Optimal management of perioperative analgesia regarding immediate and short-term outcomes after liver transplantation - A systematic review, meta-analysis and expert panel recommendations.

BACKGROUND: Adequate pain control is essential for patients undergoing liver transplantation (LT). Multiple analgesic strategies have been implemented during the perioperative period. There is no consensus on the optimal perioperative analgesia management. OBJECTIVES: To provide recommendations, on the optimal perioperative analgesia management for LT. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: A systematic review and meta-analysis following PRISMA guidelines and recommendations using GRADE. Studies describing outcomes, morbidity, mortality, pain scores, intensive care unit and hospital length of stay in patients that received different pain management techniques during and after LT were included (CRD42021243282). RESULTS: One thousand nine hundred ten articles were screened, but only two randomized controlled trials, one prospective and six retrospective studies were included. The opioid-avoidance protocols included, thoracic epidural analgesia (TEA), Transversus Abdominis Plane (TAP) block, as well as other non-opioid analgesics, resulted in improved short-term outcomes. Mortality was reduced in this group versus control cohorts (OR = 0.51; CI 0.14, 1.83; P = 0.350), Time to extubation, and intensive care unit LOS were shorter; pain scores after surgery were lower in opioid-avoidance group (percentage decrease, 35%, 12%, and 55%, respectively). However, hospital LOS was longer (percentage increase 8%). CONCLUSIONS: Opioid-avoidance analgesia management for LT results in improved short-term outcomes. (Quality of Evidence; Moderate to low | Grade of Recommendation; Weak). Medications such as acetaminophen(paracetamol), gabapentin, ketamine, tramadol and local anesthesia may be used instead of, or as adjuncts to opioids for postoperative analgesia. Overall evidence remains weak and more robust studies are required.

Ventilation Monitoring.

Ventilation or breathing is vital for life yet is not well monitored in hospital or at home. Respiratory rate is a neglected vital sign and tidal volumes together with breath sounds are checked infrequently in many patients. Medications with the potential to depress ventilation are frequently administered, and may be accentuated by obesity causing airway obstruction in the form of sleep apnea. Sepsis may adversely affect ventilation by causing an increase in respiratory rate, often a very early sign of infection. Changes in ventilation may be early signs of deterioration in the patient.

Non-invasive monitoring is coming the full circle, making our patients safer!

Non-invasive monitoring is becoming more accurate, more available and mobile. The clinical advantage that this developing technology provides is that the data may be monitored continuously; relatively unobtrusively, and transmitted directly to the caregiver. The downside of being non-invasive has been the potential loss of accuracy in the data displayed. This has been overcome in the measurement of oxygen saturation of hemoglobin by pulse oximetry, in that treatment will be instigated by a decline in oxygen saturation without necessarily an arterial blood gas analysis being performed. The development of pulse oximetry to measure hemoglobin levels (SpHb) has relied on "trend accuracy" to indicate the need for a confirmatory laboratory analysis of hemoglobin level. The study by Applegate et al. [1] confirms the trend accuracy of SpHb as an indication to perform a laboratory confirmation of hemoglobin level. This will lead to earlier laboratory screening, so that developing adverse conditions, such as postoperative bleeding, may be identified at a time that major events, such as failure to rescue can be avoided. This increased availability of non-invasive technology will make patients safer both in our hospitals and at home.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on the Role of Neuromonitoring in Perioperative Outcomes: Electroencephalography.

Electroencephalographic (EEG) monitoring to indicate brain state during anesthesia has become widely available. It remains unclear whether EEG-guided anesthesia influences perioperative outcomes. The sixth Perioperative Quality Initiative (POQI-6) brought together an international team of multidisciplinary experts from anesthesiology, biomedical engineering, neurology, and surgery to review the current literature and to develop consensus recommendations on the utility of EEG monitoring during anesthesia. We retrieved a total of 1023 articles addressing the use of EEG monitoring during anesthesia and conducted meta-analyses from 15 trials to determine the effect of EEG-guided anesthesia on the rate of unintentional awareness, postoperative delirium, neurocognitive disorder, and long-term mortality after surgery. After considering current evidence, the working group recommends that EEG monitoring should be considered as part of the vital organ monitors to guide anesthetic management. In addition, we encourage anesthesiologists to be knowledgeable in basic EEG interpretation, such as raw waveform, spectrogram, and processed indices, when using these devices. Current evidence suggests that EEG-guided anesthesia reduces the rate of awareness during total intravenous anesthesia and has similar efficacy in preventing awareness as compared with end-tidal anesthetic gas monitoring. There is, however, insufficient evidence to recommend the use of EEG monitoring for preventing postoperative delirium, neurocognitive disorder, or postoperative mortality.

New Developments in Hemodynamic Monitoring.

