- Email: [email protected]
Human Immunodeficiency Virus Disease
0899-5885/99 $8.00 + .00 Lung Failure Across the Life Span
Human Immunodeficiency Virus Disease Managing Respiratory Complications Through the Life Span Kimmith M. Jones, RN, MS, CCRN
M any lives have been affected by human immunodeficiency virus (HIV) disease. Current world estimates indicate that about 30.6 million people are living with HIV disease. Of these, 29.5 million are adults and 1.1 million are children under 15 years of age. Roughly, 11.7 million people have died from acquired immunodeficiency syndrome (AIDS) since the epidemic was first identified in the early 1980s. If the current trend continues, 60 to 70 million people should be infected with HIV by the end of the year 2000 (Global AIDS Policy Coalition). In the United States, 665,357 individuals have been reported to have developed AIDS, with the highest incidence occurring in New York (19%), California (16%), Florida (10%), Texas (7%), and New Jersey (6%) (Fig. 1). 8 Of these individuals, 401,028 have died from the disease, representing a 60% mortality rate. 8 The incidence of AIDS decreased in 1997 compared with 1996 by 15%. It is thought that the decrease is related to new therapies . Decreases were seen more in men (16%) than in women (8%), and the smallest decreases were seen in the South (12%), among African Americans (9%) and among persons infected through heterosexual contact (6% in women, 3% in men). 8 AIDS-related deaths decreased by 42% between 1996 and 1997. The largest declines in AIDS-related From the Department of Critical Care and the Emergency Center, Sinai Hospital of Baltimore, and the University of Maryland School of Nursing, Baltimore, Maryland
deaths were observed in the West (51%), among whites (52%) and among male homosexuals (49%). 8 Thirty-one of the 50 states report every case of HIV infection to the Centers for Disease Control and Prevention (CDC). In those states that report, 15% of the HIV infections occurred in the 13 to 24 age group. Women accounted for 32% of all of the HIV infections and 49% of the infections between the ages of 13 and 24 years. African Americans and Hispanics accounted for 78% of all reported HIV infections. 8 AIDS was initially described in children in 1982. Since that time, 8280 children under the age of 13 years have been reported to the CDC as having AIDS (Fig. 2). 8 Many drugs have been developed and approved for use in the pediatric population to slow the replication of the virus and to alter the immune response. As a result, the survival rate has improved. Since the general screening of blood products for HIV began in the United States in 1985, 87% of the cases of AIDS in children under 13 years old have been the result of acquired HIV infection through vertical transmission from their mothers. 16• 20 The rate of vertical transmission has declined from 26% to 8% since the introduction of zidovudine to pregnant women. Administration of zidovudine to women antepartum and postpartum and to infants 6 weeks after delivery has been shown to significantly reduce the risk of transmission to the fetus and to infants. 20 Vertical transmis-
CRITICAL CARE NURSING CLINICS OF NORTH AMERICA I Volume 11 I Number 4 I December 1999
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42% Other
19% New York
6% New Jersey 7% Texas
10% Florida
16% California
Figure 1. States with the highest incidence of AIDS. (Data from Centers for Disease Control and Prevention: HIV/AIDS Surveillance Report 10:1, 1998.)
sion is more likely to occur at the time of delive1y. During that time, fe tal exposure to maternal blood is more likely, which increases the risk of transmission. Infants and young children can also acquire infection through breastfeeding and sexual abuse. 20 Similar to adults, adolescents typically acquire HIV infection through sexual transmission and intravenous drug use.io Opportunistic illnesses appear in children with HIV at higher CD4+ levels than in adults. 16 No organ system can escape the ravages of HIV. The multisystem complications that develop are
Adults 657,077
the result of a decrease in immune system function and an increase in opportunistic J!!nesses characteristic of HIV. Understanding the complications of the disease is more crucial now than ever, because increasing numbers of individuals are being admitted to critical care environments with HIV disease. Respiratory complications commonly plague individuals with HIV from infancy to adulthood. Age can infuence the presentation of the complication, its management, and the individual's survival. Pulmonary problems are often the first manifestation of HIV infection in both children and adults. 20·29 The most common pulmonary complica-
Children
8280
Figure 2. Cumulative number of reported AIDS cases from 1981 to June, 1998. Total number reported 665,357. (Data from Centers for Disease Control and Prevention: HIV/AIDS Surveillance Report 10:1, 1998.)
HUMAN IMMUNODEFICIENCY VIRUS
tions in children include Pneumocystis canmt pneumonia (PCP), Jymphocytic interstitial pneumonia (LIP), and bacterial pneumonia . In adults, the common complications are PCP and Mycobacterium tuberculosis(MTB). Other pulmonary complications may develop and are listed in Box 1 on this page. 20
Pneumocystis Carinii Pneumonia PCP affects individuals of all ages and remains the most common AIDS-defining opportunistic infection in children and adults. PCP is also the most common complication of HIV-infected children in the pediatric intensive care unit. 16• 18 Historical data indicate that PCP accounted for almost two thirds of AIDS index diagnoses in adults; however, recent data suggest a reduction in this proportion primarily as a result of prophylaxis. As many as 85% of patients with HIV develop PCP once during the course of their disease. Improved clinical outcomes and longer life expectancy for those at risk are
Box 1 PULMONARY COMPLICATIONS OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION Infections Viruses Cytomegalovirus Respiratory syncytial virus Herpes simplex virus Parainfluenza virus Influenza virus Adenovirus Bacteria Encapsulated organisms (e.g ., Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus) Gram-negative organisms (e.g., Escherichia coli, Klebsiella species, Pseudomonas aeruginosa) Mycobacterium tuberculosis Mycobacterium avium-intracellulare Fungi Pneumocystis carinii Candida albicans Histoplasma capsulatum Cryptococcus neoformans Aspergillus species Coccidioides immitis Interstitial pneumonia Lymphoid interstitial pneumonia Pulmonary lymphoid hyperplasia Desquamative interstitial pneumonia Malignancies Kaposi's sarcoma Lymphoma
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direct results of the improved management of acute pneumonia and the routine use of secondary prophylaxis. P. cariniiwas initially thought to be a protozoan. This misconception continued for about 80 years until two independent research groups presented information indicating that the organism was a fungus. The exact lineage is still unclear; however, the connection to the fungus kingdom still exists. 29 The incidence of PCP varies with the age of the child. The younger the child, the higher is the incidence of PCP. The sooner PCP develops during the course of disease, the poorer is the prognosis. It is estimated that the risk of developing PCP in the first year of life is between 7% and 20% for infants who are HIV-positive. The median age of presentation is 5 months of age. 16• 18• 20 PCP is usually a primary infection in children and a reactivation of a latent infection secondary to severely compromised immune defenses in adults. 16• 20 P. carinii can be found in the lungs of all humans, and a majority of humans develop antibodies to P. carinii by the age of 4 years. 13• 29 The fungus establishes residence in the alveoli and attaches itself to the type I cells. 29 The immunocompetent individual can keep the fungus under control ; however, the individual with a compromised immune system cannot do the same. This leads to the overwhelming complication of respiratory failure and pneumonia. The fungus attaches to the alveolar epithelium, which leads to desquamation of the alveolar cells. A diffuse alveolitis develops as the infection progresses. The alveoli become filled with a foamy exudate consisting of alveolar macrophages and cysts containing P . carinii. 20 This results in lung tissue that is heavy and noncompliant. 18 In adults, P. carinii begins to become evident in the form of pneumonia when the individual's CD4+ cell count drops to below 200 cells per cubic millimeter and remains there. It also can present as disseminated disease; however, that is rare. Symptoms usually progress more rapidly in children, and survival times are shorter than in adults. 13 The clinical presentation in children typically consists of an acute onset of cough, fever, tachypnea, dyspnea, and retractions. Crackles or diminished breath sounds may also be present on auscultation. Hypoxemia is commonly present along with an elevated serum lactic dehydrogenase (LDH). 13· 18• 20 In addition to a decrease in Pao 2, a widened alveolar-arterial gradient and intrapulmonary shunt are present. 18 Chest radiographs are helpful in diagnosing PCP. Typically, the chest radiograph shows diffuse interstitial infiltrates or an alveolar pattern; however, patients may also present with a normal chest radiograph (Fig. 3). 18• 29 If left untreated, the infiltrates can progress, resulting in the need for intubation and mechanical ventilation (Fig. 4).
