Intensive Care Doctor-Community

Background

Shock is a clinical syndrome characterized by inadequate tissue perfusion that results in end-organ dysfunction. Shock can be divided into the following 4 categories:

• Distributive shock (vasodilation), which is a hyperdynamic process
• Cardiogenic shock (pump failure)
• Hypovolemic shock (intravascular volume loss)
• Obstructive shock (blood vessels and heart)

This article discusses distributive shock.

Distributive shock has several causes. Septic shock is the most common form of distributive shock, with considerable mortality. In the United States, this is the leading cause of noncardiac death in intensive care units (ICUs). Other causes of distributive shock include systemic inflammatory response syndrome (SIRS) due to noninfectious inflammatory conditions like burns & pancreatitis; toxic shock syndrome (TSS); anaphylaxis; drug or toxin reactions, including insect bites, transfusion reaction, and heavy metal poisoning; Addisonian crisis; hepatic insufficiency; and neurogenic shock due to brain or spinal cord injury.

Pathophysiology

In distributive shock, the inadequate tissue perfusion is caused by decreased systemic vascular resistance (SVR) and a high cardiac output. The early changes are primarily characterized by the evolution of changes in contractility and dilation of peripheral small vessels and the impact of resuscitation efforts. Early septic shock (warm or hyperdynamic) causes reduced diastolic blood, widened pulse pressure, flushed warm extremities, and brisk capillary refill from peripheral vasodilation with a compensatory increase in cardiac output. In late septic shock (cold or hypodynamic), myocardial contractility combines with peripheral vascular paralysis to induce a pressure-dependent reduction in organ perfusion. The result is hypoperfusion of critical organs such as the heart, brain, and liver.

The hemodynamic derangements observed in septic shock and SIRS are due to a complicated cascade of inflammatory mediators. Inflammatory mediators are released in response to any of a number of factors, such as: infection, inflammation, or tissue injury. For example, bacterial products such as endotoxin activate the host inflammatory response leading to increased pro-inflammatory cytokines (eg, tumor necrosis factor (TNF), interleukin (IL)-1b, and IL-6). Toll-like receptors are thought to play a critical role in responding to pathogens as well as in the excessive inflammatory response that characterizes distributive shock; these receptors are considered a possible drug targets.

Cytokines and phospholipids-derived mediators act synergistically to produce the complex alterations in vasculature (eg, increased microvascular permeability, impaired microvascular response to endogenous vasoconstrictors such as norepinephrine) and myocardial function (direct inhibition of myocyte function), which leads to maldistribution of blood flow and hypoxia. Hypoxia also induces the upregulation of enzymes that create nitric oxide, a potent vasodilator, thereby further exacerbating hypoperfusion.

The American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) Consensus Conference Committee defined the following 4 clinical subcategories of systemic inflammatory response:¹

• Systemic inflammatory response with 2 or more of the following:
• A core temperature of higher than 38° C or lower than 36° C
• A heart rate of more than 90 beats per minute; respiratory rate of more than 20 breaths per minute; WBC count of more than 12,000 10³/µL, less than 4,000 10³/µL, or more than 10% bands.
• Systemic inflammatory response with sepsis - Meets criteria for SIRS, source of infection is presumed or confirmed
• Systemic inflammatory response with severe sepsis - Sepsis plus hypoperfusion and dysfunction or organs, as evidenced by hypotension (systolic blood pressure of more than 90 mm Hg or a decrease of more than 40 mm Hg from baseline), lactic acidosis, oliguria, a change in mental status
• Systemic inflammatory response with septic shock - Severe sepsis in a patient who does not respond to intravenous fluid resuscitation and vasopressors

The coagulation cascade is also affected. In septic shock, activated monocytes and endothelial cells are sources of tissue factor that activates the coagulation cascade; cytokines such as IL-6 also play a role. The coagulation response is broadly disrupted, including impairment of antithrombin and fibrinolysis. Thrombin generated as part of the inflammatory response can trigger disseminated intravascular coagulation (DIC). DIC is found in 25-50% of patients with sepsis and is a significant risk factor for mortality.^2,3

During distributive shock, patients are at risk for diverse organ system dysfunction that may progress to multiple organ failure (MOF). Mortality from severe sepsis increases markedly with the duration of sepsis and the number of organs failing.

In distributive shock due to anaphylaxis, decreased SVR is due primarily to massive histamine release from mast cells after activation by antigen-bound immunoglobulin E (IgE), as well as increased synthesis and release of prostaglandins.

Neurogenic shock is due to loss of sympathetic vascular tone from severe injury to nervous system.

Frequency

United States

Sepsis develops in more than 750,000 patients per year. Angus and colleagues have estimated that, by 2010, 1 million people per year will be diagnosed with sepsis.⁴ From 1979-2000, the incidence of sepsis has increased by 9% per year.

International

Sepsis is a common cause of death throughout the world and kills approximately 1,400 people worldwide every day.^5,6

Mortality/Morbidity

• The mortality rate after development of septic shock is 20-80%.⁷ Recent data suggest that mortality due to septic shock has decreased slightly from new therapeutic interventions.⁸
• Higher mortality rates have been associated with advanced age, the finding of positive blood cultures, infection with antibiotic-resistant organisms such as Pseudomonas aeruginosa, elevated serum lactate levels, impaired immune function, alcohol use, and poor functional status prior to the onset of sepsis.
• Mortality rates associated with other forms of distributive shock are not well documented.

Age

Increased age correlates with increased risk of death from sepsis.

Clinical

History

• Patients with shock frequently present with tachycardia, tachypnea, hypotension, altered mental status changes, and oliguria.
• Patients with septic shock or systemic inflammatory response syndrome (SIRS) may have prior symptoms that suggest infection or inflammation of the respiratory tract, urinary tract, or abdominal cavity.
• Septic shock occurs frequently in hospitalized patients with risk factors such as indwelling catheters or venous access devices, recent surgery, or immunosuppressive therapy.
• Patients with anaphylaxis commonly have recent iatrogenic (drug) or accidental (bee sting) exposure to an allergen and coexisting respiratory symptoms, such as wheezing and dyspnea, pruritus, or urticaria.
• Adrenal insufficiency as a cause of shock should be considered in any patient with hypotension who lacks signs of infection, cardiovascular disease, or hypovolemia.
• • Long-term treatment with corticosteroids may result in inadequate response of the adrenal axis to stress, such as infection, surgery, or trauma, and subsequent onset or worsening of shock.
  • If the clinical picture is consistent with adrenal insufficiency in a person without this diagnosis, consider that this could be the first presentation of this disorder.
  • There is a high incidence of adrenal insufficiency in critically ill HIV-infected patients that varies with the criteria used to diagnose adrenal insufficiency.⁹
  • Staphylococcal toxic shock syndrome (TSS) is still observed most commonly in women who are menstruating, but it is also associated with recent soft tissue injury, cutaneous infections, postpartum and cesarean delivery, wound infections, pharyngitis and focal staphylococcal infections, such as abscess, empyema, pneumonia, and osteomyelitis. Patients often have a history of influenzalike illness (fever, arthralgias, myalgias) and a desquamating rash.
  • Pancreatitis may also be a cause of distributive shock; expect symptoms of abdominal pain that radiate to the back and nausea and vomiting.
  • Burns have been described as a cause of distributive shock.

Physical

• Cardinal features of distributive shock include the following:
  • Change in mental status
  • Heart rate - Greater than 90 beats per minute (Note that heart rate elevation is not evident if the patient is on a beta-blocker.)
  • Hypotension - Systolic blood pressure less than 90 mm Hg or a reduction of 40 mm Hg from baseline
  • Respiratory rate - Greater than 20 breaths per minute
  • Extremities - Frequently warm with bounding pulses and increased pulse pressure (systolic minus diastolic blood pressure) in early shock (Late shock may present as critical organ dysfunction.)
  • Hyperthermia - Core body temperature greater than 38.3° C or 101° F
  • Hypothermia - Core body temperate less than 36° C or 96.8° F
  • Pulse oximetry - Relative hypoxemia
  • Decreased urine output
• Underlying infection
  • Pneumonia
    • Dullness to percussion
    • Rhonchi
    • Crackles
    • Bronchial breath sounds
  • Urinary tract infection
    • Costovertebral angle tenderness
    • Suprapubic tenderness
    • Dysuria & polyuria
  • Intra-abdominal infection or acute abdomen
    • Focal or diffuse tenderness to palpation
    • Diminished or absent bowel sounds
    • Rebound tenderness
  • Gangrene or soft tissue infection
    • Pain out of proportion to lesion
    • Skin discoloration & ulceration
    • Desquamating rash
    • Areas of subcutaneous necrosis
• Anaphylaxis
  • Respiratory distress
  • Wheezing
  • Urticarial rash
  • Angioedema
• Toxic shock syndrome
  • High fever
  • Diffuse rash with desquamation on the palms and soles over a subsequent 1-2 weeks
  • Hypotension (may be orthostatic) and evidence of involvement of 3 other organ systems
  • Streptococcal TSS more frequently presents with focal soft tissue inflammation and is less commonly associated with diffuse rash.
• Adrenal insufficiency
  • Hyperpigmentation of skin, oral, vaginal, and anal mucosal membranes may be present in chronic adrenal insufficiency.
  • In acute or acute-on-chronic adrenal insufficiency brought on by physiologic stress, hypotension may be the only physical sign.

Causes

The most common etiology of distributive shock is sepsis. Other causes include SIRS due to noninfectious conditions such as pancreatitis, burns and trauma, TSS, anaphylaxis, adrenal insufficiency, drug or toxin reactions, heavy metal poisoning, hepatic insufficiency, and neurogenic shock. All these conditions share the common characteristic of hypotension due to decreased systemic vascular resistance and low effective circulating plasma volume.

• Septic shock
  • The most common sites of infection, in decreasing order of frequency, include the chest, abdomen, and genitourinary tract.
  • Septic shock is commonly caused by bacteria although viruses, fungi and parasites are also implicated. Gram-positive bacteria are being isolated more with their numbers almost similar to the gram-negative bacteria which in the past were considered to be the predominant organisms. Multidrug-resistant organisms are increasingly common.¹⁰
• SIRS (see ACCP/SCCM definition in the Pathophysiology section)
  • Infection
  • Burns
  • Surgery
  • Trauma
  • Pancreatitis
  • Fulminant hepatic failure
• Toxic shock syndrome
  • Streptococcus pyogenes (group A Streptococcus)
  • Staphylococcus aureus
• Adrenal insufficiency
  • Destruction of adrenal glands due to autoimmune disease, infection (tuberculosis, fungal infection, AIDS), hemorrhage, cancer, or surgical removal
  • Suppression of hypothalamic-pituitary-adrenal axis by exogenous steroid
  • Hypopituitarism
  • Metabolic failure in hormone production due to congenital conditions or drug-induced inhibition of synthetic enzymes (eg, metyrapone, ketoconazole)
• Anaphylaxis
  • Drugs such as penicillins and cephalosporins
  • Heterologous proteins such as Hymenoptera venom, foods, pollen, and blood serum products

Background

In 1992, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) introduced definitions for systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, and multiple organ dysfunction syndrome (MODS). The idea behind defining SIRS was to define a clinical response to a nonspecific insult of either infectious or noninfectious origin. SIRS is defined as 2 or more of the following variables:

• Fever of more than 38°C or less than 36°C
• Heart rate of more than 90 beats per minute
• Respiratory rate of more than 20 breaths per minute or a PaCO2 level of less than 32 mm Hg
• Abnormal white blood cell count (>12,000/µL or <4,000/µl>10% bands)

SIRS is nonspecific and can be caused by ischemia, inflammation, trauma, infection, or a combination of several insults. SIRS is not always related to infection. Infection is defined as "a microbial phenomenon characterized by an inflammatory response to the microorganisms or the invasion of normally sterile tissue by those organisms."

Bacteremia is the presence of bacteria within the blood stream, but this condition does not always lead to SIRS or sepsis. Sepsis is the systemic response to infection and is defined as the presence of SIRS in addition to a documented or presumed infection. Severe sepsis meets the aforementioned criteria and is associated with organ dysfunction, hypoperfusion, or hypotension. Sepsis-induced hypotension is defined as "the presence of a systolic blood pressure of less than 90 mm Hg or a reduction of more than 40 mm Hg from baseline in the absence of other causes of hypotension." Patients meet the criteria for septic shock if they have persistent hypotension and perfusion abnormalities despite adequate fluid resuscitation. MODS is a state of physiological derangements in which organ function is not capable of maintaining homeostasis.

Although not universally accepted terminology, severe SIRS and SIRS shock are terms that some authors have proposed. These terms suggest organ dysfunction or refractory hypotension related to an ischemic or inflammatory process rather than to an infectious etiology.

