Ibtesam A. Hilmi

The impact of postreperfusion syndrome on short-term patient and liver allograft outcome in patients undergoing orthotopic liver transplantation†

The greatest part of liver allograft injury occurs during reperfusion, not during the cold ischemia phase. The aim of this study, therefore, was to investigate how the severity of postreperfusion syndrome (PRS) influences short‐term outcome for the patient and for the liver allograft. Over a 2‐year period, 338 consecutive patients who presented for orthotopic liver transplantation (OLT) were included in this retrospective study. They were divided into 2 groups according to the severity of the PRS they experienced. The first group comprised 152 patients with mild or no PRS; the second group comprised 186 patients with significant PRS. Perioperative hemodynamic parameters, coagulation profiles, blood product requirements, incidence of infection, incidence of rejection and outcome data for both groups were collected and analyzed. There was no demographic difference between the groups except for age; group 2 had older patients than group 1 (54.94 ± 9.07 versus 51.52 ± 9.91, P = 0.001). Compared to group 1, group 2 patients required more red blood cell transfusions (11.31 ± 10.90 versus 8.08 ± 7.89 units, P = 0.002), more fresh frozen plasma transfusions (10.25 ± 10.96 versus 7.03 ± 7.64 units, P = 0.002), more cryoprecipitate (1.88 ± 4.72 units versus 0.61 ± 1.80 units, P = 0.001), and were more likely to suffer from fibrinolysis (52.7% versus 41.4%, P = 0.041). Interestingly, group 2 had a shorter average warm ischemia time than group 1 (33.19 ± 8.55 versus 36.21 ± 11.83 minutes, P = 0.01). Group 2 also required longer, on average, mechanical ventilation (14.95 ± 29.79 versus 8.55 ± 17.79 days, P = 0.015), remained in the intensive care unit longer (17.65 ± 31.00 versus 11.49 ± 18.67 days, P = 0.025), and had a longer hospital stay (27.29 ± 32.35 versus 20.85 ± 21.08 days, P = 0.029). Group 2 was more likely to require retransplantation (8.6% versus 3.3%, P = 0.044). In conclusion, the severity of PRS during OLT appears to be related to the outcome of patient and liver allograft. Liver Transpl 14:504–508, 2008.

Pulmonary thromboembolism during adult liver transplantation: incidence, clinical presentation, outcome, risk factors, and diagnostic predictors

BACKGROUND Intraoperative pulmonary thromboembolism (PTE) is an often overlooked cause of mortality during adult liver transplantation (LT) with diagnostic challenge. The goals of this study were to investigate the incidence, clinical presentation, and outcome of PTE and to identify risk factors or diagnostic predictors for PTE. METHODS Four hundred and ninety-five consecutive, isolated, deceased donor LTs performed in an institution for a 3 yr period (2004-6) were analysed. The standard technique was a piggyback method with veno-venous bypass without prophylactic anti-fibrinolytics. The clinical diagnosis of PTE was made with (i) acute cor pulmonale, and (ii) identification of blood clots in the pulmonary artery or observation of acute right heart pressure overload with or without intracardiac clots with transoesophageal echocardiography. RESULTS The incidence of PTE was 4.0% (20 cases); cardiac arrest preceded the diagnosis of PTE [75% (15)] and PTE occurred during the neo-hepatic phase [85% (17)], especially within 30 min after graft reperfusion [70% (14)]. Operative and 60 day mortalities of patients with PTE were higher (P<0.001) than those without PTE (30% vs 0.8% and 45% vs 6.5%). Comparison of perioperative data between the PTE group (n=20) and the non-PTE group (n=475) revealed cardiac arrest and flat-line thromboelastography in three channels (natural, amicar, and protamine) at 5 min after graft reperfusion as the most significant risk factors or diagnostic predictors for PTE with an odds ratio of 154.32 [95% confidence interval (CI): 44.82-531.4] and 49.44 (CI: 15.6-156.57), respectively. CONCLUSIONS These findings confirmed clinical significance of PTE during adult LT and suggested the possibility of predicting this devastating complication.

