Serum acidosis prior to reperfusion facilitates hemodynamic recovery following liver transplantation.

INTRODUCTION: Reperfusion is the most critical event during liver transplantation, and sustained leakage of acidic preservation solution from the liver graft contributes to marked hemodynamic instability. Recent laboratory studies with hepatocyte cultures have revealed that low pH may protect hepatocyte mitochondria against ischemia-reperfusion injury by inhibiting the mitochondrial permeability transition (MPT), the so-called "pH paradox." However, the clinical significance of this pH paradox theory remains largely unknown. In this study, we sought to determine whether there is an association between serum pH immediately prior to reperfusion and hemodynamic recovery after reperfusion and graft survival. METHODS: We analyzed retrospective data from 527 patients who underwent Orthotopic liver transplantation between 2003 and 2008. All patients were allocated to one of two groups: pH ≤ 7.32 or pH > 7.32, as measured 5 min before reperfusion. Case-control matching was performed using the propensity score to adjust for background differences between the two groups. Data were analyzed using Student's t-test and the χ (2) test. RESULTS: There were 85 patients in the pH ≤ 7.32 group and 385 patients in the pH > 7.32 group. The recovery of mean arterial pressure after hepatic artery reperfusion was significantly faster in the pH ≤ 7.32 group (slope of recovery: 0.0004 % vs. 0.0002 %/min, p = 0.041). Other parameters studied, including vasopressor dosage after reperfusion, did not show any statistically significant difference between groups. CONCLUSIONS: Our findings suggest that less aggressive treatment of acidosis with a slower rate of normalization of serum pH (from low to normal) after reperfusion promotes faster hemodynamic stabilization. These findings provide evidence to support the concept of the pH paradox, and may also substantiate the argument against the usage of alkalizing agents before reperfusion unless acidosis becomes clinically significant.

Hemodynamic recovery following postreperfusion syndrome in liver transplantation.

OBJECTIVES: The authors' current understanding of the phenomenon of significant and sustained decrease in arterial pressure following liver graft reperfusion (postreperfusion syndrome [PRS]), is derived from relatively small observational reports, and no large scale analysis of PRS exists up to date. This study investigated its incidence, risk factors, temporal course of hemodynamic recovery, and its impact on functional graft outcome. DESIGN: Retrospective observational study of 1,024 electronic records of orthotopic liver transplant recipients. SETTING: Major transplant center. MEASUREMENTS: Out of 1,024, 715 records satisfied the inclusion criteria. Data were analyzed by multivariable Cox's proportional hazard model to identify risk factors for PRS. Hemodynamic recovery patterns and functional graft outcomes were compared between the cohorts of interest (intraoperative PRS) and control (no intraoperative PRS) after propensity score-matching. Association between donor risk index and hemodynamic recovery after hepatic artery reperfusion was analyzed by a multivariable regression model. RESULTS: The overall incidence of PRS was 31.6% with associated mortality of 0.3%. Independent risk factors for PRS included older donor age, higher donor risk index, and lower central venous pressure at reperfusion. Hemodynamic recovery after PRS following portal vein reperfusion was delayed until hepatic artery reperfusion. The slope of hemodynamic recovery, expressed as %MAP/min, correlated negatively with donor risk index (p=0.014). Immediate and 1-year graft survival rates were similar in both cohorts. CONCLUSIONS: Host hemodynamic response to graft reperfusion appeared to be phasic: initial abrupt hypotension after portal vein reperfusion was followed by a period of gradual decline of blood pressure until hepatic artery reperfusion, and sustained hemodynamic recovery afterwards. The slope of hemodynamic recovery correlated negatively with the donor risk index. PRS was not associated with deterioration of post-transplant graft survival and function.

Invasive renal cell carcinoma with inferior vena cava tumor thrombus: cardiac anesthesia in liver transplant settings.