Pathophysiology

SIRS, independent of the etiology, has the same pathophysiologic properties, with minor differences in inciting cascades. Many consider the syndrome a self-defense mechanism. Inflammation is the body's response to nonspecific insults that arise from chemical, traumatic, or infectious stimuli. The inflammatory cascade is a complex process that involves humoral and cellular responses, complement, and cytokine cascades. Bone best summarized the relationship between these complex interactions and SIRS as the following 3-stage process:

• Stage I: Following an insult, local cytokine is produced with the goal of inciting an inflammatory response, thereby promoting wound repair and recruitment of the reticular endothelial system.
• Stage II: Small quantities of local cytokines are released into circulation to improve the local response. This leads to growth factor stimulation and the recruitment of macrophages and platelets. This acute phase response is typically well controlled by a decrease in the proinflammatory mediators and by the release of endogenous antagonists. The goal is homeostasis.
• Stage III: If homeostasis is not restored, a significant systemic reaction occurs. The cytokine release leads to destruction rather than protection. A consequence of this is the activation of numerous humoral cascades and the activation of the reticular endothelial system and subsequent loss of circulatory integrity. This leads to end-organ dysfunction.

Bone also endorsed a multihit theory behind the progression of SIRS to organ dysfunction and possibly MODS. In this theory, the event that initiates the SIRS cascade primes the pump. With each additional event, an altered or exaggerated response occurs, leading to progressive illness. The key to preventing the multiple hits is adequate identification of the cause of SIRS and appropriate resuscitation and therapy.

Trauma, inflammation, or infection leads to the activation of the inflammatory cascade. When SIRS is mediated by an infectious insult, the inflammatory cascade is often initiated by endotoxin or exotoxin. Tissue macrophages, monocytes, mast cells, platelets, and endothelial cells are able to produce a multitude of cytokines. The cytokines tissue necrosis factor-a (TNF-a) and interleukin (IL)–1 are released first and initiate several cascades. The release of IL-1 and TNF-a (or the presence of endotoxin or exotoxin) leads to cleavage of the nuclear factor-k B (NF-k B) inhibitor. Once the inhibitor is removed, NF-k B is able to initiate the production of mRNA, which induces the production other proinflammatory cytokines.

IL-6, IL-8, and interferon gamma are the primary proinflammatory mediators induced by NF-k B. In vitro research suggests that glucocorticoids may function by inhibiting NF-k B. TNF-a and IL-1 have been shown to be released in large quantities within 1 hour of an insult and have both local and systemic effects. In vitro studies have shown that these 2 cytokines given individually produce no significant hemodynamic response but cause severe lung injury and hypotension when given together. TNF-a and IL-1 are responsible for fever and the release of stress hormones (norepinephrine, vasopressin, activation of the renin-angiotensin-aldosterone system).

Other cytokines, especially IL-6, stimulate the release of acute-phase reactants such as C-reactive protein (CRP). Of note, infection has been shown to induce a greater release of TNF-a than trauma, which induces a greater release of IL-6 and IL-8. This is suggested to be the reason higher fever is associated with infection rather than trauma.

The proinflammatory interleukins either function directly on tissue or work via secondary mediators to activate the coagulation cascade, complement cascade, and the release of nitric oxide, platelet-activating factor, prostaglandins, and leukotrienes. Numerous proinflammatory polypeptides are found within the complement cascade. Protein complements C3a and C5a have been the most studied and are felt to contribute directly to the release of additional cytokines and to cause vasodilatation and increasing vascular permeability. Prostaglandins and leukotrienes incite endothelial damage, leading to multiorgan failure.

The correlation between inflammation and coagulation is critical to understanding the potential progression of SIRS. IL-1 and TNF-a directly affect endothelial surfaces, leading to the expression of tissue factor. Tissue factor initiates the production of thrombin, thereby promoting coagulation, and is a proinflammatory mediator itself. Fibrinolysis is impaired by IL-1 and TNF-a via production of plasminogen activator inhibitor-1. Proinflammatory cytokines also disrupt the naturally occurring anti-inflammatory mediator's antithrombin and activated protein-C (APC). If unchecked, this coagulation cascade leads to complications of microvascular thrombosis, including organ dysfunction. The complement system also plays a role in the coagulation cascade. Infection-related procoagulant activity is generally more severe than that produced by trauma.

The cumulative effect of this inflammatory cascade is an unbalanced state with inflammation and coagulation dominating. To counteract the acute inflammatory response, the body is equipped to reverse this process via counter inflammatory response syndrome (CARS). IL-4 and IL-10 are cytokines responsible for decreasing the production of TNF-a, IL-1, IL-6, and IL-8. The acute phase response also produces antagonists to TNF-a and IL-1 receptors. These antagonists either bind the cytokine, and thereby inactivate it, or block the receptors. Comorbidities and other factors can influence a patient's ability to respond appropriately. The balance of SIRS and CARS determines a patient's prognosis after an insult. Some researchers believe that, because of CARS, many of the new medications meant to inhibit the proinflammatory mediators may lead to deleterious immunosuppression.

Frequency

United States

The true incidence of SIRS is unknown. However, because SIRS criteria are nonspecific and occur in patients who present with conditions that range from influenza to cardiovascular collapse associated with severe pancreatitis, such incidence figures would need to be stratified based on SIRS severity.

Rangel-Fausto et al published a prospective survey of patients admitted to a tertiary care center that revealed 68% of hospital admissionsto surveyed units met SIRS criteria. The incidence of SIRS increased as the level of unit acuity increased. The following progression of patients with SIRS was noted: 26% developed sepsis, 18% developed severe sepsis, and 4% developed septic shock within 28 days of admission.

Pittet et al performed a hospital survey of SIRS that revealed an overall in-hospital incidence of 542 episodes per 1000 hospital days. In comparison, the incidence in the ICU was 840 episodes per 1000 hospital days.

Still, Angus et al found the incidence of severe SIRS associated with infection to be 3 cases per 1,000 population, or 2.26 cases per 100 hospital discharges. The real incidence of SIRS, therefore, must be much higher and likely depends somewhat on the rigor with which the definition is applied.

International

No difference in frequency exists based on world geography.

Mortality/Morbidity

A recently published study by Shapiro et al evaluated mortality in patients with suspected infection in the emergency department. The in-hospital mortality rates were as follows: 2.1% had a suspected infection without SIRS, 1.3% had sepsis, 9.2% had severe sepsis, and 28% had septic shock. The presence of SIRS criteria alone had no prognostic value for either in-hospital mortality or 1-year mortality. Each additional organ dysfunction increased the risk of mortality at 1 year. The authors concluded that organ dysfunction, rather than SIRS criteria, was a better predictor of mortality.

Race

No racial predilection exists for this disease entity.

Sex

Using the same logic as expressed in Frequency, the sex-based mortality risk of severe SIRS is also unknown. Females tend to have less inflammation for the same degree of proinflammatory stimuli because of the mitigating aspects of estrogen. The mortality rate among women with severe sepsis is similar to that of men who are 10 years younger; however, whether this protective effect applies to women with noninfectious SIRS is unknown.

Age

Extremes of age (young and old) and concomitant comorbidities probably negatively affect the outcome of SIRS. Young people may be able to mount a more exuberant inflammatory response to a challenge than older people and yet may be able to better modify the inflammatory state (via CARS). Young people have better outcomes of equivalent diagnoses.

Clinical

History

Despite having a relatively common physiologic pathway, systemic inflammatory response syndrome (SIRS) has numerous triggers, and patients may present in various manners. The clinician's history should be focused around the chief symptom, with a pertinent review of systems being performed. Patients should be questioned regarding constitutional symptoms of fever, chills, and night sweats. This may help to differentiate infectious from noninfectious etiologies. The timing of symptom onset may also guide a differential diagnosis toward an infectious, traumatic, ischemic, or inflammatory etiology.

• Pain, especially when it can be localized, may guide a physician in both differential diagnosis and necessary evaluation. Although providing a differential for pain in the various body parts is beyond the scope of this article, a physician should carefully obtain the duration, location, radiation, quality, and exacerbating factors associated with the pain to help establish a thorough differential diagnosis.
• In patients for whom a diagnosis cannot be made based on initial history, a complete review of systems is indicated to try an undercover potential diagnosis.
• Patients' medications should be reviewed. Medication side effects or pharmacologic properties may either induce or mask SIRS (ie, beta-blockers prevent tachycardia). Recent changes in medications should be addressed to rule out drug-drug interactions or a new side effect. Allergy information should be gathered and the specifics of the reaction should be obtained.

Physical

A focused physical examination based on a patient's symptoms is adequate in most situations. Under certain circumstances, if no obvious etiology is obtained during the history or laboratory evaluation, a complete physical examination may be indicated. Patients who cannot provide any history should also undergo a complete physical examination, including a rectal examination, to rule out an abscess or gastrointestinal bleeding.

• Three of the 4 criteria for SIRS are based on the following vital signs:
  • A fever of more than 38°C or less than 36°C
  • A heart rate of more than 90 beats per minute
  • Respiratory rate of more than 20 breaths per minute or PaCO2 level of less than 32 mm Hg
  • An abnormal white blood cell count (>12,000/µL or <4,000/µl>10% bands)
• Careful review of initial vital signs is an integral component to making the diagnosis. Repeating the review of vital signs periodically during the initial evaluation period is necessary, as multiple other factors (eg, stress, anxiety, exertion of walking to the examination room) may lead to a false diagnosis of SIRS.
• Key points
  • Extreme of ages (both young and old) may not manifest as typical criteria for SIRS; therefore, clinical suspicion may be required to diagnosis a serious illness (either infectious or noninfectious).
  • Patients receiving a beta-blocker or a calcium channel blocker are likely unable to elevate their heart rate and, therefore, tachycardia may not be present.
  • Although blood pressure is not one of the 4 criteria, it is still an important marker. If the blood pressure is low, the establishment of intravenous access and fluid resuscitation is of utmost importance. Frank hypotension associated with SIRS is uncommon unless the patient is septic or severely dehydrated. Hypotension may lead to the patient being admitted or transferred to a higher acuity unit.
  • Respiratory rate is the most sensitive marker of the severity of illness.

Causes

The differential diagnosis of SIRS is broad and includes infectious and noninfectious conditions, surgical procedures, trauma, and medications and therapies.

• The following is partial list of the infectious causes of SIRS:
  • Bacterial sepsis
  • Burn wound infections
  • Candidiasis
  • Cellulitis
  • Cholecystitis
  • Community-acquired pneumonia
  • Diabetic foot infection
  • Erysipelas
  • Infective endocarditis
  • Influenza
  • Intraabdominal infections (eg, diverticulitis, appendicitis)
  • Gas gangrene
  • Meningitis
  • Nosocomial pneumonia
  • Pseudomembranous colitis
  • Pyelonephritis
  • Septic arthritis
  • Toxic shock syndrome
  • Urinary tract infections (both male and female)
• The following is a partial list of the noninfectious causes of SIRS:
  • Acute mesenteric ischemia
  • Autoimmune disorders
  • Burns
  • Chemical aspiration
  • Cirrhosis
  • Dehydration
  • Drug reaction
  • Electrical injuries
  • Erythema multiforme
  • Hemorrhagic shock
  • Intestinal perforation
  • Medication side effect (eg, theophylline)
  • Myocardial infarction
  • Pancreatitis
  • Substance abuse (stimulants such as cocaine and amphetamines)
  • Surgical procedures
  • Toxic epidermal necrolysis
  • Transfusion reactions
  • Upper gastrointestinal bleeding
  • Vasculitis

Background

In 1914, Schottmueller wrote, "Septicemia is a state of microbial invasion from a portal of entry into the blood stream which causes sign of illness." The definition did not change significantly over the years because sepsis and septicemia were considered to refer to a number of ill-defined clinical conditions in addition to bacteriemia. In practice, the terms were often used interchangeably; however, less than one half of the patients who have signs and symptoms of sepsis have positive blood culture results.

In the late 1960s, several reports appeared describing remote organ failure (eg, pulmonary failure, liver failure) as a complication of severe sepsis. In 1975, a classic editorial by Baue was entitled "Multiple, progressive or sequential systems failure, a syndrome of the 1970s." This concept was formulated as the basis of a new clinical syndrome. Several terms were cloned thereafter, such as multiple organ failure, multiple system organ failure, and multiple organ system failure, to describe this evolving clinical syndrome of otherwise unexplained progressive physiological failure of several interdependent organ systems. More recently, the term multiple organ dysfunction syndrome (MODS) has been proposed as a more appropriate description.

