CASE REPORT March-April, Vol. 14 No. 2, 2015: 281-285

Liver allografts from donors with peritoneal contamination: report of two cases

Tomaz J. M. Grezzana Filho, Aljamir D. Chedid, Ian Leipnitz, Marcio F. Chedid, Cleber Dario P. Kruel, Cleber Rosito P. Kruel

Liver Transplant and Hepatobiliary Unit, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.

ABSTRACT

Organs from deceased donors with traumatic abdominal injury, peritoneal contamination and open abdo- men are usually discarded due to risks of transmission of severe infections to the recipient. There are no specific recommendations regarding organ utilization from these donors, but they might be an unexplored source able to attenuate organ shortage. Herein, the first successful report of a case involving liver trans- plantation using a liver allograft procured from a deceased donor with an open abdomen is outlined. This donor was a young trauma patient in which peritoneal contamination had occurred following a gunshot wound. Also included in this the report is liver transplant from a donor, who also was a trauma victim with an enteric perforation. The decision-making process to accept liver allografts from donors with a greater risk of peritoneal infection involved the absence of uncontrolled sepsis or visible contamination of the cavity. Appropriate donor-recipient matching and adequate anti-infectious management might have con- tributed to a favorable outcome, which suggest that these donors can be used as alternatives to reduce organ shortage.

Key words. Liver transplantation. Deceased donors. Open abdomen. Peritoneal contamination. Trauma patients.

INTRODUCTION al as long as adequate antimicrobial treatment has been provided.2 However, information regarding There is an increasing gap between organ demand the use of organs from donors with peritoneal con- for transplantation and donor supply. In order to tamination is scarce, and only one prior case report accommodate the growing waiting list, the trans- described the outcomes of recipients who were plant community has increased efforts to expand the transplanted using organs from a donor with an donor pool by utilization of donors with expanded open abdomen.3 Although two of the recipients of criteria, which may also include those with docu- the organs from this donor had a good outcome, mented active infection.1 However, there is a scarci- the liver transplant recipient died during in-hospi- ty of information about the safety use of grafts from tal stay. Herein, two cases of patients who under- donors who suffered penetrating abdominal trauma went liver transplantation receiving allografts including the ones whose abdominal wall was kept procured from trauma victims in which peritoneal opened. cavity had been exposed to an important degree of The presence of bacteremia in the donor has contamination, including one who had an open ab- been proven to have no impact on recipient surviv- domen are presented.

CASE REPORT Correspondence and reprint request: Tomaz J. M. Grezzana Filho, M.D., Ph.D. Hospital de Clínicas de Porto Alegre. Case 1: Av. Ramiro Barcelos 2.350, CEP 90035-903, Porto Alegre, RS, Brazil. donor with an open abdomen Tel.: 55 51 9967-4817 and abdominal packing E-mail: [email protected]

Manuscript received: August 12, 2014. A 24-year-old male with traumatic brain, abdomi- Manuscript accepted: September 16, 2014. nal, and thoracic injuries underwent laparotomy 282 Grezzana Filho TJM, et al. , 2015; 14 (2): 281-285 with splenectomy, abdominal packing, and vacuum plant week. A biopsy-proven mild acute cellular re- dressing. coverage with cefepime and van- jection was detected on POD 9, and responded to in- comycin was initiated for suspected sepsis on the creased immunosuppression without steroid bolus. fourth postoperative day (POD). Brain death was The recipient was discharged with normal liver se- declared on the sixth POD, and the following labo- rum tests on POD 25. He was alive with no signs of ratory findings were obtained: infection or disease recurrence one year after trans- plant. • Hb = 9.6g/dL. • Leukocytes = 39.810/mm3, with 13% bands. Case 2: • Platelets = 29,000 mm3. donor with penetrating abdominal trauma •Na+ = 158 mg/dL. • pH = 7.41. A 22-year-old male donor who sustained multiple

