Early postoperative care: Infectious disease considerations

Progress in

Cardiovascular Diseases VOL XxX111, NO 1 JULY/AUGUST 1990

Early Postoperative Care: Infectious Disease Considerations

Arthur Dresdale and James Diehl

A MONG THE MANY achievements of mod- ern medicine in the late 20th century, no

field has advanced more quickly than cardiac transplantation. Prior to the introduction of cyclosporine, l-year survival for orthotopic cardiac transplant recipients plateaued at 60% to 70% and 5year actuarial survival was reported at 35% to 40%.’ Infections were seen in virtually every recipient1’2 and accounted for nearly two thirds of the deaths.’ With the beginning of the cyclosporine era in the early 1980s results rapidly improved. Initial reports from the Stanford University group, the pioneers in cardiac transplantation, reported an 80% one-year survival.3 Other groups confirmed these results.4-7 Infec- tion, particularly in the early period-the first 3 months after transplantation, remained a major cause of morbidity and mortality.3-6 Pulmonary infections were especially troubling and much attention was paid to their recognition and management. 5~6~8-10 As experience has been gained with immunosuppression therapy, infectious complications have decreased in frequency and severity.“-l6 These results have been accom- plished even as the number and intensity of rejection episodes has diminished. As a result, l-year survival of operative survivors of cardiac transplantation is greater than 90% today.13,16 Remarkably, these impressive results have been observed despite a softening of recipient accep- tance criteria.

Infections remain most common in the first 90 days after transplantation. It is during this early period when immunosuppression is highest and most rejection episodes necessitating additional immunosuppressive therapy occur.12,13,16 After the first 3 months, as rejection episodes decrease

and immunosuppression is reduced, infectious complications are rare.12,13,16

Managing the infectious complications after cardiac transplantation requires an understand- ing of the increasingly sophisticated immunosuppressive regimens that have been the cornerstone in the improved prognosis for heart transplant patients. Most groups now use triple therapy with cyclosporine, azathioprine, and prednisone.13’16 Recently, the introduction of the monoclonal antibody OKT3 has proved very useful, not only for treatment of rejection, but also for prophylaxis. I7 In addition, a better under- standing of the infectious problems confronting immunosuppressed patients, particularly heart transplant recipients, has been helpful in reducing the incidence of infectious complications and managing them when they do occur.

PERIOPERATIVE CARE AND INFECTION PROPHYLAXIS

Antimicrobial Prophylaxis

Perioperative prophylactic antibiotics are widely used in cardiac surgery and it is common practice to administer a broad spectrum agent, usually a cephalosporin in cardiac allograft recipients before making the skin incision. Antibiotic prophylaxis is then continued every 6 to 8 hours for 1 to 3 days depending on the standard of practice at a given institution. The choice of

From the Department of Cardiothoracic Surgery, New England Medical Center Hospital and Tufts University School of Medicine, Boston, MA.

Address reprint requests to Arthur Dresdale, MD, Depart- ment of Cardiothoracic Surgery, New England Medical Center Hospital, 27 Bennet St, Boston, MA 021 II.

o 1990 by W.B. Saunders Company. 0033-0620/90/3301-0001$5.00/O

Progress in Cardiovascular Diseases, Vol XXXIII, No 1 (July/August), 1990: pp 1-9

2 DRESDALE AND DIEHL

antibiotic as well as its duration of administration is controversial. Antibiotic selection should be based on identification and sensitivities of the most common organisms responsible for early wound infections in a particular institution. These include Staphylococcus epidermidis, Staphylo- coccus aureus, enterococcus, gram-negative rods, and Candida albicans. 15,i8 Chest tubes, urinary, venous, and arterial catheters are potential sites of entry for infections, causing some investigators to argue for continuation of prophylactic antibiotics until all indwelling devices are removed.” Prolonged antibiotic administration, however, raises concern about fostering the emer- gence of resistant bacteria and fungal organisms. When transient candidemia occurs in immunocompromised individuals, such as transplant recipients, metastatic seeding requiring systemic antifungal therapy is very likely to occur.” It therefore seems prudent to restrict the use of prophylatic antibiotics to the shortest possible time and just as importantly to remove all invasive monitoring devices expeditiously.