Acute kidney injury following orthotopic liver transplantation: incidence, risk factors, and effects on patient and graft outcomes

BACKGROUND Liver transplant recipients frequently develop acute kidney injury (AKI), but the predisposing factors and long-term consequences of AKI are not well understood. The aims of this study were to identify predisposing factors for early post-transplant AKI and the impact of AKI on patient and graft survival and to construct a model to predict AKI using clinical variables. METHODS In this 5-year retrospective study, we analysed clinical and laboratory data from 424 liver transplant recipients from our centre. RESULTS By 72 h post-transplant, 221 patients (52%) had developed AKI [according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria]. Predisposing factors for development of AKI were female sex, weight (>100 kg), severity of liver disease (Child-Pugh score), pre-existing diabetes mellitus, number of units of blood or fresh frozen plasma transfused during surgery, and non-alcoholic steatohepatitis as the aetiology of end-stage liver disease (P≤0.05). Notably, preoperative serum creatinine (SCr) was not a significant predisposing factor. After fitting a forward stepwise regression model, female sex, weight >100 kg, high Child-Pugh score, and diabetes remained significantly associated with the development of AKI within 72 h (P≤0.05). The area under the receiver operator characteristic curve for the final model was 0.71. The incidence of new chronic kidney disease and requirement for dialysis at 3 months and 1 yr post-transplant were significantly higher among patients who developed AKI. CONCLUSIONS Development of AKI within the first 72 h after transplant impacted short-term and long-term graft survival.

Comparison of surgical methods in liver transplantation: retrohepatic caval resection with venovenous bypass (VVB) versus piggyback (PB) with VVB versus PB without VVB.

Use of piggyback technique (PB) and elimination of venovenous bypass (VVB) have been advocated in adult liver transplantation (LT). However, individual contribution of these two modifications on clinical outcomes has not been fully investigated. We performed a retrospective review of 426 LTs within a 3‐year period, when three different surgical techniques were employed per the surgeons’ preference: retrohepatic caval resection with VVB (RCR + VVB) in 104 patients, PB with VVB (PB + VVB) in 148, and PB without VVB (PB‐Only) in 174. The primary outcomes were intraoperative blood transfusion and the patient and graft survivals. Demographic profiles were similar, except younger recipient age in RCR + VVB and fewer number of grafts with cold ischemic time over 16 h in PB‐Only. PB‐Only required lesser intraoperative red blood cells (P = 0.006), fresh frozen plasma (P = 0.005), and cell saver return (P = 0.007); had less incidence of acute renal failure (P = 0.001), better patient survival (P = 0.039), and graft survival (P = 0.003). The benefits of PB + VVB were only found in shortened total surgical time (P = 0.0001) and warm ischemic time (P = 0.0001), and less incidence of acute renal failure (P = 0.001) than RCR + VVB. PB‐Only method seemed to provide the best clinical outcome. The benefit of PB was not fully achieved when it was used with VVB.

N-acetylcysteine does not prevent hepatorenal ischaemia–reperfusion injury in patients undergoing orthotopic liver transplantation

