Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents III: The 2023 Geneva revision.

The set of guidelines for good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents was developed following an international consensus conference in Copenhagen in 1996 (Viby-Mogensen et al., Acta Anaesthesiol Scand 1996, 40, 59-74); the guidelines were later revised and updated following the second consensus conference in Stockholm in 2005 (Fuchs-Buder et al., Acta Anaesthesiol Scand 2007, 51, 789-808). In view of new devices and further development of monitoring technologies that emerged since then, (e.g., electromyography, three-dimensional acceleromyography, kinemyography) as well as novel compounds (e.g., sugammadex) a review and update of these recommendations became necessary. The intent of these revised guidelines is to continue to help clinical researchers to conduct high-quality work and advance the field by enhancing the standards, consistency, and comparability of clinical studies. There is growing awareness of the importance of consensus-based reporting standards in clinical trials and observational studies. Such global initiatives are necessary in order to minimize heterogeneous and inadequate data reporting and to improve clarity and comparability between different studies and study cohorts. Variations in definitions of endpoints or outcome variables can introduce confusion and difficulties in interpretation of data, but more importantly, it may preclude building of an adequate body of evidence to achieve reliable conclusions and recommendations. Clinical research in neuromuscular pharmacology and physiology is no exception.

A comparison of pediatric liver transplant anesthesia practices with new organ procurement and transplant network pediatric policy requirements: A report from the society for the advancement of transplant anesthesia and the society for pediatric anesthesia.

INTRODUCTION: Organ Procurement and Transplant Network (OPTN) pediatric policies on knowledge and skill requirements for key personnel failed to address the Director of Anesthesia for Pediatric Liver Transplantation. A Joint Committee representing the Society for the Advancement of Transplant Anesthesia and Society for Pediatric Anesthesia (SPA) surveyed all pediatric anesthesia liver transplant practices to determine if practices were aligned with policies and what changes would be needed for compliance. METHODS: A survey of the Director or equivalent at each program collected data about specialized knowledge and skill sets. Questions focused on (1) skill and knowledge of the Director and team, (2) requirements for appointment, (3) experience in pediatrics, and (4) characteristics of the program including the availability of pediatric resources. RESULTS: Response rate was 73% (n = 63). Most responding programs had a Director (67%) with certification, selection committee, and continuing education credits outlined in existing policies. Team members met similar requirements. Alternate pathways for acquiring knowledge and skill sets were identified between programs. CONCLUSIONS: Pediatric liver transplant anesthesiologists use knowledge and skill pathways that align with the new pediatric policies. We suggest that collaborative work with oversight agencies is needed to resolve high case volume requirements originally designed for adult programs. SUMMARY: Most pediatric liver transplant anesthesiologists in the US have specialized knowledge and skills for expert care consistent with current oversight policies. Differences in pathways to acquire knowledge and skill sets were still aligned with the new policies for pediatric transplant surgeons and bylaws for the Director of Transplant Anesthesia. We conclude that minimal changes in case volume requirements to the existing Pediatric Transplant Anesthesiology Directorship criteria that authenticates the pediatric anesthesia Director's position would improve the safety of care without limiting access to transplantation.

Adult liver transplant anesthesiology practice patterns and resource utilization in the United States: Survey results from the society for the advancement of transplant anesthesia.

INTRODUCTION: Liver transplant anesthesiology is an evolving and expanding subspecialty, and programs have, in the past, exhibited significant variations of practice at transplant centers across the United States. In order to explore current practice patterns, the Quality & Standards Committee from the Society for the Advancement of Transplant Anesthesia (SATA) undertook a survey of liver transplant anesthesiology program directors. METHODS: Program directors were invited to participate in an online questionnaire. A total of 110 program directors were identified from the 2018 Scientific Registry of Transplant Recipients (SRTR) database. Replies were received from 65 programs (response rate of 59%). RESULTS: Our results indicate an increase in transplant anesthesia fellowship training and advanced training in transesophageal echocardiography (TEE). We also find that the use of intraoperative TEE and viscoelastic testing is more common. However, there has been a reduction in the use of veno-venous bypass, routine placement of pulmonary artery catheters and the intraoperative use of anti-fibrinolytics when compared to prior surveys. CONCLUSION: The results show considerable heterogeneity in practice patterns across the country that continues to evolve. However, there appears to be a movement towards the adoption of specific structural and clinical practices.

Quadratus lumborum blocks for abdominal transplant surgeries at UPMC Children's Hospital of Pittsburgh-A five year experience.

