Duration of Invasive Mechanical Ventilation Post-Liver Transplantation: Does One Size Fit All?

Abstract

There is paucity of literature on the intensive care management of children post-orthotopic liver transplantation (LT). An important component of critical care in such children is the duration of invasive mechanical ventilation (IMV) required postoperatively. Unnecessary, prolonged IMV is associated with increased frequency of hospital-acquired infections and increased utilization of critical care resources, leading to prolonged length of stay in the PICU. The main benefit of early endotracheal extubation is that this action is directly related to earlier discharge from PICU and, therefore, less resource utilization. At one time, this practice was considered unconventional, but several centers are now using a “Fast track” approach in which patients are either extubated in the operating room (OR) or immediately post-LT. Of course, careful patient selection is needed to minimize risk, and several single-center retrospective studies describe feasibility and complications (1–3). However, there remains considerable variation in approach, depending on geographic and institutional practices. In this issue of Pediatric Critical Care Medicine, Maue et al (4) discuss the clinical landscape of post-transplant critical care with a special focus on the duration and explanatory factors for IMV in children undergoing LT in 12 centers across United States. Of the 330 patients, 239 (72.4%) remained on IMV postoperatively, and 91 (27.6%) arrived to the PICU after having been extubated in the OR. Among those who returned to the PICU intubated, 146 patients remained intubated for greater than 24 hours and 93 for less than or equal to 24 hours. The factors associated with the use and duration of IMV post-LT included: younger age, higher Pediatric End-stage Liver Disease or Model for End-Stage Liver Disease scores, open fascia, and large center size. The authors also identified factors associated with prolonged IMV post-LT. All patients who were extubated before PICU admission survived. Patients who remained ventilated greater than 24 hours post-LT had a higher prevalence of bleeding and thrombotic complications, postoperative infections, graft loss, and unplanned reoperations. Here, the authors discuss the location of the patient pretransplant (i.e., home, ward, or PICU) as a factor in prolonged IMV. This new report fills an important gap in what is known about critical care provision for children post-LT. Despite differences in clinical practice among the 12 centers, there is an important message for critical care physicians and transplant anesthesiologists: “to proactively identify those children who can be extubated in the OR or immediately post-LT and therefore have some likelihood of shorter PICU stay.” However, an important question that this report raises is whether the findings can be generalized to all children with liver disease who undergo LT? Unlike the adult population, children have varying etiologies in different age groups with different prognosis. Since the new study is retrospective, Maue et al (4) do not comment on the various causes of liver failure leading to LT, the intraoperative course, or the type and quality of liver graft, yet all these factors are extremely important in determining critical care utilization post-LT. Liver failure in children is a heterogeneous entity. The clinical course could be acute, subacute, chronic, or acute-on-chronic, which has an impact on intraoperative and postoperative management. Consider patients in acute liver failure, who have a fulminant course with multiple organ involvement (including the brain with cerebral edema with raised intracranial pressure), or systemic inflammation and sepsis. These patients require multiple critical care interventions including neuroprotection with deep sedation, extracorporeal therapies, use of vasopressors, and neuroprotective ventilatory strategies. Even after LT, these patients will require ongoing neuroprotection and their duration of IMV will be much longer compared with a child with chronic decompensated liver disease (most commonly being biliary atresia with portal hypertension) who has been on the LT waiting list and admitted from home (5). Most of these children will be extubated either in the OR or within 24 hours of LT depending on the degree of liver decompensation and institutional practice. In children with acute-on-chronic liver failure, multiple organ support both before and after LT will include the need for prolonged IMV. Similarly, development of specific complications of chronic liver disease like hepatopulmonary syndrome, portopulmonary hypertension, or hepatorenal syndrome will lead to a complicated and prolonged intraoperative and postoperative course requiring skilled PICU management. Therefore, the critical care needs of children post-LT depend on the etiology, severity, and complications of liver disease for which LT is being carried out as well as interventions before LT. Another important factor that has a role in influencing critical care needs after LT is the intraoperative course of the patient. LT is complex surgery involving the hepatectomy phase, the anhepatic phase, and the reperfusion phase; each phase is associated with specific hemodynamic changes (6). The reperfusion phase can be particularly dramatic as it is characterized by severe hemodynamic changes (associated with rise in right ventricular pressures, arrhythmias with increased potassium load, vasodilatation, and requirement for vasopressors and worsening coagulopathy), which can lead to prolonged IMV (7,8). In addition, the intraoperative course depends on the etiology and severity of liver disease for which LT has being performed, the preoperative critical care needs, the type of liver graft (split graft vs whole graft vs auxiliary), the donor characteristics (donation after death by neurologic criteria, or after death by cardiac criteria, or living donor), warm and cold ischemia times, and amount of blood products administered during LT. Nafiu et al (9) and Glanemann et al (10) report that transfusion of higher amounts of intraoperative packed RBCs and fresh frozen plasma are associated with increased need for IMV, likely because of fluid overload and transfusion-associated lung injury. The volume of blood transfused during LT reflects several issues, especially coagulopathy due to underlying liver failure or due to surgical bleeding and graft dysfunction. Sahinturk et al (11) report successful extubation in the OR in almost 50% of children following LT who did not have intraoperative requirements for massive blood transfusion, high-dose vasopressors, high serum lactate levels, or an open abdomen. Duration of surgery is also an important factor that determines the timing of extubation post-LT with several studies showing shorter operating times to be associated with less need for IMV (8,12). Children undergoing living donor transplantation have shorter duration of IMV and lesser need for PICU admission post-LT because it is usually possible to schedule LT before the development of life-threatening complications or severe growth failure. Children undergoing split LT have an increased duration of IMV because excessive bleeding in the hepatectomy phase is associated with risk of postoperative cut-surface bleeding, particularly if extubated early. Therefore, while planning early extubation, one should look at the graft and donor characteristics and intraoperative clinical markers of early graft dysfunction such as severe acidosis, high lactate level, persistent coagulopathy, and hemodynamic instability requiring vasoactive agents. Taking all the above together, this report by Maue et al (4) is a welcome addition to the literature. The large, multicenter dataset prompts us to think proactively about the anticipated clinical course of children in post-LT critical care. This information can help with counseling families, rationalizing available resources, and avoiding longer PICU stay. Hence, an early, thorough preoperative multidisciplinary patient-focused approach can help plan and rationalize the postoperative PICU course (13). Enhanced Recovery After Surgery (ERAS) is one such multimodal, evidence-based, program of care developed to minimize the response to surgical stress, associated with reduced perioperative morbidity and hospital stay (14). In the ERAS program implemented in a Spanish LT center, of the 240 LT episodes in 236 adult patients over 6 years, 236 were extubated immediately after LT (< 30 min). Their observed rate of reintubation, complications post-LT, 30-day readmission rates, and 1-year survival demonstrated that fast-track post-LT was safe, effective, and feasible (15). Similarly, Mandell et al (16) evaluated the safety of early extubation in a multicenter cohort of LT patients and found the rate of adverse events to be 7.7%. However, due to diverse etiologies in varying age groups in children, the generalizability of any explanatory model and creation of fast-track programs would be challenging. In conclusion, each LT center should follow its current protocol for the timing of extubation with a selective proactive approach. Therefore, in children with a complicated preoperative and intraoperative course, it is important to balance the potential benefit of unnecessary delay in time to extubation versus the risk of premature extubation with subsequent failure and need for reintubation. More multicenter studies are needed from pediatric LT and intensive care networks in order to formulate a disease/severity-specific ERAS model in children.