Acs0821 Acquired Immunodeficiency Syndrome


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Acs0821 Acquired Immunodeficiency Syndrome

  1. 1. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 21 ACQUIRED IMMUNODEFICIENCY SYNDROME — 1 21 ACQUIRED IMMUNODEFICIENCY SYNDROME Kathleen Casey, M.D., and John Mihran Davis, M.D. Approach to Human Immunodeficiency Virus Infection In June 1981, the Centers for Disease Control and Prevention standing of HIV disease and its treatment and be familiar with (CDC) published a report of Pneumocystis carinii pneumonia prophylaxis after occupational exposure. (PCP) in five previously healthy homosexual men living in Los Angeles.1 At that time, the CDC was the sole distributor of pen- Recognition of HIV Infection tamidine, the only treatment for this rare pulmonary infection. PATHOGENESIS This outbreak represented a unique cohort for PCP, which until then had been seen only in severely immunosuppressed patients HIV is an oncovirus belonging to the who were receiving chemotherapy for disseminated cancer. Even retrovirus family. The potential of retro- in this select group, PCP was rare, and P carinii was not consid- . viruses to cause neoplasia was first recog- ered pathogenic in otherwise healthy adults.The sudden increase nized in 1911 by the American patholo- in demand for pentamidine in one geographic area raised the gist Rous, who associated them with cer- prospect of a new disease process. In July 1981, the CDC report- tain malignant disorders in animals.8 For ed a group of young homosexual men with Kaposi sarcoma.2 example, HTLV-I, a retrovirus related to Like PCP, Kaposi sarcoma was a rare lesion not commonly seen HIV, has been identified as a cause of leukemia in humans.9 in young adults. Many of these Kaposi sarcoma patients also had One of the characteristic features of retroviruses is the pres- severe infections caused by organisms associated with immu- ence of an enzyme called reverse transcriptase. This enzyme nodeficiency, including PCP, toxoplasmosis, candidiasis, crypto- allows the virus to transcribe viral RNA to DNA. The virus can coccosis, and cytomegalovirus (CMV) infections. synthesize double-stranded DNA from single-stranded DNA These two accounts represented the first recognition of AIDS. that has been liberated from the RNA-DNA hybrid. This dou- The cause of the severe immunodepression in these patients, ble-stranded DNA inserts itself into the nucleus of the host cell who were not otherwise at risk for opportunistic infection, was and serves as a template for viral replication.Thus, whenever the controversial until late 1983 and early 1984, when the human infected host cell divides, new HIV particles are also reproduced. immunodeficiency virus (HIV) was isolated in AIDS patients.3 HIV has been isolated in many cell types, but it is thought that This retrovirus—formerly known as human T cell lymphotropic helper T cells (CD4+ cells) are most frequently infected. It is virus (HTLV) type III and lymphadenopathy-associated virus believed that when an HIV-infected CD4+ cell is activated by a (LAV)—is now recognized as the agent that causes AIDS. secondary infection, the virus is replicated, resulting in the dis- Presumably, the patients in the 1981 reports had become infect- semination of mature virions and the death of the cell. ed with HIV at least 3 to 4 years earlier. The latency period between acquisition of HIV infection and In September 1987, the definition of AIDS was expanded to onset of AIDS has been estimated to be about 5 years.This esti- include symptomatic HIV-infected patients suspected of having mate is probably misleading because it is based on experience an opportunistic infection. This new definition precipitated a with patients in high-risk groups, who are frequently exposed to potentially misleading sudden increase in new cases.4 Since other infectious challenges. Exposure to these other pathogens 1986, the percentage of homosexual or bisexual AIDS patients activates the T cells that harbor HIV, which promotes dissemi- has steadily declined, and the percentage of AIDS patients who nation of the virus throughout the host and significant impair- are I.V. drug abusers or are heterosexual has increased. ment in cellular immunity. Because the incidence of concomi- June 1, 2001, marked the 20th anniversary of the AIDS epi- tant infections is lower in the general population than in high- demic. Over those 2 decades, more than 20 million people died risk groups, the latency period of HIV infection is probably of AIDS, leaving an estimated 36 million people infected.5 No longer in the general population. immediate end to the epidemic is in sight, but current therapies DIAGNOSTIC TESTS have significantly altered the course of the illness. Until the advent of highly active antiretroviral agents (HAART), it was The enzyme-linked immunosorbent assay (ELISA) and the believed that everyone with an opportunistic infection or tumor Western blot assay are designed to detect the presence of HIV associated with AIDS (e.g., Kaposi sarcoma or non-Hodgkin antibody in serum. ELISA is considered very sensitive (93% to lymphoma) would die as a direct result of severe immunosup- 100%; i.e., its false negative rate is low). The specificity of a pression; that is no longer the case.6 HIV-infected persons are repeatedly reactive ELISA approaches 99%.The weakness of the living longer, are less likely to die of opportunistic infections, and ELISA is that some persons have antibodies that react with HIV are more likely to present with relatively well-preserved immune antigens but are not specific for HIV. function.7 With this increase in the prevalence of HIV infection, The Western blot assay is more specific than ELISA but is it is all the more important that surgeons have a basic under- cumbersome and less sensitive. It is therefore not a good screen-
  2. 2. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 21 ACQUIRED IMMUNODEFICIENCY SYNDROME — 2 Approach to Human Immunodeficiency Virus Infection Potential HIV infection in surgical setting Infection is diagnosed by ELISA or Western blot assay. SUDS ELISA results must be confirmed by Western blot. Categorize patients according to CDC classification. Patients receiving HAART may not behave in accordance with CDC class. Surgical issues in infected patients Risk of HIV transmission to patient or medical personnel General clinical problems: • Immunosuppression • Renal failure Risk to patient comes from transfusion, • Cardiac dysfunction transplantation, or, theoretically, Other problems include transmission from surgical personnel (HBV • Splenomegaly or thrombocytopenia transmission is a far more significant • Central venous catheter infections possibility). • GI disease • Lymphadenopathy Risk to health care workers (HCWs) comes from infected patients. All HCWs should take precautions to prevent HIV transmission with all patients, not only those with known or suspected HIV infection. Again, transmission of hepatitis is much more common. Postexposure prophylaxis Need for prophylaxis and choice of drugs are based on (1) risk assessment of exposure, (2) size of inoculum, (3) arterial vs. venous exposure, (4) intact or nonintact skin or mucous membrane exposure. Consider possible HCV coinfection. Source is HIV positive with low viral load; Source is HIV positive with high viral load, source is of unknown HIV status but or worker has extensive skin or mucous high risk; or worker has minor skin or membrane exposure mucous membrane exposure Initiate three-drug therapy (zidovudine, Initiate two-drug therapy (zidovudine and lamivudine, and indinavir or nelfinavir) within lamivudine) within 24 hr of exposure. 24 hr of exposure.
