a low complication rate by experienced operators. Subclavian access using Seldinger technique is optimal as the need for cervical spine precautions prevents access to the jugular veins and femoral access carries a higher risk for DVT; however, in the acute setting access takes priority in the exsanguinating patients. Preference should be given to the side where a chest tube is already present when placing a subclavian line when applicable.

Once access is obtained, infusion of isotonic crystalloid is the usual starting point for a hypotensive patient. However, for those in class II or greater shock, crystalloid should only be used until blood products are available. The determination of the severity of the blood loss, the ability of the individual patient to tolerate this insult, and the strategy for controlling ongoing hemorrhage guide further resuscitation and attempt to restore normal hemodynamic parameters as soon as possible. Control of the hemorrhage is the most important step as massive volume replacement is not a substitute for denitive hemorrhage control.

10.5 Current ATLS Guidelines

10.5.1 Prehospital

Currently, emphasis is placed on early control of external hemorrhage and early transport to a trauma center. Two attempts at IV cannulation can be made but should not slow

10.6 Permissive Hypotension

A more restrictive use of resuscitation for victims of penetrating trauma may be associated with increased survival; however, results from several studies yield varying results. The goal of this strategy is to maintain victims in a state of

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