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Figure 3. Chest roentgenogram showing evidence of moderately severe Pneumocystis carinii pneumonitis. The pattern is one of diffuse alveolar disease with bilateral distribution . The superior portions of the upper lobes are usually the least involved , and the perihilar areas are the most commonly affected sites. Air bronchograms are discernible . (From Hughes W: Pneumocystis carinii pneumonitis. In Chernick V, Boat TF [eds] : Kendig's Disorders of the Respiratory Tract in Children. Philadelphia, WB Saunders , 1998, p 505 .)
Figure 4. Chest radiograph of a 3-month-old infant presenting with Pneumocystis carinii pneumonia. A, The initial radiograph shows a bilateral infiltrate most prominent in the perihilar region. 8, Chest radiograph taken 1 week later shows progression of disease with opacification of both lung fields. (From Kattan M: Pulmonary disorders in pediatric HIV infection . In Chernick V, Boat TF [eds] : Kendig's Disorders of the Respiratory Tract in Children. Philadelphia, WB Saunders, 1998, p 1157.)
HUMAN IMMUNODEFICIENCY VIRUS
Adults who develop PCP can present with a variety of signs and symptoms that usually progress slowly. These include fever, dyspnea, fatigue, anorexia, tachypnea, slow progressive dyspnea on exertion, decreased exercise tolerance, and a nonproductive cough. Unfortunately, the physical examination is not too helpful when determining the presence of PCP. Typically, the Jung examination and auscultation are normal. Sometimes, fine basilar rales can be heard. 29 There are, however, several other ways to diagnose this complication. Ninety-five percent of patients with PCP present with an elevated LDH. This is the most consistent abnormality in both adults and children. 13• 18• 20 LDH levels greater than 1000 IU/ L are often associated with PCP; however, elevated LDH is not specific for PCP. LDH is a nonspecific marker of pulmonary parenchymal damage and is not usually elevated in pneumonias from other organisms. The sensitivity of an elevated LDH for PCP has been reported to be 83% to 100%. 29 Several factors may influence the sensitivity of the serum LDH value, including the severity of illness and the specific patient population being evaluated. 29 Studies have shown a correlation between an elevated LDH and mortality. An elevated LDH, despite therapy, correlates with a lower rate of survival, a failure of therapy, and an increase in the mortality rate. 2• 21 • 30 In contrast, a low or falling LDH correlates with a better prognosis, a response to therapy, and a decline in the mortality rate. The arterial blood gas can be used as a tool to detect PCP in both children and adults. Twentyfive percent of patients have a Pao 2 greater than 80 mm Hg and show an uncompensated respiratory alkalosis. The respiratory alkalosis is caused by the body's attempt to improve the delivery of oxygen to the tissues. This results in the expiration of carbon dioxide, which leads to the development of an alkalotic state. Patients with PCP also show a widened alveolar-arterial gradient with mild to severe hypoxemia. Sputum samples are useful as a diagnostic tool. Usually, an induced sputum sample is required because of a nonproductive cough. The sensitivity of induced sputum examinations ranges from 74% to 83%. 29 Newer technology using direct and indirect fluorescent antibody techniques has improved the sensitivity of induced sputum samples. 26 Sputum induction has been used to obtain sputum samples in children, but, typically, the child is over 2 years of age for this technique to be successful. If a sputum sample cannot be obtained or the result is negative, a bronchoalveolar lavage via bronchoscopy is performed. Bronchoalveolar lavage is a reliable method for establishing a diagnosis and identifies the organism in 95% to 990Ai of the patients with PCP. 16 Once the sample is obtained, the sputum is examined using a Gomori methenamine
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silver stain technique. This test looks for the presence of P. carinii colonies within the white blood cells of the patient. In children, the diagnosis can be accomplished by obtaining either a gastric or bronchial washing to isolate the organism. Diagnosis in children relies on the identification of P. carinii from these washings or directly from lung tissue. Collaborative management of the patient with PCP is essential. The first-line drug for children and adults is trimethoprin-sulfamethoxazole (TMPSMX) (Table 1). The normal dose for adult patients experiencing moderate to severe PCP is 15 to 20 TMP/ kg/day divided into 3 to 4 doses daily. Many patients may experience adverse reactions to TMP-SMX. The most common adverse reaction is rash. Other side effects include fever, nausea and vomiting, elevated liver function studies, hyperkalemia, neutropenia, and thrombocytopenia . A positive response can usually be seen between 5 and 7 days after the initiation of therapy. Therapeutical drug levels must be obtained if the medication is administered orally or intravenously. In children, the TMP concentration should be 5 to 8 µ,g/ mL and the SMX concentration should be 100 to 120 µ,g/mL. 16 Other pharmacologic agents that have been shown to improve the course of illness include pentamidine isethionate, trimetrexate plus leucovorin with or without dapsone, and clindamycin plus primaquine (Table 2). Steroids are considered to be the standard of care in the treatment of adults with PCP. Steroids should be initiated within 72 hours of starting TMPSMX. It is hypothesized that the antipneumocystis agent kills the P. carinii and leads to pulmonary inflammation. The corticosteroids limit the inflammation that develops. 25 Reducing the inflammatory response can improve the patient's oxygenation, resulting in additional oxygen available at the tissue level. Unfortunately, controlled trials using steroids in children with PCP have not been performed; however, uncontrolled data suggest that corticosteroids are beneficial. 16• 18• 20• 23 Prednisone is the drug of choice and is administered 2 mg/kg in divided doses every 6 to 8 hours. This is administered for 1 week, followed by tapered dosing over the next 2 weeks. 16 In addition to medications, other strategies are appropriate for this patient population. These include the administration of appropriate medications, aggressive pulmonary toilet, rest to decrease oxygen demands, monitoring of arterial blood gases, and education of the patient and significant others. It is common for children with PCP to require mechanical ventilation during the course of their illness. 13 Mechanical ventilation is indicated if the Pao 2 decreases to below 60 mm Hg at a fraction of inspired oxygen (F1oi) of 50% or greater. 18 Oxygen is administered to achieve a Pao 2 above
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Table 1
TREATMENT OPTIONS FOR MODERATE TO SEVERE PNEUMOCYSTIS CARINI/ PNEUMONIA
Treatment Regimen
Trimethoprim (TMP)-sulfamethoxazole (SMX) Pentamidine isethionate Trimetrexate plus leucovorin :<:: dapsones§
Clindamycin plus primaquine
Dose(s), Route, Frequency
Side Effect(s)
15 mg/kg (TMP), IV, divided every 6-8 h*
Rash,t fever, NN, j liver function tests, j K+, neutropenia
3-4 mg/kg, IV, once daily
Nephrotoxicity, j K+, ! Ca2+/Mg 2+, j amylase, !fglucose+ Neutropenia, thrombocytopenia, rash, fever, j liver function tests, hemolytic anemia (check G6PD level), methemoglobinemia
45 mg/m 2, IV, once daily, plus 20 mg/m 2, PO, every 6 h :<:: 100 mg, PO, once daily 1800 mg, IV, divided every 6-8 h plus 30 mg (base), PO, once daily
Rash, NN, diarrhea, hemolytic anemia (check G6PD level), methemoglobinemia
• TMP-SMX is dispensed as a fixed combination.
t Mild rash that does not cause bullous skin lesions and does not involve mucous membranes can often be treated with antihistamines first and should not necessarily result in discontinuation of drug. :j: Avoid other nephrotoxic agents (nonsteroidal anti-inflammatory agents, aminoglycosides, foscarnet, amphotericin B). Risk of
hypotension can be minimized if infusion is given over a 2- to 3-h period. A study is in progress comparing TMP-SMX with trimetrexate-dapsone (plus leucovorin). IV = intravenous; PO = orally; NN = nausea and vomiting; G6PD = glucose-6-phosphate dehydrogenase; t = increased; ! = decreased. Adapted from Stansell JD, Huang L: Pneumocystis carinii pneumonia. In Sande Mf\, Volberding PA (eds): The Medical Management of AIDS, ed 5. Philadelphia, WB Saunders, 1997, p 287.