Information gained from the renal transplant experience has guided some of the newer prophylactic antimicrobial therapies. The routine use of trimethoprin-sulfamethoxazole (TMP-SMZ) has been extensively studied. Prophylactic administration not only prevents urinary tract infections, but also reduces the incidence of Pneumocystis carinii, Nocardia, and Listeria related infections. 13~15~18~1g Many cardiac transplant centers elect to use this regimen indefinitely.‘3*16

Although it has not been proved conclusively in randomized trials, most investigators concur that topical nystatin administration for at least the first 90 days after transplantation prevents oropharyngeal and gastrointestinal fungal overgrowth.13,16*1gY20

Drug prophylaxis of the herpesvirus groups has also been the subject of many clinical studies. Management of cytomegalovirus (CMV) prophylaxis will be discussed in a later section (see Infections From the Donor Heart). The incidence and the severity of reactivation infection by herpes simplex virus and varicella-zoster virus is significantly decreased by acyclovir therapy.“-” It is orally administered for the first 90 days after transplantation.16

Postoperative Care

In the time period immediately following transplantation, postoperative care is directed at pre- venting bacterial infections of the sternotomy incision, lungs, urinary tract, and vascular catheters, which must be considered in all cardiac surgical patients. The immunosuppressed state of transplant recipients, however, greatly increases the potential severity of any infection. Opportunistic infections with pathogens, such as Aspergillus, Nocardia, and Legionella, do not generally occur in the first month after transplant unless an environmental hazard exists in the hospital.‘8

Postoperatively, every effort is made to prevent nosocomial infection. Patients are cared for in an isolation room in the cardiothoracic-intensive care unit. Strict handwashing is enforced and gowns, masks, gloves, and shoe covers are worn conscientiously in the recipient’s room. Strict attention is paid to pulmonary toilet and clearing of all secretions. A high priority is placed on early extubation and rapid removal of all indwelling tubes and catheters. Once hemodynamically stable and “de-lined,” the recipient is transferred to a ward room where reverse precautions are maintained. Walks in the hospital corridors are permitted, but with the patient now gowned and masked. Discharge as early as 7 days postoperatively is emphasized. Following discharge, patients are requested to avoid densely populated public places for the first 90 days after operation and to wear masks when returning to the hospital for checkups and biopsies. In addition to the prophylactic measures outlined above, diagnostic surveillance is carried out with daily chest x-rays for the first week. If the patient remains intubated, daily roentgenographs are continued until extubation and a stable respiratory status are achieved.

DONOR CONSIDERATIONS

Donor Selection: Infectious Contraindications

The donor heart is a potential source of serious infection for the recipient. Both the human immunodeficiency virus (HIV) responsible for the acquired immune deficiency syndrome (AIDS) and the hepatitis B virus have been transmitted to kidney transplant recipients.” Therefore, it is unwise to accept organs from

INFECTIONS IN CARDIAC TRANSPLANT RECIPIENTS 3

donors in the high-risk groups for AIDS (homo- sexual males, intravenous drug abusers, hemophil- iacs). In addition, serologic testing of all potential donors for hepatitis B and HIV is mandatory prior to organ donation. No organs from a donor in a high-risk group or who tests positive for either virus should be used.

Other firm contraindications to donor organ use include systemic viral infection, encephalitis, documented bacterial sepsis, and individuals who are at high risk for occult sepsis, such as burn victims, drowning victims, and patients who have been dependent on a respirator with indwelling monitoring devices for greater than 7 days.rg

Infections From the Donor Heart

Serious and often lethal infections from toxoplasmosis, cytomegalovirus, and herpesviruses have been transmitted from the donor heart.22-3’ Because of the scarcity of acceptable donors and the brief time interval between donor identification and cardiac transplantation, the use of infected hearts will no doubt continue. The recent development of prophylactic treatment modalities appears effective in reducing the frequency and intensity of these infections. A number of serologic assays are available to accurately assess the exposure status of donor and recipient 22-25,27,30,31 Based on these results, four serologic categories of donor and recipient can be defined: (1) Donor seronegative, recipient seronegative; (2) Do- nor seronegative, recipient seropositive; (3) Donor seropositive, recipient seropositive;(4) Donor seropositive, recipient seronegative. Rational prophylaxis can be administered based on this identification and information regarding the possibility of developing overt disease.

CMV

Three clinical patterns of CMV infection may occur in transplant recipients: (1) Following inoculation of the virus by either the donor organ or by blood transfusion in seronegative recipients, a primary infection may occur. Roughly 60% of seronegative recipients who receive an organ from a seropositive donor will develop a clinically evident infection.18 (2) Reactivation of endogenous latent virus can become manifest in an immunosuppressed seropositive transplant recipient who had been infected with the virus before transplantation. (3) Reinfection of a sero-

positive recipient by a different strain of CMV carried in the donor organ or transmitted by blood transfusion also can occur.20’27,30

For category one (seronegative donor and recipient), no prophylaxis is indicated, but the recipient should only receive CMV negative blood. In categories two and three, there is no evidence that prophylactic therapy is effective. In renal transplant recipients, there is conclusive evidence that CMV immune globulin prophylaxis is effective in reducing the incidence and intensity of clinically overt disease in seronegative recipients of donors that have CMV antibodies.32 Although data to support the efficacy of prophylactic immune globulin in heart transplantation is equivocal,33 it can be administered safely. 34 Therefore, based on the proven efficacy in renal transplant patients, it seems likely that CMV immunoglobulin will be useful in category four heart transplant recipients. The immunoglobulin also should be given to seronegative recipients if the donor serology is unknown.

