SECTION V. Hematologic System
A AIDS/HIV Infection
DEFINITION
Human immunodeficiency virus (HIV) is the most significant etiology of secondary immunosuppression that can result from infection that causes depletion of immune cells. The virus exists as two main types, HIV-1 and HIV-2. Of the two, HIV-1 is more prevalent and more pathogenic. The primary targets of HIV infection are CD4 + lymphocytes. A glycoprotein on the viral envelope binds to the CD4 antigen to allow the virus to enter the T cell. HIV is a retrovirus, i.e., its genome contains 2 strands of single-stranded RNA. After the virus enters the host cell, its RNA undergoes reverse transcription to produce complementary DNA that is incorporated into the host cell DNA. Synthesis of new viral RNA then occurs in the host cell, followed by formation of new virus particles and their release to infect other CD4 + cells. Infection with HIV alters T cell function and causes cytotoxicity, leading to the characteristic decline in CD4 + cells. Exactly how HIV infection kills T cells, though, is not known and may involve several mechanisms. Ultimately, with a sufficient fall in CD4 + cells, individuals become susceptible to life-threatening opportunistic infections.
EPIDEMIOLOGY
The epidemiologic basis for HIV infection begins with transmission of the virus through certain body fluids. In 2004, it was estimated that 40 million individuals worldwide were infected with HIV, with an annual incidence of 5 million cases. Infection with HIV can progress to acquired immune deficiency syndrome (AIDS) and fatal disease. While more than 25 million individuals have died as a result of AIDS complications since the first description of the disease, early detection, evaluation, and pharmacologic intervention have become very successful in controlling HIV infection in many individuals while preserving immune system integrity.
The potential sources of transmission of HIV are blood contact, sexual transmission, and perinatal exposure (see box on p. 110).
Acute infection with HIV is characterized by a mononucleosis-like illness, in which release of inflammatory mediators, including IL-1 and TNF-α, causes symptoms such as malaise, fever, myalgias, and rash. At the same time, a transient decline in circulating CD4 + cells occurs. Over several weeks following the primary infection, antibodies directed against virus envelope proteins are produced, and cytotoxic T lymphocytes (CTLs) begin to kill infected T cells that display HIV peptides. These immune responses permit resolution of the symptoms of acute infection; however anti-HIV antibodies
Routes of HIV Transmission
Absolute
Blood
Body fluids containing blood
Possible
Cerebrospinal fluid
Pericardial fluids
Amniotic fluids
Semen, vaginal secretions
Synovial fluid
Pleural fluid
Remote
Feces
Saliva
Sputum
Sweat
Tears
Urine
Wound drainage
Nasal secretions
Not Implicated in Health Care Settings
Human breast milk
Spontaneous resolution of the acute symptoms of HIV infection is followed by a variable period of asymptomatic infection. If the infection is not treated, a gradual, progressive fall in CD4 + cells occurs in conjunction with a gradual increase in the plasma viral load. Progression to AIDS in untreated individuals occurs in an average time of 10 years, though in some individuals progression may occur much more rapidly or perhaps not at all. With respect to the latter possibility, there are reports of individuals who have not developed AIDS despite multiple exposures to HIV, suggesting that the adaptive immune system in some individuals may provide chronic protection by an as yet undefined mechanism. Clinically, AIDS is defined as a CD4 + cell count less than 200 cells/μL or by the presence of an AIDS-indicator condition (discussed later).
TREATMENT
Many years of research have produced numerous agents for combating HIV infection. Most current therapies involve a “cocktail” of antiretroviral agents that can include nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PI), and a fusion inhibitor. A combination of three or four agents, known as highly active antiretroviral therapy (HAART), is now the usual therapeutic approach.
Antiretroviral therapy of HIV infection is based on the following principles:
• Start treatment before immunodeficiency becomes evident.
• Aim to reduce plasma viral concentration as much as possible for as long as possible.
• Use a combination of three or four antiretroviral drugs, i.e., highly active antiretroviral therapy (HAART).