Multiorgan failure from sepsis

Sepsis is a clinical syndrome that complicates severe infection and is characterized by systemic inflammation and widespread tissue injury. In this syndrome, tissue is removed from the original insult that displayed the signs of inflammation, such as vasodilatation, increased microvascular permeability, and leukocyte accumulation. Multiple organ dysfunction is a continuum, with incremental degrees of physiological derangements in individual organs; it is a process rather than an event. Alteration in organ function can vary widely from a mild degree of organ dysfunction to frank organ failure. The degree of organ dysfunction has a major clinical impact. The term MODS is defined as a clinical syndrome in which the development of progressive and potentially reversible physiological dysfunction in 2 or more organs or organ systems induced by a variety of acute insults, including sepsis, is characteristic.

In 1991, the American College of Chest Physicians/Society of Critical Care Medicine Consensus Panel developed definitions of the various stages of sepsis, which are as follows:

• Infection is a microbial phenomenon in which an inflammatory response to the presence of microorganisms or the invasion of normally sterile host tissue by these organisms is characteristic.
• Bacteremia is the presence of viable bacteria in the blood.
• Systemic inflammatory response syndrome (SIRS) may follow a variety of clinical insults, including infection, pancreatitis, ischemia, multiple trauma, tissue injury, hemorrhagic shock, or immune-mediated organ injury.
• Sepsis is a systemic response to infection. This is identical to SIRS, except that it must result from infection.
• Septic shock is sepsis with hypotension (systolic BP <90>
• MODS is the presence of altered organ function in a patient who is acutely ill such that homeostasis cannot be maintained without intervention. Primary MODS is the direct result of a well-defined insult in which organ dysfunction occurs early and can be directly attributable to the insult itself. Secondary MODS develops as a consequence of a host response and is identified within the context of SIRS. The inflammatory response of the body to toxins and other components of microorganisms causes the clinical manifestations of sepsis.

The sepsis syndrome is recognized clinically by the presence of 2 or more of the following:

• Temperature greater than 38°C or less than 36°C
• Heart rate greater than 90 beats per minute
• Respiratory rate greater than 20 breaths per minute or a PaCO2 in arterial gas less than 32 mm Hg
• WBC count greater than 12,000 cells/µL, less than 4000 cells/µL, or greater than 10% band forms

Pathophysiology

Pathogenesis

Sepsis has been referred to as a process of malignant intravascular inflammation. Normally, a potent, complex, immunologic cascade ensures a prompt protective response to microorganism invasion in humans. A deficient immunologic defense may allow infection to become established; however, an excessive or poorly regulated response may harm the host through maladaptive release of indigenously generated inflammatory compounds.

Lipid A and other bacterial products release cytokines and other immune modulators that mediate the clinical manifestations of sepsis. Interleukins, tumor necrosis factor-alpha (TNF-alpha), interferon gamma (IFN-gamma), and other colony-stimulating factors are produced rapidly within minutes or hours after interactions of monocytes and macrophages with lipid A. TNF release becomes a self-stimulating process (an autocrine), and release of other inflammatory mediators, including interleukin-1 (IL-1), platelet activating factor, IL-2, IL-6, IL-8, IL-10, INF, and eicosanoids, further increases cytokine levels. This leads to continued activation of polymorphonuclear leukocytes (PMNs), macrophages, and lymphocytes; proinflammatory mediators recruit more of these cells (a paracrine process). All of these processes create a state of destructive immunologic dissonance.

Sepsis is described as an autodestructive process that permits extension of the normal pathophysiologic response to infection to involve otherwise normal tissues and results in MODS.

Specific organ involvement

Organ dysfunction or organ failure may be the first clinical sign of sepsis, and no organ system is immune from the consequences of the inflammatory excesses of sepsis.

Circulation

Significant derangement in autoregulation of circulation is typical of sepsis. Vasoactive mediators cause vasodilatation and increase the microvascular permeability at the site of infection. Nitric oxide plays a central role in the vasodilatation of septic shock. Also, impaired secretion of vasopressin may occur, which may permit persistence of vasodilatation.

Central circulation: Changes in both systolic and diastolic ventricular performance occur in sepsis. Through the use of the Frank Starling mechanism, cardiac output often is increased to maintain the BP in the presence of systemic vasodilatation. Patients with preexisting cardiac disease are unable to increase their cardiac output appropriately.

Regional circulation: Sepsis interferes with the normal distribution of systemic blood flow to organ systems; therefore, core organs may not receive appropriate oxygen delivery.

Microcirculation is the key target organ for injury in sepsis syndrome. A decrease in the number of functional capillaries causes an inability to extract oxygen maximally, which is caused by intrinsic and extrinsic compression of capillaries and plugging of the capillary lumen by blood cells. Increased endothelial permeability leads to widespread tissue edema of protein-rich fluid.

In severe sepsis and septic shock, microcirculatory dysfunction and mitochondrial depression cause regional tissue distress, therefore, regional hypoxia persists. This condition is termed microcirculatory and mitochondrial distress syndrome (MMDS). Sepsis-induced inflammatory autoregulatory dysfunction persists and oxygen need is not matched by supply, leading to multiorgan system dysfunction.

Redistribution of intravascular fluid volume resulting from reduced arterial vascular tone, diminished venous return from venous dilation, and release of myocardial depressant substances causes hypotension.

Pulmonary dysfunction

Endothelial injury in the pulmonary vasculature leads to disturbed capillary blood flow and enhanced microvascular permeability, resulting in interstitial and alveolar edema. Neutrophil entrapment within the pulmonary microcirculation initiates and amplifies the injury to alveolar capillary membranes. Acute respiratory distress syndrome (ARDS) is a frequent manifestation of these effects.

Gastrointestinal dysfunction and nutrition

The GI tract may help propagate the injury of sepsis. Overgrowth of bacteria in the upper GI tract may be aspirated into the lungs, producing nosocomial pneumonia. The normal barrier function of the gut may be affected, allowing translocation of bacteria and endotoxins into the systemic circulation and extending the septic response. Septic shock usually causes ileus, and the use of narcotics and sedatives delays institution of enteral feeding. The optimal level of nutritional intake is interfered with in the face of high protein and calorie requirements.

Liver

By virtue of the role of the liver in host defense, the abnormal synthetic functions caused by liver dysfunction can contribute to both the initiation and progression of sepsis. The reticuloendothelial system of the liver acts as a first line of defense in clearing bacteria and their products; liver dysfunction leads to a spillover of these products into systemic circulation.

Renal dysfunction

Acute renal failure often accompanies sepsis due to acute tubular necrosis. The mechanism is by systemic hypotension, direct renal vasoconstriction, release of cytokines (eg, TNF), and activation of neutrophils by endotoxins and other peptides, which contribute to renal injury.

Central nervous system dysfunction

Involvement of the CNS in sepsis produces encephalopathy and peripheral neuropathy. The pathogeneses is poorly defined.

Mechanisms of organ dysfunction and injury

The precise mechanisms of cell injury and resulting organ dysfunction in sepsis are not understood fully. Multiorgan dysfunction syndrome is associated with widespread endothelial and parenchymal cell injury because of the following proposed mechanisms:

• Hypoxic hypoxia: The septic circulatory lesion disrupts tissue oxygenation, alters the metabolic regulation of tissue oxygen delivery, and contributes to organ dysfunction. Microvascular and endothelial abnormalities contribute to the septic microcirculatory defect in sepsis. The reactive oxygen sepsis, lytic enzymes, and vasoactive substances (nitric oxide, endothelial growth factors) lead to microcirculatory injury, which is compounded by the inability of the erythrocytes to navigate the septic microcirculation.
• Direct cytotoxicity: The endotoxin, TNF-alpha, and nitric oxide may cause damage to mitochondrial electron transport, leading to disordered energy metabolism. This is called cytopathic or histotoxic anoxia, an inability to utilize oxygen even when it is present.
• Apoptosis: Apoptosis (programmed cell death) is the principal mechanism by which dysfunctional cells are eliminated normally. The proinflammatory cytokines may delay apoptosis in activated macrophages and neutrophils, but other tissues, such as the gut epithelium, may undergo accelerated apoptosis. Therefore, derangement of apoptosis plays a critical role in tissue injury of sepsis.
• Immunosuppression: The interaction between proinflammatory and anti-inflammatory mediators may lead to an imbalance. An inflammatory reaction or immunodeficiency may predominate, or both may be present.

Coagulopathy

Subclinical coagulopathy signified by a mild elevation of the thrombin or activated partial thromboplastin time (aPTT) or a moderate reduction in platelet count is extremely common, but overt disseminated intravascular coagulation (DIC) is rare. Deficiencies of coagulation system proteins, including protein C, antithrombin 3, and tissue factor inhibitors, cause coagulopathy.

Characteristics of sepsis that influence outcomes

Clinical characteristics that relate to the severity of sepsis include an abnormal host response to infection, the site and type of infection, the timing and type of antimicrobial therapy, the offending organism, and the development of shock, underlying disease, and the patients' chronic health condition. The location of patient at the time of septic shock also relates to the severity of sepsis.

Frequency

United States

Current estimates suggest that the incidence of sepsis is greater than 500,000 cases per year. Approximately 40% of patients who are septic may develop shock. Patients who are at risk include those with positive blood cultures. Prevalence rates for SIRS of sepsis vary from 20-60%.

International

A French study in 1996 found that severe sepsis was present in 6.3% of all ICU admissions.

Mortality/Morbidity

Mortality from multiorgan dysfunction syndrome remains high. Mortality rates from ARDS alone is 40-50%. Once additional organ system dysfunction occurs, the mortality rate increases as much as 90%.

Clinical

History

Symptoms of sepsis usually are nonspecific and include fever, chills, and constitutional symptoms of fatigue, malaise, anxiety, or confusion. These symptoms are not pathognomonic for infection and may be observed in a wide variety of noninfectious inflammatory conditions. They may be absent in serious infections, especially in elderly individuals.

• Sepsis, SIRS, septic shock, and multiorgan dysfunction syndrome represent a clinical continuum. The specific features exhibited depend on where the patient's case falls on that continuum. SIRS is defined by the presence of 2 or more of the following:
  • Temperature greater than 38.0°C or less than 36.0°C
  • Heart rate greater than 90 beats per minute
  • Respiratory rate greater than 20 breaths per minute
  • WBC count greater than 12,000 cells/µL, less than 4000 cells/µL, or more than 10% bands
• Fever is a common feature of sepsis. Fever from an infectious etiology results from resetting the hypothalamus so that heat production and heat loss are balanced to maintain a higher temperature. An abrupt onset of fever usually is associated with a large infectious load.
• Chills are a secondary symptom associated with fever and result from increased muscular activity in an attempt to produce heat in order to raise the body temperature to the level required to reset the hypothalamus.
• Sweating occurs when the hypothalamus returns to its normal set point and senses that the body temperature is above the desired level. Perspiration is stimulated to evaporate and cool excess body heat.
• Alteration in mental function often is observed. Mild disorientation or confusion especially is common in elderly individuals. More severe manifestations include apprehension, anxiety, and agitation, and it may eventually lead to coma. The mechanism of alteration in mental function is not known, but altered amino acid metabolism has been proposed as one cause of metabolic encephalopathy.
• Hyperventilation with respiratory alkalosis is a common feature of sepsis. Stimulation of the medullary ventilatory center by endotoxins and other inflammatory mediators has been proposed as the cause of hyperventilation.
• The following localizing symptoms are some of the most useful clues to the etiology of both fever and sepsis:
  • Head and neck infections - Earache, sore throat, sinus pain, or swollen lymph glands
  • Chest and pulmonary infections - Cough, especially if productive; pleuritic chest pain; and dyspnea
  • Abdominal and GI infections - Abdominal pain, nausea, vomiting, and diarrhea
  • Pelvic and genitourinary infections - Pelvic or flank pain, vaginal or urethral discharge, urea, frequency, urgency
  • Bone and soft tissue infections - Focal pain or tenderness, focal erythema, edema

Physical

Physical examination notes the general condition of the patient first. Observe the overall hemodynamic condition to search for signs of hyperperfusion. Look for signs suggestive of a focal infection. An acutely ill, toxic appearance is a common feature in serious infections.