Toxoplasmosis

For categories one, two, and three, there does not appear to be a high risk of developing clinical disease and prophylactic drug administration is not indicated. Patients in category four, however, are at high risk for life-threatening infection and a prophylactic drug regimen is indicated.23,24 Pyrimethamine, 25 mg daily for six weeks, has been an effective prophylaxis.24 To prevent folic acid deficiency, folinic acid in a dose of 5 mg to 15 mg per day should also be given.

DIAGNOSIS AND MANAGEMENT OF SPECIFIC ORGAN SYSTEM INFECTIONS

Despite the decrease in the frequency and severity of infectious complications after cardiac transplantation’2~‘3~15”6 the potential for life- threatening infection always is present in any immunocompromised patient. Vulnerability to serious infections increases significantly about 3 weeks following transplantation and reaches its zenith at 8 weeks, after which it declines.lg Bacterial infections caused by nosocomial gram- negative rods, enterococcus, Staphylococcus species, and fungus merit top concern in the early posttransplantation period.13,15,‘6 Early herpes simplex and varicella-zoster viral infections, often oral-cutaneous and minor in severity, have


become increasingly common in the cyclosporine era. These have been controlled easily with acyclovir. Fungal infections occur infrequently in the first posttransplant month. The incidence of Pneumocystis carinii pneumonia has markedly decreased and toxoplasmosis is infrequent,13,15 probably due in part to the prophylactic use of trimethoprin-sulfamethoxazole. Although a dra- matic reduction has been observed in pulmonary infections, the lungs remain the most common site of bacterial infection, followed in order of frequency by the blood stream and urinary tract.i3”’ Other important sites include the sternal wound, skin, central nervous system, orophar- ynx, and gastrointestinal tract.

Pulmonary Infections

Any cardiac transplant recipient who shows signs of pneumonia within the first several weeks after transplantation most likely has a bacterial infection until proved otherwise. Nevertheless, other diagnoses also must be considered. Fever associated with interstitial infiltrates from edema may signal allograft rejection. Pulmonary emboli may occur, particularly in a recipient who was moribund and bedridden preoperatively. Aspira- tion is also a consideration. Prolonged cardiopulmonary bypass or perioperative bleeding requiring massive transfusion of blood products and resulting in thrombocytopenia may be followed by adult respiratory distress syndrome (ARDS) or hemorrhage into the lung. Noncardiac pulmonary edema may also develop in blood transfusion recipients and present as hypoxemia and diffuse pulmonary infiltrate. High FIO, (~0.5) can produce oxygen toxicity that results in ARDS. Azathioprine can induce an interstitial pneumonitis as early as 3 to 6 weeks after initiation of therapy.35

Although a role exists for initiating empiric broad spectrum antibiotic therapy acutely, if the patient’s condition is critical and is deteriorating rapidly, appropriate therapeutic intervention requires rapid, accurate diagnosis. Sputum should be collected for Gram stain and culture. If less than 10 squamous epithelial cells and more than 25 polymorphonuclear leukocytes per low power field are seen, there is a high likelihood the specimen is expectorated sputum and not saliva. The diagnosis, however, can be neither made nor

excluded from a Gram stain. Definitive diagnosis requires culture results. Acid-fast staining for mycobacteria, direct fluorescent antibody examination for Legionella, and potassium hydroxide preparation for phase-contrast microscopy to identify fungal pathogens can also be performed.

If expectorated sputum is not accessible or the diagnosis remains obscure despite adequate samples, more invasive techniques must be used. These include transtracheal needle aspiration, transbronchial biopsy, bronchoalveolar lavage, percutaneous needle aspiration, and open-lung biopsy. Although there is less contamination with oropharyngeal flora in sputum obtained by transtracheal needle aspiration than in expectorated samples, the overall diagnostic yield is not superior. 36 Bronchoscopic evaluation is most effective in evaluating diffuse pulmonary infiltrates.36 In patients who have localized infiltrate, however, the diagnostic yield is poor. In addition, the efficacy of the procedure depends on the skill, judgment, and experience of the bronchoscopist. Bronchoalveolar lavage may be more effective in diagnosing diffuse pulmonary infiltrates, but results are still preliminary. Percutaneous needle aspiration and biopsy have been evaluated more extensively and are useful when selectively used for peripheral focal, nodular, and especially cavitary lesions. 19,36 However, both needle aspiration and biopsy frequently are complicated by pneu- mothorax and bleeding. Open-lung biopsy is the safest and most rapid technique available to make a specific diagnosis of a pulmonary infection in immunosuppressed patients.36 It is the procedure of choice when emergency therapy is necessary.‘9’36