I
70 mm Hg. The F102 should be kept below 0.5 to prevent oxygen toxicity. 1s Data from the last decade indicate a mortality rate of greater than 40% for the initial episode of PCP, with the majority of the survivors living less than 1 year following the episode. 20 These statistics may change with earlier recognition of PCP and initiation of therapy.
Table 2
Rare cases of disseminated P. carinii have been reported. Disseminated infections have occurred in hematopoietic tissues, liver, spleen, thymus, lymph node, thyroid, ear, eye, intestine, and bone marrow. 1s Prophylaxis should be strongly considered in some patients. Primary prophylaxis for adults and adolescents is indicated for HIV-positive patients
PRIMARY AND SECONDARY PROPHYLAXIS OPTIONS FOR PNEUMOCYST/S CARINI/
Prophylaxis Regimen
Trimethoprim (TMP)-sulfamethoxazole (SMX)* Dapsone Aerosolized pentamidine Dapsone plus pyrimethamine
Dose(s), Route, Frequency
Comments
OS tablet, PO, once daily DS tablet, PO, thrice weekly SS tablet, PO, once daily 100 mg, PO, once daily 300 mg, via Respirgard II nebulizer, every 4 wk 100 mg, PO, once daily plus 25 mg, PO, thrice weekly
Also effective prophylaxis against toxoplasmosis and many bacterial pathogens Risk of extrapulmonary P. carinii infection
Atovaquonet • TMl-SMX is dispensed as a fixed combination (single-strength [SS] tablet = TMP 80 mg/SMX 400 mg, double-strength [OS] tablet = TMP 160 mg/SMX 800 mg). t Studies are underway comparing atovaquone with dapsone and with aerosolized pentamidine for P. carinii prophylaxis. PO = orally. Adapted from Stansell JD, Huang L: Pneumocystis carinii pneumonia. In Sande MA, Volberding PA (eds): The Medical Management of AIDS, ed 5. Philadelphia, WB Saunders, 1997, p 294.
HUMAN IMMUNODEFICIENCY VIRUS
with a CD4 + cell count less than 200 cells per cubic millimeter, an unexplained fever higher than 100°F for over 2 weeks, or a history of oropharyngeal candidiasis. 12 The preferred regimen is one double-strength tablet per day of TMP-SMZ. 12 If TMP-SMZ cannot be tolerated, dapsone plus pyrimethamine plus leucovorin or aerosolized pentamidine is given through the Respiragard II (Marguest Medical Products, Englewood, CO) nebulizer. Once a patient has had an episode of PCP, medication is required for the remainder of the individual's life regardless of the CD4+ count. This concept is referred to as "secondary prophylaxis." Prophylaxis options are outlined in Table 2. Patients who do not receive prophylaxis following an episode have a 35% chance of recurrence within 6 months and a 60% chance of recurrence within 1 year. 29 In 1995, the CDC issued revised guidelines for prophylaxis against PCP for children infected with or prenatally exposed to HIVn Once the 21-day course of therapy is completed, the child requires prophylaxis for the remainder of his or her life. Primary prophylaxis is recommended for all infants known to be infected with HIV in the first year of life regardless of their CD4+ cell count because of the high incidence of PCP in this population. 16 Prophylaxis is recommended for infants born to HIV-infected mothers and for children whose HIV status is unknown. Children born to HIV-infected mothers should receive TMP-SMZ beginning 4 to 6 weeks after birth. Discontinuation of therapy should occur if the child is found not to be infected.1 2 Additional interventions for pediatric patients with respiratory distress include bronchodilators, antitussive agents, and chest physiotherapy.
Mycobacterium Tuberculosis The incidence of MTB has increased since the early 1980s. New York City has the highest incidence of MTB. 19, 22 Worldwide estimates reveal 1.7 billion people infected with MTB, with 8 million new cases and 2.9 million deaths annually. 3• 27 MTB is carried in airborne particles called "droplet nuclei. " Each particle is approximately 1 to 5 µm in size. The particles are generated when a person with pulmonary MTB sneezes, coughs, speaks, or sings. Normal air currents keep the particles airborne and can spread them throughout a room or building through the ventilation system. An infection occurs when the airborne particles are inhaled by a susceptible person into the alveoli. Once in the lung, the organism can spread throughout the body. Usually, the body attempts to reduce the spread of bacilli through the initiation of the immune response, which helps to limit the replication of the bacilli. This process occurs within 2 to 10 weeks of exposure. Some bacilli can remain dormant and viable for many years, which is re-
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ferred to as "latent MTB infection." 28 Persons who have been exposed to the MTB bacilli have a positive skin test, have no symptoms of active disease, and are not infectious. They have an estimated 10% lifetime risk of developing active MTB. 4 The clinical presentation of MTB varies with the degree of immunosuppression. Early development of MTB results in a more typical presentation. Later development is associated with an atypical presentation. is, 17 Initial complaints from patients include fever, weight loss, night sweats, and fatigue. MTB is not isolated to the lungs and can spread to other parts of the body, which are listed in Box 2 on this page. Extrapulmonary infection occurs in 40% to 75% of people with a dual diagnosis of MTB and HIV and is more common in patients with advanced HIV disease. 1s. 17 MTB is diagnosed through the use of the tuberculin skin test with purified protein derivative (PPD). The CDC recommends that a reaction of 5 mm in duration or greater to 5 tuberculin U of PPD be considered indicative of tuberculosis infection in HIVpositive individuals. 17Routine evaluation foranergy is not recommended, except for those who are at high risk. 6 The presence of anergy increases as the CD4+ count drops and is tested through intradermal administration of the Candida organism, mumps virus, or tetanus toxoid. 17 Chest radiographs can be useful in the diagnosis; however, they also may be normal or show interstitial infiltrates similar to PCP. The main diagnostic test for pulmonary MTB is the acid-fast smear and culture . This is acco mplished through the examination of three sputum specimens collected on different days. 28 Sputum smears that fail to show acid-fast bacilli do not exclude the diagnosis of MTB. Conventional laboratory methods may require 4 to 8 weeks for results to be reported. New techniques for diagnosis include radiometric culture combined with a DNA probe, which allows identification to occur in 1 to 3 weeks. The most severe form of MTB is multiple drugresistant tuberculosis (MDR-TB), which has also
BOX 2 SITES OF EXTRAPULMONARY MYCOBACTERIUM TUBERCULOSIS INFECTION Lymph nodes Bones Joints Bone marrow
Liver Urine Blood Spleen Cerebrospinal fluid Skin
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increased in the 1990s. MDR-TB is defined as any isolate of MTB that is resistant to two or more antimicrobial agents to which it is usually sensitive. MDR-TB is caused by the ingestion of only single antituberculosis agents for a prolonged period of time and erratic compliance with therapy. Factors that can influence the development of MDR-TB include delays in making the diagnosis of MTB, recognizing the presence ofMDR-TB, and initiating and maintaining isolation. In addition, inadequate ventilation in isolation rooms, lapses in isolation practices, and inadequate precautions for coughinducing procedures contribute to the occurrence of MDR-TB. 3 Collaborative management for MTB is complex and requires that the patient be compliant with therapy. The CDC recommends a four-drug regimen consisting of isoniazid, rifampin, pyrazinamide, and either streptomycin or ethambutol. 9 Rapid sputum conversion and effective treatment occur when adherence to the regimen is maintained. Therapy should continue for a total of 9 months and for at least 6 months after the patient's sputum converts.I· 5 The duration of therapy may be extended if MTB disseminates to other parts of the body. Therapy should include at least two drugs to which the organism is susceptible.17 There are individuals who should receive chemoprophylaxis. Antituberculosis medication should be provided to HIV-positive persons or those at risk for HIV infection who refuse MTB testing. In addition, individuals who have a positive PPD, who are in close contact with those already infected, or who were previously untreated after a positive PPD as well as those whose chest radiograph suggests previously untreated MTB should be treated prophylatically. 6• I2 Therapy consists of isoniazid for 12 months. HIV-infected individuals who have a positive PPD and have no evidence of active disease or a history of treatment should also receive isoniazid for 12 months.I 2 Patients should receive pyridoxine in addition to the isoniazid because of the risk of HIV-infected persons developing peripheral neuropathy.12 MTB is not a common pulmonary complication in children. Nevertheless, infants born to HIVinfected mothers should receive a tuberculin skin test between the ages of 9 and 12 months, and they should be retested every 2 to 3 years. 12 Other management strategies include education about MTB and the need to comply with treatment, assessment, and isolation. Frequent assessment for complications related to the medication regimen is important. A loose stool or diarrhea may indicate malabsorption of antituberculosis medication. The CDC recommends a room with negative airflow that exhausts to the outside and has at least six total air exchanges per hour. Particulate respirator masks should be tested for proper fit to limit exposure. Surgical masks are not appropriate,
as they are not designed to provide a tight face seal or to filter particles in the 1- to 5-µ,m range.