BACKGROUND: Adequate perioperative analgesia for pediatric abdominal transplant surgery is essential for patient recovery. However, the risks of commonly used medications such as hepatotoxicity, nephrotoxicity, bleeding concerns, and poor graft results with opioids limit pain management in this population. Thoracic epidural, continuous erector spinae plane, and type-1 quadratus lumborum blocks (QLBs) have been described and utilized in the adult population in this setting. The safety and benefits of regional anesthetic techniques in pediatrics have been widely documented for different types of procedures except pediatric abdominal transplantation, where data remains scarce. Our primary goal was to determine if QLBs provided adequate perioperative analgesia when part of a multimodal approach. Secondary objectives were to examine complications and effects on the intensive care unit (ICU) and hospital stay. METHODS: We performed a retrospective, observational study of pediatric patients who underwent abdominal transplant surgeries at the University of Pittsburgh Medical Center Children's Hospital of Pittsburgh from January 2015 to July 2021 and received a single injection QLB for pain control. Data collected included: demographics, nerve block characteristics, perioperative opioid consumption, use of non-opioid analgesia, daily pain scores, and hospital and ICU stay. RESULTS: Forty-two patients met the inclusion criteria for our study. Our results suggest that QLBs decrease opioid consumption, facilitate early extubation, prevent reintubation in the ICU, and reduce ICU and hospital stay. CONCLUSIONS: QLB is feasible and can be used as a multimodal approach for postoperative pain control in pediatric solid organ transplantation.

Educational Review: Error traps in anesthesia for pediatric liver transplantation.

Anesthetic and surgical techniques for the liver transplantation have progressed considerably over the past sixty years; however, this procedure is still fraught with substantial morbidity. To increase the safety culture associated with the liver transplantation, we detail nine error traps associated with anesthesia for pediatric liver transplantation. These potential pitfalls are divided into the operative phases: pre-operative preparation (Failure to have a dedicated anesthesia team for pediatric liver transplantation); pre-anhepatic (Failure to prepare for massive blood loss, Failure to monitor for coagulation abnormalities); anhepatic including reperfusion (Failure to prepare for clamping of the inferior vena cava, Failure to recognize metabolic changes, Failure to maintain homeostasis for reperfusion, Failure to prepare for Post-reperfusion syndrome); and post-anhepatic (Failure to optimize liver perfusion, Failure to maintain hemostatic balance). By offering practical advice on the preparation and treatment of these error traps, we aim to better prepare anesthesiologists to take care of pediatric patients undergoing the liver transplantation.

Red Blood Cell Transfusion in Pediatric Orthotopic Liver Transplantation: What a Difference a Few Decades Make.

BACKGROUND: Liver transplantation in children is often associated with coagulopathy and significant blood loss. Available data are limited. In this observational retrospective study, we assessed transfusion practices in pediatric patients undergoing liver transplantation at a single institution over the course of 9 years. METHODS: Data were retrospectively collected from patient medical records at the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center. All patients who underwent liver transplantation from January 2008 to June 2017 were included. Primary and secondary outcomes were volume of red blood cells (RBCs) transfused and mortality, respectively. RESULTS: From January 2008 to June 2017, there were 278 liver transplants in 271 patients. The number of primary transplants were 259, second retransplants 15, and third retransplants 4. Average age at transplantation was 6.9 years. Biliary atresia, maple syrup urine disease, urea cycle defect, and liver tumor were the leading indications accounting for 66 (23.7%), 45 (16.2%), 24 (8.6%), and 23 (8.3%) of transplants, respectively. Seventy-six cases (27.3%) did not require RBC transfusions. Among those transfused, 181 (89.6%) of the cases required <1 blood volume (BV). The median BV transfused among all cases was 0.21 (range, 0-9; Q1, 0; Q3, 0.45). There is a trend toward higher volume transfusions among infants (median, 0.46 BV) compared to children >12 months of age (0.12 BV). By diagnosis, the group requiring the highest median volume transfusion was patients with total parenteral nutrition-related liver failure (3.41 BV) followed by patients undergoing repeat transplants (0.6 BV). Comparison of primary versus repeat transplants shows a trend toward higher volume transfusions in third transplants (median, 2.71 BV), compared to second transplants (0.43 BV) and primary transplants (0.18 BV). Four of 271 patients (1.5%) died during admission involving liver transplantation. Nine of 271 patients (3.3%) died subsequently. Total mortality was 4.8%. CONCLUSIONS: In contrast to historically reported trends, evaluation of current transfusion practices reveals that most patients undergoing liver transplantation receive <1 BV of packed RBCs. More than 1 in 4 transplantations require no transfusion at all. Risk factors for greater transfusion need include younger age, total parenteral nutrition-related liver failure, and repeat transplantation.

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

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.

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.

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.

Incidence, outcome, and risk factors for postoperative pulmonary complications in head and neck cancer surgery patients with free flap reconstructions.