CMV Pulmonary Infections

Herpes simplex has been reported to cause pneumonitis, particularly in intubated transplant recipients. Also, primary varicella-zoster infection in immunocompromised recipients may cause a lethal bronchopneumonia.19~36~37 Both are un- common. CMV is a common cause of invasive infection in cyclosporine-treated renal and cardiac allograft recipients. 1~,1%~8,~%3%36 Dummer and

coinvestigators have reported that in patients who have primary CMV infection, clinical symptoms, including pneumonia, do not occur concom- itant with identification of viral shedding.29 They


observed a period of weeks to months between viral isolation and the development of pneumonitis. CMV pneumonia presents most commonly 6 to 12 weeks posttransplant.15~‘g.29.36 The use of antilymphocyte globulin increases the risk of invasive CMV infection.13’18 Azathioprine also promotes CMV infection.31

The classic roentgenographic presentation is a diffuse interstitial infiltrate,18,36 but CMV may appear first as a localized consolidation.37 CMV infection is a systemic invasive illness in transplant patients; multiple organ systems usually are affected. Often, a typical prodrome of fever, malaise, and myalgias has preceded the onset of pneumonia. Leukopenia with atypical lympho- cytes, thrombocytopenia, and evidence of hepatic dysfunction often are present. The gastrointestinal tract may have peptic CMV ulcerations, which sometimes cause serious bleeding.38~3g~40 Since CMV suppresses T-cell function and causes severe neutropenia, life-threatening pulmonary superinfection can be caused by a variety of microorganisms, including P carinii, Aspergil- lus, and Cryptococcus neoformans. In the presence of the clinical syndrome, a four-fold rise in serologic titer, positive buffy-coat cell cultures, and urinary tract or pharyngeal viral shedding strongly suggests the diagnosis.=’ Confirmation requires growth of the virus from lung tissue. Alternatively, the identification of pneumonitis in a biopsy specimen correlated with cytopathic changes in bronchoalveolar lavage fluid or lung tissue is diagnostic. 37 These findings, however, require from 5 to 10 days to yield results. Preliminary reports indicate CMV-specific monoclonal antibody assays can be used to make the diagnosis within hours.41,42

The use of CMV infection prophylaxis with hyperimmunoglobulin has been addressed earlier (see Donor Heart Infections). Once infection has occurred, evidence from both renal and cardiac transplant experience suggests that the guanine analogue, 9 (1,3-dihydroxy-2-proproxy-methyl)- guanine (DHPG, Ganciclovir), may be effective in the treatment of invasive CMV infections including pneumonia.43-45 This inhibitor of viral replication is similar to acyclovir but far more potent in vitro. Its major side effects are dose dependent, usually reversible, and include renal damage, bone marrow depression, nausea, and

spermatogenesis inhibition.43 In cardiac transplant patients 2.5 mg/kg intravenously every eight hours has been given for 10 to 14 days. The dosage is decreased to 1.5 mg/kg every eight hours if the white blood cell count is less than 2500/mm3. The dosing interval is increased to every 12 hours if creatinine clearance decreases to less than 50 mL/min and stopped completely for a creatinine clearance less than 20 mL/min.

Opportunistic Pulmonary Infections

Opportunistic fungal, protozoal, and mycobac- terial infections generally do not occur in the first month after transplantation unless a specific environmental risk exists. The distribution of these organisms varies among institutions. In immunosuppressed patients who have pneumonitis and central nervous system involvement, commonly encountered organisms include Crypto- coccus neoformans, Aspergillus, Coccidioides immitis, Nocardia, mycobacteria, Toxoplasma, and rarely Listeria monocytogenes.‘s,36 The incidence of nocardial infections appear to have decreased in patients receiving cyclosporine.15 Skin lesions presenting with pneumonitis should call to attention the possibility of infection with Aspergillus, Cryptococcus, and blastomycosis. Although disseminated candidal infections may involve both the central nervous system and the skin, pneumonitis is rare. Most opportunistic infections develop insidiously with the gradual appearance over a few days to a week or more on chest roentgenogram of a focal, often peripheral, nodular, or cavitary lesion. Aspiration of cyclosporine in a weak cachectic patient has caused a localized foreign body reaction producing a peripheral left-upper-lobe opacity that mimicked an infectious pulmonary process.46 Once the diagnosis of a fungal pulmonary process has been made, intravenous amphotericin B therapy remains the treatment of choice. For cryptococcal disease, 5-fluorocytosine also may be added to the treatment regimen. A few organisms, such as P carinii and occasionally Aspergillus, present with diffuse bilateral interstitial infiltrates. P carinii frequently occurs as a mixed infection with CMV pneumonitis.36