Bacterial Pneumonia
Bacterial infections accounted for 20% of initial AIDS diagnoses in children with HIV infection in 1996. 7 The child must have at least two recurrent bacterial infections within 2 years for a positive diagnosis of AIDS. 10 Staphylococcus species, Strep-
tococcus pneumoniae, Haemophilus injluenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa are the most frequently identified organisms that lead to pneumonia in children. 13• 20 Recurrent pneumonias can predispose children to chronic diseases such as bronchiectasis. Bacterial infections are diagnosed through the use of bacterial cultures when possible. Additional methods of diagnosis include roentgenography, biopsies, and bronchial lavage fluid culture. Organisms cultured from bronchial lavage fluid represent contaminants from the upper airway. Intracellular organisms present by Gram stain are highly suggestive of bacterial pneumoniaw Symptoms of bacterial pneumonia, which can be focal or diffuse, include fever, respiratory distress, and cough. Hypoxemia is also common. Appropriate antibiotics are administered for the maximum normal time range. Intravenous immune globulin has been shown to reduce bacterial infections and hospitalizations in some children with HIV infection. 24
Lymphoid Interstitial Pneumonia/ Pulmonary Lymphoid Hyperplasia
This complication is positive for the diagnosis of AIDS. Io The incidence of LIP in children has declined from 27. 7% to 20. 6% since antiretroviral therapy has become available for the pediatric population.13 LIP consists of a diffuse infiltration of the interstitium of the lung with lymphocytes.20 Pulmonary lymphoid hyperplasia (PLH) differs in that the infiltration is primarily adjacent to the bronchial and bronchiolar walls and consists of bronchialassociated lymphoid tissue hyperplasia. 20 The clinical presentation is usually one of a slow, progressive, insidious course.I 3 The child may experience a nonproductive cough, exertional dyspnea, clubbing, lymphadenopathy, hepatosplenomegaly, and parotid gland enlargement. Breath sounds may be normal, or crackles and wheezes may be heard. A mild elevation in LDH may be seen along with a widened alveolar-arterial oxygen gradient. The chest radiograph typically shows increased reticular markings or a small nodular pat-
HUMAN IMMUNODEFICIENCY VIRUS
tern. LIP-PLH becomes evident after the first year of life, with a median age of 2.5 to 3 years.13· 20 Tachypnea and hypoxemia can be seen as the disease progresses. Elevated serum immunoglobulin levels are associated with LIP-PLH.20 IgG levels above 2500 mg/dL20 are common.
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Diagnosis is determined through a lung biopsy.13· 20 Treatment is supportive and consists of oxygen and corticosteroids. 20 If bacterial pneumonia and bronchiectasis are present, intravenous antibiotics, bronchodilators, and chest physiotherapy are appropriate.13
SUMMARY HIV infection is a chronic illness that affects individuals of all ages. The pulmonary system is the most common body system affected by the disease. Management of these complications has improved over the years and has resulted in a decline in mortality. Critical care nurses should understand the complications that develop and be knowledgeable about the management to improve the patient's clinical outcomes. Assessment for complications must begin once an individual is diagnosed as being infected with HIV and continue throughout the course of the disease. Prevention is the key to limiting respiratory complications and thus improving survival rates.
REFERENCES 1. American Thoracic Society/ Centers for Disease Control and Prevention: Treatment and prevention of tuberculosis in adults and children. American Journal of Respiratory Critical Care Medicine 149:1359, 1994 2. Antinori A, Maiuro G, Pallavicini F, et al: Prognostic factors of early fatal outcome and long-term survival in patients with Pneumocystis carinii pneumonia and acquired immunodeficiency syndrome. Eur J Epidemiol 9:183, 1993 3. Barnes PF, Barrows SA: Tuberculosis in the 1990s. Ann Intern Med 119:400, 1993 4. Barnes PF, Block AB, Davidson PT, et al: Tuberculosis in patients with human immunodeficiency virus infection. N Engl J Med 324:1645, 1991 5. Centers for Disease Control: Tuberculosis and human immunodeficiency virus infection: Recommendations of the Advisory Committee for the Elimination of Tuberculosis (ACET). MMWRMorbidity and Mortality Weekly Report 38:236, 1989 6. Centers for Disease Control and Prevention: Anergy skin testing and preventive therapy for HIV infected persons: Revised recommendations. MMWR Morbidity and Mortality Weekly Report 46:1997 7. Centers for Disease Control and Prevention: HIVI AIDS Surveillance Report. 8:1996 8 Centers for Disease Control and Prevention: HIVI AIDS Surveillance Report. Atlanta, GA, 10:1, 1998 9. Centers for Disease Control and Prevention: Initial therapy for tuberculosis in the era of multidrug resistance. MMWR Morbidity and Mortality Weekly Report 42:1993 10. Centers for Disease Control and Prevention: 1994 Revised classification system for HIV infection in children less than thirteen years of age. MMWR Morbidity and Mortality Weekly Report 43:1994 11. Centers for Disease Control and Prevention: 1995 revised guidelines for prophylaxis against Pneumoncystis carinii pneumonia for children infected with or perinatally exposed to human immunodeficiency virus. MMWR Morbidity and Mortality Weekly Report 44: 1995
12. Centers for Disease Control and Prevention: 1997 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. MMWR Morbidity and Mortality Weekly Report 46:1997 13. Czarniecki L, Rothpletz-Puglia P, Oleske J: Infants and children: AIDS care management. In Ungvarski PJ, Flaskerud]H (eds): HIV/ AIDS: A Guide to Primary Care Management, ed 4. Philadelphia, WB Saunders, 1999, p 98 14. Dooley SW, Castro KG, Hutton MD, et al: Guidelines for preventing the transmission of tuberculosis in health care settings with special focus o n HIV-related issues. MMWR Morbidity and Mortality Weekly Report 39:1990 15. Haas OW, Des Prez RM: Mycobacterium tuberculosis. In Mandell CL, Bennett JE, Dolin R (eds): Principles and Practice of Infectious Diseases, ed 4. New York, Churchill Livingstone, 1995, p 2213 16. Hicks P: Human immunodeficiency virus infection. In Levin DL, Morris FC (eds): Essentials of Pediatric Intensive Care, ed 2. New York, Churchill Livingstone, 1997, p 437 17. Hopewell PC: Tuberculosis in persons with human immunodeficiency viral infection. In Sande MA, Volberding PA (eds): The Medical Management of AIDS, ed 5. Philadelphia, WB Saunders, 1997, p 311 18. Hughes, W: Pneumocystis carinii pneumonitis. In Chernick V, Boat TF (eds): Kendig's Disorders of the Respiratory Tract in Children. Philadelphia, WB Saunders, 1998, p 503 19. ]ones]L, Burwen DL, Fleming PL, et al: Tuberculosis among AIDS patients in the United States, 1993. Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 12:293, 1996 20. Kattan M: Pulmonary disorders in pediatric HIV infection. In Chernick V, Boat TF (eds): Kendig's Disorders of the Respiratory Tract in Children. Philadelphia, WB Saunders, 1998, p 1153 21. Lipman ML, Godstein E: Serum lactic dehydrogenase predicts mortality in patients with AIDS and pneumocystis pneumonia. West J Med 149:486, 1988