• PaO2 = 177 mmHg. gunshot wounds to his skull, left thigh and abdo- • Total bilirrubin = 1.4 mg/dL. men underwent laparotomy. Sutures were performed • Direct bilirubin = 0.5 mg/dL. on involved organs (small bowel and bladder), and • AST = 58 U/L. the midline incision was closed with a running su- • ALT = 60 U/L. ture. Right-sided pneumonia was diagnosed on POD • Alkaline phosphatase = 102 U/L. 2, and antibiotic coverage with cefepime was start- • Lipase = 28 U/L. ed. Brain death was declared on day 3, and the fol- lowing laboratory findings were obtained: Peripheral perfusion was normal and mean arte- rial pressure (MAP) was maintained at about 70 • Hb: 6.7 g/dL. mmHg by a norepinephrine dose of 0.01 μg/kg/min. • Leukocytes: 14.740 mm3; 9% bands. During procurement operation, abdominal packing • Platelets: 82,000 mm3. was carefully removed and abdominal cavity inspec- •Na+: 165 mg/dL. tion revealed superficial lacerations on the liver and • pH: 7.35. a small amount of dark blood on paracolic gutters •PO2: 266 mmHg. and pelvis. Peripheral blood, preservation solution, • Total bilirrubin: 1.3 mg/dL. airway secretion, and urine, as well as swabs from • Direct bilirrubin: 0.6 mg/dL. peritoneal cavity and peritoneal lavage were sam- • AST: 70 U/L. pled for microbiological analysis. Liver biopsy re- • ALT: 43 U/L. vealed normal architecture, without cell infiltrates. • Lipase: 11 U/L. The liver was transplanted into a 54-year-old male recipient with hepatitis C virus-related cirrhosis, a 6 Chest radiograph revealed a consolidation in the cm hepatocellular carcinoma, and a calculated Mod- middle third of the right lung. Peripheral perfusion el of End-Stage Liver Disease (MELD) score of 11. was normal and MAP was maintained at 65 mmHg Cold ischemia time was 504 min. On POD 1, Gram without vasopressors. On procurement, liver mac- stain from the peritoneal lavage was positive for roscopy was normal, and there was no contamina- gram-negative rods, and thus antibiotic treatment tion in the cavity. Liver biopsy revealed minimal with piperacillin-tazobactan was maintained. On sinusoidal congestion. Blood, peritoneal lavage, air- POD 3, body temperature was 37.5 oC and mild leu- way secretion, urine and preservation solution fluid kocytosis, without hemodynamic instability oc- were sampled for microbiological analysis. The liver curred. Serratia marcescens resistant only to was transplanted into a 58-year-old female recipient , but sensitive to cephalosporins and with hepatitis C virus-related cirrhosis and a 5 cm other combinations of penicillins grew from perito- hepatocellular carcinoma. There was no evidence of neal lavage (peritoneal fluid obtained from donor’s uncontrolled sepsis in the donor. Thus, cefepime peritoneal cavity after instillation of saline). The re- was kept, and was introduced to broad- cipients thus presented with subfebrile peaks associ- en the antimicrobial spectrum. Cold ischemia time ated to mild leukocytosis until POD 5, but improved was 430 min, with no occurrence of postoperative with no further intervention. Serial blood cultures clinical and/or laboratory signs of graft dysfunction. were all negative. were discontinued on On POD 1, Gram stain from peritoneal lavage was POD 7. Tacrolimus was initiated on POD 3 and positive for gram-negative rods. On POD 3, three maintained on a low trough on the first post-trans- organisms were isolated from donor peritoneal 283 Donors with peritoneal contamination. , 2015; 14 (2): 281-285 lavage: coagulase-negative Staphylococcus resistant neal contamination. Although there were no signs of to oxacillin and sensitive to vancomycin, Klebsiellla peritonitis, were isolated from cul- pneumoniae resistant only to trimethoprim/sulfame- tures obtained from peritoneal cavity in both cases. thoxazole, and Enterococcus faecium resistant to Nevertheless, no evidence of donor-related infection vancomycin, teicoplanin, , and only sensi- was detected in the recipients, suggesting that low tive to aminoglycosides. In spite of the antibiogram amounts of inoculum may not be enough to trigger findings, aminoglycosides were not introduced be- sepsis. For example, contaminations of preservation cause patient was presenting with an uneventful re- solution carry low risk of causing recipient sepsis covery. Immunosuppressive strategy was the same and may not jeopardize recipient outcomes.8,9 This as used in the previous case. The recipient was dis- reinforces the concept that as long as preemptive an- charged on POD 22. She had normal graft function tibacterial treatment is provided to the recipient, the and no evidence of infection, disease, or tumor re- presence of limited bacterial transmission may not currence one year after transplant. be deleterious to recipient outcomes. This concept is also corroborated by the fact that individuals with DISCUSSION traumatic colonic injuries, in which contamination is nearly universal, primary repair has been advo- The use of suboptimal donors is an expanding cated by several authors, with lower complication practice utilized for fulfilling the disparity between rates than two-stage surgery.10,11 organ supply and demand. Although the use of or- Although cultures obtained from the donors did gans from donors suffering from extra abdominal not change the antibiotic used in our cases, infections