Evaluation of neuraxial analgesia on outcomes for patients undergoing robot assisted abdominal surgery.

STUDY OBJECTIVE: Following robot assisted abdominal surgery, the pain can be moderate in severity. Neuraxial analgesia may decrease the activity of the detrusor muscle, reduce the incidence of bladder spasm and provide effective somatic and visceral analgesia. In this systematic review, we assessed the role of neuraxial analgesia in robot assisted abdominal surgery. DESIGN: Systematic review. SETTINGS: Robot assisted abdominal surgery. PATIENTS: Adults. INTERVENTIONS: Subsequent to a search of the electronic databases, observational studies and randomized controlled trials that assessed the effect of neuraxial analgesia instituted at induction of anesthesia or intraoperatively in adult and robot assisted abdominal surgery were considered for inclusion. The outcomes of observational studies as well as randomized controlled trials which were not subjected to meta-analysis were presented in descriptive terms. Meta-analysis was conducted if an outcome of interest was reported by two or more randomized controlled trials. MAIN RESULTS: We included 19 and 11 studies that investigated spinal and epidural analgesia in adults, respectively. The coprimary outcomes were the pain score at rest at 24 h and the cumulative intravenous morphine consumption at 24 h. Spinal analgesia with long acting neuraxial opioid did not decrease the pain score at rest at 24 h although it reduced the cumulative intravenous morphine consumption at 24 h by a mean difference (95%CI) of 14.88 mg (-22.13--7.63; p < 0.0001, I2 = 50%) with a low and moderate quality of evidence, respectively, on meta-analysis of randomized controlled trials. Spinal analgesia with long acting neuraxial opioid had a beneficial effect on analgesic indices till the second postoperative day and a positive influence on opioid consumption up to and including the 72 h time point. The majority of studies demonstrated the use of spinal analgesia with long acting neuraxial opioid to lead to no difference in the incidence of postoperative nausea and vomiting, and the occurrence of pruritus was found to be increased with spinal analgesia with long acting neuraxial opioid in recovery but not at later time points. No difference was revealed in the incidence of urinary retention. The evidence in regard to the quality of recovery-15 score at 24 h and hospital length of stay was not fully consistent, although most studies indicated no difference between spinal analgesia and control for these outcomes. Epidural analgesia in robot assisted abdominal surgery was shown to decrease the pain on movement at 12 h but it had not been studied with respect to its influence on the pain score at rest at 24 h or the cumulative intravenous morphine consumption at 24 h. It did not reduce the pain on movement at later time points and the evidence related to the hospital length of stay was inconsistent. CONCLUSIONS: Spinal analgesia with long acting neuraxial opioid had a favourable effect on analgesic indices and opioid consumption, and is recommended by the authors, but the evidence for spinal analgesia with short acting neuraxial opioid and epidural analgesia was limited.

Cognitive aids in the management of clinical emergencies: a systematic review.

Clinical emergencies can be defined as unpredictable events that necessitate immediate intervention. Safety critical industries have acknowledged the difficulties of responding to such crises. Strategies to improve human performance and mitigate its limitations include the provision and use of cognitive aids, a family of tools that includes algorithms, checklists and decision aids. This systematic review evaluates the usefulness of cognitive aids in clinical emergencies. Following a systematic search of the electronic databases, we included 13 randomised controlled trials, reported in 16 publications. Each compared cognitive aids with usual care in the context of an anaesthetic, medical, surgical or trauma emergency involving adults. Most trials used only clinicians in the development and testing of the cognitive aids, and only some trials provided familiarisation with the cognitive aids before they were deployed. The primary outcome was the completeness of care delivered to the patient. Cognitive aids were associated with a reduction in the incidence of missed care steps from 43.3% to 11% (RR (95%CI) 0.29 (0.15-0.16); p < 0.001), and the quality of evidence was rated as moderate. The use of cognitive aids was related to decreases in the incidence of errors, increases in the rate of correctly performed steps and improvement in the clinical teamwork skills scores, non-technical skills scores, subjective conflict resolution scores and the global assessment of team performance. Cognitive aids had an inconsistent influence on the time to first intervention and time to complete care of the patient's condition. It is possible that this was a reflection of how common or rare the crisis in question was as well as the experience and expertise of the clinicians and team. Sufficient thought should be applied to the development of the content and design of cognitive aids, with consideration of the pre-existing guideline ecosystem. Cognitive aids should be tested before their deployment with adequate clinician and team training.