Toxoplasmosis has gained recent attention because of the recognition of its transmission by donor allografts discussed earlier. In susceptible


individuals (seronegative recipients) an over- whelming often lethal infection becomes evident within 1 month after receiving an allograft from an infected donor. Widespread dissemination occurs with CNS impairment, hepatic dysfunction, myocarditis, and diffuse interstitial pneumonitis. Serologic testing can give presumptive evidence for the diagnosis, which can be firmly made only by finding toxoplasma tachyzoites or the presence of numerous cysts in body fluid or tissue.23

Mediastinitis and Sternal Wound Infection

Mediastinitis complicating cardiac transplantation does not seem to occur more often than in other cardiac surgical operations.‘3’15V’6,1g Staphy- Zococcus is the most common organism.47 The presentation tends to be occult. Fever,‘leukocyto- sis, and sternal instability frequently are not present. The most common finding is the presence of a pericardial effusion.

Treatment consists of adherence to the princi- ples of management of the infected sternal wound, including adequate debridement, irrigation, and appropriate antibiotic therapy. The choice of standard closure over irrigation and drainage catheters or open drainage must be based on the operative findings. Successful muscle-flap closure of cardiac-transplant-infected sternotomy wounds has been reported.47s48

Central Nervous System

In the precyclosporine era, encephalitis, brain abscess, and meningitis commonly occurred in heart transplant recipients and often were fata1.4g Recently, the incidence of central nervous system infections in cyclosporine-treated heart allograft recipients has declined precipitously.‘2,13315916 Acute meningitis is most commonly caused by Listeria monocytogenes.‘8,4g The causative organism for subacute and chronic meningitis is usually Cryptococcus neoformans, but tuberculosis, histoplasmosis, and Coccidioides immitis also must be considered among populations or in geographic regions where they are often encountered. The time of onset appears variable, rang- ing from 6 weeks to many months after transplantation. Aspergillus species are the most common fungal organisms causing central nervous system

infections in transplant recipients and produce an encephalitis or brain abscess. Usually the organisms spread to the brain from a pulmonary location and the onset may be as early as 2 to 12 weeks posttransplant. Its diagnosis is difficult and the prognosis is grave. Candida, Nocardia, and Klebsiella also may produce focal infections. The most common site of toxoplasmosis infections in immunosuppressed heart transplant patients is the brain where it usually produces a diffuse encephalitis or may lead to abscess formation.49 Despite their decreasing frequency, the potential occurrence of these infections is important to consider because their presentation is so often subtle. Symptoms of meningitis in transplant recipients often are masked by the antiinflammatory effects of immunosuppression. Signs of meningeal irritation can be demon- strated in only 60% of transplant recipients who have acute meningitis.”

The most important clues of central nervous system infection in this group of patients are fever and headache. Frequently, minor changes in the level of consciousness may be the only indication of central nervous system infection. Therefore, a high index of suspicion is mandatory. Any personality change, focal neurologic finding, or headache persisting several hours (especially with fever) is an indication for thor- ough neurologic examination. When papilledema or focal neurologic deficit is found, an emergency computed tomography (CT) scan should be performed. Serial CT scans at short intervals may be necessary.‘s,49 If neither of the above findings is present, immediate lumbar puncture must be performed. Cerebral spinal fluid should be sub- mitted for protein, glucose, cell count, Gram stain, india ink staining, and culture. Although the cerebral spinal fluid examination is useful for diagnosing meningitis, it is less effective in detect- ing abscess or encephalitis.

If an accurate diagnosis is made, efficacious therapy is available. For example, the combina- tion of pyrimethamine and a sulfa drug is effective treatment for intracranial toxoplasma infection. Certain fungal infections, such as cryptococcal meningitis, are amenable to cure or suppression with amphotericin B and 5-fluorocytosine.49


Gastrointestinal Complication

As in the case with central nervous system infections, minimal signs and symptoms may accompany gastrointestinal complications in cardiac transplant patients. Cholecystitis, pancreatitis, and gastrointestinal bleeding deserve special consideration. Cholecystitis can develop in the early postoperative period. Colon et a14’ reported nine out of 86 cardiac transplant patients who developed postoperative cholecystitis. Five of these patients underwent cholecystectomy. Emer- gency surgery, however, was needed in only one patient with gangrenous cholecystitis who had positive bile cultures for Enterobacter aerogina and Candida albicans.