• The vital signs may suggest sepsis, even if fever is absent. As noted above, tachypnea is common; tachycardia with an increased pulse pressure also is common.
• Measure the body temperature accurately. Oral temperatures often are unreliable; obtain rectal temperatures.
• Investigate signs of systemic tissue perfusion. In the early stages of sepsis, cardiac output is well maintained or even increased. Along with vasodilatory mediators, this may result in warm skin, warm extremities, and normal capillary refill. As sepsis progresses, stroke volume and cardiac output fall. Patients begin to manifest signs of poor distal perfusion, including cool skin, cool extremities, and delayed capillary refill.
• The following physical signs suggest focal, usually bacterial, infection:
  • CNS infection - Profound depression in mental status and meningismus
  • Head and neck infections - Inflamed or swollen tympanic membranes, sinus tenderness, pharyngeal exudates, stridor, cervical lymphadenopathy
  • Chest and pulmonary infections - Localized rales or evidence of consolidation
  • Cardiac infections - Regurgitant valvular murmur
  • Abdominal and GI infections - Focal tenderness, guarding or rebound, rectal tenderness, or swelling
  • Pelvic and genitourinary infections - Costovertebral angle tenderness, pelvic tenderness, cervical motion pain, and adnexal tenderness
  • Bone and soft tissue infections - Focal erythema, edema, infusion, and tenderness
  • Skin infections - Petechiae and purpura

Background

By the turn of the 20th century, it had become apparent that patients who are critically ill could exhibit metabolic acidosis unaccompanied by elevation of ketones or other measurable anions. In 1925, Clausen identified the accumulation of lactic acid in blood as a cause of acid-base disorder. Several decades later, Huckabee's seminal work firmly established that lactic acidosis frequently accompanies severe illnesses and that tissue hypoperfusion underlies the pathogenesis. In their classic 1976 monograph, Cohen and Woods classified the causes of lactic acidosis according to the presence or absence of adequate tissue oxygenation.

The normal blood lactate concentration in unstressed patients is 1-0.5 mmol/L. Patients with critical illness can be considered to have normal lactate concentrations of less than 2 mmol/L. Hyperlactatemia is defined as a mild-to-moderate (2-5 mmol/L) persistent increase in blood lactate concentration without metabolic acidosis, whereas lactic acidosis is characterized by persistently increased blood lactate levels (usually > 5 mmol/L) in association with metabolic acidosis.

Hyperlactatemia generally occurs in the settings of adequate tissue perfusion, intact buffering systems, and adequate tissue oxygenation. Lactic acidosis is associated with major metabolic dysregulation, tissue hypoperfusion, effects of certain drugs or toxins, or congenital abnormalities in carbohydrate metabolism. Cohen and Woods divided lactic acidosis into 2 categories, type A and type B. Type A is lactic acidosis occurring in association with clinical evidence of poor tissue perfusion or oxygenation of blood (eg, hypotension, cyanosis, cool and clammy extremities). Type B is lactic acidosis occurring when no clinical evidence of poor tissue perfusion or oxygenation exists.

Congenital lactic acidosis is secondary to inborn errors of metabolism, such as defects in gluconeogenesis, pyruvate dehydrogenase, the tricarboxylic acid (TCA) cycle, or the respiratory chain. These disorders generally reflect situations in which the disposal of pyruvate by biosynthetic or oxidative routes is impaired.

Lactic acidosis may not necessarily produce acidemia in a patient. The development of lactic acidosis depends on the magnitude of hyperlactatemia, the buffering capacity of the body, and the coexistence of other conditions that produce tachypnea and alkalosis (eg, liver disease, sepsis). Thus, hyperlactatemia or lactic acidosis may be associated with acidemia, a normal pH, or alkalemia.

Pathophysiology

The anaerobic metabolic pathway known as glycolysis is the first step of glucose metabolism and occurs in the cytoplasm of virtually all cells. The end-product of this pathway is pyruvate, which can then diffuse into the mitochondria and be metabolized to carbon dioxide by another, more energy-efficient metabolic pathway, the Krebs cycle. The metabolism of glucose to pyruvate also results in the chemical reduction of the enzyme cofactor oxidized form nicotinic acid dehydrogenase (NAD⁺) to nicotinic acid dehydrogenase (NADH) (reduced form).

Erythrocytes are capable of carrying out glycolysis; however, these cells do not have mitochondria and cannot use oxygen to produce adenosine triphosphate (ATP). The pyruvate formed during glycolysis is metabolized by the enzyme lactate dehydrogenase to lactate. The anaerobic pathway is very inefficient, and only 2 moles of ATP are produced for each molecule of glucose that is converted to lactate. The lactate diffuses out of the cells and is converted to pyruvate and then is aerobically metabolized to carbon dioxide and ATP. The heart, liver, and kidneys use lactate in this manner. Alternatively, hepatic and renal tissues can use lactate to produce glucose via another pathway referred to as gluconeogenesis.

The metabolism of glucose to lactate by one tissue, such as red blood cells, and conversion of lactate to glucose by another tissue, such as the liver, is termed the Cori cycle. The ability of the liver to consume lactate is concentration-dependent and progressively decreases as the level of blood lactate increases. Lactate uptake by the liver also is impaired by several other factors, including acidosis, hypoperfusion, and hypoxia.

Metabolic aspects of lactate production

The arterial concentration of lactate depends on the rates of its production and use by various organs. Blood lactate concentration normally is maintained below 2 mmol/L, although lactate turnover in healthy resting humans is approximately 1300 mmol every 24 hours. Lactate producers are skeletal muscle, the brain, the gut, and the erythrocytes. Lactate metabolizers are the liver, the kidneys, and the heart. When lactate blood levels exceed 4 mmol/L, the skeletal muscle becomes a net consumer of lactate.

Lactate is a byproduct of glycolysis and is formed in the cytosol catalyzed by enzyme lactate dehydrogenase as shown below:

This is a reversible reaction that favors lactate synthesis with the lactate-to-pyruvate ratio that is normally at 25:1. Lactate synthesis increases when the rate of pyruvate formation in the cytosol exceeds its rate of use by the mitochondria. This occurs when a rapid increase in metabolic rate occurs or when oxygen delivery to the mitochondria declines, such as in tissue hypoxia. Lactate synthesis also may occur when the rate of glucose metabolism exceeds the oxidative capacity of the mitochondria, as observed with administration of catecholamines or errors of metabolism.

Cellular energy metabolism and lactate production

Cells require a continuous supply of energy for protein synthesis. This energy is stored in the phosphate bonds of the ATP molecule. The hydrolysis of ATP results in the following reaction, where ADP is adenosine diphosphate and Pi is inorganic phosphate:

With an adequate supply of oxygen, the cells use ADP, Pi, and H⁺ in the mitochondria to reconstitute ATP. During cellular hypoxia, the hydrolysis of ATP leads to accumulation of H and Pi in the cytosol. Therefore, ATP hydrolysis is the source of cellular acidosis during hypoxia and not the formation of lactate from glucose, which neither consumes nor generates H⁺. The glycolytic process may be viewed as the following:

The hydrolysis of 2 ATP molecules formed from the metabolism of glucose produces H⁺, ADP, and Pi.

If the oxygen supply is adequate, the metabolites of ATP are recycled in the mitochondria and the cytosolic lactate concentration rises without acidosis. On the other hand, with cellular hypoxia, the equation of anaerobic glycolysis becomes the following:

A second cellular source of anaerobic ATP is the adenylate kinase reaction, also called the myokinase reaction, where 2 molecules of ADP join to form ATP and adenosine monophosphate (AMP).

This reaction leads to increased intracellular levels of AMP, Pi, and H⁺. Thus, H⁺ is able to increase during hypoxemia without the notable increase in cellular lactate concentration.

Cellular transport of lactate

Intracellular accumulation of lactate creates a concentration gradient favoring its release from the cell. Lactate leaves the cell in exchange for a hydroxyl anion (OH-), a membrane-associated, pH-dependent, antiport system. The source of extracellular OH- is the dissociation of water into OH- and H⁺. Extracellular H⁺ combines with lactate leaving the cell, forming lactic acid, while intracellular OH- binds to H⁺ generated during the hydrolysis of ATP to form water. Therefore, cellular transport of lactate helps to moderate increases in cytosolic H⁺ resulting from hydrolysis of anaerobically generated ATP.

Cellular response to hypoxia

Declines in cellular oxygen delivery lead to more oxygen extraction from the capillary blood. This action redistributes the cardiac output to organs according to their ability to recruit capillaries and also decreases the distance from the capillaries to the cells. With severe decreases in oxygen transport, compensatory increase in the oxygen extraction ratio is insufficient to sustain aerobic metabolism. Therefore, the cell must employ anaerobic sources of energy to produce ATP, resulting in the generation of lactate and H⁺.

Lactate acidosis as a metabolic monitor of shock

Shock currently is conceptualized as a clinical syndrome resulting from an imbalance between tissue oxygen demands and tissue oxygen supply. Impaired oxygen delivery is the primary problem in hypovolemic, cardiogenic, distributive (septic), and obstructive (pericardial tamponade, tension pneumothorax) forms of shock. When tissue hypoxia is present, pyruvate oxidation decreases, lactate production increases, and ATP formation continues via glycolysis. The amount of lactate produced is believed to correlate with the total oxygen debt, the magnitude of hypoperfusion, and the severity of shock. Serial lactate determinations may be helpful in patients resuscitated from shock to assess the adequacy of therapies.

Hyperlactemia and lactic acidosis in sepsis

Patients who develop severe sepsis or septic shock commonly demonstrate hyperlactemia and lactic acidosis. The pathophysiology of sepsis associated lactic acidosis has not been well understood. Increased lactate production during anaerobic and aerobic metabolism and decreased lactate clearance are likely contributors to hyperlactemia. Patients with septic shock have lactate levels of more than 5 mmol/L, a lactate-to-pyruvate ratio greater than 10-15:1, and arterial pH of less than 7.35. Following resuscitation from septic shock, some patients continue to demonstrate hyperlactemia (lactate 2-5 mmol/L), whereas blood pH is normal or alkalemic. These patients manifest increased oxygen consumption, insulin resistance, urea nitrogen excretion in urine, and a normal lactate-to-pyruvate ratio. Hyperlactemia likely occurs from increased production of pyruvate and equilibration with lactate, this has been termed "stress hyperlactemia" (Siegel JH, 1979).

The mechanism of lactic acidosis in septic shock is continuing to be debated. Several studies have shown an elevated lactate-to-pyruvate ratio in septic shock, suggesting tissue hypoxia as the cause of lactic acidosis. However, other investigators have documented hyperlactemia in the absence of hypoxia.

The additional possible mechanisms for hyperlactemia include activation of glycolysis and inhibition of pyruvate dehydrogenase. Some investigators have observed that patients with sepsis have decreased lactate clearance rather than increased lactate production (De Becker D, 1998). Skeletal muscle and lung tissue have been shown to produce lactate during sepsis. Therefore, hyperlactemia may be secondary to increased lactate production in the gut, liver, lungs, and skeletal muscles; decreased lactate clearance in the liver; or a combination of both. Still, other investigators have suggested that hyperlactemia may occur secondary to inflammatory mediators down-regulating pyruvate dehydrogenase in skeletal muscles, rather than tissue hypoxia (Vary TC, 1995). Hyperlactemia was prevented by administration of tumor necrosis factor (TNF) binding protein in a rat model of sepsis. However, this finding has not been consistently observed in other animal and clinical studies (Vary TC, 1998)

Despite the conflicting results from these studies, hyperlactemia in patients with sepsis is a marker of the severity of stress response. Hyperlactemia may possibly develop as a byproduct of overall acceleration in glycolysis in severe sepsis. This may well be an adaptive host mechanism designed to provide for efficient generation of energy in response to severe stress.

Limitations of lactic acidosis as a monitor

The use of lactate as an index of tissue perfusion has several limitations. The presence of liver disease causes a decreased ability to clear lactate during periods of increased production. Various causes of type B lactate acidosis may produce hyperlactemia and lactate acidosis in the absence of tissue perfusion. For significant increase in blood lactate to occur, lactate must be released into the systemic circulation and the rate of production must exceed hepatic, renal, and skeletal muscle uptake. Therefore, regional hypoperfusion of tissues may be present despite normal blood lactate concentrations.

Frequency

United States

Prevalence of lactic acidosis is not known and is difficult to investigate; however, abnormal lactate metabolism is frequently encountered in patients who are critically ill.

Symptomatic hyperlactatemia is associated with antiretroviral therapy. In a large cohort of adults infected with HIV, hyperlactatemia was diagnosed in 64 patients. Incidences were 18.3 per 1000 person-years with antiretroviral therapy and 35.8 per 1000 person-years for stavudine (d4T) regimens.