Predictors of Post-operative Pain and Opioid Consumption in Patients Undergoing Liver Surgery.

BACKGROUND: Post-operative pain management is a critical component of perioperative care. Patients at risk of poorly controlled post-operative pain may benefit from early measures to optimize pain management. We sought to identify risk factors for post-operative pain and opioid consumption in patients undergoing liver resection. METHODS: This is a multi-institutional prospective nested cohort study of patients undergoing open liver resection. Opioid consumption and pain scores were collected following surgery. To estimate the effects of patient factors on opioid consumption (oral morphine equivalents-OME) and on pain scores (NRS-11), we used generalized linear models and multivariable linear regression model, respectively. RESULTS: One hundred and fifty-three patients who underwent open liver resection between 2013 and 2016 were included in the study. The mean patient age was 62.2 years, and 43.3% were female. Younger patients were significantly more likely to use more opioids in the early post-operative period (16.7 OME/10 years, p < 0.001). Patient factors that were significantly associated with increased NRS-11 pain scores also included younger patient age (difference in pain score of 0.3/10 years with cough and 0.2/10 years at rest, p < 0.01 for both) as well as a history of analgesic use (difference in pain score of 0.9 with cough and 0.6 at rest, p < 0.01 and p = 0.07, respectively). CONCLUSION: Younger patients and those with a history of analgesic use are more likely to report higher post-operative pain and require higher doses of opioids. Early identification of these patients, and measures to better manage their pain, may contribute to optimal perioperative care.

Go/no-go decision in anaesthesia: wide variation in risk tolerance amongst anaesthetists.

BACKGROUND: The variability in risk tolerance in medicine is not well understood. Parallels are often drawn between aviation and anaesthesia. The aviation industry is perceived as culturally risk averse, and part of preflight checks involves a decision on whether the flight can operate. This is sometimes termed a go/no-go decision. This questionnaire study was undertaken to explore the equivalent go/no-go decision in anaesthesia. We presented anaesthetists with a range of situations in which additional risk might be expected and asked them to decide whether they would proceed with the case. METHODS: An electronic questionnaire was distributed to anaesthetic colleagues of all grades in one National Health Service Trust. Eleven scenarios, all drawn from critical incident data, were presented. Participants were invited to consider whether they would proceed, how they would modify their anaesthetic technique, and to predict whether a colleague with similar experience would make the same decision. Textual responses were analysed qualitatively. RESULTS: The scenario response rate was 28%. Consultants were significantly more likely to proceed than trainees. In no scenario was there absolute agreement over whether to proceed, even in scenarios where national guidelines would suggest a case should be cancelled. Thematic analysis suggested a wide variability in what anaesthetists consider acceptable or professional behaviour. CONCLUSIONS: It is clear that safety decisions cannot be made in isolation and that clinicians must consider operational requirements, such as throughput, when making a go/no-go decision. The level of variability in decision-making was surprising, particularly for scenarios that appeared to go against guidelines.

Donor BMI >30 Is Not a Contraindication for Live Liver Donation.

