Ongoing assessment, monitoring, and resuscitation of the severely injured patient

INTRODUCTION — Trauma remains a leading cause of death and disability in children and adults despite continuing advances in resuscitation, surgical management, and critical care [1]. Hemorrhage narrows both the technical options and the time available for safe intervention and is the proximate cause of most early traumatic deaths; the early effort to control hemorrhage and restore circulatory homeostasis forms the core of the approach to the severely injured trauma patient [2,3].

Patients with major injuries resulting in severe hemorrhage or with multisystem involvement benefit from ongoing monitoring and hemodynamic resuscitation in a critical care setting [4]. The multispecialty and multidisciplinary management of critically injured patients in the acute postinjury setting is the focus of this review.

Initial resuscitation of the trauma patient presenting to the emergency department and patients with primarily neurologic injuries (eg, traumatic brain injury or spinal cord injury) are reviewed separately. (See "Initial management of moderate to severe hemorrhage in the adult trauma patient" and "Management of acute moderate and severe traumatic brain injury" and "Acute traumatic spinal cord injury".)

CLINICAL SCENARIOS — Examples of patients warranting an intensive care management approach include:

●Damage control and resuscitation with or without an open abdomen or chest. (See "Overview of damage control surgery and resuscitation in patients sustaining severe injury" and "Management of the open abdomen in adults".)

●Thoracic or abdominal vascular injury. (See "Management of the open abdomen in adults" and "Abdominal vascular injury" and "Management of cardiac injury in severely injured patients" and "Overview of blunt and penetrating thoracic vascular injury in adults".)

●Pelvic fracture-associated hemorrhage. (See "Severe pelvic fracture in the adult trauma patient".)

●Nonoperative management of solid organ injury. (See "Management of splenic injury in the adult trauma patient" and "Management of hepatic trauma in adults".)

These patients may be admitted to the intensive care unit directly from the emergency department or from the operating room of the same hospital. With increased regionalization of care, however, such complex patients may also be transferred from other hospitals for a higher level of trauma center care [5].

ASSESSMENT

Repeat the history and physical

●Complete the history – While the patient's full history may not have been available upon their arrival to hospital, this may now be available either directly from the patient or from other sources, including family members or friends, documentation from prehospital personnel, or other medical staff. Particular attention should be paid to the mechanism of injury and circumstances that led to that injury, past medical and surgical history, home medication use, social history, and drug allergies.

●Repeat physical examination – Following the initial resuscitation with operative intervention, the initial focus of the repeat examination should be on signs and symptoms of ongoing hemorrhage or other compromise, depending on the initial injury. Reverting to the advanced trauma life support approach of a primary and secondary survey serves as a useful framework for assessing trauma patients newly admitted to the intensive care unit (ICU).

•Airway – Proper positioning of advanced airway devices, such as endotracheal tubes, should be confirmed with end-tidal carbon dioxide (CO₂) monitoring and radiographic imaging.

•Breathing – Ventilator settings should be reviewed to ensure appropriateness for the patient's pathology and any prior underlying medical comorbidity.

•Circulation – Cardiovascular status should assess the presence and type of vascular access, fluid loss and replacement volumes (from prehospital, emergency department, and operating room environments), as well as any evidence of ongoing hemorrhage. (See 'Hemodynamic management' below.)

•Neurologic examination – Neurologic evaluation should assess the level of consciousness, pupillary response to light, and the presence of any central or peripheral nervous system injury.

•Musculoskeletal injury – Identification of wounds and evaluation of the axial skeleton for deformities should also be performed.

•Evaluate for potential missed injury – The patient should be fully exposed and evaluated for any other injuries and all final imaging reports should be reviewed. Additional imaging studies should be ordered as needed for any potential missed injuries. (See "Overview of inpatient management of the adult trauma patient", section on 'Consider other potential injuries'.)

Imaging — Plain films on admission to the ICU should complement any imaging workup previously completed. An admission chest radiograph serves to document the position of the endotracheal tube, evaluate the position of any chest tubes, intravenous access devices, or evaluate for the expansion of a small or occult pneumothorax.

Bedside ultrasound imaging can be used for several purposes:

●Repeat Focused Assessment with Sonography for Trauma (FAST) examination to assess for new pericardial fluid or abdominal fluid.

●Extended FAST examination to assess for lung sliding (to rule out pneumothorax) and to evaluate for intrapleural collections (eg, hemothorax).

●Assessment of intravascular volume status and cardiac function to help guide resuscitation decisions. (See 'Measures of microcirculatory oxygen delivery' below.)

Any computed tomography (CT) scans obtained at other facilities should be uploaded for rereview by the clinical teams, and consideration should be given to obtaining formal radiology reports. The completeness of the imaging workup should also be evaluated, and additional imaging obtained as needed [6]. Patients who undergo emergency operative intervention prior to CT evaluation often benefit from postoperative or postdamage control CT imaging.

●A single center retrospective study of 89 patients including 42 penetrating and 47 blunt injuries who underwent emergency surgical exploration without prior CT demonstrated that subsequent CT imaging diagnosed new injuries in 59 patients (66 percent), which changed management in 51 patients (57 percent) [7].

●A single center retrospective study of 73 patients who underwent laparotomy for penetrating trauma reported that CT diagnosed 43 additional injuries in 38 patients (52 percent), with a subsequent intervention required in 10 patients. [8] The most common new injuries were orthopaedic (20 of 43) and genitourinary (9 of 43).

Anatomic scoring — Objective quantification of a patient's injuries and injury severity can be done using various scoring systems. The American Association for the Surgery of Trauma (AAST) organ injury scales are the most useful clinically and grade injury severity provide for each body area independently, and in many cases help to guide clinical management. Refer to specific trauma topics for these scales (eg, splenic injury (table 1), liver injury (table 2)).

Other anatomic scoring systems include the Abbreviated Injury Score (AIS), which is used to calculate the Injury Severity Score (ISS). This scoring systems is less easily used in the clinical setting, and therefore used more for comparison of patients for the purpose of research or quality improvement.

●The AIS classifies each injury per body region on a six-point scale from least to most severe.