OBJECTIVES: Resection of renal cell carcinomas (RCC) with tumor thrombus invasion into the inferior vena cava (IVC) is associated with significant perioperative morbidity and mortality. This study examined the intra- and inter-departmental collaboration among cardiac, liver transplantation, and urologic surgeons and anesthesiologists in caring for these patients. DESIGN: After IRB approval, medical records of patients who underwent resection of RCC tumor thrombus level III and IV, from 1997 to 2010 in this institution, were reviewed. Data were collected and analyzed by one way-ANOVA and chi-square test. SETTING: Major academic institution, tertiary referral center. PARTICIPANTS: This was a retrospective study based on the medical records of patients who underwent resection of RCC tumor thrombus level III and IV, from 1997 to 2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty-eight patients (82.9%) with level III thrombus and 12 patients (17.1%) with level IV thrombus were analyzed. Sixty-five (92.9%) did not require any extracorporeal circulatory support; 5 (2 with level III and 3 with level IV; 7.1%) required cardiopulmonary bypass. No patients required veno-venous bypass. Compared to patients with level III thrombus extension, patients with level IV had higher estimated blood loss (6978±2968 mL v 1540±206, p<0.001) and hospital stays (18.8±1.6 days v 8.1±0.7, p<0.001). Intraoperative transesophageal echocardiography (TEE) was utilized in 77.6% of patients with level III thrombus extension and in 100% of patients with level IV thrombus extension. Intraoperative TEE guidance resulted in a significant surgical plan modification in 3 cases (5.2%). Short-term mortality was low (n = 3, 4.3%). CONCLUSIONS: Utilization of specialized liver transplantation and cardiac surgical techniques in the resection of RCC with extension into the IVC calls for a close intra-and interdepartmental collaboration between surgeons and anesthesiologists. The transabdominal approach to suprahepatic segments of the IVC allowed avoidance of extracorporeal circulatory support in most of these patients. Perioperative management of these patients reflected the critical importance of TEE-proficient practitioners experienced in liver transplantation and cardiac anesthesia.

Crystalloid flush with backward unclamping may decrease post-reperfusion cardiac arrest and improve short-term graft function when compared to portal blood flush with forward unclamping during liver transplantation.

During liver transplant (LT), the release of vasoactive substances into the systemic circulation is associated with severe hemodynamic instability that is injurious to the recipient and/or the post-ischemic graft. Crystalloid flush with backward unclamping (CB) and portal blood flush with forward unclamping (PF) are two reperfusion methods to reduce reperfusion-related cardiovascular perturbations in our center. The primary aim of this study was to compare these two methods. After institutional review board (IRB) approval, cadaveric whole LT cases performed between 2003 and 2008 were reviewed. Patients were divided into two groups based on reperfusion methods: CB or PF. After background matching with propensity score, the effect of each method on post-operative graft function was assessed in detail. In our cohort of 478 patients, CB was used in 313 grafts and PF in 165. Thirty-day graft survival was lower, and risk of retransplantation was higher in PF. Multivariable model showed that CB is an independent factor to reduce primary non-function, cardiac arrest and improve 30-d graft survival. Also, the incidence of ischemic-type biliary lesions was significantly higher in the PF group. Reperfusion methods affect intraoperative hemodynamics and post-transplant outcome. CB allows for control over temperature and composition of the perfusate, perfusion pressure, and the rate of infusion.

Determination of the safe range of graft size mismatch using body surface area index in deceased liver transplantation.

In live donor liver transplantation, rigorous standardized criteria for matching of liver volume between donor and recipient have prevented graft loss because of size mismatch. In deceased whole liver transplantation, the safe donor-recipient size mismatch range remains unknown. We developed a multivariate survival model (generalized additive model) to estimate hazard risk of body surface area index (BSAi) for 3-year graft survival using data derived from the national registry database between 2005 and 2010. BSAi was calculated by BSA of donor divided by BSA of recipient. 24 509 patients were included in the analysis. Small-for-size (SFS) grafts with BSAi less than 0.78 had a significant impact on graft dysfunction with progressive increase of hazard risk toward the lowest end and a higher incidence of primary graft nonfunction and vascular thrombosis. Large-for-size (LFS) grafts with BSAi greater than 1.24 had a significant impact on graft dysfunction with progressive increase of hazard risk toward the largest end. Our findings suggest that donor grafts with BSAi < 0.78 could be considered 'SFS' and donor grafts with BSAi > 1.24 could be considered 'LFS', with both extremes resulting in decreased graft survival. Therefore, BSAi > 0.78 and <1.24 appears to be a safe range to avoid adverse outcome associated with size mismatch.