STUDY OBJECTIVE: Postoperative pulmonary complications (PPCs) are significant problems in patients undergoing radical head and neck cancer surgery with free flap reconstruction. The objective of the study was to identify the incidence, outcome, and risk factors for PPCs We hypothesized that preoperative pulmonary disease and amount of fluid administered during the surgery would be associated with PPCs. DESIGN: A retrospective clinical observational study. SETTING: A large academic institution. SUBJECTS: A total of 110 patients who underwent head and neck cancer surgery with microvascular free flap reconstruction between January 1, 2005 and December 31, 2011. INTERVENTIONS: No study interventions were performed. MEASUREMENTS: PPCs including pulmonary edema, pneumonia, and acute respiratory distress syndrome were clinically diagnosed. Perioperative parameters and outcomes among patients with and without PPCs were compared. Factors predictive of PPCs were identified with univariate and multiple logistic regression analyses. MAIN RESULTS: The incidence of PPCs was 32.7% (36 patients): pulmonary edema in 23.6% (26) and pneumonia in 9.1% (10). No acute respiratory distress syndrome was found. Inhospital mortality was 1.8% (2). No difference was found in survival between the patients with PPCs and those without (1 year survival was 69.4% vs 78.4%; P=.85). The patients with PPCs required longer ventilation support (median, 4 vs 2days; P=.002) and more frequent intensive care unit readmissions (30.3% vs 5.7%; P=.001) and stayed longer in the hospital (median, 17 vs 12days; P=.014). None of the preoperative parameters or intraoperative parameters including pulmonary comorbidity or the amounts of intraoperative fluid/blood administration was found as the factor to predict postoperative pulmonary compilations. CONCLUSION: The incidence of PPCs in patients undergoing radical head and neck surgery was 32.7% in 110 patients. Preoperative pulmonary disease or the amount of fluid administered during the surgery was not associated with PPCs.

Liberation From Renal Replacement Therapy After Cadaveric Liver Transplantation.

BACKGROUND: Renal failure requiring renal replacement therapy (RRT) is common in patients with end-stage liver disease (ESLD) and is associated with worse outcomes following liver transplantation (LT). We investigated the factors associated with liberation from posttransplant RRT and studied the impact of RRT on patient and graft outcomes. METHODS: A 5-year retrospective study of ESLD patients who received pretransplant RRT was conducted. Variables associated with liberation from RRT at 30 days and at 1-year posttransplant were analyzed. We used propensity matching to compare patient and graft outcomes in the study cohort to those of a control group who underwent LT but not pretransplant RRT. RESULTS: Sixty-four patients were included in the study. Twenty-four (38%) were liberated from RRT at 30 days posttransplant. Duration of pretransplant RRT (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.89-0.98) and severe postreperfusion syndrome (OR, 0.26; 95% CI, 0.08-0.87) were significantly associated with continued RRT at 1-month posttransplant. At one year, 34 (53%) patients were liberated from RRT. Age was significantly associated with lack of liberation from RRT (OR, 0.933; 95% CI, 0.875-0.995). Compared with propensity matched controls, patients who received RRT pretransplant had worse graft and patient survival at 1 year (52% vs 82%; P = 0.01, and 53% vs 83%; P = 0.003, respectively). CONCLUSIONS: In ESLD patients who received pretransplant RRT, one third were liberated from RRT at 1 month, and half at 1 year. Longer duration of pretransplant RRT, postreperfusion syndrome, and older age were associated with lower likelihood of liberation from RRT. Patients who required pretransplant RRT had worse graft and patient survivals compared to matched patients who did not require RRT. Patients who were liberated from RRT post-LT had similar outcomes to patients who never required pre-LT RRT.

Isolated small bowel transplantation outcomes and the impact of immunosuppressants: Experience of a single transplant center.

AIM: To investigate patient and graft outcomes in isolated small bowel transplant (SBTx) recipients and immunosuppressant induction agent impact on outcomes. METHODS: A retrospective review of the perioperative data of patients who underwent SBTx transplant during an 8-year period was conducted. The intraoperative data were: patient demographics, etiology of short gut syndrome, hemodynamic parameters, coagulation profiles, intraoperative fluid and blood products transfused, and development of post-reperfusion. The postoperative data were: hospital/intensive care unit stays, duration of mechanical ventilation, postoperative incidence of acute kidney injury, and 1-year patient and graft outcomes. The effects of the three immunosuppressant induction agents (Zenapax, Thymoglobulin, Campath) on patient and graft outcomes were reviewed. RESULTS: During the 8-year period there were 77 patients; 1-year patient and graft survival were 95% and 86% respectively. Sixteen patients received Zenapax, 22 received Thymoglobulin, and 39 received Campath without effects on patient or graft survival (P = 0.90, P = 0.14, respectively). The use of different immune induction agents did not affect the incidence of rejection and infection during the first 90 postoperative days (P = 0.072, P = 0.29, respectively). The Zenapax group received more intraoperative fluid and blood products and were coagulopathic at the end of surgery. Zenapax and Thymoglobulin significantly increased serum creatinine at 48 h (P = 0.023) and 1 wk (P = 0.001) post-transplant, but none developed renal failure or required dialysis at the end of the first year. CONCLUSION: One-year patient and graft survival were 95% and 86%, respectively. The use of different immunosuppressant induction agents may affect the intraoperative course and short-term postoperative morbidities, but not 1-year patient and graft outcomes.