●ISS is the sum of the squares of the highest AIS in three body regions and ranges from 1 to 75. An ISS of ≥15 is classified as severe injury and corresponds to a mortality of at least 10 percent. If any AIS body region score is 6 (identified as a currently untreatable injury), the ISS is automatically 75.

●The ISS may not be immediately apparent on the patient's arrival to the hospital until all imaging is completed and thus is not generally used to guide clinical decisions.

Laboratory studies — Severely injured trauma patients are routinely screened with standard laboratory studies, including complete blood count, serum electrolytes, arterial blood gas analysis, and standard coagulation tests. These studies provide an assessment of acidosis and coagulopathy, indicate the severity of shock (as measured by base deficit and/or lactate), guide specific component blood product administration, and serve as a baseline for the assessment of ongoing hemorrhage.

Serial measurements of arterial blood gas for pH and base deficit are indicated for monitoring the resolution of acidosis and tissue hypoperfusion in response to resuscitation. The frequency of measurement is dictated by the patient's condition. Patients who remain hemodynamically labile or in whom there is a concern for ongoing occult bleeding dictate more frequent blood draws (every two to four hours), whereas hemodynamically stable patients may have blood drawn at longer intervals (every 12 to 24 hours).

Coagulation studies — Coagulopathy is common in severely injured patients and may be related to one or more mechanisms. However, coagulopathy can occur early after injury and is biochemically evident prior to, and independent of, the development of significant acidosis, hypothermia, or hemodilution. This is termed acute traumatic coagulopathy (ATC), which is an impairment of hemostasis and activation of fibrinolysis. (See "Etiology and diagnosis of coagulopathy in trauma patients".)

Patients with ATC are at risk for massive transfusion. Patients with ATC have a three- to fourfold higher overall mortality and are eight times more likely to die in the first 24 hours [9-13]. (See 'Ongoing need for massive transfusion' below.)

We use serial thromboelastography (TEG)/rotational elastometry (ROTEM) to monitor the coagulation status of severely injured patients and to guide the correction of coagulopathy. These provide more comprehensive information in real time, readily identify hyperfibrinolysis, and reduce the time to correction of coagulopathy [14]. (See 'Management of acute traumatic coagulopathy' below.)

Where TEG/ROTEM is not available, serial prothrombin time/international normalized ratio, partial thromboplastin time, hemoglobin/hematocrit, platelet count, and fibrinogen levels should be obtained on arrival and following transfusion to verify an appropriate response to blood products and/or pharmaceutical hemostatic agents before and after operative interventions, and as dictated by the patient's clinical course.

Measures of microcirculatory oxygen delivery — The assessment of appropriate end-organ perfusion can be challenging in the severely injured patient but is important to optimize resuscitation and outcomes. Several measures are used typically in combination. It is important to avoid using variables in isolation as markers of severity. Temporal trends of multiple variables provide a better overview of both severity and response to resuscitation.

Lactic acid levels — The accumulation of L-lactic acid can occur due to tissue hypoperfusion. Initial levels that are elevated are markers of physiologic instability and mortality, and therefore are included in national resuscitation algorithms. Equally important is lactic acid clearance, which can be delayed in malperfusion states and may not be primarily related to reduced delivery of oxygen. Both the initial level and the rate of clearance must be monitored to ensure appropriate response to resuscitation.

Persistent elevation of lactate should be investigated. Possible causes include ongoing malperfusion from hemorrhage or sepsis, cryptogenic shock from an unidentified source, or shock of cardiac origin. The gastrointestinal tract and extremity compartments may be a source of ongoing lactate elevation and shock in a severely injured patient. (See 'Monitor compartment pressures' below.)

Other causes of persistent lactic acid elevation should be considered that may not be related to malperfusion. These include type B lactic acidosis, which can be caused by diabetes, medications (including albuterol, epinephrine, and metformin), malignancy, alcohol use disorder, mitochondrial dysfunction, and human immunodeficiency virus. Type D lactic acidosis is seen uncommonly but can occur in patients who have malabsorption secondary to short gut syndrome. (See "Causes of lactic acidosis".)

Whether to use lactic acid clearance (as recommended in the Surviving Sepsis Campaign) or simple measures such as capillary refill time (CRT) to guide resuscitation has been questioned. Lactic acid measurements may not be available in all settings. In addition, clearance may lag behind resolution of shock. A multicenter trial randomized adult patients with septic shock into resuscitation strategies targeting lactic acid clearance or CRT [15]. Of 424 patients randomized, there was a nonsignificant difference in 28-day mortality between the two groups. This implies that when lactic acid measurement was not available, CRT could be used as an alternative measurement.

Base deficit — The base deficit is defined as the amount of base (alkali) needed to titrate a liter of whole arterial blood to a pH of 7.40. Numerous animal and human studies show a direct correlation of base deficit with the degree of bleeding and injury severity [16-19]. Base deficit forms a measure of metabolic acidosis and is provided as part of usual blood gas analyses. Correction of the base deficit (normal values are typically -2 to +2) can be used as an endpoint of resuscitation. However, it is recommended that normalization of base deficit is combined with other clinical and physiological factors.

Mixed-venous oxygen saturations — Venous oxygen saturations are measurements sampled from the pulmonary artery (termed SvO₂) or from the superior vena cava (ScvO₂) (table 3). The former requires the use of a pulmonary artery catheter, but because these are no longer commonplace in many ICUs, the ScvO₂ is often used as a surrogate. SvO₂ and ScvO₂ both measure oxygen utilization and can also be used as resuscitation endpoints for the severely injured patient if there is a concern for cardiogenic shock complicating the hemorrhagic shock picture. Venous oxygen saturation depends on arterial oxygenation, which is itself measured by arterial oxygen saturation and cardiac output. Changes in cardiac output are influenced by volume challenges, allowing mixed-venous measurements to be surrogate markers of fluid responsiveness in the severely injured patient.

A normal range is typically between 60 to 80 percent. Low-flow states such as hemorrhage and cardiogenic shock will typically lead to abnormally low values. Studies looking at specific benefits of mixed-venous oxygen saturations in the setting of severe traumatic injury are lacking.