A matter of life or limb? A review of traumatic injury patterns and anesthesia techniques for disaster relief after major earthquakes.

BACKGROUND: All modalities of anesthetic care, including conscious sedation, general, and regional anesthesia, have been used to manage earthquake survivors who require urgent surgical intervention during the acute phase of medical relief. Consequently, we felt that a review of epidemiologic data from major earthquakes in the context of urgent intraoperative management was warranted to optimize anesthesia disaster preparedness for future medical relief operations. The primary outcome measure of this study was to identify the predominant preoperative injury pattern (anatomic location and pathology) of survivors presenting for surgical care immediately after major earthquakes during the acute phase of medical relief (0-15 days after disaster). The injury pattern is of significant relevance because it closely relates to the anesthetic techniques available for patient management. We discuss our findings in the context of evidence-based strategies for anesthetic management during the acute phase of medical relief after major earthquakes and the associated obstacles of devastated medical infrastructure. METHODS: To identify reports on acute medical care in the aftermath of natural disasters, a query was conducted using MEDLINE/PubMed, Embase, CINAHL, as well as an online search engine (Google Scholar). The search terms were "disaster" and "earthquake" in combination with "injury," "trauma," "surgery," "anesthesia," and "wounds." Our investigation focused only on studies of acute traumatic injury that specified surgical intervention among survivors in the acute phase of medical relief. RESULTS: A total of 31 articles reporting on 15 major earthquakes (between 1980 and 2010) and the treatment of more than 33,410 patients met our specific inclusion criteria. The mean incidence of traumatic limb injury per major earthquake was 68.0%. The global incidence of traumatic limb injury was 54.3% (18,144/33,410 patients). The pooled estimate of the proportion of limb injuries was calculated to be 67.95%, with a 95% confidence interval of 62.32% to 73.58%. CONCLUSIONS: Based on this analysis, early disaster surgical intervention will focus on surviving patients with limb injury. All anesthetic techniques have been safely used for medical relief. While regional anesthesia may be an intuitive choice based on these findings, in the context of collapsed medical infrastructure, provider experience may dictate the available anesthetic techniques for earthquake survivors requiring urgent surgery.

Rapid assessment and safe management of severe pulmonary hypertension with milrinone during orthotopic liver transplantation.

The incidence of porto-pulmonary hypertension (PPHN) in patients with end stage liver disease is 8.5%. Evidence indicates that proceeding with orthotopic liver transplantation (OLT) in patients diagnosed with severe PPHN (mean pulmonary artery pressure [mPAP]>45 mmHg) at the time of OLT surgery is associated with high perioperative mortality. We describe a case of severe PPHN that was diagnosed by right heart catheterization at the time of surgery. We quickly determined the reversibility of PPHN with a bolus of milrinone and proceeded with OLT. Further episodes of pulmonary hypertension were successfully managed with continuous milrinone infusion and transesophageal echocardiography monitoring. Reversibility via vasodilator trial after identification of high pulmonary artery pressures (PAP) may be an important indication of the feasibility of OLT. Milrinone may be useful for the rapid identification of the reversibility of high PAP and may be an effective agent to control abrupt increases in PAP during OLT.

Surgery under extreme conditions in the aftermath of the 2010 Haiti earthquake: the importance of regional anesthesia.