The increased prevalence of obesity worldwide threatens the pool of living liver donors. Although the negative effects of graft steatosis on liver donation and transplantation are well known, the impact of obesity in the absence of hepatic steatosis on outcome of living donor liver transplantation (LDLT) is unknown. Consequently, we compared the outcome of LDLT using donors with BMI <30 versus donors with BMI ≥30. Between April 2000 and May 2014, 105 patients received a right-lobe liver graft from donors with BMI ≥30, whereas 364 recipients were transplanted with grafts from donors with BMI <30. Liver steatosis >10% was excluded in all donors with BMI >30 by imaging and liver biopsies. None of the donors had any other comorbidity. Donors with BMI <30 versus ≥30 had similar postoperative complication rates (Dindo-Clavien ≥3b: 2% vs. 3%; p = 0.71) and lengths of hospital stay (6 vs. 6 days; p = 0.13). Recipient graft function, assessed by posttransplant peak serum bilirubin and international normalized ratio was identical. Furthermore, no difference was observed in recipient complication rates (Dindo-Clavien ≥3b: 25% vs. 20%; p = 0.3) or lengths of hospital stay between groups. We concluded that donors with BMI ≥30, in the absence of graft steatosis, are not contraindicated for LDLT.

First-Degree Living-Related Donor Liver Transplantation in Autoimmune Liver Diseases.

Liver transplantation (LT) is the treatment of choice for end-stage autoimmune liver diseases. However, the underlying disease may recur in the graft in some 20% of cases. The aim of this study is to determine whether LT using living donor grafts from first-degree relatives results in higher rates of recurrence than grafts from more distant/unrelated donors. Two hundred sixty-three patients, who underwent a first LT in the Toronto liver transplant program between January 2000 and March 2015 for autoimmune liver diseases, and had at least 6 months of post-LT follow-up, were included in this study. Of these, 72 (27%) received a graft from a first-degree living-related donor, 56 (21%) from a distant/unrelated living donor, and 135 (51%) from a deceased donor for primary sclerosing cholangitis (PSC) (n = 138, 52%), primary biliary cholangitis (PBC) (n = 69, 26%), autoimmune hepatitis (AIH) (n = 44, 17%), and overlap syndromes (n = 12, 5%). Recurrence occurred in 52 (20%) patients. Recurrence rates for each autoimmune liver disease were not significantly different after first-degree living-related, living-unrelated, or deceased-donor LT. Similarly, time to recurrence, recurrence-related graft failure, graft survival, and patient survival were not significantly different between groups. In conclusion, first-degree living-related donor LT for PSC, PBC, or AIH is not associated with an increased risk of disease recurrence.

Live donor liver transplantation: a valid alternative for critically ill patients suffering from acute liver failure.

We report the outcome of live donor liver transplantation (LDLT) for patients suffering from acute liver failure (ALF). From 2006 to 2013, all patients with ALF who received a LDLT (n = 7) at our institution were compared to all ALF patients receiving a deceased donor liver transplantation (DDLT = 26). Groups were comparable regarding pretransplant ICU stay (DDLT: 1 [0-7] vs. LDLT: 1 days [0-10]; p = 0.38), mechanical ventilation support (DDLT: 69% vs. LDLT: 57%; p = 0.66), inotropic drug requirement (DDLT: 27% vs. LDLT: 43%; p = 0.64) and dialysis (DDLT: 2 vs. LDLT: 0 patients; p = 1). Median evaluation time for live donors was 24 h (18-72 h). LDLT versus DDLT had similar incidence of overall postoperative complications (31% vs. 43%; p = 0.66). No difference was detected between LDLT and DDLT patients regarding 1- (DDLT: 92% vs. LDLT: 86%), 3- (DDLT: 92% vs. LDLT: 86%), and 5- (DDLT: 92% vs. LDLT: 86%) year graft and patient survival (p = 0.63). No severe donor complication (Dindo-Clavien ≥3 b) occurred after live liver donation. ALF is a severe disease with high mortality on liver transplant waiting lists worldwide. Therefore, LDLT is an attractive option since live donor work-up can be expedited and liver transplantation can be performed within 24 h with excellent short- and long-term outcomes.

Benefit of Treating Hepatocellular Carcinoma Recurrence after Liver Transplantation and Analysis of Prognostic Factors for Survival in a Large Euro-American Series.