Mortality/Morbidity

• Patients who have an arterial lactate level of more than 5 mmol/L and a pH of less than 7.35 are critically ill and have a very poor prognosis. The multicenter trials have shown a mortality rate of 75% in these patients.
• 
  
• In another study, the median survival for patients with lactic acidosis and shock was 28 hours. Of these patients, 56% survived 24 hours and only 17% of the patients were discharged from the hospital. Nearly half of these patients showed evidence of multiorgan failure, and survival also correlated with the level of systolic blood pressure. Patients with a systolic blood pressure of less than 90 mm Hg had a 12.5% survival rate compared to patients with systolic pressures more than 90 mm Hg, who had a 55% survival rate at 72 hours.
• 
  
• In a recent observational study of intensive care patients, mortality rate was highest for patients with lactic acidosis (56%) compared to anion gap acidosis (39%). A stepwise logistic regression model identified serum lactate, anion gap acidosis, phosphate, and age as independent predictors of mortality. Overall, patients with metabolic acidosis were nearly twice as likely to die as patients without metabolic acidosis. (Gunnerson KJ, 2006)

Clinical

History

Lactic acidosis frequently occurs during strenuous exercise in healthy people, bearing no consequence. However, development of lactic acidosis in disease states is ominous, often indicating a critical illness of recent onset. Therefore, a careful history should be obtained to evaluate the underlying pathophysiologic cause of shock that contributed to lactic acidosis. Furthermore, a detailed history of ingestion of various prescription drugs or toxins from the patient or a collateral history from the patient's family should be obtained.

• The clinical signs and symptoms associated with lactic acidosis are highly dependent on the underlying etiology. No distinctive features are specific for hyperlactatemia.
• 
  
• Lactate acidosis is present in patients who are critically ill from hypovolemic, septic, or cardiogenic shock.
• 
  
• Lactate acidosis always should be suspected in the presence of elevated anion gap metabolic acidosis.
• 
  
• Lactic acidosis is a serious complication of antiretroviral therapy. A history of antiretroviral treatment should be obtained.
• 
  

Physical

The clinical signs usually indicate tissue hypoperfusion. Severe hypotension, oliguria or aneuria, deteriorating mental status, and tachypnea always are present when the cause of lactic acidosis is tissue hypoxemia.

• Clinical signs of impaired tissue perfusion include the following:
• • Hypotension
  • 
    
  • Alteration in sensorium
  • 
    
  • Peripheral vasoconstriction
  • 
    
  • Oliguria
  • 
    
• The following findings may be late manifestations of shock and are relatively insensitive indicators of hypoperfusion. Patients also demonstrate the following:
• • Tachypnea
  • 
    
  • Hypotension
  • 
    
  • Deteriorating mental status
  • 
    
• Kussmaul hyperventilation (deep sighing respiration) may be observed if the severity of the acidosis is sufficient to elicit a degree of respiratory compensation.
• 
  
• Because sepsis accounts for most cases of lactic acidosis, fever (>38.5°C) or hypothermia (35°C) commonly is present in addition to symptoms and signs indicating the organ where the sepsis originated.
• 
  

Causes

Classification of acquired causes of lactic acidosis is as follows:

• Type A - Due to tissue hypoxia
• • Tissue hypoperfusion - Abnormal vascular tone or permeability, left ventricular failure, decreased cardiac output
  • 
    
  • Reduced arterial oxygen content - Asphyxia, hypoxemia (PaO₂ <35>
  • 
    
• Type B - Not due to tissue hypoxia
• • B1 (common disorders) - Sepsis, hepatic failure, renal failure, diabetes mellitus, cancer, malaria, cholera
  • 
    
  • B2 (drugs or toxins) - Biguanides, acetaminophen, ethanol, nalidixic acid, salicylates, isoniazid, methanol, streptozotocin, ethylene glycol, sorbitol, cyanide, parenteral nutrition, nitroprusside, lactulose, niacin, theophylline, catecholamines, cocaine, diethyl ether, vitamin deficiency, papaverine, paraldehyde
  • 
    
  • B3 (other conditions) - Strenuous muscular exercise, grand mal seizures, D-lactic acidosis

Introduction

Trauma has been dubbed the forgotten epidemic and the neglected disease of modern society. Trauma annually impacts hundreds of thousands of individuals and costs billions of dollars in direct expenditures and indirect losses. Trauma care has improved over the past 20 years, largely from improvements in trauma systems, assessment, triage, resuscitation, and emergency care.

However, an Institute of Medicine report identified a US crisis in access and distribution to emergency care that may impact trauma system efficiency and effectiveness. Similarly, a predicted deficit in critical care practitioners may similarly degrade the post-emergency department care of the critically injured patient. The American College of Surgeons Committee on Trauma (ACS-COT) and the American Association for the Surgery of Trauma (AAST) acute care surgery initiative is designed to integrate trauma, emergency general surgery, and surgical critical care and to bolster new trainee interest in this field. Its impact on postinjury care is unclear as beta sites are now being recruited.

Work must still be done to continuously improve trauma care nationally, regionally, and institutionally, and the ACS-COT applies rigorous standards to performance improvement prior to verifying US trauma centers. For this improvement to occur, the ongoing application of the unique principles and practice of intensive care medicine is necessary.

Trauma Systems

Initial Assessment

Principles involved in the initial assessment of a patient with major trauma are those outlined by the AmericanCollege of Surgeons (ACS) in their Advanced Trauma Life Support (ATLS) guidelines or those of the AustralasianCollege of Surgeons in the Early Management of Severe Trauma guidelines. The principles involved consist of (1) preparation and transport; (2) primary survey and resuscitation, including monitoring, urinary and nasogastric tube insertion, and radiography; (3) secondary survey, including special investigations, such as CT scanning or angiography; (4) ongoing reevaluation; and (5) definitive care.

Preparation and communication

Trauma-receiving hospitals should receive advance communication from emergency medical services care providers about the impending arrival of seriously injured patients. The patient's mechanism of injury, vital signs, field interventions, and overall status should be communicated. This allows for the in-house trauma team to be called and for the emergency department staff to make appropriate preparations.

The trauma team members vary based on world geography but incorporate many similar elements, including representation from emergency medicine, trauma, critical care, with or without anesthesia, nursing, respiratory therapy, blood bank, radiology, social services, and registration. A team leader is identified, and it is the team leader's responsibility to ensure that the resuscitation proceeds in an organized and efficient manner through the diagnostic and therapeutic protocols. Additional consultants may be engaged in response to specific injuries. In addition to this team, many trauma centers also have a trauma care coordinator (usually a nurse), who follows the patient through his or her hospital course.

On the patient's arrival, a concise transfer of the patient from the paramedics should occur. One person should be talking, while everyone else is listening; this is crucial information for the whole team. In many trauma centers, the team leader is a senior or chief resident in surgery or emergency medicine, with close supervision from appropriate attending staff. Increasingly, mid-level practitioners (eg, physician associates, nurse practitioners) may serve in this role as well.

Most trauma centers use a system of prehospital triage that characterizes patients into those with physiologic derangements and those who have a suggestive mechanism of injury. Those patients with obvious derangements should prompt a full team response, while patients with less injury may be cared for by a modified team complement.

Primary survey

The primary survey aims to identify and treat immediately life-threatening injuries relying on the ABCDE system. This system comprises airway control with stabilization of the cervical spine, breathing (work and efficacy), circulation including the control of external hemorrhage, disability or neurologic status, and exposure or undressing of the patient while also protecting the patient from hypothermia. These elements are explored below.

Airway with control of the cervical spine

Airway assessment should proceed while maintaining the cervical spine in a neutral position. The latter is achieved by using a rigid cervical immobilization collar. Airway clearance maneuvers are extensively described elsewhere and are not reviewed in this article.

When the airway is in jeopardy, or when the GCS score is less than 8, an artificial airway is essential. Airway control is commonly achieved by means of rapid-sequence orotracheal intubation (OETT) performed with in-line stabilization of the cervical spine. Correct placement of the endotracheal tube is confirmed (1) by the aid of an end-tidal carbon dioxide monitoring device, (2) by observation of the tube passing through the vocal cords, and (3) by auscultation of the chest.

Several well-defined options for achieving airway control must be established in the event that OETT placement is not able to be achieved. These options include laryngeal mask airway (LMA), intubating LMA, fiberoptic intubation, percutaneous cricothyroidotomy, and surgical cricothyroidotomy (tracheostomy in children). Tracheal inspection is essential to determine if there is peritracheal crepitus or deviation from the midline indicating potential direct airway injury or intrathoracic pulmonary or major vascular injury.

Breathing

One must next assess the adequacy of gas exchange. This is most readily accomplished by visual inspection of thoracic cage movement, palpation of the thoracic cage movement, and auscultation of gas entry. One is assessing for inequalities from one side to the other, crepitus, and local movement asymmetry as in paradoxic thoracic cage movement in flail chest. One is also evaluating for signs of impending respiratory failure, such as uncoordinated thoracic cage and abdominal wall movement, accessory muscle use, and stridor.

Inadequate ventilation may result in hypoxemia, hypercarbia, cyanosis, depressed level of consciousness, bradycardia, tachycardia, hypertension, or hypotension. As a general rule, until stability has been assured, administer high-flow oxygen by mask to all patients to abrogate the potential for hypoxemia.

Classic signs of a tension pneumothorax, hemothorax, or combined hemopneumothorax include tracheal deviation, jugular vein distension, hypoxia, tachycardia, and hypotension. Intrathoracic tension physiology is a clinical diagnosis and requires immediate decompression. This is initially commonly accomplished with a 14-gauge catheter-over-needle assembly placed in the second intercostal space (ICS) midclavicular line (MCL). Patients treated in this way should have a tube thoracostomy placed to manage simple pneumothorax and to evacuate thoracic cavity blood when present. Life-threatening hemorrhage identified when placing a tube thoracostomy may be managed with a resuscitative thoracostomy.

Circulation and hemorrhage control

Emergent treatment of patients with exsanguinating hemorrhage or shock can be life-saving. This assessment includes identifying and managing rapid external hemorrhage. This can often be achieved with a simple pressure dressing, but surgical intervention may be required. As more experience is gained with procoagulant dressings (used principally by the military), external hemorrhage control may gain pharmacologic support embedded in dressings.

Shock in trauma patients, defined as inadequate organ perfusion and tissue oxygenation, is most commonly caused by hemorrhage leading to hypovolemia, but many other causes are readily identified, including cardiac tamponade, tension pneumothorax or hemothorax, and spinal cord injury. Signs of shock include tachypnea, tachycardia, decreased pulse pressure, hypotension, pallor, delayed capillary refill, oliguria, and a depressed level of consciousness. In patients with hypovolemia, the neck veins may be flat. A normal mental status generally implies an adequate cerebral perfusion pressure, while diminished mentation may be associated with shock with or without intracranial trauma.

ATLS readily identifies 4 different classes of shock. Class I and II shock generally does not need red cell mass restoration and is well managed with asanguineous fluids for plasma volume expansion. Hypotension and disordered mentation generally indicate at least class III shock and should prompt plasma volume expansion and red cell mass repletion if the hypotension fails to resolve after an initial 2000-cc crystalloid bolus, according to ATLS.

A systematic approach for detecting the source of hypovolemic shock should consider 5 sources of ongoing hemorrhage, as follows: (1) external (eg, from the scalp, skin, or nose), (2) pleural cavities, (3) peritoneal cavity, (4) pelvis/retroperitoneum, and (5) long-bone fracture. Fracture alignment and stabilization is essential in limiting blood loss. Pelvic fractures may be initially stabilized with a pelvic binder or a wrapped sheet secured with a towel clip as a means of reducing pelvic volume to limit hemorrhage.

Disability

During the acute resuscitation period, a brief assessment of neurologic status should be performed. This assessment should include the patient's posture (ie, any asymmetry, decerebrate or decorticate posturing), pupil asymmetry, pupillary response to light, and a global assessment of patient responsiveness.
A recommended system is the AVPU method, as follows: A = Patient is awake, alert, and appropriate; V = Patient responds to voice; P = Patient responds to pain; U = Patient is unresponsive.

A complementary assessment using the GCS should be made at this time, during the secondary survey, and at any time that the patient's mental status appears to change. A more detailed assessment of the patient's neurologic status is to be made during the secondary survey.

Exposure

Patients should be completely disrobed during the initial assessment and the subsequent secondary survey. This helps ensure that significant injuries are not missed. At the same time, efforts to prevent significant hypothermia, using a warm ambient room (28-30°C), overhead heating, and warmed IV fluids, should be instituted. The patient's temperature should be measured on arrival at the emergency department, and strenuous efforts should be made to avoid significant hypothermia during resuscitation and therapeutic intervention.

Ancillary monitors

Urinary drainage catheters are commonly placed to assess for genitourinary system hemorrhage and to monitor urine flow. Precautions to avoid urethral injury should be taken for patients with pelvic trauma and for those who have blood at the urethral meatus. Digital rectal examination to identify a high-riding prostate should precede catheter insertion. Abnormal findings from the rectal examination or concern as to the continuity of the urethra should prompt a retrograde urethrocystogram to identify a urethral injury. If identified, a suprapubic catheter should be inserted, and a urologist should be consulted.