The 12 January 2010 earthquake that struck Port-au-Prince, Haiti caused >200,000 deaths, thousands of injuries requiring immediate surgical interventions, and 1.5 million internally displaced survivors. The earthquake destroyed or disabled most medical facilities in the city, seriously hampering the ability to deliver immediate life- and limb-saving surgical care. A Project Medishare/University of Miami Miller School of Medicine trauma team deployed to Haiti from Miami within 24 hours of the earthquake. The team began work at a pre-existing tent facility in the United Nations (UN) compound based at the airport, where they encountered 225 critically injured patients. However, non-sterile conditions, no means to administer oxygen, the lack of surgical equipment and supplies, and no anesthetics precluded the immediate delivery of general anesthesia. Despite these limitations, resuscitative care was administered, and during the first 72 hours following the event, some amputations were performed with local anesthesia. Because of these austere conditions, an anesthesiologist, experienced and equipped to administer regional block anesthesia, was dispatched three days later to perform anesthesia for limb amputations, debridements, and wound care using single shot block anesthesia until a better equipped tent facility was established. After four weeks, the relief effort evolved into a 250-bed, multi-specialty trauma/intensive care center staffed with >200 medical, nursing, and administrative staff. Within that timeframe, the facility and its staff completed 1,000 surgeries, including spine and pediatric neurological procedures, without major complications. This experience suggests that when local emergency medical resources are completely destroyed or seriously disabled, a surgical team staffed and equipped to provide regional nerve block anesthesia and acute pain management can be dispatched rapidly to serve as a bridge to more advanced field surgical and intensive care, which takes longer to deploy and set up.

Is the immediate reversal of diastolic dysfunction of cirrhotic cardiomyopathy after liver transplantation a sign of the metabolic etiology?

Cirrhotic cardiomyopathy currently is believed to be a multifactorial entity. This communication describes a case of immediate intraoperative recovery of diastolic function following liver transplantation. This suggests that an underlying metabolic inhibition of myocardial metabolism is an important factor in the development of cardiomyopathy in end-stage liver disease. Liver Transpl 15:1417-1419, 2009. (c) 2009 AASLD.

Recommendations From the Society for the Advancement of Transplant Anesthesiology: Liver Transplant Anesthesiology Fellowship Core Competencies and Milestones.

Liver transplantation is a complex procedure performed on critically ill patients with multiple comorbidities, which requires the anesthesiologist to be facile with complex hemodynamics and physiology, vascular access procedures, and advanced monitoring. Over the past decade, there has been a continuing debate whether or not liver transplant anesthesia is a general or specialist practice. Yet, as significant data have come out in support of dedicated liver transplant anesthesia teams, there is not a guarantee of liver transplant exposure in domestic residencies. In addition, there are no standards for what competencies are required for an individual seeking fellowship training in liver transplant anesthesia. Using the Accreditation Council for Graduate Medical Education guidelines for residency training as a model, the Society for the Advancement of Transplant Anesthesia Fellowship Committee in conjunction with the Liver Transplant Anesthesia Fellowship Task Force has developed the first proposed standardized core competencies and milestones for fellowship training in liver transplant anesthesiology.

Hemodynamic and metabolic efficacy of dopamine versus norepinephrine in a brain-dead swine model.

We tested the hypothesis that hepatosplanchnic and systemic hemodynamics are improved with equi-effective doses of dopamine (DA) versus norepinephrine (NE) in a brain-dead swine model. Pigs (n = 18) were anesthetized and ventilated. Brain death was induced by epidural balloon inflation, hypoventilation, and hypoxia. After 30 minutes, mechanical ventilation was restored without anesthesia. During 60 and until 480 minutes, half received DA (10 microg/kg/minute) and half received NE (0.1 microg/kg/minute) titrated to a mean arterial pressure (MAP) > 60 mm Hg with supplemental fluid to maintain a central venous pressure > 8 mm Hg. Hemodynamics, hepatic laser Doppler blood flow, and hepatic and gastric tissue oxygenation with near-infrared spectroscopy were continuously monitored. Serial blood samples were analyzed for blood gases and electrolytes, coagulation changes, and serum chemistries. Balloon inflation caused brain death and autonomic storm, and 8 of 18 were nonsurvivors. After 30 minutes, the MAP, mixed venous O(2) saturation, and partial pressure of arterial oxygen values decreased to 37 +/- 2 mm Hg, 38 +/- 4, and 49 +/- 8 mm Hg, respectively. Serum lactate increased to 5.4 +/- 0.7 mM. Among survivors (n = 10), MAP stabilized with either pressor. Urine output was maintained (>1 mL/kg/hour), but creatinine increased >30% with respect to the baseline. Tachyphylaxis developed with NE but not with DA (P < 0.05). Cardiac index was higher with DA versus NE (P < 0.05). There were no differences in stroke volume, metabolic indices, or liver blood flow. Liver tissue O(2) was higher with DA versus NE at 8 hours (P < 0.05). Coagulation tests and liver enzymes were similar with NE versus DA (P > 0.05). In conclusion, after brain death, cardiac index and hepatic oxygenation were significantly improved with equi-effective doses of DA versus NE.

