Published online Jan 27, 2018. doi: 10.4254/wjh.v10.i1.62
Peer-review started: October 26, 2017
First decision: December 1, 2017
Revised: December 20, 2017
Accepted: December 29, 2017
Article in press: December 29, 2017
Published online: January 27, 2018
Postoperative intensive care unit complications after liver transplantation in young children are common, and associated with significant morbidity and mortality. Risk factors for these early complications are poorly studied.
Postoperative intensive care unit complications in young children can require reoperation, threaten liver graft viability, and prolong length of stay. These complications include thrombosis of vessels necessary for blood flow to the liver graft (i.e. hepatic artery thrombosis and portal vein thrombosis), other life-threatening events requiring intensive care management (i.e. bile leak, bowel perforation, intraabdominal infection, or retransplant), or death. Identifying risk factors for these complications can generate hypotheses for future research testing, leading to improved outcomes after liver transplantation.
The authors aimed to determine potentially modifiable prespecified acute care variables that may be associated with prespecified primary and secondary acute intensive care postoperative outcomes in young liver transplant recipients at our center over the past 10 years. In addition, the authors aimed to explore novel potential predictors of adverse outcomes, including written comments made about abnormal liver vessels or biliary anatomy in the dictated operating report, measures of postoperative fluid balance, and measures of post-operative coagulation status. The authors identified risk factors that are potentially modifiable and that should be confirmed by future research.
This study was a retrospective chart review including all consecutive children of age less than 3-years-old having had a liver transplant done at the Western Canadian referral center from June 2005 to June 2015. Prespecified potential predictor variables and primary and secondary outcomes were recorded using standard definitions and a case report form. Associations between potential predictor variables and outcomes were determined using univariate and multiple logistic (odds ratio, OR; 95% confidence interval, CI) or linear (effect size, ES; 95%CI) regressions.
There were several important results from this study. First, although pediatric intensive care unit (PICU) patient (92%) and graft (80%) survivals were high, patients experienced a combination of significant postoperative complications, including hepatic artery thrombosis (19%), portal vein thrombosis (17%), bile leak (23%), bowel perforation (8%), intraabdominal bleeding (11%), abdominal compartment syndrome (12%), and intraabdominal infection (28%). These complications necessitated reoperation of the abdomen for 51% (median 2 episodes, interquartile range 1-4), retransplantation for 14%, and renal replacement therapy for 14% of all patients. Second, there were few independent predictors of our primary and secondary outcomes. When adjusted for prespecified clinically important variables (weight, year, pediatric end-stage liver disease score, and surgeon) and those variables significant at P ≤ 0.10 on univariate analysis, whole liver graft had higher risk of complications (of hepatic artery thrombosis, ventilator days, any severe complication, any thrombosis, and graft loss). A novel predictor, the lower the antithrombin level on day 2-5 post-operative, had higher risk of complications (ventilator days, any severe complication, any thrombosis, and graft loss). The independent association of surgeon with outcomes (of any thrombosis, any severe complication, and ventilator days) has not, to our knowledge, previously been reported. Third, the authors found no statistically significant change in outcomes over time on multiple regressions. Fourth, the authors found no statistically significant association of recipient weight with adverse outcomes on multiple regressions. Fifth, some of the novel predictors the authors examined were not associated with complication rates on multiple regressions. This included: growth failure (below 5th percentile on weight or height), surgical comments about concerning anatomy of the transplant vessels (hepatic artery or portal vein) or biliary tract, whether fascia was closed on admission to PICU, measures of postoperative fluid status (e.g., use of furosemide, lowest central venous pressure, and highest hemoglobin), and measures of anticoagulation (e.g., achieving a therapeutic heparin level). Future study is required to confirm our findings. Treatment with antithrombin concentrate intravenously should be considered for low antithrombin levels in studies of anticoagulation protocols.
Patients under 3-years-old having liver transplant had high patient (92%) and graft (80%) survival. These patients not infrequently experienced a combination of significant postoperative complications, including hepatic artery thrombosis, portal vein thrombosis, bile leak, bowel perforation, intraabdominal bleeding, abdominal compartment syndrome, and intraabdominal infection, sometimes necessitating reoperation of the abdomen, retransplantation, and kidney dialysis. Whole liver graft was independently associated with a higher risk of complications. Surgeon was independently associated with a higher risk of complications. A novel predictor, the lower the antithrombin level on day 2-5 postoperative, was independently associated with a higher risk of complications. Antithrombin is an anticoagulant produced by the liver, with its effect mediated by irreversibly inhibiting plasma serine proteases (including activated factors X and thrombin); this effect is greatly accelerated by heparin. In addition, antithrombin has antiinflammatory properties. Although antithrombin does not have beneficial effects in critically ill patients in general, it has not been studied in the setting of liver transplant patients who are high risk for thrombosis. Other centers should determine whether antithrombin levels are associated with outcomes after liver transplant in young children, and a prospective trial comparing anticoagulation strategies that incorporate antithrombin treatment should be considered. In addition, more study is needed to determine what accounts for differences in outcomes among surgeons.
The findings are hypothesis generating and require confirmation by other centers, ideally in prospective studies. Future prospective observational research is needed to confirm the findings that whole liver graft, surgeon, and low antithrombin postoperatively are risk factors for complications. If confirmed, future randomized controlled trials of anticoagulation strategies after liver transplant in young children are needed, and these should include monitoring and treatment of antithrombin levels.