16 Immunology and Infectious Disorders
Pearls
• The critically ill child may have immune compromise and is at risk for a variety of healthcare-acquired infections. The critical care nurse must be alert for evidence of inflammation and infection and signs of developing sepsis.
• It is likely that adherence to prevention measures can reduce risk of healthcare-acquired infections such as catheter-related bloodstream infections, ventilator-associated pneumonia, and urinary tract infections.
• Children with septic shock require early and aggressive fluid resuscitation, vasoactive support, early antibiotic therapy, and support of organ system function.
Anatomy and physiology: immunology
Immunology Overview
Developmental Considerations
At the time of birth, a neonate is considered to be fundamentally immunocompromised for several reasons.14 First, although infants born at term have passively acquired immunity from maternal antibodies that were transferred transplacentally before birth, the titers of these antibodies quickly wane, leaving the infant without immunity to most specific pathogens. Until exposure to common pathogens by natural infection or immunization, infants lack durable organism-specific immunity. In addition, the function of specific components of the immune system does not mature until approximately 2 years of age. Until that time, infants are unable to make a robust antibody response to pathogens that have polysaccharide molecules on their surface. This developmental defect explains why the incidence of invasive pneumococcal infection, an organism with a polysaccharide coat, is relatively high in young children.
Infectious Disease Overview
Infection is a common cause and can be a common complication of critical illness in hospitalized children.45 Common community-acquired infections such as bacterial pneumonia and viral infections can lead to life-threatening illnesses in both immunocompetent and immunocompromised children. Local and systemic complications of community-acquired infections include respiratory failure, shock, and renal insufficiency. Critically ill children are also at high risk of healthcare-acquired infections including catheter-associated bloodstream infections, ventilator-associated pneumonia, and surgical site infections. These infections can be caused by viruses, bacteria, or fungal organisms.
Colonization and Infection
At birth, a neonate is normally essentially sterile. Within hours, however, bacteria from both the environment and people who handle the infant are transferred onto and begin to grow on the baby’s skin and mucous membranes.20 These bacteria are typically referred to as colonizing flora. The predominant colonizing organisms vary with anatomic site. For example, skin organisms such as Staphylococcus epidermidis can be found on almost all keratinized skin. In contrast, anaerobic and gram-negative organisms are typically found only in the intestinal tract. Colonizing flora typically do not cause inflammation or invasive infection. Many infections, however, do arise from the patient’s colonizing flora, often when a medical device breaches the integrity of skin or mucous membranes or when skin or mucous membranes become inflamed.
Common clinical conditions
Allergic Reactions and Anaphylaxis
Etiology
Allergic or “hypersensitivity” reactions occur when the body mounts an exaggerated or inappropriate immune response to a substance perceived as foreign, resulting in local or general tissue damage. Such reactions are usually classified by severity and involvement,1 as in types I to IV (Table 16-1).
Type | Description | Example |
Type I (anaphylactic reaction) | Triggered in response to an exposure to an environmental antigen Mediated by IgE antibodies that bind to specific receptors on the surface of mast cells and basophils Results in the release of a host of mediators to produce a classic anaphylactic response | Anaphylaxis Asthma Allergic rhinitis, hay fever |
Type II (tissue specific hypersensitivity) | Triggered by the presence of an antigen found only on a cell or tissue Mediated by antibody (usually IgM, but also IgG) through two different mechanisms (complement and Fc receptors on phagocytes) Results in the destruction of the antibody-coated cell with consequences dependent on the cell or body that is destroyed (e.g., RBC, WBC, or platelet) | ABO incompatibility Rh incompatibility Drug-induced thrombocytopenia |
Type III (immune complex reaction) | Triggered by the formation of antigen-antibody complexes that activate the complement cascade Immune complexes are formed in the circulation and are later deposited in blood vessels or healthy tissue. Multiple forms of the response exist depending on the type and location of the antigen Results in local edema and neutrophil attraction, and thus degradative lysosomal enzymes resulting in tissue injury | Serum sickness Glomerulonephritis |
Type IV (delayed hypersensitivity) | Triggered by the recognition of an antigen mediated by activated T lymphocytes and release of lymphokines, which then stimulate the macrophage to phagocytize foreign invaders and some normal tissue Results in a delayed onset. Does not have an antibody component; this response is strictly a cellular reaction | Contact sensitivities such as poison ivy and dermatitis Tuberculin reactions Graft rejection |
RBC, Red blood cell; WBC, white blood cell.
From Roberts KE, Brinker D, Murante B. Hematology and immunology. In Slota M, editor: Core curriculum for pediatric critical care nursing, ed 2. Philadelphia, 2006, Saunders Elsevier, p. 597.
Anaphylaxis is an allergic hypersensitivity reaction to a foreign protein or drug that causes a systemic response. Exposure to the antigen may be oral or intravenous, or through inhalation or via direct contact. The anaphylactic reaction can occur within seconds or minutes after exposure.42
Clinical Signs and Symptoms
Signs and symptoms of hypersensitivity or anaphylaxis can develop within seconds or minutes after exposure. Patients often initially describe a sense of impending doom, accompanied by pruritus and flushing. This can evolve rapidly into other clinical manifestations of hypersensitivity (Table 16-2).