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22. Markowitz N, Hansen NI, Hopewell PC, et al: Incidence of tuberculosis in the United States among HN-infected persons. Ann Intern Med 126:123, 1997 23. McLaughlin GE, Virdee SS, Schleien CL, et al: Effect of corticosteroids on survival of children with acquired immunodeficiency syndrome and Pneumocystis carlnii-related respiratory failure. J Pediatr 126: 821, 1995 24. National Institute of Child Health and Human Development: Intravenous immune globulin for the prevention of bacterial infections in children with symptomatic human immunodeficiency virus infection. N Engl J Med 325:73, 1991 25. National Institutes of Health-University of California Expert Panel for Corticosteroids as Adjunctive Therapy for Pneumocystis Pneumonia: Consensus statement on the use of corticosteroids as adjunctive therapy for pneumocystis pneumonia in the acquired immunodeficiency syndrome. N Engl J Med 323: 1500, 1991
26. Ng VL, Yajko DM, McPhaul LW, et al: Evaluation of an indirect fluorescent-antibody stain for detection of Pneumocystis carlnii in respiratory specimens. J Clin Microbiol 28:975, 1990 27. Pablos-Mendez A, Sterling TR, Frieden TR: The relationship between delayed or incomplete treatment and all-cause mortality in patients with tuberculosis. JAMA 276:1223, 1996 28. Staat HA, Sheran M, Herr R: Adolescents and adults: Care management of AIDS-indicator diseases. In Ungvarski PJ, FlaskerudJH (eds): HIV/ AIDS: A Guide to Primary Care Management, ed 4. Philadelphia, WB Saunders, 1999, p 194 29. Stansell JD , Huang L: Pneumocystis carlnii pneumonia. In Sande MA, Volberding PA (eds): The Medical Management of AIDS, ed 5. Philadelphia, WB Saunders, 1997, p 275 30. Zaman MK, White DA: Serum lactate dehydrogenase levels and Pneumocystis carlnii pneumonia. Diagnostic and prognostic significance. Am Rev Respir Dis 137:796, 1988.
Address reprint requests to Kimmith M. Jones, RN, MS, CCRN Sinai Hospital of Baltimore 2401 West Belvedere Avenue Baltimore, MD 21215-5271
Human Immunodeficiency Virus Disease Managing Respiratory Complications Through the Life Span Kimmith M. Jones, RN, MS, CCRN
M any lives have been affected by human immunodeficiency virus (HIV) disease. Current world estimates indicate that about 30.6 million people are living with HIV disease. Of these, 29.5 million are adults and 1.1 million are children under 15 years of age. Roughly, 11.7 million people have died from acquired immunodeficiency syndrome (AIDS) since the epidemic was first identified in the early 1980s. If the current trend continues, 60 to 70 million people should be infected with HIV by the end of the year 2000 (Global AIDS Policy Coalition). In the United States, 665,357 individuals have been reported to have developed AIDS, with the highest incidence occurring in New York (19%), California (16%), Florida (10%), Texas (7%), and New Jersey (6%) (Fig. 1). 8 Of these individuals, 401,028 have died from the disease, representing a 60% mortality rate. 8 The incidence of AIDS decreased in 1997 compared with 1996 by 15%. It is thought that the decrease is related to new therapies . Decreases were seen more in men (16%) than in women (8%), and the smallest decreases were seen in the South (12%), among African Americans (9%) and among persons infected through heterosexual contact (6% in women, 3% in men). 8 AIDS-related deaths decreased by 42% between 1996 and 1997. The largest declines in AIDS-related From the Department of Critical Care and the Emergency Center, Sinai Hospital of Baltimore, and the University of Maryland School of Nursing, Baltimore, Maryland
deaths were observed in the West (51%), among whites (52%) and among male homosexuals (49%). 8 Thirty-one of the 50 states report every case of HIV infection to the Centers for Disease Control and Prevention (CDC). In those states that report, 15% of the HIV infections occurred in the 13 to 24 age group. Women accounted for 32% of all of the HIV infections and 49% of the infections between the ages of 13 and 24 years. African Americans and Hispanics accounted for 78% of all reported HIV infections. 8 AIDS was initially described in children in 1982. Since that time, 8280 children under the age of 13 years have been reported to the CDC as having AIDS (Fig. 2). 8 Many drugs have been developed and approved for use in the pediatric population to slow the replication of the virus and to alter the immune response. As a result, the survival rate has improved. Since the general screening of blood products for HIV began in the United States in 1985, 87% of the cases of AIDS in children under 13 years old have been the result of acquired HIV infection through vertical transmission from their mothers. 16• 20 The rate of vertical transmission has declined from 26% to 8% since the introduction of zidovudine to pregnant women. Administration of zidovudine to women antepartum and postpartum and to infants 6 weeks after delivery has been shown to significantly reduce the risk of transmission to the fetus and to infants. 20 Vertical transmis-
CRITICAL CARE NURSING CLINICS OF NORTH AMERICA I Volume 11 I Number 4 I December 1999
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42% Other
19% New York
6% New Jersey 7% Texas
10% Florida
16% California
Figure 1. States with the highest incidence of AIDS. (Data from Centers for Disease Control and Prevention: HIV/AIDS Surveillance Report 10:1, 1998.)
sion is more likely to occur at the time of delive1y. During that time, fe tal exposure to maternal blood is more likely, which increases the risk of transmission. Infants and young children can also acquire infection through breastfeeding and sexual abuse. 20 Similar to adults, adolescents typically acquire HIV infection through sexual transmission and intravenous drug use.io Opportunistic illnesses appear in children with HIV at higher CD4+ levels than in adults. 16 No organ system can escape the ravages of HIV. The multisystem complications that develop are
Adults 657,077
the result of a decrease in immune system function and an increase in opportunistic J!!nesses characteristic of HIV. Understanding the complications of the disease is more crucial now than ever, because increasing numbers of individuals are being admitted to critical care environments with HIV disease. Respiratory complications commonly plague individuals with HIV from infancy to adulthood. Age can infuence the presentation of the complication, its management, and the individual's survival. Pulmonary problems are often the first manifestation of HIV infection in both children and adults. 20·29 The most common pulmonary complica-
Children
8280
Figure 2. Cumulative number of reported AIDS cases from 1981 to June, 1998. Total number reported 665,357. (Data from Centers for Disease Control and Prevention: HIV/AIDS Surveillance Report 10:1, 1998.)
