In this cohort of HTx recipients, a POP occurred in 33.7% of patients and was mainly caused by Enterobacteriaceae or Pseudomonas aeruginosa, and consistently increased mortality at 30 days and 1 year. Preoperative mechanical ventilation and postoperative blood transfusion, which were indirectly linked to postoperative bleeding, were identified as the main risk factors for POP after the HTx.
In a Californian cohort of 620 HTx recipients, infections were the main cause of morbidity and mortality, while bacterial pathogenesis was involved in only 43% of cases.(8)In addition,most of the instances of pneumonia occurring later after the HTx were due to Cytomegalovirus, Aspergillus fumigatus and Pneumocystis carinii.((7) However, the authors did not investigate infections within the perioperative period but only investigated infectious events after the HTx in immunocompromised patients. In our cohort, almost all of the POP cases were bacterial. Community germs (Oropharyngeal flora, Streptococcus pneumoniae, Haemophilus influenza and Staphylococcus aureus) were responsible for only a small proportion of pneumonia (10%), and the most frequently implicated organisms in POP were Enterobacteriaceae (53%)or Pseudomonas aeruginosa36%). However, the microbiology of POP pathogens in HTx patients remained comparable to that in conventional cardiac surgery patients.(6) This point should be considered when choosing the appropriate empirical antimicrobial therapy for pneumonia in HTx recipients within the perioperative period. Therefore, the administration of unusual anti-infective drugs, such as antifungals or antivirals, must be based on clinical and paraclinical arguments and not solely on the induced immunosuppression. Infections with “opportunistic” pathogens were rare (3 pulmonary aspergillosis, 1 pulmonary abscess with C. albicans and 3 HSV pneumonias) and appeared late in the infectious history and mainly in the patients with recurrent pneumonia. In our cohort, 19 recipients developed recurrent POP. Their 30-day and 1-year mortalities were similar to the recipients with only 1 episode of POP, but the durations of mechanical ventilation and hospitalization were longer in HTx recipients with recurrent POP. A large predominance of pathogens from the digestive tract (Enterobacteriaceae and Pseudomonas aeruginosa) can be explained by the bacterial translocation phenomena following cardiac surgery. (16,17). Indeed, haemodynamic instability, low cardiac output and systemic inflammatory response syndrome induced during cardiac surgery can lead to intestinal ischaemia and bacterial translocation. (16) Moreover, recipients with POP are assisted more by VA-ECMO in the postoperative period due to haemodynamic instability or low blood flow during the transplantation that may predispose patients to infections. (10)
In our cohort, 68% of the recipients benefited from an emergency graft attribution, and 32% were assisted by VA-ECMO before transplantation. VA-ECMO is an efficient temporary device, and its early use is efficient for preventing organ failure, especially in the occurrence of renal insufficiency. In our institute, all patients with VA-ECMO (whether or not in a transplant project) are extubated as soon as possible to prevent the risk of pneumonia and ICU weakness. Early extubation allows neurological evaluation and participation in physiotherapy to select the best candidates for transplant projects. Thus, unlike the international registries, the use of VA-ECMO before transplantation did not appear to be a risk factor for POP in our study. (3) VA-ECMO has demonstrated its interest in the management of patients with primary graft failure, thus improving the prognosis of the recipients.(18) More than two-thirds of our recipients were assisted by VA-ECMO after transplantation, and although patients with postoperative pneumonia appeared to be more assisted, VA-ECMO does not appear to be a risk factor for POP. Nosocomial infections, especially ventilator-associated pneumonia, are frequent in patients assisted by VA-ECMO (19), and HTx recipients assisted by VA-ECMO are known to develop nosocomial infections and pneumonia.(10) Moreover, the low cardiac output syndrome may explain the increased incidence of POP after HTx in comparison with conventional cardiac surgery (33.7% vs 5.7%,), in which the incidence of intra- and postoperative haemodynamic instability is less important.(4) In our cohort, a large proportion of recipients presented risk factors for primary graft dysfunction, such as allosensitization (54%), preoperative VA-ECMO support (32%) or mechanical ventilation at the time of transplantation (9%).(18,20,21) Preoperative VA-ECMO support did not increase the rate of POP, while postoperative haemodynamic instability requiring VA-ECMO support was more frequent in group of patients with POP. Altogether, these findings suggest that tissue hypoperfusion occurring during low cardiac output syndrome could contribute to digestive bacterial translocation and may influence the pathogens involved in early POP in HTx recipients.
The association of increased incidence of POP and transfusion or reoperation for bleeding are additional arguments to explain the blood-forming origin of POP(10) and this unusual high rate of Enterobacteriaceae and Pseudomonas aeruginosa in POP after HTx. Transfusion per se is an additional process that is known to increase the rate of postoperative infections after the first transfusion of packed red blood cells (22) and to increase 28-day mortality.(23) The modulation of the immune response by transfusion may promote the development of postoperative infectious complications.(24,25) A transfusion in patients supported with VA-ECMO is also known to increase infectious complications.(26) In the present study, beyond the risk associated with low cardiac output and surgical reoperation itself, 34% of HTx recipients received a postoperative transfusion despite a restrictive strategy of blood transfusion in our institution, thereby increasing the risk of postoperative pneumonia.Anticipation of perioperative bleeding disorders and meticulous surgical haemostasis are necessary to prevent haemorrhagic risks.
In this work, preoperative mechanical ventilation also appears to be a major risk factor for POP after HTx and is already known to be a risk factor for healthcare-related pneumoniaand mortality, regardless of the context of HTx. (3,27) The bacterial colonization of the tracheobronchial tree and alteration of fluid clearance are well known and have been reported to be the main pathophysiological mechanisms of pneumonia during mechanical ventilation.(28) Regarding the effect of mechanical ventilation on POP in HTx recipients, a haematogenic mechanism is more likely to be involved. Therefore, mechanical ventilation as a major risk factor might be reflective of the HTX recipients’ postoperative severity, given that fast-track management is the priority in all HTx recipients, including those with VA-ECMO support after the transplantation. Indeed, given this risk factor, we extubate all patients with VA-ECMO (whether or not the recipient is in a transplant project) to prevent the risk of pneumonia.
Plasmapheresis has been shown to prevent AMR in sensitized recipients.(11,12) However, this more aggressive immunosuppression therapy may increase the recipients’ exposure to infectious complications.(29)In kidney transplantation, Chung et al. showed that the administration of rituximab and plasma exchanges increased the risk of postoperative infectious complications.(29) In the present study, HTx recipients treated with plasmapheresis and/or IVIg treatment did not have more instances of POP than other HTx recipients, suggesting that this therapy is not the main mechanism involved in sensitized HTx recipients.
Our work has several limitations. First, this is a retrospective and monocentric study with a relatively small sample size. Nevertheless, none of the patients were lost to follow-up, and no data are missing from this cohort. Second, the population studied is relatively unusual, with a high rate of sensitized recipients receiving HTx. However, the proportion of sensitized recipients is increasing, possibly because the technological means to detect pfDSA are evolving. Third, the proportion of HTx recipients assisted with postoperative VA-ECMO support is coherent in this study. Due to the rarity of heart grafts and to the graft distribution prioritization programme, the number of primary graft dysfunctions as well as the preoperative severity of recipients is increasing. Nevertheless, our study provides important information on this type of population.