PURPOSE: To identify prognostic factors after hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). METHODS: We retrospectively reviewed the combined experience at Toronto General Hospital and Hospital Vall d'Hebron managing HCC recurrence after LT (n = 121) between 2000 and 2012. We analyzed prognostic factors by uni- and multi-variate analysis. Median follow-up from LT was 29.5 (range 2-129.4) months. Median follow-up from HCC recurrence was 12.2 (range 0.1-112.5) months. RESULTS: At recurrence, 31.4 % were treated with curative-intent treatments (surgery or ablation), 42.1 % received palliative treatment, and 26.4 % received best supportive care. The 1-, 3-, and 5-year survivals, respectively, after HCC recurrence were 75, 60, and 31 %, vs. 60, 19, and 12 %, vs. 52, 4, and 5 % (p < 0.001). By multivariate analysis, not being amenable to a curative-intent treatment [hazard ratio (HR) 4.7, 95 % confidence interval (CI) 2.7-8.3, p < 0.001], α-fetoprotein of ≥100 ng/mL at the time of HCC recurrence (HR 2.1, 95 % CI 1.3-2.3, p = 0.002) and early recurrence (<12 months) after LT (HR 1.6, 95 % CI 1.1-2.5, p = 0.03) were found to be poor prognosis factors. A prognostic score was devised on the basis of these three independent variables. Patients were divided into three groups, as follows: good prognosis, 0 points (n = 22); moderate prognosis, 1 or 2 points (n = 84); and poor prognosis, 3 points (n = 15). The 1-, 3-, and 5-year actuarial survival for each group was 91, 50, and 50 %, vs. 52, 7, and 2 %, vs. 13, 0, and 0 %, respectively (p < 0.001). CONCLUSIONS: Patients with HCC recurrence after transplant amenable to curative-intent treatments can experience significant long-term survival (~50 % at 5 years), so aggressive management should be offered. Poor prognosis factors after recurrence are not being amenable to a curative-intent treatment, α-fetoprotein of ≥100 ng/mL, and early (<1 year) recurrence after LT.

Living vs. deceased donor liver transplantation provides comparable recovery of renal function in patients with hepatorenal syndrome: a matched case-control study.

Outcomes of living versus deceased donor liver transplantation in patients with chronic liver disease and hepatorenal syndrome (HRS) was compared using a matched pair study design. Thirty patients with HRS receiving a live donor liver transplantation (LDLT) and 90 HRS patients receiving a full graft deceased donor liver transplantation (DDLT) were compared. LDLT versus DDLT of patients with HRS was associated with decreased peak aspartate aminotransferase levels (339 ± 214 vs. 935 ± 1253 U/L; p = 0.0001), and similar 7-day bilirubin (8.42 ± 7.89 vs. 6.95 ± 7.13 mg/dL; p = 0.35), and international normalized ratio levels (1.93 ± 0.62 vs. 1.78 ± 0.78; p = 0.314). LDLT vs. DDLT had a decreased intensive care unit (2 [1-39] vs. 4 [0-93] days; p = 0.004), and hospital stay (17 [4-313] vs. 26 [0-126] days; p = 0.016) and a similar incidence of overall postoperative complications (20% vs. 27%; p = 0.62). No difference was detected between LDLT and DDLT patients regarding graft survival at 1 (80% vs. 82%), at 3 (69% vs. 76%) and 5 years (65% vs. 76%) (p = 0.63), as well as patient survival at 1 (83% vs. 82%), 3 (72% vs. 77%) and 5 years (72% vs. 77%) (p = 0.93). The incidence of chronic kidney disease post-LT (10% vs. 6%; p = 0.4) was similar between both groups. LDLT results in identical long-term outcome when compared with DDLT in patients with HRS.

Outcomes after hepatic resection and subsequent multimodal treatment of recurrence for multifocal hepatocellular carcinoma.

