Cytomegalovirus: More Dangerous to the Cardiac Surgical Patient Than We Thought?
1990; Elsevier BV; Volume: 97; Issue: 1 Linguagem: Inglês
10.1378/chest.97.1.3
ISSN1931-3543
Autores Tópico(s)Organ Transplantation Techniques and Outcomes
ResumoCytomegalovirus (CMV) has long been known to be dangerous to the immunocompromised patient, to pregnant women, and to premature infants,1Adler SE Transfusion-associated cytomegalovirus infections. Rev Inf Dis 1983; 5:977-93Google Scholar but not, we thought, to cardiac surgical patients.In 1960, Kreel et al2Kreel I Zaroff LI Canter JW Krasna I Baronofsky ID A syndrome following total body perfusion.Surg Gynecol Obstet. 1960; 111: 317-321PubMed Google Scholar described a febrile illness occurring after heart surgery that resembled infectious mononucleosis. This post-perfusion syndrome was subsequently shown to be caused by CMV3Kääriäinen L Klemola E Pahoheimo J Rise of cytomegalovirus antibodies in an infectious-mononucleosis-like syndrome after transfusion.Br Med J. 1966; 5498: 1270-1272Crossref Scopus (156) Google Scholar transmitted in or reactivated by blood transfusions.4Prince AM Szmuness W Millian SJ David DS A serologic study of cytomegalovirus infections associated with blood transfusions.N Engl J Med. 1971; 284: 1125-1131Crossref PubMed Scopus (142) Google Scholar, 5Paloheimo JA von Essen R Klemola E Kääriäinen L Siltanen P Subclinical cytomegalovirus infections and cytomegalovirus mononucleosis after open heart surgery.Am J Cardiol. 1968; 22: 624-630Abstract Full Text PDF PubMed Scopus (73) Google Scholar, 6Endresen K Gjesdal K Orstavik I Sivertssen E Reikvam Å Ulstrup JC Aalen OO Primary cytomegalovirus infection following open heart surgery.Acta Med Scand. 1985; 218: 423-428Crossref PubMed Scopus (5) Google Scholar, 7Adler SP Baggett J McVoy M Transfusion-associated cytomeglovirus infections in seropositive cardiac surgery patients.Lancet. 1985; ii: 743-746Abstract Scopus (54) Google Scholar This mild disease may cause diagnostic confusion after heart operations, but its self-limited nature has given it a clinical significance only slightly worse than the common cold. Now, with the report in this issue, (see page 18) Domart and colleagues have raised the specter that CMV infection after heart operations may be far more sinister.They describe a series of 115 patients referred to them at the Hôpital Bichat with bacterial mediastinitis after heart operations. Twenty five percent of these patients had CMV cultured from urine, blood or both. The presence of this virus (VE +) correlated with increased morbidity from the infection, longer hospitalization, increased failure rate of the primary treatment (systemic antibiotics plus mediastinal and sternal debridement with closure over drainage tubes), and a higher late mortality (after 15 days of hospitalization)—55 percent in those shedding the virus (VE 4+) compared with 25 percent in those not shedding the virus (VE–).The authors did not demonstrate a correlation between those who were VE + and those with elevated IgG antibodies to CMV. However, their methodology could not have detected any correlation: viral cultures were obtained after the mediastinitis was manifest and at about the same time as the CMV antibody levels were drawn. The rise in CMV antibody after new infection or reactivation of the virus does not occur until about two to five months later.5Paloheimo JA von Essen R Klemola E Kääriäinen L Siltanen P Subclinical cytomegalovirus infections and cytomegalovirus mononucleosis after open heart surgery.Am J Cardiol. 