Organ System | Clinical Manifestation(s) |
Cutaneous/ocular | Flushing, urticaria, angioedema, cutaneous and/or conjunctival pruritus, warmth, and swelling |
Respiratory | Nasal congestion, rhinorrhea, throat tightness, wheezing, shortness of breath, cough, hoarseness |
Cardiovascular | Dizziness, weakness, syncope, chest pain, palpitations |
Gastrointestinal | Dysphagia, nausea, vomiting, diarrhea, bloating, cramps |
Neurologic | Headache, dizziness, blurred vision, and seizure (very rare and often associated with hypotension) |
Other | Metallic taste, feeling of impending doom |
Data from Linzer JF: Pediatrics, anaphylaxis. 2008. Emedicine, http://emedicine.medscape.com/article/799744-overview.
Once the clinical manifestations of the reaction become systemic, anaphylaxis is present. Mild symptoms include irritability, coughing, anxiety, disorientation, erythema, hives, and itching. Severe symptoms include dyspnea; cyanosis; difficulty speaking; swelling of the tongue, face, and airways; intense coughing; chest tightness; wheezing; stridor; laryngospasm; seizures; sense of impending doom; hypotension; and cardiorespiratory arrest.23
Management
Establish vascular access, ideally with two large-bore vascular catheters and be prepared to administer fluid boluses (to treat relative hypovolemia resulting from vasodilation and increased capillary permeability) and vasoactive support (e.g., an epinephrine infusion) to restore and maintain adequate blood pressure and systemic perfusion. (For further information, please refer to Chapter 6.)
Medications typically used to treat anaphylactic reactions include oxygen, IM epinephrine (an infusion may be needed for refractory hypotension), diphenhydramine (and possibly an H2-blocker antihistamine), albuterol nebulizer, and methylprednisolone.10,23 Antihistamines are administered to antagonize the effects of histamine. Bronchodilators relax bronchial smooth muscles. Corticosteroids are antiinflammatory agents to enhance the effects of bronchodilators. (For further information, please refer to Chapter 6.)
Skin testing may help identify patients who may experience a hypersensitivity reaction with a known high-risk agent. Patients are given a small intradermal test dose of the agent and are monitored for at least 20 minutes.17 Emergency equipment and medications should be readily available. Patients receiving medications or agents with a higher risk of producing anaphylactic reaction and those with a history of anaphylaxis should be identified and monitored appropriately.
When a patient has a known allergy or hypersensitivity reaction to a drug, premedications may be prescribed before the agent is administered. Medications commonly used for pretreatment are corticosteroids, antihistamines, and antipyretics.17 Patients with known hypersensitivity responses should wear medical alert jewelry and should have an anaphylaxis kit (epinephrine autoinjector pen) readily available.
Systemic Inflammatory Response Syndrome (SIRS)
Etiology
In 1992, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) introduced definitions3 for systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, and multiple organ dysfunction syndrome (MODS).
SIRS is a state of inflammatory/immune activation. SIRS is present when the adult patient demonstrates two or more of the following variables3,8a:
• Altered temperature: fever of more than 38° C rectal or less than 36° C rectal
• Tachypnea (age related) or a PaCO2 less than 32 mm Hg
• Abnormal white blood cell count: greater than 12,000/mm3 or less than 4000/mm3 or greater than 10% bands
SIRS is nonspecific and can be caused by a number of diverse clinical conditions (Table 16-3), including ischemia, inflammation, trauma, infection, or a combination of several insults. SIRS does not always occur as a result of infection. A number of underlying conditions may predispose patients to infections with specific pathogens and the development of SIRS (Table 16-4).
Infectious Causes | Noninfectious Causes |
Bacterial sepsis Burn wound infections Candidiasis Cellulitis Cholecystitis Community-acquired pneumonia Infective endocarditis Influenza Intraabdominal infections Meningitis Healthcare-acquired pneumonia Pyelonephritis Toxic shock syndrome Urinary tract infections | Autoimmune disorders Burns Chemical aspiration Dehydration Erythema multiforme (Stevens-Johnson syndrome) Hemorrhagic shock Intestinal perforation Pancreatitis Surgical procedures Transfusion reactions Upper gastrointestinal bleeding Vasculitis |
From Burdette SD, et al: Systemic inflammatory response syndrome. Emedicine, http://emedicine.medscape.com/article/168943-overview. Updated July 20, 2010. Accessed April 27, 2011.