Oxygen extraction ratio — The oxygen extraction ratio (OER) measures the ratio of consumption of oxygen (VO₂) to delivery of oxygen (DO₂). In the normal resting state, the DO₂ should be sufficient to maintain aerobic metabolism at the tissue level. The OER is calculated using the following equation:

It can also be calculated as:

The normal value will vary depending on organ system. As an example, cardiac OER is over 60 percent whereas renal OER may be under 15 percent.

With increasing metabolic demand or decreasing oxygen delivery, OER will rise to ensure the maintenance of aerobic metabolism. Once a critical level for oxygen delivery is reached, the OER cannot increase further and anaerobic metabolism due to tissue hypoxia occurs. Organs have variable critical levels depending on their DO₂ (and hence higher OER) needs.

●Conditions leading to high OER due to abnormally low DO₂ include anemia, impaired cardiac contractility, hypoxemic hypoxia, and shock states.

●Conditions leading to high OER due to abnormally high VO₂ include fever, inflammation (secondary to trauma or burns), hypermetabolic states such as hyperthyroidism or burns, increased muscular activity including seizures, and increased work of breathing.

●Conditions causing a low OER may be due to increased DO₂ such as in hyperoxia states (hyperbaric oxygen therapy or extracorporeal membrane oxygenation).

●Conditions causing a low OER may be due to decreased VO₂ due to abnormally low metabolism, low muscular activity, poor nutritional states, and histotoxic hypoxia (eg, from cyanide poisoning).

Ongoing need for massive transfusion — Rapid clinical assessment can identify the potential for coagulopathy and empiric need for massive transfusion based upon the mechanism and severity of injuries, hemodynamic status of the patient, and evidence of active hemorrhage (eg, positive FAST or brisk bleeding from a chest tube) [20-22]. Establishing a hospital-based massive transfusion protocol (MTP) and activating the MTP in a timely manner is associated with improved mortality. This is most often done in the emergency department, but some patients remain at risk for massive hemorrhage after their index operation or even when a conservative nonoperative approach is selected (eg, liver injury). On arrival to the ICU, patients should be reassessed for ongoing hemorrhage that may indicate the need for MTP activation or continuation.

Clinician gestalt alone has proven an unreliable predictor of this need. In a survey of nearly 1000 patients for whom a trauma surgeon was asked to predict the need for massive transfusion, sensitivity was 66 percent and specificity of 64 percent (positive predictive value of only 35 percent) [23].

Scoring systems to predict ongoing massive hemorrhage can improve prediction. Examples include the Assessment of Blood Consumption (ABC) score [20], Revised Assessment of Bleeding and Transfusion (RABT) [24], Trauma-Associated Severe Hemorrhage (TASH) score [22], and McLaughlin score [23,25]. The easiest of these are the ABC and RABT scores:

●ABC – The ABC score assigns one point each for tachycardia (heart rate ≥120), hypotension (systolic blood pressure ≤90), penetrating mechanism, and positive FAST examination. Based on the initial retrospective study describing this score, a score of two or more has a sensitivity of 75 percent, a specificity of 86 percent and an area under the receiver-operator curve of 0.86 for predicting the need for massive transfusion [20]. However, subsequent prospective validation has not proven as favorable.

●RABT – The RABT score was developed to improve sensitivity and to maintain simplicity for massive transfusion prediction. The score assigns one point each to presence of a penetrating injury, positive FAST examination, shock index >1, and a pelvic fracture. Scores ≥2 predict the need for massive transfusion. A multicenter retrospective validation study in 1018 trauma patients who required a massive transfusion showed the RABT score to have higher sensitivity (78 versus 69 percent) and specificity (91 versus 82 percent) than the ABC score [24]. This score serves as one of the inclusion criteria for ongoing randomized controlled trial evaluating whole blood-based massive transfusion [26].

Using a smartphone app [27] or a machine learning algorithm [28] may further improve transfusion prediction while lowering the cognitive burden on providers in these crisis scenarios.

MONITORING

Vital signs — All severely injured patients should have continuous telemetry monitoring of their heart rate and blood pressure. These vital signs must be monitored and documented on an hourly basis. Early signs of abnormal perfusion may first be indicated by changes in the heart rate and blood pressure. Noninvasive blood pressure monitoring must be done using a pressure cuff that is appropriately sized for the patient. The bladder length should be at least 80 percent, and the width at least 40 percent of the limb circumference. Abnormally high pressures can be recorded with a cuff that is too small for the patient, and vice versa.

Invasive blood monitoring is through the use of arterial lines. To avoid errors, the pressure transducer must be level with the patient's phlebostatic axis. Changes in patient position may lead to erroneous readings. Dampening of the arterial waveform may occur if there are obstructions to blood flow at the catheter tip or in the tubing and can lead to erroneous blood pressure measurements. Utilization of central arterial pressure monitoring (eg, common femoral or brachial arteries) may provide a more reliable pressure reading in patients with shock compared with those placed in peripheral arteries (eg, radial artery) [29,30]. (See "Intra-arterial catheterization for invasive monitoring: Indications, insertion techniques, and interpretation".)

Urine output — Severely injured patients should have close attention paid to their urine output. Ideally, this is done by placing a urinary catheter and measuring hourly urine output. Appropriate urine output is at least 0.5 mL/kg/hour. A decreasing trend can be an indicator of hypovolemia.

The color of the urine (eg, red to brown color, "tea-colored," "cola-colored") may indicate the presence of rhabdomyolysis; however, urinalysis is required to distinguish myoglobinuria due to rhabdomyolysis from hematuria. Rhabdomyolysis may be associated with muscle injury (eg, crush injury, compartment syndrome, tourniquet use) (table 4), toxins (table 5), or malignant hyperthermia. (See "Rhabdomyolysis: Epidemiology and etiology" and "Prevention and treatment of heme pigment-induced acute kidney injury (including rhabdomyolysis)" and "Rhabdomyolysis: Clinical manifestations and diagnosis".)

The urinary catheter may also be used to monitor temperature and intrabdominal pressure. (See 'Temperature' below and 'Monitor compartment pressures' below.)

Temperature — During the course of operative intervention and ongoing shock resuscitation, central temperature monitoring (eg, via urinary catheter or esophageal temperature probe) should be performed until normothermia is achieved and maintained. (See 'Correction of hypothermia' below.)