  3. 3. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 21 ACQUIRED IMMUNODEFICIENCY SYNDROME — 3 ing test; it is used most effectively for confirming ELISA results. Unfortunately, the system does not take into account the However, most blood banks will not use blood that has demon- immune reconstitution that occurs with HAART. After success- strated a positive ELISA reaction, even if HIV antibody was not ful treatment with HAART, patients originally classified as hav- detected by Western blot testing.10 ing AIDS (on the basis of their CD4+ count or level of immuno- The Single-Use Diagnostic System (SUDS; Murex compromise) often will no longer have signs and symptoms in Diagnostics, Norcross, Georgia) provides a rapid ELISA tech- accordance with their original CDC classification. A number of nology that can yield a reliable result in 15 minutes. A positive studies have now shown that secondary prophylaxis for PCP, SUDS result must still be confirmed by Western blot assay. CMV retinitis, Toxoplasma encephalitis, and cryptococcal menin- SUDS is especially useful in occupational-injury investigation. gitis may be safely discontinued in patients whose CD4+ counts There is a window period of 25 days between infection with have risen and remained above 200 cells/µl because of HAART.15 HIV and seroconversion detectable by ELISA. It has been esti- Similarly, recent studies of gynecologic procedures in HIV- mated that since 1985, when all banked blood began to be test- infected patients have found that postoperative infection rates ed for HIV, 35 persons in the United States have contracted HIV correlate only with the current CD4+ count. In these studies, a infection from transfusions containing blood collected from an CD4+ level below 200 cells/µl at the time of the procedure was HIV-infected individual during this window period.11,12 For that an independent risk factor for surgical complications, whereas reason, on August 8, 1995, the Food and Drug Administration the previous nadir had no influence on outcome.14 recommended that all blood donated for transfusion be screened for the p24 antigen (the core structural protein of HIV).13 Surgical Issues Additional laboratory tests that may help in the diagnosis of GENERAL patients believed to have HIV infection in whom HIV antibody screening yields negative results include DNA polymerase chain As a group, HIV-infected patients pre- reaction (PCR), antigen testing after immune complex disrup- sent the surgeon with three notable clini- tion, and RNA reverse transcriptase PCR.14 cal problems: immunosuppression, renal In February 2002, the FDA approved a nucleic acid test system failure, and cardiac dysfunction. Surgeons that detects ribonucleic acid from HIV and hepatitis C virus need to be aware of the immune status of (HCV) in whole blood and blood component donors, thus per- their HIV-infected patients, because this mitting earlier results than tests based on detection of antibodies has the greatest bearing on outcome. For or antigens (http://www.fda/gov/cber/approvltr/hivhcvgen022702L. example, in HIV-infected patients with htm). Like ELISA, the nucleic acid test has a window period dur- normal CD4+ counts, the risk of infectious complications after ing which the virus can be present but escape detection; however, surgery for a perforated appendix is comparable to the risk in this window period is substantially shorter than that associated patients without HIV infection. In patients with AIDS (< 200 with antibody-based tests (12 versus 22 days, on average, for HIV; CD4+ cells/µl), the risk of infection is higher, though it is from 25 versus 82 days, on average, for HCV). opportunistic organisms associated with severe immunosuppres- sion rather than common pathogens.16-20 Renal failure in HIV-infected patients can be the result of spe- CDC Classification of HIV Infection cific HIV-related nephropathy, which occurs in up to 10% of this In 1993, the CDC revised the classification of the HIV-infect- population.21 Another possible cause is drug toxicity from antivi- ed adult and adolescent [see Table 1]. In this classification, a ral and antimicrobial medications: pentamidine, foscarnet, and CD4+ count below 200 cells/µl is considered an indicator of aminoglycosides cause acute tubular necrosis; acyclovir, indi- AIDS, regardless of the patient’s symptoms. Once classified into navir, and sulfadiazine cause intratubular obstruction. a given group, a patient is not reclassified to a more favorable Until recently, the risk of cardiac disease in HIV-infected category, even if symptoms resolve or the CD4+ cell count rises. patients had not been as well documented as that of renal fail- However, if the disease progresses or the CD4+ count falls, the ure. With HIV-infected patients living longer, the problems of patient is reclassified into the next less-favorable group.This sys- acquired heart disease have been increasingly appreciated.22-24 tem allows uniformity in patient classification for research trials In addition, malignancy has been increasingly recognized over and scientific communication and, of particular importance, the past 2 decades as a consequence of HIV infection. Initially, facilitates formulation of health care policy and strategy. the occurrence of AIDS-defining tumors, such as B cell lym- Table 1—1993 Revised Classification for HIV Infection and Expanded AIDS Surveillance Case Definition for Adolescents and Adults81 Clinical Categories A B C CD4+ T Cell Categories Asymptomatic, Acute Symptomatic, Not A AIDS Indicator (Primary) HIV, or PGL or C Conditions Conditions ≥ 500/µl A1 B1 C1 200–499/µl A2 B2 C2 < 200/µl AIDS-indicator A3 B3 C3 T cell count PGL—persistent generalized lymphadenopathy
  4. 4. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 21 ACQUIRED IMMUNODEFICIENCY SYNDROME — 4 phoma and Kaposi sarcoma, was thought to relate to the gitis, necessitating emergency surgical interventions.12 immunosuppression of the host. Other tumors have now been Choledochoenteric bypass is thought to provide the best palliation associated with HIV infection, including squamous cell cancers in these patients. It is not known whether the biliary tree is ever of the cervix and anus and lung cancer. It is believed that at some cleared of the pathogens. Candida infection and Kaposi sarcoma point after infection with HIV, activation of oncogenes and loss have also caused cholangitis, necessitating bypass surgery.17 The of tumor suppressor genes give rise to microsatellite alterations. gallbladder is infected with unusual pathogens in over 50% of These are highly pleomorphic segments of DNA associated with HIV-infected patients with cholangitis; therefore, the gallbladder the AIDS-defining malignancies.25-27 