1968; 22: 624-630Abstract Full Text PDF PubMed Scopus (73) Google Scholar Only if the CMV antibody titers had been drawn serially over a longer period following the original operation could any meaningful correlation be made between virus shedding and antibody rise.In part because the patients reported by Domart et al were referred from other institutions, some important questions cannot be answered by this study. We do not know the denominator from which these patients were derived and hence, cannot calculate the overall infection rate. We cannot ask about the correlation between the presence of CMV infection and the incidence of mediastinitis.Another difficulty in the methodology might have skewed the results by failure to detect some (VE+) patients. The first positive culture in the VE+ patients occurred at 37 ± 22 days (range 9-98 days), whereas the last negative culture in the VE – patients occurred at 39 ± 25 days. Thus, many of the VE – patients might have demonstrated positive cultures had each patient's cultures been obtained over a period extending to at least the last day (98 days) of positive culture in the VE+ patients.Despite these shortcomings, the implications of this article are ominous. Cardiac surgical patients may, in fact, fall into an immunocompromised group. Circumstantial evidence that this may be so is the extraordinarily high rate of mediastinitis (21 to 44 percent) in patients receiving no prophylactic antibiotics or in whom inadequate serum levels were present during the heart operation.8Austin TW Coles JC Burnett R Goldbach M Aortocoronary bypass procedures and sternotomy infections: a study of anti-staphylococcal prophylaxis.Can J Surg. 1980; 23: 483-485PubMed Google Scholar, 9Fong IW Baker CB McKee DC The value of prophylactic antibiotics in aorto-coronary bypass operations: a double-blind randomized trial.J Thorac Cardiovasc Surg. 1979; 78: 908-913PubMed Google Scholar, 10Goldmann DA Hopkins CC Karchmer AW Abel RM McEnany MT Akins C et al.Cephalothin prophylaxis in cardiac valve surgery. A prospective, double-blind comparison of two-day and six-day regimens.J Thorac Cardiovasc Surg. 1977; 73: 470-479Abstract Full Text PDF PubMed Google Scholar CMV probably further immunocompromises these patients. The amount of exogenous blood transfused correlates with the incidence of increased antibody titers to the virus4Prince AM Szmuness W Millian SJ David DS A serologic study of cytomegalovirus infections associated with blood transfusions.N Engl J Med. 1971; 284: 1125-1131Crossref PubMed Scopus (142) Google Scholar, 5Paloheimo JA von Essen R Klemola E Kääriäinen L Siltanen P Subclinical cytomegalovirus infections and cytomegalovirus mononucleosis after open heart surgery.Am J Cardiol. 1968; 22: 624-630Abstract Full Text PDF PubMed Scopus (73) Google Scholar, 6Endresen K Gjesdal K Orstavik I Sivertssen E Reikvam Å Ulstrup JC Aalen OO Primary cytomegalovirus infection following open heart surgery.Acta Med Scand. 1985; 218: 423-428Crossref PubMed Scopus (5) Google Scholar, 7Adler SP Baggett J McVoy M Transfusion-associated cytomeglovirus infections in seropositive cardiac surgery patients.Lancet. 1985; ii: 743-746Abstract Scopus (54) Google Scholar,11Pass RF Epidemiology and transmission of cytomegalovirus.J Inf Dis. 1985; 152: 243-248Crossref PubMed Scopus (122) Google Scholar Since we have no means of directly treating CMV infection, this study suggests that the morbidity of blood transfusion may be even higher than was thought, and reemphasizes the importance of its reduction through the use of blood salvage techniques, and auto-donation. Since the transmission/reactivation of CMV through blood transfusion can be prevented by using deglycerolyzed red cells or blood from CMV antibody negative donors,12Wilhelm JA Matter L Schopfer K The risk of transmitting cytomegalovirus to patients receiving blood transfusions.J Inf Dis. 1986; 154: 169-171Crossref PubMed Scopus (55) Google Scholar an argument could be made for employing these two methods when transfusions become necessary for the cardiac surgical patient.Perhaps this study from Hôpital Bichat will encourage a prospective study of cardiac surgical patients that will examine the incidence of CMV antibody rise after operation, the incidence of viral shedding over a long period after operation, and will correlate these with the incidence of mediastinitis, its severity, and the incidence of perioperative blood transfusion. Cytomegalovirus (CMV) has long been known to be dangerous to the immunocompromised patient, to pregnant women, and to premature infants,1Adler SE Transfusion-associated cytomegalovirus infections. Rev Inf Dis 1983; 5:977-93Google Scholar but not, we thought, to cardiac surgical patients. In 1960, Kreel et al2Kreel I Zaroff LI Canter JW Krasna I Baronofsky ID A syndrome following total body perfusion.Surg Gynecol Obstet. 