Dynamic measures of end-organ perfusion — Dynamic measures of end-organ perfusion are used selectively for trauma patients not responding to conventional resuscitation. Their use depends on the skill of the bedside clinician with ultrasound, or the presence/absence of an arterial line for determination of pulse pressure variation (PPV).

Shock index — The shock index (SI) is a simple and reproducible means to rapidly evaluate appropriate perfusion or evolving shock in the setting of severe injury. SI is defined as the heart rate divided by the systolic blood pressure. A normal SI is between 0.5 and 0.7 in healthy adults. SI is inversely linearly related to multiple other indices including cardiac index and mean arterial pressure. In severely injured patients, SI >0.9 is predictive of mortality within 24 hours [31].

Stroke volume and pulse pressure variation — Stroke volume variation (SVV) represents the change in arterial pulse pressure that occurs during the respiratory cycle. In the spontaneously breathing patient with inspiration, there will be a fall in arterial pressure, and vice versa. This pattern reverses in the mechanically ventilated patient because of changes in intrathoracic pressure. Normally, the variation will be less than 10mmHg [32]. The difference can be measured through an arterial line tracing and is termed PPV (figure 1).

Both SVV and PPV measure preload responsiveness and can be used to assess appropriate fluid resuscitation. SVV has a high sensitivity and specificity when compared with other invasive measures of stroke volume such as pulmonary capillary occlusion pressure [33]. Values greater than 12 percent are likely to predict fluid responsiveness whereas values under 8 percent likely demonstrate euvolemia.

Various devices allow these measurements. These include modern telemetry monitoring of the arterial line tracing, esophageal Doppler devices, and pulse contour cardiac output monitors. To ensure an accurate measurement of SVV or PPV, the patient should be ventilated using a controlled mode with tidal volumes of at least 8 cc/kg with minimal positive end-expiratory pressure. The patient should also be in sinus rhythm and not under treatment with a vasodilator agent.

Bedside point-of-care ultrasound — Multiple variables can be assessed using bedside point-of-care transthoracic cardiac ultrasonography, which has the specific advantage of being noninvasive and repeatable. This requires specific training, but is evolving as a rapid, dynamic mechanism to determine fluid responsiveness and general cardiac function in the severely injured patient. However, it carries a disadvantage of requiring specific training and being user-dependent on both the quality and interpretation of acquired images [34].

Specific anatomic structures to be evaluated include left-ventricular (LV) function, right-ventricular (RV) function and size, the presence or absence of a pericardial effusion, interventricular septal deviation, and the inferior vena cava (IVC). These can provide information on preload, afterload, ventricular function, pericardial disease, and fluid responsiveness.

Evaluation of LV function can assist in determining the type of shock.

●A hyperdynamic ventricle that is small or has an end-diastolic area of under 10 cm² implies normal cardiac response to a hypovolemic state such as hemorrhage or sepsis. In this situation, the LV outflow tract (LVOT) may also appear narrowed during systole. The LVOT diameter and velocity time integer can be measured to calculate stroke volume and SVV, allowing assessment of volume responsiveness.

●Depressed LV function may imply cardiogenic shock either directly due to intrinsic cardiac pathology (acute or chronic) or secondary to myocardial depression from other processes such as sepsis. This may allow the adjustment of vasoactive support medications to improve both contractility and afterload. An RV that is the same or larger in size compared with the LV, or interventricular septal bowing into the LV can imply RV dysfunction or failure. This may occur in the setting of acute pathology such as pulmonary embolism or RV infarction, or exacerbations of chronic problems such as pulmonary hypertension or chronic lung disease. The presence of RV dysfunction should prompt a search for a causative pathology, and may allow the initiation of pulmonary vasodilators, inotropic support, and/or diuresis depending on the underlying diagnosis.

IVC measurement may allow prediction of fluid responsive [35,36]. Measurements are taken from the subxiphoid long-axis view typically around the confluence of the hepatic veins. The M-mode allows for measurements to be established during both phases of the respiratory cycle.

●In the ventilated patient, static IVC diameters less than 1.2 cm likely suggest hypovolemia, while diameters over 2.5 cm are more likely explained by hypervolemia or elevated right-atrial pressure secondary to an obstructive pathology such as pulmonary embolism or pericardial tamponade. These values are not as predictive in spontaneously breathing patients.

●The IVC collapsibility index (IVCCI) measures the dynamic change of the IVC diameter during the respiratory cycle. It is calculated as:

IVCCI <10 percent likely equated to a right atrial pressure of >15 mmHg, implying hypervolemia. IVCCI >50 percent is highly suggestive of hypovolemia and these patients are often responsive to further fluid challenge [37].

Passive leg raise — Passive leg raising (PLR) may predict volume responsive by "autotransfusion" of pooled venous blood from the legs. This volume is approximately 300 cc. As this volume is already part of the circulation, and no extraneous fluid is being administered, the effects resemble a fluid challenge but are rapidly reversible. PLR has the advantages of being simple, noninvasive, and repeatable without the restrictions associated with other measures of fluid responsiveness. Unlike other measures of volume responsiveness, PLR is not affected by breathing mode, dysrhythmias, or lung compliance. It does require a direct measurement of cardiac output and cannot rely solely on simple blood pressure measurement [38]. However, it cannot be used when positional changes are contraindicated. It is unreliable when the patient is in pain or has an elevated intra-abdominal pressure. Also, its use in severely hypovolemic patients is unreliable as the volume of blood returned to the heart may not be enough to elicit a true change in cardiac output.

PLR measurement requires the patient to initially be in the semirecumbent position and a cardiac output measurement is obtained. The patient's upper torso is then flattened while the leg is elevated at least 45 degrees. At least 30 to 90 seconds should elapse before cardiac output is remeasured. Finally, the patient should be returned to the semirecumbent position and a final cardiac output measurement taken to assess responsiveness. A 10 percent increase in stroke volume (and hence cardiac output) is interpreted as a positive test. This carries an 86 percent sensitivity and 90 percent specificity [39]. A 10 percent increase in pulse pressure carries a sensitivity of 79 percent and specificity of 85 percent [39]. One unvalidated study suggested that end-tidal CO₂ monitoring can be used to determine responsiveness to PLR [40]. An increase of 5 percent predicted an increase in cardiac index of at least 15 percent (71 percent sensitivity and 100 percent specificity).