Hemodynamic monitoring is an essential part of the perioperative management of the cardiovascular patient. It helps to detect hemodynamic alterations, diagnose their underlying causes, and optimize oxygen delivery to the tissues. Furthermore, hemodynamic monitoring is necessary to evaluate the adequacy of therapeutic interventions such as volume expansion or vasoactive medications. Recent developments include the move from static to dynamic variables to assess conditions such as cardiac preload and fluid responsiveness and the transition to less-invasive or even noninvasive monitoring techniques, at least in the perioperative setting. This review describes the available techniques that currently are being used in the care of the cardiovascular patient and discusses their strengths and limitations. Even though the thermodilution method remains the gold standard for measuring cardiac output (CO), the use of the pulmonary artery catheter has declined over the last decades, even in the setting of cardiovascular anesthesia. The transpulmonary thermodilution method, in addition to accurately measuring CO, provides the user with some additional helpful variables, of which extravascular lung water is probably the most interesting. Less-invasive monitoring techniques use, for example, pulse contour analysis to originate flow-derived variables such as stroke volume and CO from the arterial pressure signal, or they may measure the velocity-time integral in the descending aorta to estimate the stroke volume, using, for example, the esophageal Doppler. Completely noninvasive methods such as the volume clamp method use finger cuffs to reconstruct the arterial pressure waveform, from which stroke volume and CO are calculated. All of these less-invasive CO monitoring devices have percentage errors around 40% compared with reference methods (thermodilution), meaning that the values are not interchangeable.

Anesthesia for Liver Transplantation.

The provision of anesthesia for a liver transplant program requires a dedicated team of anesthesiologists. Liver transplant anesthesiologists must have an understanding of liver physiology and anatomy; the spectrum of clinical disease associated with liver dysfunction; the impact of warm and cold ischemia times, surgical techniques in liver transplantation, and the impact of ischemia-reperfusion syndrome; and optimal practices to protect the liver. The team must provide a 24-hour service, be actively involved in the selection committee process, and stay current with advances in the subspecialty.

Significance of measured intraoperative portal vein flows after thrombendvenectomy in deceased donor liver transplantations with portal vein thrombosis.

Adequate portal vein (PV) flow in liver transplantation is essential for a good outcome, and it may be compromised in patients with portal vein thrombosis (PVT). This study evaluated the impact of intraoperatively measured PV flow after PV thrombendvenectomy on outcomes after deceased donor liver transplantation (DDLT). The study included 77 patients over a 16-year period who underwent PV thrombendvenectomy with complete flow data. Patients were classified into 2 groups: high PV flow (>1300 mL/minute; n = 55) and low PV flow (≤1300 mL/minute; n = 22). Postoperative complications and graft survival were analyzed according to the PV flow. The 2 groups were similar in demographic characteristics. Low PV flow was associated with higher cumulative rates of biliary strictures (P = 0.02) and lower 1-, 2-, and 5-year graft survival (89%, 85%, and 68% versus 64%, 55%, and 38%, respectively; P = 0.002). There was no difference in the incidence of postoperative PVT between the groups (1.8% versus 9.1%; P = 0.19). No biliary leaks or hepatic artery thromboses were reported in either group. By multivariate analyses, age >60 years (hazard ratio [HR], 3.04, 95% confidence interval [CI], 1.36-6.82; P = 0.007) and low portal flow (HR, 2.31; 95% CI, 1.15-4.65; P = 0.02) were associated with worse survival. In conclusion, PV flow <1300 mL/minute after PV thrombendvenectomy for PVT during DDLT was associated with higher rates of biliary strictures and worse graft survival. Consideration should be given to identifying reasons for low flow and performing maneuvers to increase PV flow when intraoperative PV flows are <1300 mL/minute. Liver Transplantation 23 1032-1039 2017 AASLD.

Low Measured Hepatic Artery Flow Increases Rate of Biliary Strictures in Deceased Donor Liver Transplantation: An Age-Dependent Phenomenon.

BACKGROUND: This study was conducted to determine effect of lower measured hepatic arterial (HA) flow (<400 mL/min) on biliary complications and graft survival after deceased donor liver transplantation. Hepatic artery is the main blood supply to bile duct and lack of adequate HA flow is thought to be a risk factor for biliary complications. METHODS: A retrospective review of 1300 patients who underwent deceased donor liver transplantation was performed. Patients with arterial complications were excluded to eliminate potential contribution to biliary complications from HA thrombosis. Patients were divided into low (<400 mL/min; N = 201) and high (≥400 mL/min; N = 1099) HA flow groups. Incidence of biliary complications and graft survival were analyzed. RESULTS: HA flows less than 400 mL/min were associated with increased rate of biliary strictures in younger donors (<50 years old), and in patients with duct-to-duct anastomoses (P = 0.028). Lower HA flows were associated with decreased graft survival (P = 0.013). Donor older than 50 years was associated with increased rate of biliary strictures (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.14-2.45; P = 0.0085) and graft failure (HR, 1.68; 95% CI, 1.35-2.1; P <0.0001) on multivariate analyses. HA flow less than 400 mL/min was associated with biliary strictures (HR, 1.53; 95% CI, 1.04-2.24; P = 0.0297) on univariate analysis only. CONCLUSIONS: HA flow less than 400 mL/min was associated with higher rate of biliary strictures in younger donors with duct-to-duct reconstruction and lower graft survival. A consideration should be given to increase the intraoperative HA flow to prevent biliary strictures in such patients.