BACKGROUND Glutathione (GSH) acts as a free radical scavenger that may be helpful in preventing reperfusion injury. N-acetylcysteine (NAC) replenishes GSH stores. The aims of this study were to evaluate the efficacy of NAC in improving liver graft performance and reducing the incidence of post-operative acute kidney injury (AKI). METHODS Our study was a randomized, double-blind, placebo-controlled trial of 100 patients; 50 received placebo and 50 received a loading dose of 140 mg/kg of intravenous (IV) NAC over 1 h followed by 70 mg/kg IV repeated every 4 h for a total of 12 doses. Both groups were followed up for 1 year post-orthotopic liver transplant (OLT). We recorded liver function tests, renal function tests, graft survival, patient survival, plasma GSH and duration of hospital and ICU stay. In addition to serum creatinine (SCr) levels, we analysed cystatin C and beta-trace as independent measures of glomerular filtration. All clinical data were recorded daily for the first week after the surgery, then on Days 14, 21, 30, 90 and 180 and at the end of the first year. RESULTS IV NAC did not affect survival, graft function or risk of AKI. However, GSH levels were highly variable with only 50% of patients receiving NAC exhibiting increased levels and fewer patients developed AKI when GSH levels were increased. Additional risk factors for AKI in the post-transplant period were female gender (P = 0.05), increased baseline serum bilirubin (P = 0.004) and increased baseline SCr levels (P = 0.02). CONCLUSIONS IV NAC was not effective in reducing renal or hepatic injury in the setting of liver transplantation. The dose and duration of NAC used, though higher than most renal protection studies, may have been ineffective for raising GSH levels in some patients.

Anesthetic management in upper extremity transplantation: the Pittsburgh experience.

BACKGROUND: Hand/forearm/arm transplants are vascularized composite allografts, which, unlike solid organs, are composed of multiple tissues including skin, muscle, tendons, vessels, nerves, lymph nodes, bone, and bone marrow. Over the past decade, 26 upper extremity transplantations were performed in the United States. The University of Pittsburgh Medical Center has the largest single center experience with 8 hand/forearm transplantations performed in 5 recipients between January 2008 and September 2010. Anesthetic management in the emerging field of upper extremity transplants must address protocol and procedure-specific considerations related to the role of regional blocks, effects of immunosuppressive drugs during transplant surgery, fluid and hemodynamic management in the microsurgical setting, and rigorous intraoperative monitoring during these often protracted procedures. METHODS: For the first time, we outline salient aspects of upper extremity transplant anesthesia based on our experience with 5 patients. We highlight the importance of minimizing intraoperative vasopressors and improving fluid management and blood product use. RESULTS: Our approach reduced the incidence of perioperative bleeding requiring re-exploration or hemostasis and shortened in-hospital and intensive care unit stay. Functional, immunologic and graft survival outcomes have been highly encouraging in all patients. CONCLUSIONS: Further experience is required for validation or standardization of specific anesthetic protocols. Meanwhile, our recommendations are intended as pertinent guidelines for centers performing these novel procedures.

Cardiac arrest during adult liver transplantation: A single institution's experience with 1238 deceased donor transplants

Liver transplantation (LT) is one of the highest risk noncardiac surgeries. We reviewed the incidence, etiologies, and outcomes of intraoperative cardiac arrest (ICA) during LT. Adult cadaveric LT recipients from January 1, 2001 through December 31, 2009 were reviewed. ICA was defined as an event requiring either closed chest compression or open cardiac massage. Cardiac arrest patients who recovered with only pharmacological interventions were excluded. Data included etiologies and outcomes of ICA, intraoperative deaths (IDs) and hospital deaths (HDs), and potential ICA risk factors. ICA occurred in 68 of 1238 LT recipients (5.5%). It occurred most frequently during the neohepatic phase (60 cases or 90%), and 39 of these cases (65.0%) experienced ICA within 5 minutes after graft reperfusion. The causes of ICA included postreperfusion syndrome (PRS; 26 cases or 38.2%) and pulmonary thromboembolism (PTE; 24 cases or 35.3%). A higher Model for End‐Stage Liver Disease (MELD) score was found to be the most significant risk factor for ICA. The ID rate after ICA was 29.4% (20 cases), and the HD rate was 50.0% (34 cases). The 30‐day patient survival rate after ICA was 55.9%, and the 1‐year survival rate was 45.6%: these rates were significantly lower (P < 0.001) than those for non‐ICA patients (97.4% and 85.1%, respectively). In conclusion, the incidence of ICA in adult cadaveric LT was 5.5% with an intraoperative mortality rate of 29.4%. ICA most frequently occurred within 5 minutes after reperfusion and resulted mainly from PRS and PTE. A higher MELD score was identified as a risk factor. Liver Transpl 19:1262–1271, 2013.