wall should be sent for culture, and the pathologist should be alert- Treatment of patients with AIDS involves multimodal therapy ed so that the tissue may be processed with special stains.33-36 and consultation with oncology and infectious disease special- Acute perforations of the GI tract from CMV infection, cryp- ists. It is beyond the scope of this discussion to describe the spe- tosporidiosis, and candidiasis, as well as from necrotic lymphoma, cific therapeutic approaches to the complications of HIV infec- have been reported in HIV-infected patients.18,37,38 Obstruction of tions; however, three principal problems must be addressed. the GI tract by Kaposi sarcoma or lymphoma may also be an indi- First, any opportunistic infection or secondary malignant disor- cation for resection, bypass, or colostomy. One study of AIDS der must be treated; second, the underlying immunodeficiency patients requiring a laparotomy identified four distinct clinical must be corrected; and finally, the cause—HIV infection—must syndromes that called for surgical intervention: (1) peritonitis sec- be controlled. The role of the surgeon in the management of ondary to CMV enterocolitis and perforation; (2) non-Hodgkin these chronically ill, and sometimes critically ill, patients lymphoma of the GI tract (usually the terminal ileum), presenting includes performing diagnostic biopsies, giving supportive care, as obstruction or bleeding; (3) Kaposi sarcoma of the GI tract; and and managing complications of malignancy of infection. (4) mycobacterial infection of the retroperitoneum or the spleen.39 Another GI lesion that has been increasingly associated with SPLEEN homosexual men who are infected with HIV is squamous cell car- The role of splenectomy in patients with marked cinoma of the anus (SCCA). It is estimated that the risk of devel- splenomegaly or with thrombocytopenia must be individualized. oping SCCA is nearly 25 times greater in HIV-infected homosex- Some experts believe that coinfections such as HCV infection ual men than in the general population. The underlying relation- contribute to the development of HIV-related immune throm- ship is not well understood, because the development of SCCA is bocytopenic purpura (ITP). Thrombocytopenia occurs in AIDS not related to the duration of the HIV infection. Some experts patients as a result of the deposition of circulating immune com- believe that human papillomavirus 16 (HPV-16) and HPV-18 are plexes on platelets rather than as a result of a specific antiplatelet important cofactors in the evolution of SCCA.40,41 antibody.28,29 Splenectomy has been extremely effective in the LYMPHADENOPATHY management of AIDS-related ITP, with a success rate of over 90%. Occasionally, patients who have debilitating fevers associ- Another group of HIV-infected patients defined by the CDC ated with significantly enlarged spleens experience dramatic pal- comprises those with persistent generalized lymphadenopathy— liation after splenectomy. Some data indicate that splenectomy that is, palpable lymphadenopathy with nodes measuring greater favors a slower progression of HIV dissemination and progres- than 1 cm in diameter in at least two extrainguinal sites and per- sion to AIDS.30,31 In patients with massive splenomegaly and sisting for longer than 3 months. Before the introduction of HIV fever, simple splenomegaly is sometimes difficult to distinguish antibody testing, the relationship of such lymphadenopathy to from abscess or parenchymal necrosis, and splenectomy may be systemic manifestations of immunosuppression (systemic symp- indicated to resolve the uncertainty. In addition, splenectomy toms, neurologic symptoms, secondary infections, or cancers) may be indicated in instances in which there is merely a likeli- was not known. It is now clear that lymphadenopathy is part of hood of injury and in those in which a large spleen compresses the general clinical spectrum associated with HIV infection, and the stomach, thereby contributing to malnutrition. that opportunistic infection, Kaposi sarcoma, or large cell lym- phoma will develop in some, if not all, patients with lymph- IMPLANTABLE VENOUS ACCESS DEVICES adenopathy. The precise reason that lymphadenopathy occurs in Placement of an indwelling central venous catheter is a some, but not all, patients with HIV infection is not known. request frequently directed to the general surgeon from the pri- Lymph node biopsy in these patients is only of academic mary care physician, infectious disease consultant, or hematolo- interest because of the development of serologic tests for HIV gist caring for an AIDS patient. Long-term venous access for infection.37 The histologic appearance of a clinically enlarged treating fungal infections or, occasionally, for providing nutri- lymph node has prognostic value (see below); however, when the tional support in patients with debilitating diarrheal syndromes decision as to whether to perform a lymph node biopsy is being can enhance the care of these patients. However, lines are often made, the value of the biopsy findings must be weighed against placed when the patient is febrile, as a result of either the under- the value of the information that can be obtained by means of lying infection or treatment with amphotericin B. Therefore, a clinical staging with the ratio of helper T cells to suppressor T close watch should be kept postoperatively to ensure that fevers cells and the total lymphocyte count.The total number of helper are not related to a catheter infection. Although catheter-related T cells in the circulation has been correlated with the risk of infection develops in as many as 30% of AIDS patients with AIDS in patients with generalized lymphadenopathy20,42-44; the implanted lines, these infections do not increase mortality.32 The Walter Reed classification provides the most detailed clinical high rate of infection relates in part to the high incidence of staging system.43,45 Should the clinical condition warrant, a Staphylococcus colonization in these patients. lymph node biopsy may help in the diagnosis of an opportunis- tic infection. Performing a gallium scan to locate the most suspi- GASTROINTESTINAL DISEASES cious node can enhance the yield of the biopsy. Cryptosporidiosis and CMV infection of the biliary tree have Four basic histologic patterns have been described in persis- been reported to cause both acute cholecystitis and acute cholan- tent generalized lymphadenopathy and have been correlated