Factors associated with mortality within 24h of liver transplantation: An updated analysis of 65,308 adult liver transplant recipients between 2002 and 2013.

STUDY OBJECTIVES: Intracardiac and pulmonary thromboembolism (ICPTE), its risk factors and contribution to 24-hour mortality after adult liver transplantation for end-stage liver disease. DESIGN: Retrospective analysis of Standard Transplant Analysis and Research electronic database files. SETTING: Perioperative. PATIENTS: Electronic files of 65,308 adult liver transplant recipients between 2002 and 2013 obtained from Organ Procurement and Transplantation Network. INTERVENTIONS: Mortality cause analysis and design of a multivariable logistic regression model for predicting the risk of 24-hour mortality due to devastating ICPTE. MEASUREMENTS: Perioperative mortality, donor and recipient demographics, donor cause of death, graft ischemic times, etiologies of recipient end-stage liver disease, functional status, comorbidities, and laboratory values. MAIN RESULTS: 41,324 patients were included. 38,293 (92.6%) survived 30days after transplantation. Postoperative 24-hour mortality was 547 (1.3%) and 2484 (6.0%) within subsequent 30days. Uncontrolled hemorrhage (57 patients, 0.14%), devastating ICPTE (54 patients, 0.13%) and primary graft failure (49 patients, 0.12%) contributed the most and equally to the 24-hour mortality. For the ICPTE, recipients' prior history of pulmonary embolism, portal vein thrombosis, functional status (Karnofsky score) <20, preoperative ventilator support, diabetes mellitus and Asian ethnicity emerged as significant independent hazard factors on multivariable regression analysis. These risk factors were expressed as an index to calculate the overall hazard of a devastating ICPTE; c-statistics 0.70 (p<0.001). CONCLUSIONS: Devastating ICPTE contributes significantly to the 24-hour mortality after adult cadaveric liver transplantation. Its most significant risk factors could be expressed as an index with a good predictive accuracy. Further studies of perioperative factors with potential impact on ICPTE and related mortality and morbidity are needed.

Stable perfluorocarbon emulsions for the delivery of halogenated ether anesthetics.

BACKGROUND: Research into injectable volatile anesthetics has been ongoing for approximately 40 years, with limited success, in an attempt to address the deficiencies of inhalational anesthesia. The purpose of this work was to formulate and optimize volatile anesthetic carrier emulsions based on our prior work in perfluorocarbon emulsions. METHODS: Perfluorocarbons were screened for their volatilty and emulsion stability. Optimal anesthetic emulsions were manufactured by high pressure homogenization of a select, clinically relevant perfluorocarbon, isoflurane and a surfactant-containing aqueous phase. Longitudinal particle size, polydispersity and isoflurane content analysis was performed. Observational studies of in vivo efficacy and safety were performed in 225-300 g Lewis Rats (n = 34) with blood chemistry and post study tissue pathology analysis. RESULTS: Emulsion particle size and isolflurane content in select emulsions were stable at room temperature greater than 300 days. This stability was depedent on perfluorocarbon molecular weight and boiling point. in vivo, emulsions demonstrated a rapid onset and offset. Variability in onset metrics (loss of righting reflex, pain reflexes and time to recovery) was less than 40% amongst individual emulsion preparations (n = 9) utilized in induction trials. No adverse effects due to the intravenous administration of emulsions were observed in blood chemistry results or post-study pathological examination. CONCLUSIONS: These formulations showed stability, safety and efficacy. In addition to induction and general anesthesia, these emulsions could have utility in global health or in military applications where equipment and resources are limited.