1960; 111: 317-321PubMed Google Scholar described a febrile illness occurring after heart surgery that resembled infectious mononucleosis. This post-perfusion syndrome was subsequently shown to be caused by CMV3Kääriäinen L Klemola E Pahoheimo J Rise of cytomegalovirus antibodies in an infectious-mononucleosis-like syndrome after transfusion.Br Med J. 1966; 5498: 1270-1272Crossref Scopus (156) Google Scholar transmitted in or reactivated by blood transfusions.4Prince AM Szmuness W Millian SJ David DS A serologic study of cytomegalovirus infections associated with blood transfusions.N Engl J Med. 1971; 284: 1125-1131Crossref PubMed Scopus (142) Google Scholar, 5Paloheimo JA von Essen R Klemola E Kääriäinen L Siltanen P Subclinical cytomegalovirus infections and cytomegalovirus mononucleosis after open heart surgery.Am J Cardiol. 1968; 22: 624-630Abstract Full Text PDF PubMed Scopus (73) Google Scholar, 6Endresen K Gjesdal K Orstavik I Sivertssen E Reikvam Å Ulstrup JC Aalen OO Primary cytomegalovirus infection following open heart surgery.Acta Med Scand. 1985; 218: 423-428Crossref PubMed Scopus (5) Google Scholar, 7Adler SP Baggett J McVoy M Transfusion-associated cytomeglovirus infections in seropositive cardiac surgery patients.Lancet. 1985; ii: 743-746Abstract Scopus (54) Google Scholar This mild disease may cause diagnostic confusion after heart operations, but its self-limited nature has given it a clinical significance only slightly worse than the common cold. Now, with the report in this issue, (see page 18) Domart and colleagues have raised the specter that CMV infection after heart operations may be far more sinister. They describe a series of 115 patients referred to them at the Hôpital Bichat with bacterial mediastinitis after heart operations. Twenty five percent of these patients had CMV cultured from urine, blood or both. The presence of this virus (VE +) correlated with increased morbidity from the infection, longer hospitalization, increased failure rate of the primary treatment (systemic antibiotics plus mediastinal and sternal debridement with closure over drainage tubes), and a higher late mortality (after 15 days of hospitalization)—55 percent in those shedding the virus (VE 4+) compared with 25 percent in those not shedding the virus (VE–). The authors did not demonstrate a correlation between those who were VE + and those with elevated IgG antibodies to CMV. However, their methodology could not have detected any correlation: viral cultures were obtained after the mediastinitis was manifest and at about the same time as the CMV antibody levels were drawn. The rise in CMV antibody after new infection or reactivation of the virus does not occur until about two to five months later.5Paloheimo JA von Essen R Klemola E Kääriäinen L Siltanen P Subclinical cytomegalovirus infections and cytomegalovirus mononucleosis after open heart surgery.Am J Cardiol. 