HUMAN IMMUNODEFICIENCY VIRUS
tions in children include Pneumocystis canmt pneumonia (PCP), Jymphocytic interstitial pneumonia (LIP), and bacterial pneumonia . In adults, the common complications are PCP and Mycobacterium tuberculosis(MTB). Other pulmonary complications may develop and are listed in Box 1 on this page. 20
Pneumocystis Carinii Pneumonia PCP affects individuals of all ages and remains the most common AIDS-defining opportunistic infection in children and adults. PCP is also the most common complication of HIV-infected children in the pediatric intensive care unit. 16• 18 Historical data indicate that PCP accounted for almost two thirds of AIDS index diagnoses in adults; however, recent data suggest a reduction in this proportion primarily as a result of prophylaxis. As many as 85% of patients with HIV develop PCP once during the course of their disease. Improved clinical outcomes and longer life expectancy for those at risk are
Box 1 PULMONARY COMPLICATIONS OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION Infections Viruses Cytomegalovirus Respiratory syncytial virus Herpes simplex virus Parainfluenza virus Influenza virus Adenovirus Bacteria Encapsulated organisms (e.g ., Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus) Gram-negative organisms (e.g., Escherichia coli, Klebsiella species, Pseudomonas aeruginosa) Mycobacterium tuberculosis Mycobacterium avium-intracellulare Fungi Pneumocystis carinii Candida albicans Histoplasma capsulatum Cryptococcus neoformans Aspergillus species Coccidioides immitis Interstitial pneumonia Lymphoid interstitial pneumonia Pulmonary lymphoid hyperplasia Desquamative interstitial pneumonia Malignancies Kaposi's sarcoma Lymphoma
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direct results of the improved management of acute pneumonia and the routine use of secondary prophylaxis. P. cariniiwas initially thought to be a protozoan. This misconception continued for about 80 years until two independent research groups presented information indicating that the organism was a fungus. The exact lineage is still unclear; however, the connection to the fungus kingdom still exists. 29 The incidence of PCP varies with the age of the child. The younger the child, the higher is the incidence of PCP. The sooner PCP develops during the course of disease, the poorer is the prognosis. It is estimated that the risk of developing PCP in the first year of life is between 7% and 20% for infants who are HIV-positive. The median age of presentation is 5 months of age. 16• 18• 20 PCP is usually a primary infection in children and a reactivation of a latent infection secondary to severely compromised immune defenses in adults. 16• 20 P. carinii can be found in the lungs of all humans, and a majority of humans develop antibodies to P. carinii by the age of 4 years. 13• 29 The fungus establishes residence in the alveoli and attaches itself to the type I cells. 29 The immunocompetent individual can keep the fungus under control ; however, the individual with a compromised immune system cannot do the same. This leads to the overwhelming complication of respiratory failure and pneumonia. The fungus attaches to the alveolar epithelium, which leads to desquamation of the alveolar cells. A diffuse alveolitis develops as the infection progresses. The alveoli become filled with a foamy exudate consisting of alveolar macrophages and cysts containing P . carinii. 20 This results in lung tissue that is heavy and noncompliant. 18 In adults, P. carinii begins to become evident in the form of pneumonia when the individual's CD4+ cell count drops to below 200 cells per cubic millimeter and remains there. It also can present as disseminated disease; however, that is rare. Symptoms usually progress more rapidly in children, and survival times are shorter than in adults. 13 The clinical presentation in children typically consists of an acute onset of cough, fever, tachypnea, dyspnea, and retractions. Crackles or diminished breath sounds may also be present on auscultation. Hypoxemia is commonly present along with an elevated serum lactic dehydrogenase (LDH). 13· 18• 20 In addition to a decrease in Pao 2, a widened alveolar-arterial gradient and intrapulmonary shunt are present. 18 Chest radiographs are helpful in diagnosing PCP. Typically, the chest radiograph shows diffuse interstitial infiltrates or an alveolar pattern; however, patients may also present with a normal chest radiograph (Fig. 3). 18• 29 If left untreated, the infiltrates can progress, resulting in the need for intubation and mechanical ventilation (Fig. 4).
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Figure 3. Chest roentgenogram showing evidence of moderately severe Pneumocystis carinii pneumonitis. The pattern is one of diffuse alveolar disease with bilateral distribution . The superior portions of the upper lobes are usually the least involved , and the perihilar areas are the most commonly affected sites. Air bronchograms are discernible . (From Hughes W: Pneumocystis carinii pneumonitis. In Chernick V, Boat TF [eds] : Kendig's Disorders of the Respiratory Tract in Children. Philadelphia, WB Saunders , 1998, p 505 .)
Figure 4. Chest radiograph of a 3-month-old infant presenting with Pneumocystis carinii pneumonia. A, The initial radiograph shows a bilateral infiltrate most prominent in the perihilar region. 8, Chest radiograph taken 1 week later shows progression of disease with opacification of both lung fields. (From Kattan M: Pulmonary disorders in pediatric HIV infection . In Chernick V, Boat TF [eds] : Kendig's Disorders of the Respiratory Tract in Children. Philadelphia, WB Saunders, 1998, p 1157.)
HUMAN IMMUNODEFICIENCY VIRUS
Adults who develop PCP can present with a variety of signs and symptoms that usually progress slowly. These include fever, dyspnea, fatigue, anorexia, tachypnea, slow progressive dyspnea on exertion, decreased exercise tolerance, and a nonproductive cough. Unfortunately, the physical examination is not too helpful when determining the presence of PCP. Typically, the Jung examination and auscultation are normal. Sometimes, fine basilar rales can be heard. 29 There are, however, several other ways to diagnose this complication. Ninety-five percent of patients with PCP present with an elevated LDH. This is the most consistent abnormality in both adults and children. 13• 18• 20 LDH levels greater than 1000 IU/ L are often associated with PCP; however, elevated LDH is not specific for PCP. LDH is a nonspecific marker of pulmonary parenchymal damage and is not usually elevated in pneumonias from other organisms. The sensitivity of an elevated LDH for PCP has been reported to be 83% to 100%. 29 Several factors may influence the sensitivity of the serum LDH value, including the severity of illness and the specific patient population being evaluated. 29 Studies have shown a correlation between an elevated LDH and mortality. An elevated LDH, despite therapy, correlates with a lower rate of survival, a failure of therapy, and an increase in the mortality rate. 2• 21 • 30 In contrast, a low or falling LDH correlates with a better prognosis, a response to therapy, and a decline in the mortality rate. The arterial blood gas can be used as a tool to detect PCP in both children and adults. Twentyfive percent of patients have a Pao 2 greater than 80 mm Hg and show an uncompensated respiratory alkalosis. The respiratory alkalosis is caused by the body's attempt to improve the delivery of oxygen to the tissues. This results in the expiration of carbon dioxide, which leads to the development of an alkalotic state. Patients with PCP also show a widened alveolar-arterial gradient with mild to severe hypoxemia. Sputum samples are useful as a diagnostic tool. Usually, an induced sputum sample is required because of a nonproductive cough. The sensitivity of induced sputum examinations ranges from 74% to 83%. 29 Newer technology using direct and indirect fluorescent antibody techniques has improved the sensitivity of induced sputum samples. 26 Sputum induction has been used to obtain sputum samples in children, but, typically, the child is over 2 years of age for this technique to be successful. If a sputum sample cannot be obtained or the result is negative, a bronchoalveolar lavage via bronchoscopy is performed. Bronchoalveolar lavage is a reliable method for establishing a diagnosis and identifies the organism in 95% to 990Ai of the patients with PCP. 16 Once the sample is obtained, the sputum is examined using a Gomori methenamine