Pancreatitis has been the most common gastrointestinal tract complication reported after cardiac transplantation4’ It is known to occur following cardiopulmonary bypass.” Pancreati- tis also has been attributed to the immunosuppressive drugs used in transplant recipients.40 Pancre- atic cultures often may be negative in heart transplant patients who require laparotomy for severe pancreatitis; the mortality rate for this group of patients is high.

CMV can cause pancreatitis as well as gastric outlet obstruction. 3g,40 CMV also can cause severe mucosal ulcerations in the esophagus, stom- ach, duodenum, jejunum, ileum, and colon, which produce massive hemorrhage.38-40 Fatal diffuse bleeding from vasculitis and ulceration through- out the small intestine can occur in patients who have disseminated CMV disease. Endoscopy with biopsy of suspicious mucosal lesions should be performed. Arteriography may be required to identify the bleeding site. If a long segment of bowel precluding surgical resection is involved, intraarterial vasopression infusion can be used to control the hemorrhage.40 Prophylaxis as well as treatment of CMV infections has been discussed previously. These modalities offer hope that such complications will occur less frequently and can be managed more effectively in the future.

INFECTION RISK ASSOCIATED WITH PRETRANSPLANT MECHANICAL

CIRCULATORY SUPPORT

Mechanical circulatory support increasingly is used as a “bridge to transplantation” in patients who otherwise would die while waiting for a

donor heart. Intraaortic balloon counterpulsa- tion, extracorporeal membrane oxygenation (ECMO), left and right ventricular centrifugal assist pumps, and the pneumatically-driven total artificial heart all have been used.5’W54 Manage- ment presents a dual challenge because the prospect of certain infection from a prosthetic device (if used long enough) must be considered in a patient who will require intense immunosuppression after transplantation.55 Indeed, the incidence of infections in these patients has been higher than other cardiac transplant recipients. Bacterial mediastinitis and empyema, as well as fungal sepsis, appears to occur more often in patients who have been supported by the total artificial heart than in those who have been bridged with ventricular assist devices.1h251W54S56357 The duration of mechanical support may explain this observation. In three series reporting the use of the total artificial heart as a “bridge,” the average length of time the device was used ranged from 8.7 days to 11 days.51353354 By compar- ison, in a fourth series, centrifugal pumps and ECMO were reported to be used for an average of only 1.6 days.52 (Table 1)

Not all of these infections, however, are neces- sarily fatal. Through 1986, 40 of the 58 patients (70%) reported, who underwent heart transplantation after requiring mechanical support, had survived.5s Infection was responsible for about 10% of the deaths. The presence of percutaneous drive lines or vascular cannula as well as the need for two procedures requiring cardiopulmonary bypass increases the chance of infection. These factors must be considered in the evaluation, selection, and management of cardiac transplant candidates.

Table 1. Duration of Mechanical Circulatory Support

Before Transplantation

Average Duration Flange (dav?.) (davs)

Total artificial heart

Pennoch et al5’

Griffith et al53

Cabrol et aIs

Ventricular assist devices

Pennoch et al5’

Bolman et aIs

10.9 0.5-45

8.7 2-18

11.2 2-28

7.2 0.3-42

1.6 0.5-3


REFERENCES

1. Copeland JG, Mammana RB, Fuller JK, et al: Heart transplantation, four years’ experience with conventional immunosuppression. JAMA 251:1563-1566, 1984

2. Cooper DKC, Lanza RP, Oliver S, et al: Infectious complications after heart transplantation. Thorax 38:822- 828,1983

3. Modry DL, Oyer PE, Jamieson SW, et al: Cyclosporine in heart and heart-lung transplantation. Can J Surg 28:274- 282,1985

4. Griffith BP, Hardesty RL, Deeb M, et al: Cardiac transplantation with cyclosporine A and prednisone. Ann Surg 196:324-329,1982

5. Griffith BP, Hardesty RL, Bahnson HT: Powerful but limited immunosuppression for cardiac transplantation with cyclosporine and low-dose steroid. J Thorac Cardiovasc Surg 87:35-42, 1984

6. Frazier OH, Cooley DA, Painvin GA, et al: Cardiac transplantation at the Texas Heart Institute: Comparative analysis of two groups of patients (1968-1969 and 1982- 1983). Ann Thorac Surg 39:303-307,198s

7. Reece IJ, Frazier OH, Painvin A, et al: Early results of cardiac transplantation at the Texas Heart Institute. Thorax 39:676-680, 1984

8. Mammana RB, Peterson EA, Fuller JK, et al: Pulmo- nary infections in cardiac transplant patients: Modes of diagnosis, complications, and effectiveness of therapy. Ann Thorac Surg 36:700-705, 1983