1968; 22: 624-630Abstract Full Text PDF PubMed Scopus (73) Google Scholar Only if the CMV antibody titers had been drawn serially over a longer period following the original operation could any meaningful correlation be made between virus shedding and antibody rise. In part because the patients reported by Domart et al were referred from other institutions, some important questions cannot be answered by this study. We do not know the denominator from which these patients were derived and hence, cannot calculate the overall infection rate. We cannot ask about the correlation between the presence of CMV infection and the incidence of mediastinitis. Another difficulty in the methodology might have skewed the results by failure to detect some (VE+) patients. The first positive culture in the VE+ patients occurred at 37 ± 22 days (range 9-98 days), whereas the last negative culture in the VE – patients occurred at 39 ± 25 days. Thus, many of the VE – patients might have demonstrated positive cultures had each patient's cultures been obtained over a period extending to at least the last day (98 days) of positive culture in the VE+ patients. Despite these shortcomings, the implications of this article are ominous. Cardiac surgical patients may, in fact, fall into an immunocompromised group. Circumstantial evidence that this may be so is the extraordinarily high rate of mediastinitis (21 to 44 percent) in patients receiving no prophylactic antibiotics or in whom inadequate serum levels were present during the heart operation.8Austin TW Coles JC Burnett R Goldbach M Aortocoronary bypass procedures and sternotomy infections: a study of anti-staphylococcal prophylaxis.Can J Surg. 1980; 23: 483-485PubMed Google Scholar, 9Fong IW Baker CB McKee DC The value of prophylactic antibiotics in aorto-coronary bypass operations: a double-blind randomized trial.J Thorac Cardiovasc Surg. 1979; 78: 908-913PubMed Google Scholar, 10Goldmann DA Hopkins CC Karchmer AW Abel RM McEnany MT Akins C et al.Cephalothin prophylaxis in cardiac valve surgery. A prospective, double-blind comparison of two-day and six-day regimens.J Thorac Cardiovasc Surg. 1977; 73: 470-479Abstract Full Text PDF PubMed Google Scholar CMV probably further immunocompromises these patients. The amount of exogenous blood transfused correlates with the incidence of increased antibody titers to the virus4Prince AM Szmuness W Millian SJ David DS A serologic study of cytomegalovirus infections associated with blood transfusions.N Engl J Med. 1971; 284: 1125-1131Crossref PubMed Scopus (142) Google Scholar, 5Paloheimo JA von Essen R Klemola E Kääriäinen L Siltanen P Subclinical cytomegalovirus infections and cytomegalovirus mononucleosis after open heart surgery.Am J Cardiol. 1968; 22: 624-630Abstract Full Text PDF PubMed Scopus (73) Google Scholar, 6Endresen K Gjesdal K Orstavik I Sivertssen E Reikvam Å Ulstrup JC Aalen OO Primary cytomegalovirus infection following open heart surgery.Acta Med Scand. 1985; 218: 423-428Crossref PubMed Scopus (5) Google Scholar, 7Adler SP Baggett J McVoy M Transfusion-associated cytomeglovirus infections in seropositive cardiac surgery patients.Lancet. 1985; ii: 743-746Abstract Scopus (54) Google Scholar,11Pass RF Epidemiology and transmission of cytomegalovirus.J Inf Dis. 1985; 152: 243-248Crossref PubMed Scopus (122) Google Scholar Since we have no means of directly treating CMV infection, this study suggests that the morbidity of blood transfusion may be even higher than was thought, and reemphasizes the importance of its reduction through the use of blood salvage techniques, and auto-donation. Since the transmission/reactivation of CMV through blood transfusion can be prevented by using deglycerolyzed red cells or blood from CMV antibody negative donors,12Wilhelm JA Matter L Schopfer K The risk of transmitting cytomegalovirus to patients receiving blood transfusions.J Inf Dis. 1986; 154: 169-171Crossref PubMed Scopus (55) Google Scholar an argument could be made for employing these two methods when transfusions become necessary for the cardiac surgical patient. Perhaps this study from Hôpital Bichat will encourage a prospective study of cardiac surgical patients that will examine the incidence of CMV antibody rise after operation, the incidence of viral shedding over a long period after operation, and will correlate these with the incidence of mediastinitis, its severity, and the incidence of perioperative blood transfusion.
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