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silver stain technique. This test looks for the presence of P. carinii colonies within the white blood cells of the patient. In children, the diagnosis can be accomplished by obtaining either a gastric or bronchial washing to isolate the organism. Diagnosis in children relies on the identification of P. carinii from these washings or directly from lung tissue. Collaborative management of the patient with PCP is essential. The first-line drug for children and adults is trimethoprin-sulfamethoxazole (TMPSMX) (Table 1). The normal dose for adult patients experiencing moderate to severe PCP is 15 to 20 TMP/ kg/day divided into 3 to 4 doses daily. Many patients may experience adverse reactions to TMP-SMX. The most common adverse reaction is rash. Other side effects include fever, nausea and vomiting, elevated liver function studies, hyperkalemia, neutropenia, and thrombocytopenia . A positive response can usually be seen between 5 and 7 days after the initiation of therapy. Therapeutical drug levels must be obtained if the medication is administered orally or intravenously. In children, the TMP concentration should be 5 to 8 µ,g/ mL and the SMX concentration should be 100 to 120 µ,g/mL. 16 Other pharmacologic agents that have been shown to improve the course of illness include pentamidine isethionate, trimetrexate plus leucovorin with or without dapsone, and clindamycin plus primaquine (Table 2). Steroids are considered to be the standard of care in the treatment of adults with PCP. Steroids should be initiated within 72 hours of starting TMPSMX. It is hypothesized that the antipneumocystis agent kills the P. carinii and leads to pulmonary inflammation. The corticosteroids limit the inflammation that develops. 25 Reducing the inflammatory response can improve the patient's oxygenation, resulting in additional oxygen available at the tissue level. Unfortunately, controlled trials using steroids in children with PCP have not been performed; however, uncontrolled data suggest that corticosteroids are beneficial. 16• 18• 20• 23 Prednisone is the drug of choice and is administered 2 mg/kg in divided doses every 6 to 8 hours. This is administered for 1 week, followed by tapered dosing over the next 2 weeks. 16 In addition to medications, other strategies are appropriate for this patient population. These include the administration of appropriate medications, aggressive pulmonary toilet, rest to decrease oxygen demands, monitoring of arterial blood gases, and education of the patient and significant others. It is common for children with PCP to require mechanical ventilation during the course of their illness. 13 Mechanical ventilation is indicated if the Pao 2 decreases to below 60 mm Hg at a fraction of inspired oxygen (F1oi) of 50% or greater. 18 Oxygen is administered to achieve a Pao 2 above
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Table 1
TREATMENT OPTIONS FOR MODERATE TO SEVERE PNEUMOCYSTIS CARINI/ PNEUMONIA
Treatment Regimen
Trimethoprim (TMP)-sulfamethoxazole (SMX) Pentamidine isethionate Trimetrexate plus leucovorin :<:: dapsones§
Clindamycin plus primaquine
Dose(s), Route, Frequency
Side Effect(s)
15 mg/kg (TMP), IV, divided every 6-8 h*
Rash,t fever, NN, j liver function tests, j K+, neutropenia
3-4 mg/kg, IV, once daily
Nephrotoxicity, j K+, ! Ca2+/Mg 2+, j amylase, !fglucose+ Neutropenia, thrombocytopenia, rash, fever, j liver function tests, hemolytic anemia (check G6PD level), methemoglobinemia
45 mg/m 2, IV, once daily, plus 20 mg/m 2, PO, every 6 h :<:: 100 mg, PO, once daily 1800 mg, IV, divided every 6-8 h plus 30 mg (base), PO, once daily
Rash, NN, diarrhea, hemolytic anemia (check G6PD level), methemoglobinemia
• TMP-SMX is dispensed as a fixed combination.
t Mild rash that does not cause bullous skin lesions and does not involve mucous membranes can often be treated with antihistamines first and should not necessarily result in discontinuation of drug. :j: Avoid other nephrotoxic agents (nonsteroidal anti-inflammatory agents, aminoglycosides, foscarnet, amphotericin B). Risk of
hypotension can be minimized if infusion is given over a 2- to 3-h period. A study is in progress comparing TMP-SMX with trimetrexate-dapsone (plus leucovorin). IV = intravenous; PO = orally; NN = nausea and vomiting; G6PD = glucose-6-phosphate dehydrogenase; t = increased; ! = decreased. Adapted from Stansell JD, Huang L: Pneumocystis carinii pneumonia. In Sande Mf\, Volberding PA (eds): The Medical Management of AIDS, ed 5. Philadelphia, WB Saunders, 1997, p 287.
I
70 mm Hg. The F102 should be kept below 0.5 to prevent oxygen toxicity. 1s Data from the last decade indicate a mortality rate of greater than 40% for the initial episode of PCP, with the majority of the survivors living less than 1 year following the episode. 20 These statistics may change with earlier recognition of PCP and initiation of therapy.
Table 2
Rare cases of disseminated P. carinii have been reported. Disseminated infections have occurred in hematopoietic tissues, liver, spleen, thymus, lymph node, thyroid, ear, eye, intestine, and bone marrow. 1s Prophylaxis should be strongly considered in some patients. Primary prophylaxis for adults and adolescents is indicated for HIV-positive patients
PRIMARY AND SECONDARY PROPHYLAXIS OPTIONS FOR PNEUMOCYST/S CARINI/
Prophylaxis Regimen
Trimethoprim (TMP)-sulfamethoxazole (SMX)* Dapsone Aerosolized pentamidine Dapsone plus pyrimethamine
Dose(s), Route, Frequency
Comments
OS tablet, PO, once daily DS tablet, PO, thrice weekly SS tablet, PO, once daily 100 mg, PO, once daily 300 mg, via Respirgard II nebulizer, every 4 wk 100 mg, PO, once daily plus 25 mg, PO, thrice weekly
Also effective prophylaxis against toxoplasmosis and many bacterial pathogens Risk of extrapulmonary P. carinii infection
Atovaquonet • TMl-SMX is dispensed as a fixed combination (single-strength [SS] tablet = TMP 80 mg/SMX 400 mg, double-strength [OS] tablet = TMP 160 mg/SMX 800 mg). t Studies are underway comparing atovaquone with dapsone and with aerosolized pentamidine for P. carinii prophylaxis. PO = orally. Adapted from Stansell JD, Huang L: Pneumocystis carinii pneumonia. In Sande MA, Volberding PA (eds): The Medical Management of AIDS, ed 5. Philadelphia, WB Saunders, 1997, p 294.
HUMAN IMMUNODEFICIENCY VIRUS
with a CD4 + cell count less than 200 cells per cubic millimeter, an unexplained fever higher than 100°F for over 2 weeks, or a history of oropharyngeal candidiasis. 12 The preferred regimen is one double-strength tablet per day of TMP-SMZ. 12 If TMP-SMZ cannot be tolerated, dapsone plus pyrimethamine plus leucovorin or aerosolized pentamidine is given through the Respiragard II (Marguest Medical Products, Englewood, CO) nebulizer. Once a patient has had an episode of PCP, medication is required for the remainder of the individual's life regardless of the CD4+ count. This concept is referred to as "secondary prophylaxis." Prophylaxis options are outlined in Table 2. Patients who do not receive prophylaxis following an episode have a 35% chance of recurrence within 6 months and a 60% chance of recurrence within 1 year. 29 In 1995, the CDC issued revised guidelines for prophylaxis against PCP for children infected with or prenatally exposed to HIVn Once the 21-day course of therapy is completed, the child requires prophylaxis for the remainder of his or her life. Primary prophylaxis is recommended for all infants known to be infected with HIV in the first year of life regardless of their CD4+ cell count because of the high incidence of PCP in this population. 16 Prophylaxis is recommended for infants born to HIV-infected mothers and for children whose HIV status is unknown. Children born to HIV-infected mothers should receive TMP-SMZ beginning 4 to 6 weeks after birth. Discontinuation of therapy should occur if the child is found not to be infected.1 2 Additional interventions for pediatric patients with respiratory distress include bronchodilators, antitussive agents, and chest physiotherapy.