Acquired immunodeficiency syndrome (AIDS) | Predisposes to SIRS from both typical and unusual pathogens, particularly pneumococcus |
Hemoglobin SS (Sickle Cell) disease | 400-Fold increased risk of sepsis caused by pneumococcus and Salmonella, among other pathogens |
Congenital heart disease (with few exceptions) | Risk for endocarditis (see Endocarditis in Chapter 8) and SIRS |
Genitourinary anomalies | May increase the risk of urosepsis |
Significant burns | Risk of SIRS, caused by skin flora and nosocomial gram-negative pathogens in particular |
Splenic dysfunction or absence, as well as complement, immunoglobulin, and properdin deficiency | Predispose to infection from encapsulated organisms and resulting sepsis |
Hematologic and solid-organ malignancies (before or during treatment) | Increased risk for SIRS from many organisms |
Hospitalization (particularly if prolonged, in the critical care unit, or with invasive devices) | Increased risk of SIRS; prolonged stay and invasive devices increase risk of infection |
Indwelling devices or prosthetic material and other breaches in barrier protective function | Increased risk of SIRS |
Modified from Burdette SD, et al: Systemic inflammatory response syndrome. Emedicine, http://emedicine.medscape.com/article/168943-overview. Updated July 20, 2010. Accessed April 27, 2011.
Pathophysiology
More than 15 years ago, Bone4 described the relationship between these complex inflammatory interactions. He described SIRS and MOSF as a five-stage process (Table 16-5). His definitions remain very helpful today.
From Bone RC: Immunologic dissonance: a continuing evolution in our understanding of the systemic inflammatory response syndrome (SIRS) and the multiple organ dysfunction syndrome (MODS). Ann Intern Med 125(8):680-687, 1998.
The cumulative effect of this inflammatory cascade is an unbalanced state with inflammation and coagulation. To counteract the acute inflammatory response, the body is equipped to reverse this process via a counter-inflammatory response syndrome (CARS). Co-morbidities 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.4
If SIRS continues to progress, cardiac output may fall, peripheral vascular resistance may increase, and shunting of blood may ensue (i.e., cold shock). This results in development of tissue hypoxia, end-organ dysfunction, metabolic acidosis, end-organ injury and/or failure, and can be fatal.35
Clinical Signs and Symptoms
Fever is the most common presenting symptom of children with SIRS. Fever is one component of the triad of hyperthermia (or hypothermia), tachypnea, and tachycardia that typifies the earliest, mildest manifestation of SIRS. The international consensus terminology defines SIRS in children as present when the patient demonstrates two or more of the following (see details in Box 16-1)18:
• Alteration in temperature: fever of more than 38° C rectal or temperature less than 36° C rectal
• Alteration in heart rate (age related): tachycardia or bradycardia (in infants)
• Tachypnea (age related) or a PaCO2 less than 32 mm Hg
• Abnormal white blood cell count (greater than 12,000/mm3 or less than 4000/mm3 or greater than 10% bands)
Box 16-1 Pediatric Signs of Sepsis/Systemic Inflammatory Response Syndrome
Manifested by two or more of the following four criteria:
Mean heart rate more than 2 standard deviations (SD) above normal for age in absence of external stimulus, chronic drugs, or painful stimuli OR
Otherwise unexplained persistent elevation over a 0.5- to 4-h time period
Mean heart rate less than the 10th percentile for age in absence of external vagal stimulus, ß-blocker drugs, or congenital heart disease
Leukocyte count elevated or depressed for age (not secondary to chemotherapy-induced leukopenia) or more than 10% immature neutrophils
Modified from Goldstein B, et al: International pediatric sepsis consensus conference. Pediatr Crit Care Med 6(1):5, 2005.
Management
Treatment of SIRS is focused on treating the inciting cause. Empiric antibiotics are not administered routinely to all patients. Indications for empiric antimicrobial therapy include suspected or diagnosed infectious etiology, hemodynamic instability, neutropenia, and asplenia.8a Broad spectrum antibiotics are initiated when there is concern for an infectious cause but no definitive infection has been diagnosed.
Drotrecogin alpha, a recombinant form of human recombinant activated protein C (APC), reduces microvascular dysfunction by reducing inflammation and coagulation and increasing fibrinolysis. It has been hypothesized that APC may be beneficial in the management of SIRS. However, the supporting evidence to date is limited. In the prospective, randomized multicenter controlled PROWESS trial,2 mortality was reduced by 28% in adult patients with severe sepsis who received APC. Patients who received APC also demonstrated significantly more bleeding than control patients. However, a Cochrane meta-analysis of adult trials25 involving over 4000 patients (including some children who were not randomized) did not find overall evidence of improved survival when APC was administered; a multicenter pediatric study was halted because excessive bleeding occurred when children received APC.
Fluid resuscitation should be initiated in those patients who exhibit signs of hypovolemia and hypovolemic shock (see section, Sepsis and Septic Shock and Chapter 6). All patients require establishment of adequate intravenous access. Administer isotonic fluids boluses (typically 20 mL/kg boluses; smaller volumes may be used in children with poor myocardial function) as needed to treat shock and monitor hemodynamic status closely.22,33 If signs of shock are present, antibiotics, aggressive fluid resuscitation and vasoactive support should be provided within the first hour after the onset of symptoms (see section, Sepsis and Septic Shock and Chapter 6).5
Assess and support adequate oxygenation and ventilation. The oxyhemoglobin saturation in the superior vena cava (SCVO2) allows tracking of the balance between oxygen delivery and oxygen use; therapy should be titrated to maintain this SCVO2 70% or higher.5 Patients with increased oxygen requirement should receive supplementary oxygen. Intubation and mechanical ventilation may be required in some patients.