Monitor compartment pressures

●Abdominal pressures – In the massively resuscitated patient, the early institution of intra-abdominal pressure monitoring is also appropriate to evaluate for the development of abdominal compartment syndrome and the need for abdominal decompression. (See "Abdominal compartment syndrome in adults", section on 'Measurement of intra-abdominal pressure'.)

●Extremity compartment pressures – Trauma patients requiring significant resuscitation are at risk for extremity compartment syndrome, particularly if there are associated extremity injuries such as long bone fracture or vascular injuries. Continuous measurement of the anterior compartment of the injured extremity using solid-state devices may improve diagnostic accuracy in at-risk patients [41]. (See "Pathophysiology, classification, and causes of acute extremity compartment syndrome" and "Acute compartment syndrome of the extremities".)

MANAGEMENT

Hemodynamic management — Damage control resuscitation principles begin in the prehospital phase or emergency department phase of care and should be applied throughout all phases of damage control. In general, damage control should be initiated in patients with multisystem trauma, or any injured patient at risk for or who manifests hypothermia, coagulopathy, and/or metabolic acidosis. (See "Overview of damage control surgery and resuscitation in patients sustaining severe injury".)

The goals of ongoing resuscitation in the intensive care unit (ICU) are to continue fluid resuscitation, correct coagulopathy, warm the patient, and obtain any further testing or imaging that may be needed to better define the full extent of injuries. These measures, along with appropriate airway and ventilatory management, will help to normalize tissue oxygen delivery and resolve acidosis and coagulopathy. (See 'Assessment' above and 'Monitoring' above.)

Fluid therapy — Intravenous fluid therapy should generally be minimized in critically injured patients. The volume of resuscitation is guided by bedside ultrasound and biomarkers of end-organ perfusion and can be administered using a combination of blood products guided by laboratory measures and judicious small volume fluid boluses. Endpoints of this approach include improvement in clinical parameters (eg, normalization or improvement of vital signs, normalization of urine output) or measured variables (eg, clearance of lactate, improvement in base deficit, achievement of pulse pressure variation <10 percent). Circulatory overload should be avoided as this can further compromise end organ function (eg, poor gas exchange, oliguria) and can lead to compartment syndromes. (See "Abdominal compartment syndrome in adults" and "Pathophysiology, classification, and causes of acute extremity compartment syndrome".)

The use of hypertonic saline as a low-volume maintenance fluid has also been investigated. The only study available suggests that this strategy may minimize total body sodium overload (ie, edema and anasarca), resulting in a higher rate of functional abdominal fascial closure during phase 3 [42]. However, this finding needs to be validated in larger, appropriately designed studies. (See "Management of the open abdomen in adults".)

Vasoactive medications — Patients in hemorrhagic shock or posthemorrhagic shock may require vasopressor or inotropic support (table 6) to support adequate end organ perfusion during resuscitation. (See "Intraoperative use of vasoactive agents".)

The concept of vasopressin hormone deficiency has also emerged as an appealing target for physiologic intervention in these patients. A randomized controlled trial of severely injured patients in hemorrhagic shock receiving either vasopressin (4 U bolus followed by ≤0.04 U/min infusion for 48 hours; 49 patients) or placebo (51 patients) demonstrated a decreased need for blood product resuscitation in patients in the treatment arm (1.4 L versus 2.9 L) [43].

Transfusion — Patients without an ongoing risk for massive transfusion based upon injury severity, shock, and abnormal coagulation should receive transfusion in response to specific laboratory deficits (table 7) [44-46]. (See 'Ongoing need for massive transfusion' above.)

Trauma patients who remain at risk benefit from a balanced transfusion strategy throughout the resuscitation phase. A disadvantage is the potential hazards associated with plasma and platelet transfusion (eg, acute respiratory distress syndrome). Although transfusion-related lung injury is a concern, a large retrospective analysis did not find any significant increase in number of ventilator days in patients who received balanced transfusion [47].

Balanced component transfusion — Balanced component transfusion provides a lower ratio of packed red blood cells (pRBCs) to other blood components, including plasma and platelets relative to historic transfusion schemes [48]. Studies of severe hemorrhage following injury have demonstrated increased survival with a 1:1:1 ratio of plasma, pRBCs, and platelets [49-51]. This is largely due to mitigation of the acute traumatic coagulopathy (ATC) [52,53]. This ratio has become standard of care for massive transfusion in trauma patients. An important benefit of balanced resuscitation is the resulting reduction in overall blood transfusions and its associated risks. (See "Initial management of moderate to severe hemorrhage in the adult trauma patient", section on 'Transfusion'.)

●The PROMMTT (PRospective, Observational, Multicenter, Major Trauma Transfusion) study was a prospective observational cohort study of 1245 patients receiving at least 1 unit of RBC within six hours of arrival to one of 10 level I trauma centers in the United States, including 905 patients who received at least 3 units RBC within 24 hours [50]. Using a multivariate Cox model, an increased ratio of plasma:RBC (hazard ratio [HR] 0.31, 95% CI 0.16-0.58) and platelets:RBC (HR 0.55, 95% CI 0.31-0.98) was independently associated with reduced six-hour mortality, a time period when death from active hemorrhage is predominant. Patients with ratios <1:2 were three- to fourfold more likely to die by six hours than those receiving ratios of >1:1. Importantly, plasma and platelet ratios were not associated with 24-hour or 30-day mortality. In a later subanalysis of 619 patients from this study, whether "early" (defined as within either 2.5 hours or within the first 3 to 6 blood product units administered) transfusion of plasma was protective was evaluated. The authors found that "early" transfusion of plasma was associated with reduced 24-hour (odds ratio [OR] 0.47, 95% CI 0.27-0.84) and 30-day (OR 0.44, 95% CI 0.27-0.73) mortality compared with patients who received lower plasma:RBC ratios or who did not received early plasma but "caught up" to ratios approaching 1:1 by 24 hours [52]. Inadequate numbers precluded similar analysis of early platelet transfusion. Overall, the study suggested that the benefit of hemostatic resuscitation is principally clinically relevant in preventing death by hemorrhage within the first six hours and that competing risks from nonhemorrhagic causes of death overshadowed mortality differences at later time points.