  5. 5. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 21 ACQUIRED IMMUNODEFICIENCY SYNDROME — 5 Figure 1 Lymph node viewed under low power exhibits explosive Figure 2 Lymph node viewed under low power exhibits follicular follicular hyperplasia. involution. Figure 3 Lymph node viewed under low power exhibits a mixed pat- Figure 4 Lymph node viewed under low power exhibits a pattern tern of both explosive follicular hyperplasia and follicular involution. of lymphocyte depletion. with prognosis: explosive follicular hyperplasia, follicular involu- longed survival, even if they have Kaposi sarcoma. The presence tion, a mixed pattern, and a lymphocyte-depleted pattern. of follicular involution in a lymph node is associated with a sur- Explosive follicular hyperplasia describes a pattern of enlarged vival time of less than 1 year. Lymphocyte depletion was seen as confluent follicles with disruption of the medullary zone of the a terminal finding in several autopsy cases, suggesting that the lymph node [see Figure 1]. Follicular involution is associated with pattern represents the end stage of the hyperplastic process.25 a hypocellular, frequently hyalinized follicle and with hyperplasia The pathologic findings reflect a progressive loss of the CD4+- of the paracortical areas [see Figure 2]. The mixed pattern con- bearing area of the lymph node. tains explosive follicular hyperplasia and follicular involution in After a lymph node is removed from an HIV-infected patient the same lymph node [see Figure 3]. Finally, the lymphocyte- and before the tissue is removed from the operative field, repre- depleted pattern is characterized by the total absence of follicu- sentative specimens should be placed in sterile containers for lar and paracortical areas. The loss of lymphocytes in the lymph routine bacterial culture, culture and smear for tuberculosis, fun- node is associated with the predominance of histiocytes and gal culture, and viral culture. Tissue from the same lymph node plasma cells [see Figure 4]. should then be delivered to the pathologist as quickly as possi- The presence of enlarged follicles is associated with a good ble. It is important that culture material from the same lymph immunologic response and slower progression of disease, where- node be examined microscopically, because granulomas or actu- as the presence of involuted, hyalinized follicles is more fre- al organisms may be detected before the culture results are avail- quently associated with opportunistic infections, Kaposi sarco- able. Data from the pathologist may aid the microbiology labo- ma, and lymphoma. Evidence suggests that patients with either ratory staff in its handling of the cultures. explosive follicular hyperplasia or the mixed pattern of explosive The pathologist needs to receive the fresh, gently handled follicular hyperplasia and follicular involution have rather pro- specimen, in saline, as soon after the biopsy as possible, for two
  6. 6. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 21 ACQUIRED IMMUNODEFICIENCY SYNDROME — 6 important reasons. First, because the tissue is not in formalin, it HCV, because the process by which they are purified inactivates will rapidly autolyze if not processed immediately. Second, if the the virus particles. Since adequate antibody testing became avail- diagnosis is lymphoma, the pathologist must have the tissue when able in May 1985, the incidence of undetected HIV in transfused it is fresh to perform lymphocyte marker studies. Because differ- blood has been extremely low, and only anecdotal cases involving ent lymphomas respond to different chemotherapeutic regimens, contaminated blood have been reported to the CDC. It is cur- the cell type of the lymphoma is critical. Most surgical pathology rently estimated that the risk of receiving a unit of blood that is laboratories are equipped to perform membrane marker studies contaminated with HIV is one in 150,000 (< 0.0007%).48 on lymph node tissue. To minimize the risk of HIV being transmitted by transfusion, patients have increasingly requested the use of predeposited autologous blood donations (PAD) or blood donated by family Prevention of Disease Transmission members or friends (directed donations). This approach has GENERAL been increasingly discouraged by blood bank and hospital administrators.49 Both directed donations and PAD are very A key question for surgeons, operating expensive methods of preserving homeostasis during surgery. room committees, infection control com- Half of the PAD units of blood are discarded. In addition, the mittees, and clinicians involved with risk of an ABO mismatch error is as great as the risk of HIV endoscopy is how to effectively clean transmission in standard bank blood. The use of intraoperative instruments, equipment, or other inani- blood salvage and acute normovolemic hemodilution in combi- mate objects to be used with AIDS nation with intravenous iron and erythropoietin provides a rea- patients. Those agents that are effective sonable alternative to blood transfusion.50 against mycobacteria, the most resistant group of organisms encountered in this population, are also the agents considered Transplantation most effective against other bacterial and viral pathogens.46 A Because it has been shown that HIV can be present in semen, complete list of agents and their efficacies can be obtained from blood, urine, tears, breast milk, cerebrospinal fluid, and saliva the Disinfectants Branch of the Office of Pesticides, United States and because it is suspected that HIV can be present in all secre- Environmental Protection Agency, 401 M Street, S.W., tions and excretions, as well as all body tissues,51 potential Washington, DC 20460. donors of tissue for transplantation must be tested for serum Agents are classified according to whether they are to be used antibodies to HIV to prevent inadvertent transfer of the virus. for sterilization, disinfection, or antisepsis.47 Agents that sterilize Parenthetically, transmission of HIV by artificial insemination inanimate objects kill all microbial organisms as well as bacterial endospores. Disinfectants are not quite as effective, in that they has also been documented, so this risk should be considered are not capable of killing bacterial spores. In many cases, an agent whenever artificial insemination is planned.52 may serve as a disinfectant when placed in contact for a short Transmission from Surgical Personnel time with the object requiring cleansing and may be capable of sterilizing surgical instruments that are exposed to it for longer An HIV-infected surgeon could theoretically transmit the virus periods. Disinfectants are subclassified as having high-level, to his or her patients. Although this concern has been well publi- intermediate-level, or low-level germicidal activity. High-level cized,53 there have been no documented reports of transmission agents are effective against bacterial spores. Intermediate-level from