• Monitor plasma viral load and CD4 + cell count.
• Change to a different regimen if plasma viral concentration increases.
Drugs used for treatment of HIV infection include the following:
• Nucleoside reverse transcriptase inhibitors (NRTIs): zidovudine, lamivudine, didanosine, emtricitrabine, stavudine, and abacavir
• Nonnucleoside RTIs (NNRTIs): delavirdine, efavirenz, and nevirapine
• Protease inhibitors: amprenavir, indinavir, ritonavir, saquinavir, and tipranavir
• Fusion inhibitors: enfuvirtide
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
The NRTIs bind to and inhibit the viral reverse transcriptase enzyme responsible for production of HIV RNA. The prototype agent in this class is zidovudine, also known as AZT, which was the first antiretroviral drug to be approved by the Food and Drug Administration for treatment of HIV infection. Resistance to zidovudine may occur with certain HIV strains, and the most significant side effect of AZT therapy is bone marrow suppression, which causes anemia and neutropenia.
Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Like the NRTIs, the NNRTIs bind to and inhibit the viral reverse transcriptase enzyme, but at a different molecular site. Resistance to NNRTI monotherapy can readily occur, and adverse effects include skin rash and, uncommonly, Stevens-Johnson syndrome. NNRTIs are metabolized by hepatic CYP3A4, and agents can either induce or inhibit this cytochrome P450 isoform. Thus the practitioner should be prepared for possible interactions with other drugs, including some anesthetic agents that are metabolized by CYP3A4.
Protease Inhibitors (PIs)
The viral enzyme protease catalyzes production of viral core structural proteins from immature polypeptide precursors. By inhibiting this enzyme, protease inhibitors (PIs) cause production of altered, noninfectious virions. Adverse effects of the PIs include Cushing-like signs and symptoms (e.g., central obesity, buffalo hump, glucose intolerance). Like the NNRTIs, the PIs can either induce or inhibit CYP3A4, and drug interactions should be anticipated.
Fusion Inhibitors
The newest class of antiretroviral agents is the fusion inhibitors, which prevent viral adherence to and entry into the host cell. Enfuvirtide is the prototype fusion inhibitor. It is injected subcutaneously, and clearance does not involve cytochrome P450 enzymes.
Therapeutic modalities may fail due to patient nonadherence, inadequate potency of antiretroviral agents, or viral resistance. Ongoing research continues to address resistance and investigate multiple strains of the virus that may not respond to current therapeutic modalities.
ANESTHESIA MANAGEMENT
The HIV-infected patient may require a variety of surgical interventions. Although several studies have evaluated the effects of surgery and anesthesia in HIV-infected patients, to date there is no conclusive evidence to support any particular set of recommendations. Most alterations caused by various anesthetic agents and techniques are transient and have not been shown to contribute to any adverse outcome.
It is important to understand the patient’s status both in response to and the application of antiretroviral therapy and other treatments when an operative procedure is planned. Appreciation of both recent and past therapeutic efforts and the patient’s response is important in preparing the HIV‑infected patient for anesthesia and related care. Consultation with and participation of the patient’s primary care provider in the planning process can be beneficial.
When anesthesia care is planned, attention should focus on possible end-organ and systemic dysfunction. Clinically significant alterations occur in many organ systems, particularly in the advanced disease stages of HIV infection, when vigilant monitoring and, at times, intensive intervention may be necessary. The patient (or his or her legal representative or caregiver) should be included in the planning and evaluation of potential care options. Informed consent may be the responsibility of a legal guardian or durable power of attorney designee for the patient who may be mentally incompetent.
The immunocompromised patient may have combined deficiencies that predispose to significant or fatal outcomes. It is important to remember that microorganisms that are not routinely pathogenic can cause the demise of these patients. Meticulous implementation of infection-control measures throughout the perioperative period should be a primary focus in the care of these vulnerable patients. Respiratory isolation should be used when it is either known or suspected that airborne pathogens may be transmitted. Examples of such pathogens include the causative agents of tuberculosis and varicella. The immune system compromise resulting from HIV infection markedly increases the susceptibility to tuberculosis, and recurrent or newly acquired tuberculosis is frequently the cause of death for persons infected with HIV. A striking clinical feature of tuberculosis in HIV-infected patients is a high incidence of extrapulmonary involvement, usually with concomitant pulmonary presentation.