International Liver Transplant Society Practice Guidelines: Diagnosis and Management of Hepatopulmonary Syndrome and Portopulmonary Hypertension.

Two distinct pulmonary vascular disorders, hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) may occur as a consequence of hepatic parenchymal or vascular abnormalities. HPS and POPH have major clinical implications for liver transplantation. A European Respiratory Society Task Force on Pulmonary-Hepatic Disorders convened in 2002 to standardize the diagnosis and guide management of these disorders. These International Liver Transplant Society diagnostic and management guidelines are based on that task force consensus and should continue to evolve as clinical experience dictates. Based on a review of over 1000 published HPS and POPH articles identified via a MEDLINE search (1985-2015), clinical guidelines were based on, selected single care reports, small series, registries, databases, and expert opinion. The paucity of randomized, controlled trials in either of these disorders was noted. Guidelines are presented in 5 parts; I. Definitions/Diagnostic criteria; II. Hepatopulmonary syndrome; III. Portopulmonary hypertension; IV. Implications for liver transplantation; and V. Suggestions for future clinical research.

Ratio of hepatic arterial flow to recipient body weight predicts biliary complications after deceased donor liver transplantation.

OBJECTIVES: Adequate hepatic arterial (HA) flow to the bile duct is essential in liver transplantation. This study was conducted to determine if the ratio of directly measured HA flow to weight is related to the occurrence of biliary complications after deceased donor liver transplantation. METHODS: A retrospective review of 2684 liver transplants carried out over a 25-year period was performed using data sourced from a prospectively maintained database. Rates of biliary complications (biliary leaks, anastomotic and non-anastomotic strictures) were compared between two groups of patients with HA flow by body weight of, respectively, <5 ml/min/kg (n = 884) and ≥5 ml/min/kg (n = 1800). RESULTS: Patients with a lower ratio of HA flow to weight had higher body weight (92 kg versus 76 kg; P < 0.001) and lower HA flow (350 ml/min versus 550 ml/min; P < 0.001). A lower ratio of HA flow to weight was associated with higher rates of biliary complications at 2 months, 6 months and 12 months (19.8%, 28.2% and 31.9% versus 14.8%, 22.4% and 25.8%, respectively; P < 0.001). CONCLUSIONS: A ratio of HA flow to weight of < 5 ml/min/kg is associated with higher rates of biliary complications. This ratio may be a useful parameter for application in the prevention and early detection of biliary complications.

Dexmedetomidine infusion for analgesia up to 48 hours after lung surgery performed by lateral thoracotomy.

Patients undergoing a lateral thoracotomy for pulmonary resection have moderate to severe pain postoperatively that is often treated with opioids. Opioid side effects such as respiratory depression can be devastating in patients with already compromised respiratory function. This prospective double-blinded clinical trial examined the analgesic effects and safety of a dexmedetomidine infusion for postthoracotomy patients when administered on a telemetry nursing floor, 24 to 48 hours after surgery, to determine if the drug's known early opioid-sparing properties were maintained. Thirty-eight thoracotomy patients were administered dexmedetomidine intraoperatively and overnight postoperatively and then randomized to receive placebo or dexmedetomidine titrated from 0.1 to 0.5 µg·kg·h(-1) the day following surgery for up to 24 hours on a telemetry floor. Opioids via a patient-controlled analgesia pump were available for both groups, and vital signs including transcutaneous carbon dioxide, pulse oximetry, respiratory rate, and pain and sedation scores were monitored. The dexmedetomidine group used 41% less opioids but achieved pain scores equal to those of the placebo group. The mean heart rate and systolic blood pressure were lower in the dexmedetomidine group but sedation scores were better. The mean respiratory rate and oxygen saturation were similar in the two groups. Mild hypercarbia occurred in both groups, but periods of significant respiratory depression were noted only in the placebo group. Significant hypotension was noted in one patient in the dexmedetomidine group in conjunction with concomitant administration of a beta-blocker agent. The placebo group reported a higher number of opioid-related adverse events. In conclusion, the known opioid-sparing properties of dexmedetomidine in the immediate postoperative period are maintained over 48 hours.