surgeon to patient. Furthermore, the CDC has not recom- disinfectants are less effective against spores but are mycobacte- mended restricting HIV-positive surgeons from operating.54 ricidal. Low-level disinfectants do not kill Mycobacteria and some Unlike surgeon-to-patient transmission of HIV, HBV trans- fungi. Antiseptic agents are used on tissue and therefore must be mission from surgeon to patient is a significant concern. In a less toxic than sterilants or disinfectants. well-documented report involving a nonimmunized cardiac According to current CDC recommendations, agents classi- surgeon who acquired HBV infection in the workplace, trans- fied by the United States Environmental Protection Agency as mission of the virus occurred in 19 of 122 patients (16%) on sterilants can be used for sterilization or high-level disinfection, whom the surgeon operated over a 12-month period.55 The sur- depending on contact time. All instruments entering the blood- geon’s blood was positive for hepatitis B e antigen (HBeAg), stream or other sterile tissues should be sterilized before use. and sweat from inside his glove was found to contain both HBV Instruments that contact mucosal surfaces, such as endoscopes, antigen and HBV DNA. No deficiencies were found in the sur- should receive high-level disinfection, which can be achieved geon’s infection control practice by the CDC, which suggested with solutions of glutaraldehyde (2%), hydrogen peroxide (3% that the virus might have spread through microperforations in to 6%), or formaldehyde (1% to 8%). his gloves. This case did not receive the same publicity that cases of HIV transmission have received in the lay press. RISKS TO PATIENTS However, its significance is clear: contact between health care workers who are HBV (HBeAg) positive and patients should be Transfusions restricted. Fresh whole blood, packed red blood cells, platelets, plasma, RISKS TO HEALTH CARE WORKERS cryoprecipitate, and leukocytes can all carry HIV. In addition, clotting factor concentrates that are not generated by recombi- The CDC now recommends that precautions to prevent HIV nant methods may also carry the virus. Some preparations of transmission be taken with all patients, not only those known to γ-globulin can temporarily cause a false positive ELISA result for be infected with HIV or at high risk for such infection [see 8:21 HIV, but they do not contain the virus or transmit it to recipients. Viral Infection].18,20,38,39 It is important that any hospital person- Albumin and plasma extracts (Plasmanate), although prepared nel who come in contact with patients, their patients’ tissues, or from whole blood, do not carry HIV, hepatitis B virus (HBV), or their blood, body fluids, or excreta know of the potential risk in
  7. 7. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 21 ACQUIRED IMMUNODEFICIENCY SYNDROME — 7 RISKS TO SURGEONS Table 2—Preventable Exposures to HIV among Health Care Workers*49 HIV Transmission The risk that a surgeon will acquire an HIV infection while Number of Health Care Workers Circumstances of treating a patient who has undetected AIDS is quite low.54,56 The (% of 938 Exposed Health Preventable Exposure Care Workers) CDC has prospectively evaluated nearly 1,500 health care work- ers who cared for AIDS patients. Serum samples were taken Recapping of needle 152 (16%) from these workers when they first began to work with AIDS Injury from improper disposal of patients and were stored in anticipation of a test for HIV. Of 119 (13%) needle or sharp object these workers, 666 were exposed to HIV through needlesticks or Contamination of open wound 93 (10%) through cuts from sharp instruments. When tests were per- Use of needle-cutting device 9 (1%) formed on these exposed individuals, none were found to have Total preventable exposures 373 (40%) undergone seroconversion after their exposure to HIV. However, two health care workers for whom no baseline blood sample had *The total sample under surveillance consisted of 938 health care workers exposed to blood or other body fluids of a patient with AIDS or an AIDS-related illness. been drawn did test positive for antibody to HIV after an injury. Because they did not belong to a known risk group for AIDS, they were believed to have generated antibody to HIV as a result of exposure in the workplace. On the basis of this study, the risk handling materials from these patients and take appropriate pre- to a health care worker of acquiring HIV infection after an acci- cautions. Patients in high-risk groups should be placed on dental needle-stick exposure was concluded to be 2 divided by enteric precautions to protect health care workers not only from 666, or 0.3%. A follow-up study found the rate of infection to be HIV infection but also from HBV infection (up to 80% of such 0.5%.60 Subsequent surveillance of health care workers identi- patients are HBV carriers). As part of any operative procedure fied 151 individuals who acquired HIV infection in the work- on HIV-infected patients, all operating room, nursing, and anes- place [see Table 3]; 49 had proven seroconversion, and 102 were thesia personnel, as well as employees of surgical pathology lab- HIV positive but had no HIV-negative baseline serum sample. oratories and any other laboratories, should employ universal The CDC conducted a serosurvey of 770 surgeons practicing precautions. Employees in ancillary areas, such as housekeeping in two inner-city areas where more than 3,000 cases of AIDS and dietary services and the venipuncture team, need to be have been reported.61 Accompanying the assay for HIV, HBV, trained in the use of universal precautions. and HCV was a questionnaire designed to elucidate the practice Exposure to the virus in the workplace is considered to be patterns of the surgeons tested. Of the 770 surgeons, 1 (0.13%) preventable in many cases.56 Most injuries result from careless- was HIV positive; he had practiced for more than 25 years and ness in handling sharp objects, such as needles [see Table 2]. Self- had performed more than 300 operations in the past year. The inflicted puncture incurred in the course of recapping used nee- study did not specify how the surgeon acquired HIV, and it was dles is the most common cause of inadvertent exposure to HIV. noted that he did not participate in high-risk behavior. To date, Consequently, the most important rule to follow when handling used needles is to discard them uncapped in a container that is large enough to accommodate the attached syringe.Tissue spec- Table 3—Health Care Workers with imens, wastes, soiled linen, blood samples, and sharp objects (e.g., surgical instruments, needles, and glassware) must be han- Documented or Suspected HIV Infection9 