is a current practice, the presence of we consider collecting donor samples for microbio- active abdominal infection is still considered a con- logical analysis in this specific scenario in order to traindication for organ utilization. In this setting, guide further adjustments in the antibiotic therapy trauma victims with peritoneal contamination are of upmost importance. In the only previous report in rarely considered as suitable donors. In such in- which a patient with an “open abdomen” was used stances, risks for donor-recipient infection trans- as a multiple organ donor, a multidrug-resistant missions have not yet been established. Optimal Pseudomonas aeruginosa was isolated in postopera- anti-infectious management plays a decisive role in tive cultures obtained from kidney, heart, and liver decreasing the risk of infection transmission.4 This recipients. According to this report, there were two includes collecting cultures from all sources and postoperative deaths, apparently not caused by do- starting the recipients on preemptive antibiotic nor-derived infections. However, a virulent organ- coverage. ism (multidrug-resistant Pseudomonas aeruginosa) Despite the potential for infectious transmissions was identified in all four organ recipients, including that may lead to recipient death, our liver trans- the liver recipient who did not survive. Detection of plant program has decided to consider all abdominal this virulent organism allowed for the tailoring of trauma victims with limited peritoneal contamina- antimicrobial therapy for the other recipients. tion as potential candidates for liver donation. To We recommend that a conservative approach the best of our knowledge, this is the first report of should be taken when accepting organs from donors procurement and successful liver transplantation in which abdominal cavity has been recently violat- using a liver allograft from a deceased donor with an ed. The key point on evaluating donors with perito- “open abdomen”. Successful evidence of the use of a neal contamination would be to discriminating liver allograft from a deceased donor with a gunshot between contamination of the peritoneal cavity and to the abdomen resulting in intestinal perforation infectious peritonitis. A similar concept is utilized in that had been sewn also is presented in this report. lung transplantation, in which organs with contam- Bacteremia occurs in about 5% of the organ do- ination of the airways may be utilized, but organs nors.2,5 Although it has been recently reported that with parenchymal infection (pneumonia) are usually donor-derived bacteremia may occur despite antibi- discarded.12 otic prophylaxis,6 infectious transmission can usual- Although organs from bacteremic donors have ly be avoided when an adequate antibiotic regimen is been used successfully, such expansion of the donor provided to the recipient.5,7 In our experience, be- pool requires consideration of the infectious risk as- sides providing antibacterial treatment to the donor sociated with suboptimal donors.13 In such instanc- and also to the recipient, there must be an absence es, consulting with local infectious diseases service of uncontrolled systemic infection and visible perito- may be helpful for tailoring the most appropriate 284 Grezzana Filho TJM, et al. , 2015; 14 (2): 281-285 empirical bacterial coverage based on each specific ACKNOWLEDGMENT local infectious epidemiology. Although a recent study showed that liver recipients might be more The authors thank Ms. Jessica J. Murphy for vulnerable to donor-derived bacteremia, the presence grammatical review. of infection had no significant impact on outcomes, suggesting that livers from bacteremic donors can be DISCLOSURE utilized safely for transplantation.14 The presence of bacteremia by multidrug-resistant agents seems to The authors of this manuscript have no conflicts impose higher risks of severe donor-derived sepsis of interest to disclose. and death.3 We believe that patients with an “open abdomen” and unequivocal sings of gross peritonitis FUNDING or bacteremia associated to an “open abdomen” should not be considered as potential liver donors, This study was not supported by any funding. especially those with bacteremia caused by multid- rug-resistant agents. AUTHORSHIP As occurs with most marginal liver donors, care- ful selection associated to donor-recipient matching TJMGF participated in research design, collecting is crucial to achieving favorable outcomes in this the research data, and writing of the manuscript; setting. As was performed in the cases presented ADC, IL, MFC, CDPK and CRPK participated in re- herein, we believe that liver allografts from patients search design, and writing of the manuscript. with peritoneal colonization should be matched to recipients with preserved cardiopulmonary and re- REFERENCES nal function, since critically ill patients are usually 1 Renz JF, Kin C, Kinkhabwala M, Jan D, Varadarajan R, more vulnerable to any amount of contamination. Goldstein M, Brown R Jr, et al. Utilization of extended do- It is not our practice to transplant patients with a nor criteria liver allografts maximizes donor use and pa- calculated MELD below 15, but the recipients in- tient access to liver transplantation. 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