Mycobacterium Tuberculosis The incidence of MTB has increased since the early 1980s. New York City has the highest incidence of MTB. 19, 22 Worldwide estimates reveal 1.7 billion people infected with MTB, with 8 million new cases and 2.9 million deaths annually. 3• 27 MTB is carried in airborne particles called "droplet nuclei. " Each particle is approximately 1 to 5 µm in size. The particles are generated when a person with pulmonary MTB sneezes, coughs, speaks, or sings. Normal air currents keep the particles airborne and can spread them throughout a room or building through the ventilation system. An infection occurs when the airborne particles are inhaled by a susceptible person into the alveoli. Once in the lung, the organism can spread throughout the body. Usually, the body attempts to reduce the spread of bacilli through the initiation of the immune response, which helps to limit the replication of the bacilli. This process occurs within 2 to 10 weeks of exposure. Some bacilli can remain dormant and viable for many years, which is re-
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ferred to as "latent MTB infection." 28 Persons who have been exposed to the MTB bacilli have a positive skin test, have no symptoms of active disease, and are not infectious. They have an estimated 10% lifetime risk of developing active MTB. 4 The clinical presentation of MTB varies with the degree of immunosuppression. Early development of MTB results in a more typical presentation. Later development is associated with an atypical presentation. is, 17 Initial complaints from patients include fever, weight loss, night sweats, and fatigue. MTB is not isolated to the lungs and can spread to other parts of the body, which are listed in Box 2 on this page. Extrapulmonary infection occurs in 40% to 75% of people with a dual diagnosis of MTB and HIV and is more common in patients with advanced HIV disease. 1s. 17 MTB is diagnosed through the use of the tuberculin skin test with purified protein derivative (PPD). The CDC recommends that a reaction of 5 mm in duration or greater to 5 tuberculin U of PPD be considered indicative of tuberculosis infection in HIVpositive individuals. 17Routine evaluation foranergy is not recommended, except for those who are at high risk. 6 The presence of anergy increases as the CD4+ count drops and is tested through intradermal administration of the Candida organism, mumps virus, or tetanus toxoid. 17 Chest radiographs can be useful in the diagnosis; however, they also may be normal or show interstitial infiltrates similar to PCP. The main diagnostic test for pulmonary MTB is the acid-fast smear and culture . This is acco mplished through the examination of three sputum specimens collected on different days. 28 Sputum smears that fail to show acid-fast bacilli do not exclude the diagnosis of MTB. Conventional laboratory methods may require 4 to 8 weeks for results to be reported. New techniques for diagnosis include radiometric culture combined with a DNA probe, which allows identification to occur in 1 to 3 weeks. The most severe form of MTB is multiple drugresistant tuberculosis (MDR-TB), which has also
BOX 2 SITES OF EXTRAPULMONARY MYCOBACTERIUM TUBERCULOSIS INFECTION Lymph nodes Bones Joints Bone marrow
Liver Urine Blood Spleen Cerebrospinal fluid Skin
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increased in the 1990s. MDR-TB is defined as any isolate of MTB that is resistant to two or more antimicrobial agents to which it is usually sensitive. MDR-TB is caused by the ingestion of only single antituberculosis agents for a prolonged period of time and erratic compliance with therapy. Factors that can influence the development of MDR-TB include delays in making the diagnosis of MTB, recognizing the presence ofMDR-TB, and initiating and maintaining isolation. In addition, inadequate ventilation in isolation rooms, lapses in isolation practices, and inadequate precautions for coughinducing procedures contribute to the occurrence of MDR-TB. 3 Collaborative management for MTB is complex and requires that the patient be compliant with therapy. The CDC recommends a four-drug regimen consisting of isoniazid, rifampin, pyrazinamide, and either streptomycin or ethambutol. 9 Rapid sputum conversion and effective treatment occur when adherence to the regimen is maintained. Therapy should continue for a total of 9 months and for at least 6 months after the patient's sputum converts.I· 5 The duration of therapy may be extended if MTB disseminates to other parts of the body. Therapy should include at least two drugs to which the organism is susceptible.17 There are individuals who should receive chemoprophylaxis. Antituberculosis medication should be provided to HIV-positive persons or those at risk for HIV infection who refuse MTB testing. In addition, individuals who have a positive PPD, who are in close contact with those already infected, or who were previously untreated after a positive PPD as well as those whose chest radiograph suggests previously untreated MTB should be treated prophylatically. 6• I2 Therapy consists of isoniazid for 12 months. HIV-infected individuals who have a positive PPD and have no evidence of active disease or a history of treatment should also receive isoniazid for 12 months.I 2 Patients should receive pyridoxine in addition to the isoniazid because of the risk of HIV-infected persons developing peripheral neuropathy.12 MTB is not a common pulmonary complication in children. Nevertheless, infants born to HIVinfected mothers should receive a tuberculin skin test between the ages of 9 and 12 months, and they should be retested every 2 to 3 years. 12 Other management strategies include education about MTB and the need to comply with treatment, assessment, and isolation. Frequent assessment for complications related to the medication regimen is important. A loose stool or diarrhea may indicate malabsorption of antituberculosis medication. The CDC recommends a room with negative airflow that exhausts to the outside and has at least six total air exchanges per hour. Particulate respirator masks should be tested for proper fit to limit exposure. Surgical masks are not appropriate,
as they are not designed to provide a tight face seal or to filter particles in the 1- to 5-µ,m range.
Bacterial Pneumonia
Bacterial infections accounted for 20% of initial AIDS diagnoses in children with HIV infection in 1996. 7 The child must have at least two recurrent bacterial infections within 2 years for a positive diagnosis of AIDS. 10 Staphylococcus species, Strep-
tococcus pneumoniae, Haemophilus injluenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa are the most frequently identified organisms that lead to pneumonia in children. 13• 20 Recurrent pneumonias can predispose children to chronic diseases such as bronchiectasis. Bacterial infections are diagnosed through the use of bacterial cultures when possible. Additional methods of diagnosis include roentgenography, biopsies, and bronchial lavage fluid culture. Organisms cultured from bronchial lavage fluid represent contaminants from the upper airway. Intracellular organisms present by Gram stain are highly suggestive of bacterial pneumoniaw Symptoms of bacterial pneumonia, which can be focal or diffuse, include fever, respiratory distress, and cough. Hypoxemia is also common. Appropriate antibiotics are administered for the maximum normal time range. Intravenous immune globulin has been shown to reduce bacterial infections and hospitalizations in some children with HIV infection. 24
Lymphoid Interstitial Pneumonia/ Pulmonary Lymphoid Hyperplasia
This complication is positive for the diagnosis of AIDS. Io The incidence of LIP in children has declined from 27. 7% to 20. 6% since antiretroviral therapy has become available for the pediatric population.13 LIP consists of a diffuse infiltration of the interstitium of the lung with lymphocytes.20 Pulmonary lymphoid hyperplasia (PLH) differs in that the infiltration is primarily adjacent to the bronchial and bronchiolar walls and consists of bronchialassociated lymphoid tissue hyperplasia. 20 The clinical presentation is usually one of a slow, progressive, insidious course.I 3 The child may experience a nonproductive cough, exertional dyspnea, clubbing, lymphadenopathy, hepatosplenomegaly, and parotid gland enlargement. Breath sounds may be normal, or crackles and wheezes may be heard. A mild elevation in LDH may be seen along with a widened alveolar-arterial oxygen gradient. The chest radiograph typically shows increased reticular markings or a small nodular pat-
HUMAN IMMUNODEFICIENCY VIRUS
tern. LIP-PLH becomes evident after the first year of life, with a median age of 2.5 to 3 years.13· 20 Tachypnea and hypoxemia can be seen as the disease progresses. Elevated serum immunoglobulin levels are associated with LIP-PLH.20 IgG levels above 2500 mg/dL20 are common.
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Diagnosis is determined through a lung biopsy.13· 20 Treatment is supportive and consists of oxygen and corticosteroids. 20 If bacterial pneumonia and bronchiectasis are present, intravenous antibiotics, bronchodilators, and chest physiotherapy are appropriate.13
SUMMARY HIV infection is a chronic illness that affects individuals of all ages. The pulmonary system is the most common body system affected by the disease. Management of these complications has improved over the years and has resulted in a decline in mortality. Critical care nurses should understand the complications that develop and be knowledgeable about the management to improve the patient's clinical outcomes. Assessment for complications must begin once an individual is diagnosed as being infected with HIV and continue throughout the course of the disease. Prevention is the key to limiting respiratory complications and thus improving survival rates.
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