dled with extreme care. Dressings and other disposable materi- als should be discarded in specially marked containers and not No. of Workers Health Care with the regular hospital refuse. Workers With Documented With Suspected The use of double gloves has been shown to minimize the pos- HIV (%)* HIV (%)† sibility of contact with patient blood through small defects in the gloves, and it reduces the likelihood of blood contact with skin Dental 0 7 (7%) when a glove puncture occurs.57,58 The following are additional Mortician 0 3 (3%) precautions health care workers should take when handling any Emergency medical 0 9 (9%) potentially infectious materials: team/paramedic 1. Wear gloves when handling body fluids. Health aide 1 (2%) 12 (12%) 2. Wear a gown to prevent contamination of clothing. Housekeeper 1 (2%) 7 (7%) 3. Wash hands after contact with body fluids. Laboratory technician 18 (37%) 15 (15%) 4. Place fluid from a potentially contaminated host in two imper- Nurse 19 (39%) 24 (24%) vious containers. Physician 5. Clean spills with either a 1:10 dilution of 5.25% sodium Surgeon 9 4 (4%) Nonsurgeon 6 (12%) 10 (10%) hypochlorite in water or with some other type of sterilant. 6. Wear masks and protective eyeglasses when there is a possi- Respiratory therapist 1 (2%) 2 (2%) bility of aerosolization of material. Surgical technician 2 (4%) 1 (1%) Other 1 (2%) 8 (8%) Even health care workers who do not have exfoliative der- matitis or an open wound should wear gloves during patient Total 49 102 care. Evidence suggests that the affinity of HIV for Langerhans *Evidence of seroconversion after occupational exposure to HIV. cells may permit the virus to invade a host through intact skin or † HIV seropositivity in health care workers with occupational exposure to HIV who do not mucous membranes.59 have behavioral or transfusion risks for HIV infection.
  8. 8. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 21 ACQUIRED IMMUNODEFICIENCY SYNDROME — 8 20 ber of needle sticks or punctures contaminated with the patient’s 18 body fluids, (2) the percentage of HIV-infected patients in the sur- geon’s patient population, and (3) the number of years a surgeon 16 is at risk for acquiring an HIV infection. If the risk of HIV trans- 14 mission by a contaminated needle is 0.3% to 0.5%, if the HIV- infected population is 10%, if the number of needle sticks averages Log Particles/ml 12 30 a year, and if the surgeon has 40 years of exposure, then the life- time risk of acquiring HIV infection can be as high as 60%.70 10 HEPATITIS TRANSMISSION 8 The primary health risk to surgeons caring for patients with 6 HIV infection or AIDS is that of acquiring hepatitis B or hepatitis C. The hepatitis D virus (HDV) has been identified as posing an 4 additional risk of death in patients with acute hepatitis; persons who 2 are infected with both HBV and HDV have a higher mortality.71 The epidemiology of hepatitis B has been well studied because 0 there are numerous antigen and antibody markers of the virus in Hepatitis B AIDS the blood of chronic carriers. On the basis of data from assays of Figure 5 The numbers of infectious viral particles per milliliter these markers, it is estimated that more than 200,000 persons in of blood in patients with active hepatitis B infections and in AIDS the United States acquire new HBV infections each year.72 Of these patients are compared.67 200,000, 25% will have symptoms of hepatitis, 5% will require hospitalization for their acute illness, and 1% to 2% of these hos- pitalized patients will develop fatal fulminant hepatitis [see Figure 6]. there has been no documented seroconversion in operating room Between 5% and 10% of patients infected with HBV become personnel after a solid-bore needle injury in the OR. chronic carriers—that is, they do not effectively clear the antigen Transmission via skin contact with body fluids was document- from their systems, and they have a subclinical hepatic infection ed in the case of a woman whose infant had received a transfu- for prolonged periods. This group of patients is at risk for cirrho- sion from an HIV-infected donor at 3 months of age. The moth- sis, with subsequent hepatic failure or hepatoma. Many chronic er was closely involved in the baby’s care and took no precautions hepatitis carriers are unable to clear the infection because of against contact with the child’s blood and body fluids. Seventeen immunosuppression as a result of another disease process, such as months after the child received the contaminated blood, the advanced HIV infection. AIDS patients are very likely to have had mother tested positive on ELISA for HIV. No other risk factors an HBV infection and to be chronic carriers. HIV-infected accounted for the change in the mother’s HIV antibody titer.62 patients are also less likely to manifest an inflammatory response Exposure to blood in the OR has been of great concern to all to hepatic infections. The CDC has estimated that as many as operating room personnel since the AIDS epidemic began. The 80% of homosexual men, intravenous drug users, mentally average practicing surgeon has 30 parenteral exposures to blood retarded persons, and hemodialysis patients have serologic mark- a year.63 The fact that hollow-bore needles carry more blood than ers indicating a previous HBV infection.73 Household contact or solid-bore needles may be the reason that transmission in the sexual relations with these high-risk individuals also involves a sig- operating room has not yet occurred. Four studies from the early nificant risk of acquiring HBV infection. It is estimated that up to 1990s established a blood-skin exposure rate of approximately 60% of such contacts have positive serology for HBV. 20% and a parenteral exposure rate of approximately 4% during surgical procedures.46,64-66 Long operative procedures requiring 60 transfusions are most likely to be associated with blood exposure. Annual Number of Cases (thousands) Types of procedures that pose a high risk of exposure to blood 50 are cardiac surgery; obstetrics, especially cesarean sections; trau- ma surgery; and emergency surgery. Special care must be taken to minimize exposure in these procedures; eye protection and use 40 of double gloves are barrier precaution measures that can reduce the likelihood of contact with the patient’s blood. 30 Transmission of HIV to hospital workers is uncommon when compared with transmission of HBV because of the relatively low concentration of HIV in the blood of AIDS patients [see Figure 20 5].The concentration of virus particles is estimated to be 104 par- ticles/ml in an AIDS patient, whereas it is 1013 particles/ml in a 10 patient who has an active HBV infection.67 Although HIV transmission is uncommon in the hospital envi- ronment, the risk to surgeons is very real.This is evidenced by the 0 fact that even the lower reported rate of transmission by needle Overt Hospitalized Carriers Deaths Hepatitis B Patients stick, 0.3%, is comparable to the 0.4% (1 in 250) rate of transmis- sion by unprotected anal intercourse, which is considered high-risk Figure 6 The annual incidence of hepatitis B infection in the behavior.68,69 Three independent factors are important in deter- United States is 200,000 cases. Various subgroups of hepatitis B mining a surgeon’s risk of acquiring HIV infection: (1) the num- patients are shown.72