●The PROPPR (Pragmatic, Randomized Optimal Platelet and Plasma Ratios) trial randomly assigned 680 severely injured patients identified as at risk of requiring massive transfusion from 12 North American level I trauma centers to transfusions of plasma, platelets, and red blood cells in ratios of either 1:1:1 or 1:1:2 [49,51]. Additional center-specific standard-of-care interventions, including prerandomization blood product and the use of cryoprecipitate and antifibrinolytics, were not controlled, making the separation between groups difficult to evaluate. There were no significant differences in primary outcomes of 24-hour or 30-day mortality between the groups. Like the PROMMTT study, death from hemorrhage was significantly less common in the 1:1:1 cohort at three hours after injury; however, no significant difference was seen at any later time point. No differences in the rates of complications were seen between groups (eg, acute respiratory distress syndrome, multiorgan failure, venous thromboembolism, sepsis).

Many types of plasma are available, and although studies of balanced transfusion have predominantly used fresh frozen plasma (FFP), there is interest in evaluating the utility other types of plasma (eg, liquid plasma, freeze dried plasma) that may be more readily available for use for trauma patients [48]. (See "Clinical use of plasma components", section on 'Plasma products'.)

Whole blood transfusion — Typically, whole blood, when used, is administered in the early phase of resuscitation. Whether continued use of whole blood in the later phases of care will provide a benefit has not been demonstrated, although a multicenter trial is underway [54].

While transfusion ratios of 1:1:1 mirror the content of whole blood, whole blood is a more concentrated product due to the reduced volume of additive solutions, including anticoagulants, compared with an equivalent 1:1:1 transfusion [55]. An in-vitro study has also demonstrated superior viscoelastic maximal clot formation for noncomponent banked whole blood compared with 1:1:1 component "reconstituted" whole blood [56]. Military experience from the wars in Iraq and Afghanistan demonstrated a benefit for using whole blood over component therapy in managing traumatic hemorrhagic shock with reduced mortality in patients who received warm, fresh whole blood administered in military hospitals as well as by far-forward surgical teams [21,57-64].

Resources to support whole blood transfusion in civilian trauma continue to improve with the implementation of prehospital whole blood programs in some regions of the United States and greater availability of whole blood in Level 1 trauma centers [55,65-70]. Observational studies of uncrossmatched group O+ whole blood administration in civilian trauma centers have shown that whole blood administration is safe in patients who require resuscitation [55,64,67,71-75]. Some, but not all, of these studies have demonstrated a survival benefit; the variable outcomes likely relate to differences in the populations studied, with a benefit for whole blood transfusion more associated with shock, traumatic coagulopathy, and need for massive transfusion. In a retrospective review using the American College of Surgeons Trauma Quality Improvement Program database, 432 severely injured patients who received whole blood transfusion as part of a massive transfusion protocol (MTP; using balanced component transfusion protocol) were compared with 2353 patients receiving MTP-only [67]. The use of whole blood was associated with improved survival at 24 hours (HR 0.63, 95% CI 0.41-0.96), and at 30 days (HR 0.53, 95% CI 0.31-0.93). Similarly, in a prospective study that included 348 patients in whom an MTP was activated, 24-hour survival was improved for those that received low-titer group O whole blood compared with those who received component transfusion (unadjusted mortality: 8 versus 19 percent; adjusted HR 0.21, 95% CI 0.07-0.67) [55]. The association with improved 24-hour survival was the greatest for patients presenting in shock or with traumatic coagulopathy. The whole blood cohort also received less total volume of blood products at 72 hours (48 versus 82 mL/kg). There was no difference in the risk of adverse events or organ injury for the use of low-titer group O whole blood in nongroup O compared with group O patients.

Viscoelastic hemostatic assay-guided transfusion — The rapid turnaround and multifaceted information provided by point-of-care viscoelastic hemostatic assays (VHAs) including thromboelastography (TEG) and rotational thromboelastometry (ROTEM) provide improved criteria for transfusion in acutely injured patient and reduce blood product consumption (pRBCs, plasma); however, whether mortality is improved is uncertain [76]. Protocols based upon TEG clotting time, clot formation time, amplitude, and clot lysis index (table 8) have been suggested based upon single-center experiences [21,77-83]. (See "Etiology and diagnosis of coagulopathy in trauma patients", section on 'Viscoelastic hemostatic assays'.)

VHA-guided "thrombostatic" resuscitation protocols may emerge as the standard [84]. Where TEG/ROTEM is available, we agree with Guidelines from the Eastern Association for the Surgery of Trauma (EAST) that suggest VHA-based goal-directed resuscitation for trauma patients requiring massive transfusion [85]. Conventional coagulation assays may be performed in parallel to facilitate communication with practitioners unfamiliar with TEG parameters. At centers where TEG is not available, empiric balanced transfusion strategies guided by standard coagulation assays remain standard of care.

The basis of the EAST recommendation was a systematic review and metaanalysis that reported a lower rate of transfusion, lower number of transfused units of pRBCs, lower number of patients and units of transfused FFP, and less need for procedures to manage bleeding (angioembolization, endoscopy, surgery) in patients who were manage with VHA-guided transfusion. However, most of the cited studies were single-center, observational studies [21,77-82,86-91].

Two trials have addressed this issue in severely injured patients but with differing mortality outcomes:

●The first trial randomly assigned 111 severely injured patients to a transfusion protocol managed by goal-directed TEG or by conventional coagulation assays (ie, international normalized ratio [INR], fibrinogen, platelet count) [90]. The initial transfusion (4 units of pRBCs, 2 units of plasma) was triggered by activation of the MTP (at the treating clinician's discretion) while awaiting results of coagulation tests (standard or TEG). Subsequent transfusions were guided by the assigned coagulation testing. There were no significant differences in injury severity score (ISS) between the groups. The risk of death was significantly higher for the conventional group compared with the TEG group (HR 2.17, 95% CI 1.03-4.6). Just over one-half of the deaths (16 of 31) occurred within six hours of arrival in the emergency department. Death rates in the conventional versus TEG groups were 12 of 55 (21.8 percent) versus 4 of 56 (7.1 percent) at 6 hours, and 20 of 55 (36.4 percent) versus 11 of 56 (19.6 percent) at 28 days. These outcomes may be due to differences in the timing of transfusion and ratio of blood products given. Although there were no differences in the overall volume of transfusion at 24 hours, the standard assay group received more plasma and platelets during the first several hours of resuscitation.