Gastric drainage tubes should be orally inserted into all major trauma patients requiring endotracheal intubation. Even in the absence of brain injury, oral gastric tube insertion is preferred to decrease the likelihood of sinusitis from drainage pathway obstruction. Children, in particular, are prone to gastric dilatation, which can significantly impair their respiration and lead to hemodynamic compromise. Immediate decompression may be life-saving. Ongoing monitoring of pulse rate, blood pressure, respiratory rate, oxygen saturation, and temperature is a standard of care in the US.

Radiology

Initial imaging in the resuscitation room should be limited to a portable anteroposterior (AP) chest radiograph plus an AP pelvic image if the patient was involved in a high-speed motor vehicle collision or a fall from a height. Prior recommendations for lateral cervical radiography have been supplanted by routine pan-cervical imaging with image reformation using CT scanning, especially if the patient will undergo a brain CT scan.

Definitive clearing of the neck is managed in different ways in different institutions, but certain common features are identified. Patients with a clear sensorium and no distracting injuries may be clinically cleared if there is no neck pain on palpation and active flexion/extension/rotation. Patients with a normal CT scan but an abnormal mental status should remain in a rigid cervical immobilization device until they may participate in a physical examination or they undergo early (<72 h postinjury) MRI to detect the presence of ligamentous injury.

Chest radiographs should be assessed for the position of tubes and lines, the presence of treatable life-threatening conditions, including space-occupying lesions, mediastinal widening, lung parenchymal injuries, and injuries to the thoracic cage or vertebral column.

A high-energy pelvic fracture identified on physical examination or pelvis film may substantially contribute to shock. Persistent hypotension suggests the need for early operative external stabilization, operative extraperitoneal pelvic packing, or angioembolization. Technique selection depends on the facility's resources and practitioner skill set.

Secondary survey

The secondary survey follows in the wake of correction of immediately life-threatening injury and completion of the primary survey. Thus, the secondary survey may not occur until after an emergency operation has been completed. The secondary survey includes a detailed history, complete physical examination, additional radiologic examinations, and special diagnostic studies. Many institutions include the focused assessment with sonography in trauma (FAST) examination as part of the primary survey rather than part of the secondary survey.

The history should include an assessment of the following items, which can be remembered by using the AMPLE acronym: A = Allergies; M = Medications; P = Past medical, surgical, and social history; L = Last meal; and E = Events leading to injury, scene findings, notable interventions, and recordings en route to the hospital.

Detailed examination

Head and face and neurology

Palpate the entire cranium and face evaluating for injury and instability. Sutures, staples, or Rainey clips may be helpful in controlling bleeding from large scalp flaps. Palpate for facial crepitus and a mobile middle third of the face as a clue to potential difficulty in airway control. Hemotympanum and the presence of bruising around the eyes (ie, raccoon eyes) and mastoid process (ie, Battle sign) suggest basal skull fracture.

Recheck the pupils, and repeat GCS scoring. Evaluate the cranial nerves, peripheral motor and sensory function, coordination, and reflexes. Identify any neurologic asymmetry. Patients with lateralizing signs and those with an altered level of consciousness (GCS score of <14) should undergo cranial CT scanning. Patients with traumatic brain injury (TBI) are particularly susceptible to secondary brain injury, in particular from hypoperfusion, hypoxia, hypercarbia, hyperglycemia, hyperthermia, and seizure activity. While primary brain injury and primary brain damage (induced apoptosis after primary brain injury) are beyond the clinician's control, secondary injury is a preventable complication with careful attention to detail.

Neck

Maintaining cervical spine stabilization when removing a rigid cervical immobilization device is imperative. Penetrating injuries of the neck may require angiographic, bronchoscopic, or radiologic examination depending on the level of injury (ie, zone I, II, or III). In particular, zone II injuries that violate the platysma may be readily explored, while those injuries in zone I or III benefit from additional investigation because of the difficulty in identifying and controlling injuries in those zones.

Chest

Reexamine the chest. Initiate further investigations as indicated by physical examination findings or radiography results. While aortography was previously identified as the criterion standard investigation to identify aortic transaction, CT angiography has essentially replaced intra-arterial contrast injection. Transesophageal echocardiography using an omniplane probe may be safely used as well but suffers from difficulty with technology access after hours, dependence on user skill set, problematic probe insertion in patients requiring cervical immobilization, and blind spots at the aortic arch.

Abdomen

Inspect, percuss, palpate, and auscultate the abdomen, noting tenderness and examining for fullness, rigidity, guarding, or an obvious bruit (rare). Remember that blood is not always a peritoneal irritant, and hemoperitoneum may occur without obvious external signs.

Inspection of the abdomen may be confounded by distracting injuries and impaired consciousness from TBI, intoxicants, or prescription medications. FAST scans are routine in most emergency departments and serve to establish the presence or absence of fluid in 4 distinct domains: pericardium, right upper quadrant, left upper quadrant, and pelvis. Diagnostic peritoneal lavage is now rarely used. Extended FAST scanning may also interrogate the thoracic cavity for evidence of pneumothorax. The practitioner should be aware that FAST scanning is not organ-based imaging, and FAST scanning should not be used to establish the presence or absence of solid organ injury. Hemodynamically acceptable patients with a positive FAST scan generally undergo CT scanning to establish the source of presumed hemorrhage. Patients with a positive FAST scan who are unstable generally proceed to operative intervention in the emergency department (cardiac tamponade) or the operating room (intraperitoneal hemorrhage).

FAST scanning does not evaluate the retroperitoneum, and a normal FAST scan may coexist with substantial retroperitoneal hemorrhage. Also, a positive FAST scan may indicate ascites instead of blood, especially in those with renal or hepatic impairment.

Limbs

Inspect, palpate, and move the limbs to determine their anatomic and functional integrity. Pay attention to the adequacy of the peripheral circulation and integrity of the nerve supply. Arterial insufficiency in patients with a displaced fracture or dislocation requires immediate treatment, generally fracture reduction and/or joint relocation. Pulse inequality should be assessed by means of an ankle-brachial index with diagnostic intervention reserved for those with an absolute ABI difference of 0.2 or greater from one side to the other. Liberal use of diagnostic plain radiography is essential in excluding extremity fracture in patients with mixed mechanisms of injury and in those who cannot participate in an examination because of significant TBI, intoxicants, or other causes.

Log roll

The log roll refers to the slow controlled turning of the patient to each side to assess the dependent part of the supine trauma patient. Care must be taken to avoid secondary injury from an as-yet undiagnosed unstable fracture. This examination concentrates on the back of the head, neck, back, and buttocks, and it includes a rectal examination. The log roll also provides a convenient time to remove the long immobilization board. The board has not been shown to prevent injury in the presence of an unstable vertebral fracture, but it is highly correlated with pressure ulceration in patients who remain on the board for prolonged periods of time (ie, until diagnostic intervention is complete).

This procedure should be carried out by at least 4 people. The first person stabilizes the head and neck, the second and third persons turn the patient, and the fourth person examines the patient's dorsum and performs the digital rectal examination. At the completion of the examination, and if the patient is not on an x-ray film bearing stretcher, the chest x-ray plate is readily positioned behind the patient. Spine imaging most commonly proceeds as part of the CT scan using reformatted images. This technique has been demonstrated to have equal, and in some studies superior, efficacy to AP and lateral thoraco-lumber spine imaging for fracture identification.

Reevaluation

During the secondary survey, the ABCDE system should be used to constantly reevaluate the patient, and an ongoing diagnostic and therapeutic plan should be revised, as indicated, by the patient's response to intervention and diagnostic test results.

Prolonged Emergency Department Management

The Institute of Medicine identified an emergency department crisis in US health care. Emergency departments are overcrowded and understaffed for the overutilization by those with and without insurance. Additionally, with the decline in subspecialty coverage, critically injured patients are increasingly being transferred to regional resource trauma centers (ie, Level 1 centers). This regionalization further stresses an already stressed emergency medicine system. Exacerbating this problem is the overcrowding of the current intensive care unit (ICU) beds in the trauma facilities. Thus, it is expected that prolonged emergency department length of stay will occur in the oversubscribed trauma facility. An increasing role is therefore anticipated for the emergency medicine practitioner in the prolonged emergency department management of the trauma patient.

The initial management and injury identification detailed above initiates multiple pathways for the trauma patient that may lead to discharge home, transfer to a specialty facility (ie, burn center), hospital admission (general ward, step-down unit [intermediate dependency unit], ICU [high dependency unit]), operating room, or angiography suite. The specific management is beyond the scope of this article, but management of the injured patient is often collaborative because of the nature of the injury complex, as well as manpower limitations.

With the rise of acute care surgery, as promulgated by the American College of Surgeons Committee on Trauma and the American Association for the Surgery of Trauma, the trauma surgeon increasingly covers trauma, surgical critical care, and emergency general surgery. Therefore, the emergency medicine practitioner who is resident in the emergency department needs to assume a larger role in the management of trauma patients who are awaiting a destination bed for ongoing management.

Generation of jointly agreed upon guidelines for management is essential in ensuring smooth, high-quality care for the injured patient. Often, subspecialty input is of significant benefit in guideline generation (ie, management and clearance of the cervical spine). Additionally, several guidelines have been generated by the Eastern Association for the Surgery of Trauma (EAST; www.east.org) that address injured patient management in general as well as with regard to specific injury complexes.

Subsequent Critical Care Considerations

The information presented thus far describes the initial evaluation of the patient sustaining serious injury. The wide multitude of individual injuries precludes describing each on in detail. Instead, the critical care considerations that are important in the subsequent care of the critically injured patient are explored. They are conveniently grouped into the following domains: neurologic injury, acute respiratory failure, organ failure, anemia, coagulopathy, thermal dysregulation, sepsis, unnecessary fluid administration, damage control sequelae, and acid-base imbalance.

Neurologic Injury

Traumatic brain injury (TBI) occurs commonly in the setting of major trauma and significantly contributes to poor outcomes. Despite advances in all aspects of trauma care, severe TBI carries a mortality rate of approximately 30%. Conservative estimates place the incidence of TBI at 200 cases per 100,000 patients.

Outcome prediction is usually straightforward in those with minimal injury as well as in those with severe injury. Prediction is difficult for those with moderate and severe injury but not unsurvivable injury patterns. Survivors of severe and moderately severe head injuries are likely to be left with some degree of disability. These disabilities may vary from subtle changes in behavior, including depression or loss of independence and earning power, to major cognitive, sensory, or motor deficits.

Some patients unfortunately progress to or never awaken from a chronic vegetative state. It is in these patients that end-of-life discussions to establish a goal of therapy are perhaps most useful. Quite often, consultation with an ethics team or a palliative care team is helpful for both the critical care team and the family.

Treatment principles

The principles of treatment of a patient with TBI apply equally at the time of initial assessment as they do during ongoing inpatient care. These principles are aimed at preventing secondary brain injury. Secondary brain injuries include but are not limited to hypotension, hypoxemia, hypercarbia, fever, seizure, uncontrolled hyperglycemia leading to cerebral hyperglycosis, acidosis, severe alkalosis, and hyperthermia. Sound prehospital care has a significant impact on patient outcome. This involves adequate oxygenation and ventilation and the maintenance of an adequate cerebral perfusion pressure as measures to avoid secondary brain injury. Primary brain injury occurs at the time of the trauma and is not modifiable by the practitioner.

Secondary brain damage is different from secondary brain injury. Secondary brain damage is the term applied to the apoptosis that is identified in the injured but not irreparably damaged cells after a primary brain injury. Thus, the practitioner is limited at present to avoiding secondary brain injury as the others are not subject to control.

Prehospital assessment

The initial assessment is the same as for any trauma patient. Immediate protection from secondary injury by avoiding hypoxia and hypotension and by preventing hypercarbia improves patient outcome. Early airway control in patients with a clinically significant depressed level of consciousness (GCS score of 8 or acute decreased in GCS score by 2) is essential in supporting outcomes and in avoiding secondary brain injury.

Hospital assessment

Hospital assessment involves the history of trauma, physical examination, evaluation of posture and pupillary responses, and additional investigations.

The history of trauma is gained from the patient, witnesses at the scene, attending ambulance staff, and knowledge of the mechanism of injury.

The severity of the injury is defined by carefully examining the patient's mental status by using the GCS score, posture, and pupillary responses.

The GCS score quantifies the patient's neurologic status and enables the rapid and uniform communication of the initial assessment of the patient's possible neurologic injury. The GCS score is a familiar descriptor used in the emergency department. It is derived from observation and responses to eye opening, best motor responses, and best verbal responses (see the Table below).

In the absence of confounding factors, such as illicit and prescription drugs and alcohol use, a low GCS score is a strong predictor of a poor prognosis. Of the 3 parameters assessed following injury, the best motor response elicited appears to be the most accurate prognostic indicator. A GCS score of 3-8 indicates a severe head injury, whereas a GCS score of 14-15 is mild. A GCS score of 15 is normal. A GCS score of 8 defines coma.