  9. 9. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 21 ACQUIRED IMMUNODEFICIENCY SYNDROME — 9 50 infection has occurred. Although administration of antiretroviral therapy is recommended,77 to date, no prospective trials have 45 been performed to confirm its effectiveness in humans. A retro- spective case-control study published in 1996 supported the post- 40 exposure use of zidovudine.78 The current recommendations for Positive Hepatitis B Serology (%) prophylaxis after a needle-stick injury are based on the likelihood 35 of transmission from the incident.79 In lower-risk situations, the risk of drug toxicity must be carefully weighed against the bene- 30 fits of protection against HIV transmission. The average risk of acquiring HIV after a percutaneous expo- 25 sure is estimated to be 0.3%,80 and the risk of acquiring HIV through mucocutaneous exposure approaches approximately 20 0.09%. It has been shown that the more blood transferred by a hollow-bore needle, the greater the likelihood of transmission. 15 Clearly, patient factors such as viral burden and the presence of syncytia-inducing strains of virus will also influence the likelihood 10 of seroconversion. Host factors such as cytotoxic T cell responses and perhaps T cell C3a/C5a receptors may also influence the out- 5 come.With all this in mind, the CDC has formulated specific rec- ommendations for postexposure prophylaxis (PEP).81 0 Because systemic infection after HIV exposure is thought not Medical First-Year Second-Year Attending to occur immediately in primates, prompt initiation of antiretro- Students Surgical Surgical Surgeons viral therapy may sufficiently inhibit the initial replication to keep Residents Residents the inoculum of virus low and allow for effective immune clear- Figure 7 The prevalence of positive serology for hepatitis B ance. Animal models are imperfect but have suggested that great- increases among individuals in successive stages of a surgical est efficacy of PEP was achieved when therapy was instituted career.72 within 24 hours of exposure. Overall efficacy of PEP is impossi- ble to ascertain, because the incidence is fortunately low enough Exposure to hepatitis carriers is a risk for health care workers, not to allow for a prospective study with sufficient statistical particularly for those who work with blood products [see 8:20 power to determine efficacy. Viral Infection]. Physicians involved with direct patient care are at The current recommendations are based partly on the combi- especially high risk.74 Those in administrative situations who do nation of simian studies, the experience with ziduvodine in a ret- not have clinical contact with patients have a relatively low risk of rospective case-control study of health care workers, and collec- acquiring hepatitis, whereas surgeons, particularly cardiac sur- tive experience with the prevention of vertical transmission geons and transplant surgeons, are at especially high risk. The through the use of antiviral prophylaxis. It is also recognized that risk of hepatitis infection also increases with age.71,75 The inci- as HIV-infected patients are increasingly likely to have been dence of positive hepatitis B serology is between 12% and 13% treated with a variety of retroviral agents, their likelihood of hav- in students in their last year of medical school, nearly 20% in sur- ing multidrug-resistant strains of HIV increases correspondingly. gical residents at the end of their first year, and about 25% in sur- Arbitrary selection of PEP agents may not be optimal; it is pos- gical residents after the second year. During the course of an sible that knowledge of the patient’s antiretroviral history and the unimmunized senior surgeon’s career, the risk of having hepati- results of genotypic antiretroviral resistance studies may need to tis B approaches 50% [see Figure 7]. These risks are exceedingly be taken into account for optimal PEP selection. Whenever pos- high and emphasize the importance of widespread use of the sible, physicians familiar with the source patient and local resis- hepatitis B vaccine [see 8:20 Viral Infection]. tance patterns should be consulted on the choice of PEP regi- At least two studies have shown that there are numerous mens. However, institution of PEP should never be delayed for unimmunized practicing surgeons who finished medical school, consultation, because the regimen can always be altered later if training, or both before the hepatitis B vaccine first became avail- further information is obtained. able.61,76 These surgeons are at substantial risk for HBV infection The choice of agents is largely empirical, but the need for PEP and consequently need to be immunized. Surgeons who were and the number of drugs to be used should be predicated on (1) immunized 5 or more years ago should have their titers checked; the risk assessment of the injury, taking into account the source’s if titers are low, a booster is advisable. HIV status (and, if the patient is HIV positive, the patient’s clin- ical status and viral load); (2) solid-bore versus hollow-bore nee- dle injury (large or small inoculum); (3) whether the source nee- Postexposure Prophylaxis dle was used for arterial or venous puncture; and (4) whether the injury involved intact or nonintact skin or mucous membrane MANAGEMENT AFTER EXPOSURE TO HIV exposure. If a health care worker is injured by a A two-drug PEP regimen is probably adequate for situations sharp object that was contaminated by in which the source is known to be HIV positive but thought to exposure to fluid or tissue from an HIV- have a relatively low viral load, in which the source’s HIV status positive patient, a series of blood samples is unknown but he or she is known to participate in high-risk should be drawn at the time of injury and activity, or in which the worker sustains either a minor percuta- again at 6 weeks and 3, 6, and 12 months neous or mucous membrane exposure. A three-drug regimen after the injury to determine whether HIV would be advised with more severe percutaneous exposure, with