9. Dummer JS, Hardy A, Poorsattar A, et al: Early infections in kidney, heart, and liver transplant recipients on cyclosporine. Transplantation 36:259-267, 1983

10. Baumgartner WA: Infection in cardiac transplantation. Heart Transplant 3:75-80, 1983

11. Reece IJ, Painvin GA, Zeluff B, et al: Infection in cyclosporine-immunosuppressed cardiac allograft recipients. Heart Transplant 3:239-242, 1984

12. Dresdale AR, Drusin RE, Lamb J, et al: Reduced infection in cardiac transplant recipients. Circulation 72:237- 240,1985

13. Andreone PA, Olivari MT, Elick B, et al: Reduction of infectious complications following heart transplantation with triple drug immunotherapy. J Heart Transplant 5:13-19, 1986

14. Baumgartner WA, Augustine S, Borkon AM, et al: Present expectations in cardiac transplantation. Ann Thorac Surg 43585590, 1987

15. Hofflin JM, Potasman I, Baldwin JC, et al: Infectious complications in heart transplant recipients receiving cyclosporine and corticosteroids. Ann Intern Med 106:209-216, 1987

16. Bolman RM, Cance C, Spray T, et al: The changing face of cardiac transplantation: The Washington University Program, 19851987. Ann Thorac Surg 45:192-197,1988

17. Bristow MR, Gilbert EM, Renlund DG, et al: Use of OKT3 monoclonal antibody in heart transplantation: Review of the initial experience. J Heart Transplant 7:1-10, 1988

18. Gentry LO, Zeluff BJ: Diagnosis and treatment of infection in cardiac transplant patients. Surg Clin North Am 66:459-465,1986

19. Tolkoff-Rubin NE, Rubin RH: Infection in the organ transplant recipient, in Cerilli JG (ed): Organ Transplanta- tion and Replacement. Philadelphia, PA, Lippincott, pp 445-461,1988

20. Migliori RJ, Simmons RL: Infection prophylaxis after organ transplantation. Transplant Proc 20:395-399, 1988

21. Chou S, Gallagher JG, Merigan TC: Controlled clinical trial of intravenous acyclovir in heart-transplant patients with mucocutaneous herpes simplex infections. Lancet 1: 1392- 1394,198l

22. Ryning FW, McLeod R, Maddox JC, et al: Probable transmission of toxoplasma gondii by organ transplantation. Ann Intern Med 90:47-49,1979

23. Luft BJ, Naot Y, Araujo FG, et al: Primary and reactivated toxoplasma infection in patients with cardiac transplants. Ann Intern Med 99:27-31, 1983

24. Hakim M, Esmore D, Wallwork J, et al: Toxoplasmo- sis in cardiac transplantation. Br Med J 292:1108, 1986

25. Wreghitt TG, Gray JJ, Balfour AH: Problems with serological diagnosis of toxoplasma gondii infections in heart transplant recipients. J Clin Path01 39:1135-l 139, 1986

26. Pollard RB, Arvin AM, Gamberg P, et al: Specific cell-mediated immunity and infections with herpes viruses in cardiac transplant recipients. Am J Med 73:679-687, 1982

27. Preiksaitis JK, Rosno S, Grumet C, et al: Infections due to herpesviruses in cardiac transplant recipients: Role of the donor heart and immunosuppressive therapy. J Infect Dis 147:974-981,1983

28. Hakim M, Wreghitt TG, English TAH, et al: Signifi- cance of donor transmitted disease in cardiac transplantation. Heart Transplant 4:302-306, 1985

29. Dummer JS, White LT, Ho M, et al: Morbidity of cytomegalovirus infection in recipients of heart or heart-lung transplants who received cyclosporine. J Infect Dis 152: 1182- 1191,1985

30. Chou S: Cytomegalovirus infection and reinfection transmitted by heart transplantation. J Infect Dis 155:1054- 1056,1987

31. Gregor B, Doller G, Schareck WD, et al: Incidence and clinical course of cmv (and herpes simplex) infections under triple drug therapy. Transplant Proc 19:4057-4060, 1987

32. Snydman DR, Werner BG, Heinze-Lacey B, et al: Use of cytomegalovirus immune globulin to prevent cytomegalovirus disease in renal-transplant recipients. N Engl J Med 317:1049-1054, 1987

33. Schafers H-J, Haverich A, Wahlers T, et al: Cytomeg-

alovirus prophylaxis after heart transplantation using specific hyperimmunoglobulin. Transplant Proc 194061-4062, 1987