GCS Score

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Assess the patient's posture and pupillary response. In patients who are comatose, note any decerebrate or decorticate posture and pupillary responses to light (normal response is constriction).

Operative versus nonoperative treatment in the setting of head trauma

Typical indications for operative intervention are as follows: (1) extra-axial collections with mass effect, (2) significant mass effect from contusion or hemorrhage resulting in a shift of intracranial structures, (3) penetrating head injury with necrotic foreign body tracks, (4) removal of a foreign body if it compromises neurologic function, and (5) significantly depressed (>1 cm) skull fractures.

Nonoperative or medical therapies are aimed at avoiding secondary brain injury. The 2 major management philosophies following TBI are as follows: ICP management versus cerebral perfusion pressure (CPP) management. The ICP management theorists argue that all efforts should be made to keep the ICP at less than 20 mm Hg. The CPP proponents argue that the ICP may be greater than 20 mm Hg if the CPP is greater than 60 mm Hg. CPP can be estimated by subtracting the ICP from the mean arterial pressure (MAP). It is likely that both schools of thought have merit, and the optimal strategy is a combination of both.

Major management techniques used in the ICU are described below.

• PO₂ of greater than 100 Torr to avoid cerebral tissue hypoxia
• PCO₂ of 35-40 Torr to avoid cerebral hyperemia or excessive vasoconstriction and induction of cerebral ischemia
• Maintenance of a neutral cervical spine position to avoid impairment of cerebral venous drainage
• Avoidance of jugular venous lines on the ipsilateral side of a brain injury
• Drainage of CSF with an external ventricular drainage (EVD) catheter when the ICP is greater than 20 mm Hg
• Isovolemic dehydration for patients with cerebral edema and a high ICP
• Avoidance of any unnecessary glucose for the first 48 hours after injury
• Avoidance of hyposmolarity to prevent increasing cerebral edema

Controversy surrounds nursing patients in the head-of-bed up position, as this may decrease cerebral oxygen delivery.

Mannitol is generally avoided in the patient without cerebral edema because of the risk of hypovolemia from excessive intravascular volume loss. The use of craniectomy is controversial in the management of cerebral edema. Interrogate for intra-abdominal hypertension in the patient with intractably elevated ICP, as there are reports of successful management with abdominal decompression.

ICP can be measured by various routes and devices; however, the criterion standard is considered to be a fluid-coupled ventriculostomy catheter inserted into a lateral ventricle (normal ICP <15>

Acute Respiratory Failure

Acutely injured patients often present with hypoxemia, hypercarbia, and an unsupportable work of breathing, leading to urgent or emergent airway control. The causes of acute respiratory failure are multitudinous, but they all require management of both oxygenation and ventilation. Acutely hypovolemic patients may suffer severe hypotension with positive pressure ventilation, and they will need vigorous plasma volume expansion to address hypovolemia.

As patients age, COPD is an increasingly prevalent comorbid disease process. Thus, the clinician must be ready to adjust mechanical ventilation to address the expected abnormalities of gas exchange that characterize different pulmonary conditions of reduced compliance, increased resistance, or restriction. The clinician should decide what minute ventilation (V_E) is desired for a given patient, and then the clinician should decide on the respiratory rate based upon the desired tidal volume derived from the patient’s ideal body weight (V_E = V_T X RR).

Acutely injured patients without acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) do not need to be managed along a specific ventilatory pathway, but all means of mechanical ventilation should ensure that lung injury is not initiated. This means specifying PEEP, flow rate, and waveform, and assessing the resultant peak and plateau pressures for each patient. An initial ABG is ideal to assess whether the targeted minute ventilation was correct with regard to CO₂ clearance. Avoid establishing a “one ventilator prescription fits all” method of managing acute respiratory failure (ie, AC 14, V_T 700, 100%,⁺ 5 for all), as ventilator prescription, like fluid prescription, should be individualized to optimize pulmonary dynamics.

Similarly, each clinician should have a well-designed rescue plan for patients who are unable to be adequately oxygenated on their initial ventilator mode once the settings have been optimized. Available options include pressure control ventilation, airway pressure release ventilation, high frequency oscillation ventilation, and prone positioning in conjunction with volume cycled/pressure cycled/APRV modes. No single mode has demonstrated superiority with regard to outcome, but certain modes offer unique advantages versus other modes.

The author prefers APRV, as it is a modified form of CPAP that allows for spontaneous breathing at 2 different pressure levels, affords for reduced sedation, and has been demonstrated to enhance cardiac performance and to abrogate basilar consolidation. The interested reader is referred to established works describing this mode in detail.

The established trauma patient may develop respiratory failure in-house from pulmonary embolism or pulmonary sepsis, and the clinician should be keenly aware of the timing of acute respiratory failure to structure an appropriate differential diagnosis.

The longer a patient is mechanically ventilated, the greater is the likelihood that the patient will develop ventilator associated pneumonia (VAP). VAP reduction bundles have demonstrated efficacy in reducing VAP incidence and include head-of-bed elevation of greater than 30 degrees, oral hygiene measures, spontaneous breathing trials to assess liberation from mechanical ventilation readiness (if not contraindicated), infection control practice adherence, and, promisingly, silver impregnated endotracheal tubes to address biofilm-related promotion of tracheal colonization leading to infection.

Of course, appropriate antibiotic prescription practices that reduce induction pressures for resistant pathogen genesis aid in reducing hospital associated pneumonia (HAP) and health care associated pneumonia (HCAP), as well as VAP. In several studies, the invasive diagnosis of VAP has been demonstrated to be more cost effective than traditional diagnostic criteria (fever, bronchorrhea, leukocytosis, and radiographic infiltrate), principally by establishing confidence in the diagnosis of “no pneumonia” and by eliminating treatment of a diagnosis that is not present. This also curbs selection pressure for resistant pathogen genesis, and most notably influences prevalence rates for MRSA, VRE, and ESBL producing gram-negative rods. Acute respiratory failure is often a prelude to other organ failures in the critically injured patient.

Multisystem Organ Failure

Acute renal injury and acute renal failure

While prior literature was replete with widely varying definitions of renal failure and renal insufficiency, the Acute Dialysis Quality Initiative (ADQI; www.ADQI.net) and the Acute Kidney Injury Network (AKIN) proposed and then validated a new set of specific diagnostic criteria to characterize renal perturbations in a precise fashion.

The criteria are known as the RIFLE criteria (R = Risk, I = Injury, F = Failure, L = Loss, E = End-stage renal disease). Importantly, the RIFLE criteria also correlate rather closely with mortality in hospitalized patients. The most recent ADQI Consensus Conference (ADQI 5) specifically addressed whether fluid therapy created or mitigated the risk for acute kidney injury (AKI).

AKI, like the remainder of the RIFLE definitions, weds a period of oliguria with a measurable but small increase in serum creatinine concentration. Larger increases and more persistent oliguria define acute renal failure. ADQI 5 identified that the most consistent risk factor for AKI is a period of hypoperfusion and that there is some animal data and lesser human data that hyperchloremia plays a role in AKI initiation when plasma volume expansion is used to treat hypovolemia. Other important causes of acute kidney injury and acute renal failure (ARF) and progression along the RIFLE pathway include radiocontrast nephropathy and rhabdomyolysis.

Radiocontrast nephropathy (RCN) appears to be an issue in discrete patient populations. Risk factors include preexisting chronic kidney disease, hypovolemia, hypotension, diabetes, and iodinated contrast exposure dose. Trauma patients receiving multiple diagnostic studies are at particular risk for RCN because of repeated iodinated contrast material exposure; for example, an initial CT scan, a carotid/vertebral CT angiogram, and then perhaps a traditional celiac angiogram for angioembolization, all within a 24-hour period.

Prophylactic regimens have explored plasma volume expansion with a variety of fluids and electrolyte compositions, most recently NaHCO₃ based solutions, coupled with N -acetyl cysteine (NAC) plus ascorbic acid. The most robust data support the use of NaHCO₃ (D₅ W+150 mEq/L NaHCO₃) plasma volume expansion prior to and following radiocontrast material administration. It is unclear whether the effect is unique to bicarbonate as an anion, to the simple abrogation of HCMA when present, or to an absolute or relative reduction in chloride concentration. At present, no convincing data support the use of NAC or vitamin C. There is no role for mannitol in RCN prevention, and mannitol may be injurious by inducing dehydration and a hyperosmolar state. No outcome benefit has been identified for prophylactic dialysis for RCN prevention.

Trauma patients are also at risk for rhabdomyolysis following various injuries, most notably a crush injury, and oxygenated reperfusion of a limb with more than 6 hours of warm ischemia time. The current recommendation is vigorous plasma volume expansion to establish urine flows of approximately 1.5 cc/kg body weight (BW) per hour. Patients who received aggressive, early therapy had lesser degrees of renal injury than those receiving lesser amounts of fluid therapy. If a patient is able to achieve the above urine output target, then urinary alkalinization is unnecessary and will not confer an outcome advantage. Patients who cannot reach the target may benefit from alkalinization using NaHCO₃.

At present, there is no evidence-based role for mannitol in managing rhabdomyolysis, and there is evidence of potential harm from inducing hyperosmolarity. Avoidance of inducing HCMA is a supportive goal based on experimental data identifying that hyperchloremia can decrease renal blood flow and glomerular filtration rate in an independent fashion.

It is likely that a more precise understanding of AKI/ARF and progression of renal disease will await large-scale studies of the natural history of renal biomarkers in serum (cystatin) and urine (kidney injury marker-1, N -acetyl-b-D glucosaminidase [tubular damage], glutathione transferase-a [proximal tubular damage], and neutrophil gelatinase-associated lipocalin [putative indicator of renal ischemia]).

Similarly, understanding the precise relationship among endothelial glycocalyx integrity and plasma volume expander selection, dose, and timing requires a more in-depth investigation into the molecular underpinnings of that particular system and its behavior in the low oxygen tension environment of the renal medulla.

Hepatic failure

A common organ to fail besides the lungs and the kidneys is the liver. Hepatic failure is a marker of the patient's overall status. It is not uncommon to identify hyperbilirubinemia with concomitant sepsis, but acute hepatic failure, identified as hypoproteinemia, coagulopathy, jaundice, and ascites, is a grave sign. The clinician should look for treatable causes of fulminant hepatic failure, including acute portal vein thrombosis, hepatic vein thrombosis, intoxicants, medication reactions, undisclosed cirrhosis, blood transfusion incompatibility, hepatic artery injury, and acute viral hepatitis.

Adrenal insufficiency

Adrenal insufficiency, absolute or relative, may accompany adrenal hemorrhage after injury, but it appears to do so less frequently than as a result of sepsis.

At present, no consensus exists as to how to diagnose adrenal insufficiency (absolute cortisol level vs stimulation test vs clinical scenario without testing), as to how to treat (glucocorticoid alone vs the addition of mineralocorticoid), or as to how to terminate therapy once it is initiated (abrupt cessation at 7 d vs taper over a total of 10-14 d).

Glycemic control failure

Hyperglycemia may be considered another endocrine system failure in that the native system is unable to meet the demands placed upon it in those without preexisting diabetes. Current data support glycemic control by a continuous infusion of insulin in patients requiring mechanical ventilation as a means of improving sepsis relevant as well as other outcomes. The target range is currently unclear and spans 110-150 mg/dL. Increasing data documents the deleterious effects of hypoglycemia, in particular in those with TBI, when engaging in tight glycemic control (intensive insulin therapy; IIT). It is currently unclear if the benefits ascribed to tight glycemic control are time limited (ie, only realized over the first 2-7 d) or whether benefits accrue over prolonged periods (ie, the ventilated patient spending 3 mo in the ICU).

Anemia/bone marrow failure

Injured patients may commonly develop anemia as a result of external losses (eg, scene hemorrhage, intraoperative losses), underproduction, and excessive blood sampling. Hemolysis is a much less common cause of anemia following injury. It is clear that patients who are bleeding should be transfused with packed red blood cells for restoration of red cell mass and with fresh frozen plasma, as required, for coagulopathy correction. The optimal target hemoglobin level has yet to be established. Current evidence documents that a hemoglobin level of 7 g/dL may be safely maintained in the critically ill without untoward effects on mortality or cardiac appropriate outcome variables compared to a hemoglobin level of 9 g/dL.

The reader should note that these studies excluded patients with active myocardial ischemia, but they did include patients with known coronary artery disease. It is clear that red blood cell transfusion is associated with unfavorable immunomodulation, especially with older banked blood, and it has been strongly correlated with an increased risk of infection and ALI. While most of the blood in the United States is leukoreduced, it is not WBC free. The absolute impact of leukoreduction is less clear than one might like but has become established as a standard. All blood transfused in the European Union is leukoreduced by law.