BACKGROUND: The role of liver resection in patients with multifocal hepatocellular carcinoma (HCC) with well preserved liver function is controversial. This study was conducted to evaluate the outcomes of such patients. METHODS: This was a retrospective analysis of patients who underwent liver resection for multifocal HCC between 1992 and 2011. Postoperative outcomes, survival and predictors of outcomes were analysed. RESULTS: Of 46 patients who underwent hepatic resection for multifocal HCC, 38 had Barcelona Clinic Liver Cancer stage B disease. Major hepatectomy was performed in 27 patients, and major complications occurred in nine (20 per cent). The 90-day postoperative mortality rate was 7 per cent. Overall 1-, 2-, 3- and 5-year survival rates were 78, 64, 59 and 53 per cent respectively (median 70 months), whereas corresponding recurrence-free survival rates were 53, 32, 30 and 27 per cent (median 14 months). Recurrence developed in 28 (61 per cent) of the 46 patients, affecting the liver only in 22. Three-quarters of patients with recurrence underwent further therapy. Major hepatectomy (hazard ratio (HR) 0.37, 95 per cent confidence interval 0.14 to 0·95; P = 0·038), microvascular (HR 3·44, 1·35 to 8·74; P = 0·009) and macrovascular (HR 2·68, 1·11 to 6·43; P = 0·028) invasion, and cirrhosis (HR 3·15, 1·12 to 8·86; P = 0·029) were associated with overall survival. Microvascular invasion (HR 2·81, 1·06 to 7·40; P = 0·037), cirrhosis (HR 3·12, 1·41 to 6·88; P < 0·001) and bilobar disease (HR 2·93, 1·09 to 7·88; P = 0·033) were associated with recurrence-free survival. CONCLUSION: In selected patients with multifocal HCC and well preserved liver function, long-term survival is possible after liver resection and subsequent aggressive treatment of recurrence.

Planned versus unplanned portal vein resections during pancreaticoduodenectomy for adenocarcinoma.

BACKGROUND: The management of portal vein (PV) involvement by pancreatic adenocarcinoma during pancreaticoduodenectomy (PD) is controversial. The aim of this study was to compare the outcomes of unplanned and planned PV resections as part of PD. METHODS: An analysis of PD over 11 years was performed. Patients who had undergone PV resection (PV-PD) were identified, and categorized into those who had undergone planned or unplanned resection. Postoperative and oncological outcomes were compared. RESULTS: Of 249 patients who underwent PD for pancreatic adenocarcinoma, 66 (26·5 per cent) had PV-PD, including 27 (41 per cent) planned and 39 (59 per cent) unplanned PV resections. Twenty-five of 27 planned PV resections were circumferential PV-PD, whereas 25 of 39 unplanned PV resections were partial PV-PD. Planned PV resections were performed in slightly younger patients (mean(s.d.) 60(9) versus 65(10) years; P = 0·031), and associated with longer operating times (mean(s.d.) 602(131) versus 458(83) min; P < 0·001) and more major complications (26 versus 5 per cent; P = 0·026). Planned PV resections were associated with a lower rate of positive margins (4 versus 44 per cent; P < 0·001) despite being carried out for larger tumours (mean(s.d.) 3·9(1·4) versus 2·9(1·0) cm; P = 0·002). There was no difference in survival between the two groups (P = 0·998). On multivariable analysis, margin status was a significant predictor of survival. CONCLUSION: Although planned PV resections for pancreatic adenocarcinoma were associated with higher rates of postoperative morbidity than unplanned resections, R0 resection rates were better.

Routine induction therapy in living donor liver transplantation prevents rejection but may promote recurrence of hepatitis C.

BACKGROUND: Routine induction therapy in living donor liver transplantation (LDLT) has not been well described. METHODS: We reviewed outcomes of induction therapy with rabbit antithymocyte globulin (rATG) or basiliximab within 1 year of LDLT. RESULTS: Between 2002 and 2007, 184 adults underwent LDLT and received induction therapy in addition to standard immunosuppression. Acute cellular rejection (ACR) developed in 17 of 130 patients (13.1%) who received rATG and 13 of 54 patients (24.1%) who received basiliximab (P = .066). The interval between transplantation and rejection as well as rejection severity was similar in patients who received rATG and those who received basiliximab. Hepatitis C (HCV) recurrence requiring initiation of antiviral therapy was more common in patients who received rATG compared with basiliximab (34.5% vs 8.7%; P = .021), and in those who received induction combined with tacrolimus as opposed to cyclosporine (38.5% vs 3.9%; P = .001). rATG and basiliximab were associated with excellent patient and graft survivals well as low rates of opportunistic infections and malignancies. CONCLUSION: Induction with rATG or basiliximab was well tolerated and highly effective at preventing ACR within 1 year of LDLT, but may be associated with a higher risk of clinically significant HCV recurrence in some patients.