34. Metselaar HJ, Velzing J, Rothbarth PH, et al: A pharmocokinetic study of anti-cytomegalovirus hyperimmu- noglobulins in cytomegalovirus seronegative cardiac transplant recipients. Transplant Proc 19:4063-4065, 1987

35. Rosenow EC, Wilson WR, Cockerill FR: Pulmonary disease in the immunocompromised host. Mayo Clin Proc 60:473-487, 1985, (part I)

36. Wilson WR, Cockerill FR, Rosenow EC: Pulmonary


disease in the immunocompromised host. Mayo Clin Proc 60:610-631, 1985 (part II)

37. Schulman LL: Cytomegalovirus pneumonitis and lo- bar consolidation. Chest 91:558-561, 1987

38. Bramwell NH, Davies RA, Koshal A, et al: Fatal gastrointestinal hemorrhage caused by cytomegalovirus duo- denitis and ulceration after heart transplantation. J Heart

Transplant 6:303-306, 1987

39. Steed DL, Brown B, Reilly JJ, et al: General surgical complications in heart and heart-lung transplantation. Sur- gery 98~139-145, 1985

40. Colon R, Frazier OH, Kahan BD, et al: Complications

in cardiac transplant patients requiring general surgery. Surgery 103:32-38,1988

41. van der Bij W, van Dij RB, van Son WJ, et al: Antigen test for early diagnosis of active cytomegalovirus infection in heart transplant recipients. J Heart Transplant 7:106-l 10,

1988

42. Emanuel D, Peppard J, Stover D, et al: Rapid immu-

nodiagnosis of cytomegalovirus pneumonia by bronchoalveo-

lar lavage using human and murine monoclonal antibodies. Ann Intern Med 104:476-481, 1986

43. Watson FS, O’Connell JB, Amber IJ, et al: Treatment of cytomegalovirus pneumonia in heart transplant recipients

with 9 (1,3-dihydroxy-2-proproxymethyl)-guanine (DHPG) J Heart Transplant 7:102-105, 1988

44. Shabtai M, Luft B, Waltzer WC, et al: Massive cytomegalovirus pneumonia and myocarditis in a renal transplant recipient: Successful treatment with DHPG. Trans-

plant Proc 20:562-563, 1988

45. Cantarovich M, Hiesse C, Lantz 0, et al: Treatment of cytomegalovirus infections in renal transplant recipients with 9-(1, 3-dihydroxy-2-propoxymethyl) guanine. Transplanta-

tion45:1139-1141, 1988

46. Gould K, Freeman R, Odom NJ, et al: Pulmonary

“cyclosporinoma” mimicking infection after heart transplantation. J Heart Transplant 6:375-377, 1987

47. Trento A, Dummer GS, Hardesty RL, et al: Medias- tinitis following heart transplantation: Incidence, treatment, and results. Heart Transplant 3:336-340, 1984

48. Pearl SN, Weiner MA, Dibbell DG: Sternal infection

after cardiac transplantation 83:632-634, 1982

49. Britt RH, Enzmann DR, Remington JS: Intracranial

infection in cardiac transplant recipients. Ann Neurol 19:107-

119,198l

50. Feiner H: Pancreatitis after cardiac surgery. Am J

Surg 131:684-688, 1976

5 1. Pennock JL, Pierce WS, Campbell DB, et al: Mechan-

ical support of the circulation followed by cardiac transplan-

tation. J Thorac Cardiovasc Surg 92:994-1004, 1986

52. Bolman RM, Spray TL, Cox JL, et al: Heart transplan-

tation in patients requiring preoperative mechanical support.

J Heart Transplant 6:273-280, 1987

53. Griffith BP, Hardesty RL, Kormos RL, et al: Tempo-

rary use of the jarvik-7 total artificial heart before transplan-

tation. N Engl J Med 316:130-134, 1987

54. Cabrol C, Gandjbakhch I, Pavie A, et al: Total

artificial heart as a bridge for transplantation: La pitie’ 1986

to 1987. J Heart Transplant 7:12-17, 1988

55. Rice LB, Karchmer AW: Artificial heart implantation:

What limitations are imposed by infectious complications?

JAMA 259:894-895,1988

56. Oako TE, Pai WE, Pennock JL, et al: Aortic rupture

caused by fungal aortitis: Successful management after heart

transplantation. J Heart Transplant 7:162-164, 1988

57. Kunim CM, Dobbins JJ, Melo JC, et al: Infectious

complications in four long-term recipients of the jarvik-7

artificial heart. JAMA 259:860-864, 1988

58. Pai WE, Pierce WS: Combined registry for the clinical

use of mechanical ventricular assist pumps and the total

artificial heart: First official report-1986. J Heart Transplant

6:68-70, 1987

Documents

Early postoperative care: Infectious disease considerations