  10. 10. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 21 ACQUIRED IMMUNODEFICIENCY SYNDROME — 10 Table 4—Nucleoside Reverse levels of mitochondrial depletion are reached, the patient Transcriptase Inhibitors becomes symptomatic [see Table 4]. All the nucleoside transcrip- tase inhibitors have been associated with hepatotoxicity to some degree. All these agents may also cause increased levels of lactic Agent Toxicity acid, which may be asymptomatic or present as fulminant lactic acidosis and shock. Patients on combination therapy that Zidovudine Marrow suppression, myopathy, nausea includes both didanosine and stavudine seem to be at particular Stavudine Peripheral neuropathy, pancreatitis, increased liver function tests risk for severe lactic acidosis and hepatic steatosis. Patients may present with nausea, vomiting, abdominal pain, and diarrhea Lamivadine Nausea, possible lipoatrophy, especially with concur- rent stavudine and become progressively more acidotic and hypotensive. Didanosine Pancreatitis, peripheral neuropathy, diarrhea Lactate levels in excess of 10 mmol/L are associated with multi- Abacavir Life-threatening hypersensitivity reaction in approxi- organ failure and a mortality of greater than 80%. Symptoms mately 5% may develop gradually or suddenly and may occur from weeks to years after the start of antiretroviral therapy. Routine moni- toring of lactic acid levels is of no benefit, because the results of extensive exposure of intact skin or mucous membranes, or such monitoring are not predictive of progression to sympto- when the source is thought to have a high viral load. Because all matic lactic acidemia. Once patients become asymptomatic, the the drugs used for PEP can have significant side effects, even in keys to survival are early recognition, discontinuance of the the short term, the potential risks of two-drug or three-drug offending drugs, and adequate oxygenation of tissues. therapy should be weighed against the likelihood of acquiring an Nonnucleoside Reverse Transcriptase Inhibitors HIV infection. With cases in which the source patient can be identified but the HIV status is unknown, a rapid HIV test such The nonnucleoside reverse transcriptase inhibitors [see Table as the SUDS should be employed. If the results of such testing 5] are increasingly used in triple-drug regimens.They are known is negative, PEP should not be given. If rapid testing is not avail- to cause rashes and have also been associated with hepatitis. able, PEP can be offered until the source patient is proved to be Nevirapine has been implicated in fulminant hepatic failure in HIV negative by conventional tests. the setting of postexposure prophylaxis and in South African For the choice of agents, the 1998 CDC guidelines suggest women. There is some concern that it may be more hepatotoxic ziduvodine and lamivudine (3TC) for two-agent therapy, with in patients with hepatitis C infection. the addition of indanivir or nelfinavir for three-drug therapy. Protease Inhibitors Zidovudine and 3TC are now available in a combination pill that The protease inhibitors [see Table 6] have been more frequent- is taken twice a day, which makes it a more convenient alterna- ly associated with metabolic syndromes involving alterations in tive; however, the increasing prevalence of the 184 mutation that fat metabolism, blood glucose, and lipids than with hepatitis or confers 3TC resistance makes this less likely to be effective in sit- lactic acidemia. Hypercholesterolemia and hypertriglyceridemia uations involving patients who have been treated with 3TC. have been associated with HAART, especially in regimens that Newer drugs such as efavirenz may offer more tolerable alterna- include protease inhibitors. It is well recognized that there is a tives to adding a protease inhibitor, as was recommended in the past. The 2001 guidelines leave the choice more open to local expertise. No discussion of occupational exposure is complete without Table 5—Nonnucleoside Reverse mention of HCV coinfection. Approximately 40% of all HIV- Transcriptase Inhibitors infected patients are coinfected with HCV; in intravenous drug users, the incidence of HCV coinfection can be as high as 90%. Agent Toxicity Medical personnel exposed to HCV via occupational injury should undergo baseline testing for HCV antibodies and a base- Nevirapine Rash, fever, hepatitis line alanine transaminase (ALT) determination, with repeat test- Delavirdine Rash, fever, hepatitis ing in 4 to 6 months. There is no prophylactic regimen available, Efavirenz Rash, somnolence, insomnia, nightmares but some authorities recommend early intervention with HCV therapy (interferon alfa and ribavirin) if HCV remains detectable—a finding that would indicate persistence of infection. TOXICITIES OF HIGHLY ACTIVE ANTIVIRAL THERAPY Table 6—Protease Inhibitors Nucleoside Reverse Transcriptase Inhibitors Agent Toxicity Long-term exposure to antiretroviral agents has not only improved survival but also introduced a variety of significant tox- Indinavir Nephrolithiasis, elevated bilirubin, fat redistribution, icities that physicians evaluating an HIV-infected patient must hyperglycemia, dry mouth take into account. Nucleoside toxicities became apparent with Nelfinavir Diarrhea, abdominal pain the introduction of the first nucleoside reverse transcriptase Ritonavir Femoral numbness, diarrhea, hyperlipidemia inhibitor, zidovudine, 15 years ago, but a multitude of side Saquinavir Diarrhea, liver function abnormalities effects are now known to be associated with all agents in this Amprenavir Diarrhea, nausea class. These agents appear to be toxic primarily through their Lopinavir/ritonavir Diarrhea, hyperlipidemia ability to inhibit mitochondrial DNA synthesis. When critical
  11. 11. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 21 ACQUIRED IMMUNODEFICIENCY SYNDROME — 11 higher incidence of cardiac disease in HIV-infected patients tests to attempt to identify occult coronary disease. Patients on receiving HAART than in age-matched control patients and that protease inhibitors have been found to have insulin resistance the presence of other traditional risk factors such as smoking even in the absence of overt diabetes, which also contributes to and hypertension magnifies the risk. This has led most HIV increased risk of coronary artery disease. For that reason, when practitioners to aggressively attempt to correct lipid abnormali- HIV-infected patients with blood lipid abnormalities are being ties through the use of lipid-lowering agents. The increased risk evaluated for elective surgical procedures, it is prudent to of premature cardiac disease has also led physicians to consider include a cardiac assessment. 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