Prevention of autoimmune diabetes by ectopic pancreatic ß-cell expression of interleukin-35.

Interleukin (IL)-35 is a newly identified inhibitory cytokine used by T regulatory cells to control T cell-driven immune responses. However, the therapeutic potential of native, biologically active IL-35 has not been fully examined. Expression of the heterodimeric IL-35 cytokine was targeted to ß-cells via the rat insulin promoter (RIP) II. Autoimmune diabetes, insulitis, and the infiltrating cellular populations were analyzed. Ectopic expression of IL-35 by pancreatic ß-cells led to substantial, long-term protection against autoimmune diabetes, despite limited intraislet IL-35 secretion. Nonobese diabetic RIP-IL35 transgenic mice exhibited decreased islet infiltration with substantial reductions in the number of CD4(+) and CD8(+) T cells, and frequency of glucose-6-phosphatase catalytic subunit-related protein-specific CD8(+) T cells. Although there were limited alterations in cytokine expression, the reduced T-cell numbers observed coincided with diminished T-cell proliferation and G1 arrest, hallmarks of IL-35 biological activity. These data present a proof of principle that IL-35 could be used as a potent inhibitor of autoimmune diabetes and implicate its potential therapeutic utility in the treatment of type 1 diabetes.

Adult living liver donors have excellent long-term medical outcomes: the University of Toronto liver transplant experience.

Right lobe living donor liver transplantation is an effective treatment for selected individuals with end-stage liver disease. Although 1 year donor morbidity and mortality have been reported, little is known about outcomes beyond 1 year. Our objective was to analyze the outcomes of the first 202 consecutive donors performed at our center with a minimum follow-up of 12 months (range 12-96 months). All physical complications were prospectively recorded and categorized according to the modified Clavien classification system. Donors were seen by a dedicated family physician at 2 weeks, 1, 3 and 12 months postoperatively and yearly thereafter. The cohort included 108 males and 94 females (mean age 37.3 +/- 11.5 years). Donor survival was 100%. A total of 39.6% of donors experienced a medical complication during the first year after surgery (21 Grade 1, 27 Grade 2, 32 Grade 3). After 1 year, three donors experienced a medical complication (1 Grade 1, 1 Grade 2, 1 Grade 3). All donors returned to predonation employment or studies although four donors (2%) experienced a psychiatric complication. This prospective study suggests that living liver donation can be performed safely without any serious late medical complications and suggests that long-term follow-up may contribute to favorable donor outcomes.

Intraoperative 'no go' donor hepatectomies in living donor liver transplantation.

Donor safety is the paramount concern of living donor liver transplantation (LDLT). Although LDLT is employed worldwide, there is little data on rates and causes of 'no go' hepatectomies-patients brought to the operating room for possible donor hepatectomy whose procedure was aborted. We performed a single-center, retrospective review of all patients brought to the operating room for donor hepatectomy between October 2000 and November 2008. Of 257 right lobe donors, the donor operation was aborted in 12 cases (4.7%). The main reasons for stopping the operation were aberrant ductal or vascular anatomy (seven cases), unsuitable liver quality (three cases) or unexpected intraoperative events (two cases). Over the median period of follow-up of 23 months, there were no long-term complications of patients with aborted donor procedures. This report focuses exclusively on an important issue: the frequency and causes of no go decisions at a single large volume North American LDLT center. The rate of no go donor hepatectomies should be as low as possible without compromising donor safety--however, even with rigorous preoperative evaluation the rate of donor abortions will be significant. The default surgical position should always be to abort the donor operation if there is an unexpected finding that places the donor at increased risk.