Although equipment preparedness is important for every patient to whom anesthesia is administered, it is of particular significance with the immunocompromised patient. Meticulous attention to behaviors and adherence to strict aseptic technique in providing care to these most vulnerable patients is paramount to safe practice and quality patient care. The anesthesia machine and its multitude of components should be adequately maintained, cleaned, and disinfected, and appropriate sterile components should be changed between each use, in accordance with both approved infection-control practices and manufacturers’ recommendations.
A multitude of clinical presentations have the potential to affect anesthesia management in the patient infected with HIV. Oxygenation and metabolic functions are frequently impaired during progressive HIV infection. Pulmonary infections can alter both gas exchange and lung perfusion and create ventilation-perfusion mismatch. Dehydration and hypovolemia secondary to gastrointestinal disturbances can further complicate the patient’s clinical course. A thorough preoperative assessment, including current physical examination, laboratory results, and radiographic examination, combined with other studies as indicated by patient presentation and current disease state, is critical prior to anesthesia.
Complications from HIV
Wasting syndrome may be seen in HIV-infected patients and results from disturbances in food absorption and metabolism. This syndrome is defined as profound, involuntary weight loss greater than 10% of baseline body weight. Chronic diarrhea frequently contributes to this scenario. Parenteral nutrition and appetite stimulation are usually required when this syndrome is persistent. Preoperative assessment should include evaluation of volume status and related physiologic studies to plan appropriate management.
Neurologic evaluation is essential for HIV-infected patients. Both the central and peripheral nervous systems can be impaired due to direct disease effects, concomitant opportunistic infections, or adverse effects of therapeutic agents used to combat viral insult. Peripheral neuropathies may result in considerable discomfort or physical limitations, while autonomic neuropathy may result in some degree of cardiovascular instability requiring immediate or continuous intervention. AIDS-related dementia can influence both motor and cognitive states, particularly in advanced disease states.
Non-Hodgkin’s lymphoma, manifesting as a space-occupying lesion within the central nervous system, may require surgical or chemotherapeutic intervention. Kaposi’s sarcoma, a cancer that invades endothelial tissues, can attack both skin and internal organs. Women infected with HIV may develop cervical dysplasia and cancers.
As HIV infection progresses to AIDS, advanced disease combinations emerge that would otherwise be resisted in the immunocompetent host. These opportunistic disease processes increase in both manifestation and severity as the immune system fails. Both acute and chronic bacterial infections tend to plague HIV-infected individuals. Mycobacterium avium-intracellulare (MAI) infection is characterized by intractable diarrhea and resultant wasting states. Splenic and pulmonary infections with MAI lead to severe thrombocytopenia and tuberculosis. MAI attacks the immunosuppressed host easily and is transmittable.
Several viral infections can occur or recur from previously dormant states as HIV disease progresses. Herpes simplex and varicella infections can invade oral and esophageal tissues and the central nervous system. Cytomegalovirus can affect the gastrointestinal and pulmonary systems, resulting in colitis and pneumonia. Retinal invasion may lead to marked visual disturbances and blindness. Ganciclovir is used to treat cytomegalovirus infection.
Opportunistic protozoal infections can develop in persons with advanced HIV infection. Pneumocystis carinii pneumonia is responsible for the majority of deaths secondary to opportunistic infection in HIV-infected persons. Fever and impaired gas exchange frequently result in hypoxemia, and pneumothorax is not uncommon. Toxoplasmosis encephalitis can affect both central nervous system function and the sensorium. Cryptosporidiosis can trigger considerable diarrhea, resulting in significant dehydration and related electrolyte imbalance. Volume status must be judiciously evaluated and monitored.
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