●A later multicenter trial (ITACTIC) randomized 396 patients to VHA (201 patients) or conventional coagulation (195 patients) guided interventions [92]. At 24 hours, the proportion of patients who were alive and free of massive transfusion was similar (VHA: 67 percent, conventional coagulation test [CCT]: 64 percent; OR 1.15, 95% CI 0.76-1.73). Mortality at 28 days was also similar (VHA: 25 percent, CCT: 28 percent; OR 0.84, 95% CI 0.54-1.31). There were also no significant differences in other secondary outcomes or serious adverse events.

An example thromboelastogram-guided transfusion protocol from Denver Health Medical Center, providing normal ranges and transfusion cutoffs derived from cut-point analysis in 190 severely injured trauma patients (table 9) [90,93]. Practical points on the use of TEG in trauma include:

●The Denver group reported that TEG "G" values and thrombin generation parameters obtained six hours after arrival were significantly associated with survival, while the INR was not [83].

●A retrospective evaluation of TEG used in 44 combat patients reported that maximal amplitude correlated more strongly with 24-hour transfusion requirements than standard laboratory values [94].

Care must be taken in the interpretation of TEG results in severely injured patients, particularly in patients with low clinical suspicion of active hemorrhage. Confounders may exist for which TEG will not be accurate [76]. As an example, in a single-center prospective study of 264 alcohol-intoxicated (out of 415) general trauma patients, alcohol level was associated with prolongation of the R-time and decrease in the alpha angle in adjusted analysis; however, an adjusted analysis showed that alcohol intoxication was a negative predictor of INR-defined coagulopathy and was not associated with transfusion requirements or overall mortality [95].

Management of acute traumatic coagulopathy — ATC is an impairment of hemostasis and activation of fibrinolysis that occurs early after injury and is biochemically evident prior to, and independent of, the development of significant acidosis, hypothermia, or hemodilution. Activation of the thrombomodulin-protein C system is a principle pathway mediating ATC [11,96]. (See "Etiology and diagnosis of coagulopathy in trauma patients", section on 'Trauma-induced coagulopathy'.)

Tranexamic acid — For patients at risk for ATC, empiric administration of tranexamic acid (TXA) reduces all-cause and bleeding related mortality. TXA is a lysine analog that binds to the kringle domains of plasminogen, preventing rearrangement into its active form. The optimal risk/benefit ratio conceptually appears to be those patients with hyperfibrinolysis and acute life-threatening hemorrhage who can be treated within three hours of injury [97-99], but not all patients benefit [100-104]. (See "Initial management of moderate to severe hemorrhage in the adult trauma patient", section on 'Moderate to severe ongoing hemorrhage'.)

Empiric dosing — When empiric dosing is elected, the following dosing regimen is suggested [98,105-109]:

•Administer a loading dose of 1 g intravenously over 10 minutes within three hours of the traumatic injury followed by the infusion of 1 g over eight hours.

•Some authors have advocated for an initial 2 g bolus, which eliminates the need for the subsequent infusion. However, there are insufficient data to determine which dosing regimen is better [110].

•The initial loading dose is provided in the prehospital period or in the emergency department and the infusion is continued in the operating room or ICU.

Two large studies formed the principal evidence base for empiric antifibrinolytic therapy with TXA in injured patients. These are summarized:

●CRASH-2 trial – The Clinical Randomization of Antifibrinolytic in Significant Hemorrhage (CRASH-2) trial was a prospective, randomized, placebo-controlled trial of empirically administered TXA conducted in over 20,000 trauma patients worldwide with, or at risk of, significant bleeding. The authors identified a significant decrease in both all-cause (14 versus 16 percent) and hemorrhage-related (4.9 versus 5.7 percent) mortality [98]. The wide breadth of clinical settings and patient populations enrolled was a notable strength of this study. However, inclusion criteria were broad, with only one-half of enrolled patients receiving any blood products or requiring emergency surgery for injuries. Further, based on the observed 1.5 percent absolute risk reduction for mortality, 67 patients would need to be empirically treated with TXA to save one life. No differences were seen in the incidence of thromboembolic complications or in head-injury-related mortality. Subsequent additional analysis of these data showed that the survival benefit of empiric TXA was only seen in patients treated within three hours of injury; treatment beyond three hours appeared to increase the risk of death due to bleeding [111].

●MATTERS study – The Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) study retrospectively evaluated TXA in 293 of 896 combat-injured patients with respect to total blood product use, thromboembolic complications, and mortality [99]. In this study, TXA-treated patients had lower unadjusted mortality compared with non-TXA-treated patients (17 versus 24 percent, with an absolute risk reduction of 6.5 percent), despite more severe injury in the TXA cohort. Based on this absolute risk reduction, the number needed to treat to save one life is 15; this is further reduced to as low as seven in the subset of patients requiring massive transfusion (absolute risk reduction 14 percent). Importantly, thromboembolic complications were more common in the TXA-treated cohort, although this was not significant in multivariate analysis. Severe traumatic brain injury was an independent predictor of mortality in this study, even when adjusted for TXA treatment.

VHA-based dosing — Although we generally would not delay the initial dose of TXA in high-risk patients [112], patients who present with the "shutdown" fibrinolytic phenotype are conceptually at risk of harm from TXA treatment and at higher risk for thromboembolic complications and long-term organ failure [102-104]. Thus, in clinical settings in which immediate access to TEG/ROTEM allows early determination of the presenting fibrinolytic phenotype, we suggest VHA-guided treatment of hyperfibrinolysis with an initial dose of TXA, followed by repeat TEG to guide ongoing transfusion and to determine whether another dose of TXA is needed. Patients who present with physiologic or subphysiologic levels of fibrinolysis are unlikely to benefit from TXA.