Esophageal tear: an unusual complication after difficult endotracheal intubation.

Esophageal perforation is a serious life threatening injury that may occur during inadvertent esophageal intubation. We report two cases of iatrogenic esophageal perforation after attempted endotracheal intubation. Our experience confirms that early diagnosis (as in the first case) is associated with a more favorable outcome. Therefore, a high index of suspicion is required for early diagnosis of this complication because the symptoms are often nonspecific and may be delayed.

Acute kidney injury after orthotopic liver transplantation using living donor versus deceased donor grafts: A propensity score-matched analysis: Acute Kidney Injury after Liver Transplantation

Acute kidney injury (AKI) is a common complication after liver transplantation (LT). Few studies investigating the incidence and risk factors for AKI after living donor liver transplantation (LDLT) have been published. LDLT recipients have a lower risk for post‐LT AKI than deceased donor liver transplantation (DDLT) recipients because of higher quality liver grafts. We retrospectively reviewed LDLTs and DDLTs performed at the University of Pittsburgh Medical Center between January 2006 and December 2011. AKI was defined as a 50% increase in serum creatinine (SCr) from baseline (preoperative) values within 48 hours. One hundred LDLT and 424 DDLT recipients were included in the propensity score matching logistic model on the basis of age, sex, Model for End‐Stage Liver Disease score, Child‐Pugh score, pretransplant SCr, and preexisting diabetes mellitus. Eighty‐six pairs were created after 1‐to‐1 propensity matching. The binary outcome of AKI was analyzed using mixed effects logistic regression, incorporating the main exposure of interest (LDLT versus DDLT) with the aforementioned matching criteria and postreperfusion syndrome, number of units of packed red blood cells, and donor age as fixed effects. In the corresponding matched data set, the incidence of AKI at 72 hours was 23.3% in the LDLT group, significantly lower than the 44.2% in the DDLT group (P = 0.004). Multivariate mixed effects logistic regression showed that living donor liver allografts were significantly associated with reduced odds of AKI at 72 hours after LT (P = 0.047; odds ratio, 0.31; 95% confidence interval, 0.096‐0.984). The matched patients had lower body weights, better preserved liver functions, and more stable intraoperative hemodynamic parameters. The donors were also younger for the matched patients than for the unmatched patients. In conclusion, receiving a graft from a living donor has a protective effect against early post‐LT AKI. Liver Transpl 21:1179–1185, 2015.

Central venous thrombosis and perioperative vascular access in adult intestinal transplantation

BACKGROUND Venous access is crucial in intestinal transplantation, but a thrombosed venous system may prevent the use of central veins of the upper body. The incidence of venous thrombosis and the necessity to perform alternative vascular access (AVA) in intestinal transplant recipients have not been fully investigated. METHODS Records of adult patients who underwent intestinal transplantation between January 1, 2001, and December 31, 2009, were reviewed. Contrast venography was performed as pre-transplantation screening. Vascular accesses at the transplantation were categorized as I (percutaneous line via the upper body veins), II (percutaneous line via the lower body veins), and III (vascular accesses secured surgically, with interventional radiology, or using non-venous sites). Categories II and III were defined as AVA. Risk factors for central venous thrombosis and those for requiring AVA were analysed, respectively. RESULTS Among 173 patients, central venous obstruction or stenosis (<50% of normal diameter) was found in 82% (141 patients). AVA was required in 4.6% (eight patients: four in each category II and III). Large-bore infusion lines were placed via the femoral arteries in all category III patients without complications. Existing inferior vena cava filter and hypercoagulable states were identified as the risk factors for the use of AVA, but not for central venous thrombosis. Outcomes of patients who underwent AVA were similar to those of patients without AVA. CONCLUSIONS The majority of adult patients undergoing intestinal transplantation had at least one central venous stenosis or obstruction. The recipient outcomes were comparable when either standard vascular access or AVA was used for transplantation.