Anemia management with erythropoiesis stimulating agents (ESAs) has drawn intense scrutiny and criticism, polarizing clinicians and patients. The latest trial of ESAs in trauma patients (EPO III) noted a significant improvement in trauma patient survival when treated with erythropoietin. It appeared that the effect was separate and distinct from the hematinic effect of the delivered erythropoietin dose. This suggests another mechanism of action for erythropoietin that merits investigation. Nonetheless, EPO therapy is not inexpensive and has not been universally adopted mainly based on cost analysis.

Skin failure

Patients in the ICU after major trauma are often total body water and salt overloaded. They may or may not have concomitant intravascular volume overload; hypovolemia commonly coexists with total body water and salt excess.

In this set of patients in particular, one finds an increased risk of pressure ulceration. Despite routine turning and repositioning, patients may develop pressure ulceration. None of the pressure ulceration risk scoring systems were developed to address this unique patient population. Rather, the scales were developed for general ward patients and have thus been applied to a patient population in which they were not originally validated. Therefore, it is not uncommon to identify patients with a lower score who nonetheless develops an "unanticipated" ulcer.

Rigid cervical immobilization devices and TLSO braces present another significant risk for pressure ulceration in the trauma patient. Thus, early clearance of the cervical spine, when feasible, is an optimal manner in which to reduce ulceration. Careful attention to TLSO brace fit is essential, as many patients undergo significant body habitus alteration with large changes in total body fluid (acutely) or total body mass (more slowly, especially after a major septic episode).

Coagulopathy and Massive Transfusion

Trauma patients are at risk for coagulopathy via several mechanisms.

First, patients with hemorrhagic shock will lose clotting factors. This loss will be further compounded by plasma volume expansion leading to dilution of clotting factors. Second, hypothermia impairs the enzyme kinetics of the serine based proteases. (Clotting factors are enzymes.) Major efforts are devoted to the maintenance of intraoperative normothermia, and normothermia has been associated with reductions in surgical site infection. Third, acidosis also impairs the enzyme kinetics of those same proteases.

Surgical hemorrhage should be differentiated from microvascular hemorrhage. Surgical bleeding requires a physical repair to correct. Microvascular hemorrhage requires restoration of clotting factors, correction of hypothermia, correction of clotting cofactors (eg, calcium, magnesium, oxygen), abrogation of thrombocytopenia, and correction of acidosis. Microvascular hemorrhage control also commonly requires cavity packing and is further augmented by procoagulants, like recombinant activated factor VII (rfVIIa).

The reader should note that different doses have demonstrated efficacy for different conditions. There is no single agreed upon dose to be used for trauma-associated hemorrhage. Moreover, since rfVIIa has a half-life of approximately 2.5 hours, it is unclear whether patients should be routinely redosed or await a clearly defined need.

Also, the discordance between correction of PT and aPTT and the clinical resolution of hemorrhage is not an infrequent report. Nonetheless, rfVIIa has become an integral part of the massive transfusion protocols at many trauma centers. With massive transfusion, the trauma patient is at risk for alloimmunization, major and minor histocompatibility reaction, hemolysis, and, with transfusion of fresh frozen plasma, transfusion-associated lung injury (TRALI). TRALI requires supportive care and does not respond to steroids or antibiotics.

Sepsis

Sepsis is a ubiquitous condition throughout ICUs worldwide.

Trauma patients are no different than other patients with regard to sepsis management, source control, adherence to sepsis bundles, and outcome, with one exception. In the immediate peri-injury period, and particularly with major solid organ injury (AAST Grade III and greater) or with intraaxial or extraaxial central nervous system injury, the use of activated protein C is problematic. The major limitation of activated protein C is hemorrhage risk. The individual practitioner must weigh the risk of hemorrhage based on the time postinjury compared to the benefit of activated protein C.

Attention should be paid to antibiotic selection in that patients hospitalized for more than 4 days, especially in an ICU, should be covered for nosocomial pathogens according to the local antibiogram instead of community acquired pathogens.

As hospital acquired, health care associated, or ventilator associated pneumonia is a common infection leading to sepsis in trauma patients, one should address the diagnosis using bronchoscopy and bronchoalveolar lavage instead of the traditional 4 criteria (ie, fever, leukocytosis, bronchorrhea, and radiographic infiltrate). An invasive approach has been demonstrated to be more sensitive, more specific, and more accurate leading to confidence in the diagnosis of “no pneumonia” and reductions in total care cost and the incidence of multidrug resistant infection.

The Surviving Sepsis Campaign has made a number of recommendations for best practices in ICUs to avoid and manage sepsis. These recommendations are conveniently grouped into time-sensitive bundles. Importantly, these recommendations address timely antibiotic administration, appropriate cultures, goal-directed fluid administration, glycemic control, head-of-bed elevation, oral hygiene, and regular reassessment of the appropriateness of weaning, as well as the appropriate use of activated protein C. Adherence to the bundles is less than uniform, but adherence is strongly associated with enhanced survival from sepsis.

Plasma Volume Expansion Considerations

Recently, significant attention has been focused on the sequelae of plasma volume expansion. In the wake of the negative press devoted to the pulmonary artery catheter, many companies developed less invasive monitoring techniques that have shifted monitoring attention from a pressure-based system to a flow-based system. Examples include the LiDCO and PICCO systems with routine monitoring of stroke volume. In fact, anesthesia guidelines in the United Kingdom require start and end of case monitoring and recording of stroke volume in operating room cases requiring monitoring. Similar extensions to the ICU or high-dependency unit are anticipated. Accordingly, these techniques allow one to determine the point at which additional plasma volume expansion will not lead to a further increase in cardiac performance (ie, no further volume recruitable cardiac performance).

When plasma volume expansion proceeds, despite no increase in flow-based parameters, edema is a predictable result. In multiple venues (eg, colon, biliary surgery), excess fluid administration has been associated with increased postoperative pain, weight gain, lung injury, ICU and ventilator length of stay, postoperative nausea and vomiting, diplopia, skin bullae, diuretic use, and fluid and electrolyte abnormalities. One study demonstrated a reduced incidence of intraabdominal hypertension when using colloids instead of crystalloid fluids for plasma volume expansion. The reduced intraabdominal hypertension was ascribed to a reduced total fluid need based on the increased efficacy of colloids compared to crystalloids.

Damage Control Surgery Sequelae

In 1993, Rotondo coined the term “damage control” to describe a salvage philosophy for patients suffering from exsanguinating hemorrhage.¹ This technique uses field recognition of hemorrhagic shock, abbreviated initial laparotomy (hemorrhage control plus contamination control), planned or unplanned re-exploration (relief of abdominal compartment syndrome when necessary; restoration of GI continuity, enteral access, definitive or temporary abdominal wall closure), definitive reconstruction for those with a nondefinitive closure method that was initially used, and ultimate rehabilitation. Using damage control techniques will leave a large number of patients with an open abdomen that requires management. These patients are at risk for enterocutaneous fistula formation, tertiary peritonitis, large volume transperitoneal fluid loss (artificially reduces plasma creatinine by serving as a modified form of peritoneal dialysis), and GI injury during re-exploration.

Moreover, despite having a temporary abdominal wall closure with one of a number of techniques, these patients are at risk for recurrent abdominal compartment syndrome (ACS). ACS is defined by the World Society for Abdominal Compartment Syndrome (www.wsacs.org) as an intra-abdominal pressure of greater than 20 mm Hg with an attributable organ failure. Trauma patients are at risk for primary (usually related to hemorrhage or visceral edema) and secondary abdominal compartment syndrome (usually related to visceral edema or ascites). Decompression is the criterion standard for management. This may be done in the operating room or at the bedside in the ICU. Increasingly, abdominal re-exploration is also performed at the bedside with no acutely identified negative sequelae.

The earlier the patient’s abdomen is closed, the less the ICU length of stay and accrued risk for complications. Previously, patients with open abdomens were routinely heavily sedated and neuromuscularly blocked. Currently, sedation without neuromuscular blockade is the norm and avoids prolonged neuromuscular blockade syndrome and a host of other well-documented complications.

Vacuum-assisted closure (VAC; KCI Corporation) and the Wittmann patch are 2 techniques that are useful to help achieve primary fascial closure. For those who are not able to be closed, either Vicryl mesh (2 thicknesses) with an overlying split-thickness skin graft or skin flaps will achieve a temporary closure that leaves the patient with a planned giant ventral hernia. A waiting period of 6-12 months is generally undertaken prior to reconstruction.

Alternatively, abdominal wall closure with AlloDerm (human acellular dermis; LifeCell Corporation) has been increasingly used as a regenerative matrix. Mixed results were initially achieved because of improper placement techniques and improper tensioning. Currently, underlay techniques and proper tensioning guidelines have helped make this a successful strategy for abdominal wall reconstruction, both acutely and in those with a planned giant ventral hernia. Many other options exist, including permanent meshes and component separation of parts techniques.

Metabolic Acid-Base Imbalance

In the United States, the standard for plasma volume expansion is crystalloid fluids, principally as lactated Ringer's solution, but 0.9% NSS is also commonly used for part of the resuscitation (especially with packed RBC transfusion).

In the late 1990s, the distinct entity of hyperchloremic metabolic acidosis (HCMA) was identified as a consequence of plasma volume expansion with solutions rich in chloride relative to human plasma. Acute sequelae include the need for increased minute ventilation to buffer the induced acidosis, immune activation, altered intracellular communication, induction of a cytokine storm, RBC swelling, and induced coagulopathy. Increasingly commonly, buffering of HCMA occurs by using a nonchloride maintenance fluid, such as D₅ W+75 mEq NaHCO₃/L at a body weight calculated maintenance rate. One review noted that there is a discrete and increased mortality associated with HCMA that is different from the mortality rate for lactic acidosis.

Currently, the best available data establish that resolution of lactic acidosis correlates closely with survival. It is also clear that many trauma patients have an elevated lactate level without an explainable acid-base abnormality. These patients have hyperlactatemia, not lactic acidosis. The elevated lactate level is related to increased endogenous catecholamines that increased carbon moiety flux through the glycolytic cascade producing lactate and pyruvate in a normal ratio. No pH changes accrue, but the lactate level is readily measurable. The major error stems from believing that the elevated lactate represents hypoperfusion and providing additional plasma volume expansion. The end result is to increase plasma chloride leading to HCMA as above.

Metabolic alkalosis is uncommon as a presenting acid-base disorder, except in those with comorbid diseases who are managed using loop diuretics that induce metabolic alkalosis (ie, furosemide). In general, alkalosis is a late finding and reflects either deliberate buffering of HCMA or induced alkalosis from diuretic therapy managing the increased total body water and salt that remains from the initial resuscitation. Most alkaloses are chloride responsive and provision of either KCl or salt in enteral feeds. Since the average 70-kg person needs 1-2 mEq Na⁺ per kilogram of body weight (BW) per day, the average person needs less than the 9 grams of Na⁺ per day. Each liter of NSS has 9 grams of sodium chloride, and a regular diet has 9 grams of sodium chloride. Thus, one may add salt tablets (3- to 9-g aliquots) to tube feeds to repair metabolic alkalosis.

Avoiding HCMA is a readily achievable goal. Using fluids with physiologic concentrations of chloride for resuscitation eliminates HCMA. However, since LR and NSS have supraphysiologic concentrations of chloride, one must usually compensate for the increased chloride load. In particular, using a "custom" fluid, such as ½ NSS+75 mEq NaHCO₃, as resuscitation fluid works well instead of LR or NSS.

Colloid plasma volume expansion also works well since one delivers one third less chloride per cc of plasma volume expansion because of intravascular retention. The reader should note that despite the current but unsubstantiated concern that starch resuscitation in sepsis leads to acute kidney injury or acute renal failure, no such concern exists for hemorrhagic shock.

Keywords

critical care considerations in trauma, trauma critical care considerations, acute care surgery, surgical critical care, critical care considerations, trauma, traumatic injury, advanced trauma life support, ATLS, ABCs, injury, emergency department care, emergency medicine, triage, trauma scoring, trauma score, polytrauma, Glasgow Coma Scale, Revised Trauma Score, Abbreviated Injury Score, Injury Severity Score, neurotrauma evaluation, traumatic head injury, chest trauma, cardiac tamponade, flail chest, hemothorax, pneumothorax, blunt aortic injury, aortic transection, abdominal trauma, pelvic trauma, hemoperitoneum, intensive care medicine, FAST, CT scanning, blood component therapy, massive transfusion protocol, activated factor seven, damage control techniques

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, David Galler, MD, BSc, MBChB, and coauthors, Adrian Skinner, MBChB, AFA, BHB, and Alex Ng, MBChB, FRACS, to the development and writing of this article.