Other agents — In addition to repletion of coagulation factors by transfusion, several pharmaceutical hemostatic agents are available for the treatment of severe coagulopathy in the injured patient, including prothrombin complex concentrate and desmopressin.

●Cryoprecipitate – Fibrinogen is the first coagulation factor to decrease after massive hemorrhage. In a database review, among 476 patients, 70 (15 percent) had hypofibrinogenemia on admission, which was an independent risk factor for massive transfusion [113]. Early cryoprecipitate administration resulted in the fastest correction of hypofibrinogenemia and the authors suggested that early administration of cryoprecipitate should be considered. However, a later multicenter trial randomly assigned 799 patients who required activation of a MTP to cryoprecipitate (3 pools of cryoprecipitate within 90 minutes of randomization) or standard care according the institution's protocol [114]. The median ISS was 29. All-cause mortality at 28 days was similar between the groups (cryoprecipitate: 25.3 percent; standard care 26.1 percent; OR 0.96, 95% CI 0.75-1.23). Safety outcomes or incidence of thrombotic complications was also similar (12.9 versus 12.7 percent).

●Prothrombin complex concentrate – Prothrombin complex concentrate (PCC) is a factor concentrate enriched for factors II, VII, IX, and X originally developed for hemorrhagic complications of hemophilia B [115]. The clinical use of PCC has been well studied in the reversal of warfarin anticoagulation, since PCC is preferentially rich in the vitamin K-dependent clotting factors [116]. Some centers have used PCC to correct coagulopathy after trauma, and preliminary studies in animal models of hemorrhagic shock are promising, but PCC has not been thoroughly evaluated in trauma patients [117]. A systematic review identified four studies evaluating PCC in trauma patients [118]. Mortality was significantly reduced for patients with bleeding who received PCC compared with those who did not (19.7 versus 28.2 percent; OR 0.64, 95% CI 0.46-0.88). In the PCC group, pRBC transfusion was also reduced and coagulopathy was corrected faster. Clinical trials are underway to further define the role of PCC in patients who are not on oral anticoagulants.

●Desmopressin – Desmopressin was developed for the treatment of inherited bleeding diatheses [119] and to counteract uremic bleeding [120]. There is insufficient clinical evidence to support the use of desmopressin in the trauma population except in those patients with preexisting bleeding diatheses [121]. Preliminary animal studies show that desmopressin administration improves but does not completely correct hypothermia or acidosis-induced platelet dysfunction, but clinical validation of these experimental data needs to be performed [122,123]. (See "Uremic platelet dysfunction".)

●Other antifibrinolytic agents – Other antifibrinolytic agents, such as aminocaproic acid and aprotinin, have not been evaluated in patients with traumatic coagulopathy [124]. (See "Thrombotic and hemorrhagic disorders due to abnormal fibrinolysis", section on 'Therapies for hyperfibrinolytic states'.)

Correction of hypothermia — Hypothermia is one component of the "vicious triad" leading to coagulopathy (in addition to acidosis and hemodilution). (See "Etiology and diagnosis of coagulopathy in trauma patients", section on 'Hypothermia'.)

Specific measures to correct hypothermia include controlling physical exposure, the administration of warmed fluids, and passive rewarming with blankets and forced-air devices. Rapid identification and control of bleeding is vital to preserve normal temperature. In the case of moderate or severe hypothermia and coagulopathy, central rewarming may be needed. (See "Overview of post-anesthetic care for adult patients", section on 'Hypothermia or hyperthermia'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Abdominal compartment syndrome" and "Society guideline links: General issues of trauma management in adults".)

SUMMARY AND RECOMMENDATIONS

●Damage control and resuscitation – In severely injured patients, damage control resuscitation principles include maintenance of hemostasis, volume resuscitation, correction of coagulopathy, and maintenance of normothermia throughout the course of care. (See 'Assessment' above.)

●Reassessment and monitoring – Patient imaging should be reviewed in detail and the imaging workup completed based upon reassessment of the patient. The tertiary survey should be completed after admission to the intensive care unit (ICU). Early invasive blood pressure monitoring should be strongly considered.

●Several scoring systems such as the Assessment of Blood Consumption (ABC) score, Trauma-Associated Severe Hemorrhage (TASH) score, and Revised Assessment of Bleeding and Transfusion (RABT) score, as well as markers of volume administration such as the critical administration threshold or resuscitation intensity score, can identify patients who may require a massive transfusion.

●Laboratory studies – The frequency of laboratory studies can be guided by the clinical condition and course of the patient.

•Microcirculatory oxygen delivery – Lactic acid levels, base deficit, mixed-venous oxygen saturations, and calculation of the oxygen extraction ratio (OER) can provide information on microcirculatory oxygen delivery. (See 'Laboratory studies' above.)

•Coagulopathy – Coagulation studies, including viscoelastic hemostatic assays (VHAs), can provide information to guide correction of coagulopathy. VHAs measures viscoelastic properties of clot formation providing information on clot initiation, clot strength, and fibrinolysis, and is emerging as an important tool for identifying patients with acute traumatic coagulopathy (ATC) and for real-time monitoring of ongoing resuscitation efforts in injured patients.

●Assessment of volume status – The use of stroke volume variation (SVV) or pulse pressure variation (PPV), in addition to bedside point-of-care ultrasound, can provide additional information regarding the need for ongoing volume resuscitation. (See 'Dynamic measures of end-organ perfusion' above.)

●Volume resuscitation and transfusion

•For patients with ongoing bleeding or coagulopathy, we suggest whole blood or a balanced component transfusion, targeting ratios of packed red blood cells (pRBCs), fresh frozen plasma (FFP) or similar products (eg, PF24), and platelets approaching 1:1:1 over protocols with lower ratios (Grade 2C). Crystalloid resuscitation should be minimized. (See 'Balanced component transfusion' above.)

•When the technology is available, we suggest early VHA-directed management of fibrinolysis rather than treatment based on conventional coagulation assays. At centers where VHA is not available, empiric plasma-forward transfusion strategies guided by standard coagulation assays remains standard of care. (See 'VHA-based dosing' above.)