Organ Donor Management: Part 1. Toward a Consensus to Guide Anesthesia Services During Donation After Brain Death.

Worldwide 715 482 patients have received a lifesaving organ transplant since 1988. During this time, there have been advances in donor management and in the perioperative care of the organ transplant recipient, resulting in marked improvements in long-term survival. Although the number of organs recovered has increased year after year, a greater demand has produced a critical organ shortage. The majority of organs are from deceased donors; however, some are not suitable for transplantation. Some of this loss is due to management of the donor. Improved donor care may increase the number of available organs and help close the existing gap in supply and demand. In order to address this concern, The Organ Donation and Transplantation Alliance, the Association of Organ Procurement Organizations, and the Transplant and Critical Care Committees of the American Society of Anesthesiologists have formulated evidence-based guidelines, which include a call for greater involvement and oversight by anesthesiologists and critical care specialists, as well as uniform reporting of data during organ procurement and recovery.

Society for the Advancement of Transplant Anesthesia: Liver Transplant Anesthesia Fellowship-White Paper Advocating Measurable Proficiency in Transplant Specialties Training.

The anesthesia community has openly debated if the care of transplant patients was generalist or specialist care ever since the publication of an opinion paper in 1999 recommended subspecialty training in the field of liver transplantation anesthesia. In the past decade, liver transplant anesthesia has become more complex with a sicker patient population and evolving evidence-based practices. Transplant training is currently not required for accreditation or certification in anesthesiology, and not all anesthesia residency programs are associated with transplant centers. Yet there is evidence that patient outcome is affected by the experience of the anesthesiologist with liver transplants as part of a multidisciplinary care team. Requests for a formal review of the inequities in training opportunities and requirements led the Society for the Advancement for Transplant Anesthesia (SATA) to begin the task of developing post-graduate fellowship training recommendations. In this article, members of the SATA Working Group on Transplant Anesthesia Education present their reasoning for specialized education and conclusions about which pathways can better prepare trainees to care for complex transplant patients.

Lingual Tonsil Hypertrophy: rescuing the airway with videolaryngoscopy.

Lingual tonsils are lymphatic tissues located at the base of the tongue that may hypertrophy causing difficulty and sometimes inability to ventilate or intubate during anesthesia. Routine airway assessment fails to diagnose lingual tonsil hypertrophy. There is limited experience with use of videolaryngoscopy in cases of lingual tonsil hypertrophy. We present a case of difficult airway due to unanticipated lingual tonsil hypertrophy successfully managed by atypical video laryngoscope positioning.

Detrimental graft survival of size-mismatched graft for high model for end-stage liver disease recipients in liver transplantation.

BACKGROUND: In orthotopic liver transplantation (OLT) size-mismatch may cause adverse outcomes. We previously reported on a method to predict donor-recipient size-mismatch using the body surface area index (BSAi). In this study, we hypothesized that graft survival of size-mismatch transplantation deteriorates with higher model for end-stage liver disease (MELD) score at transplantation. METHODS: We evaluated non-parametrically the association of BSAi and MELD with 1-year graft survival with a generalized additive model. For derivation, transplantations performed between 2005 and 2010 were used. The associations were then validated by comparing Kaplan-Meier estimates between patient groups stratified according to estimated risk, using transplantations from 2011-2013. RESULTS: A total of 30,870 OLT were included in the study with 16,466 in the validation group. The derivation model revealed that graft survival significantly decreased with higher or lower BSAi, and with higher MELD (P < 0.0001). Validation confirmed the correlation of observed graft survival with estimated risk categories. CONCLUSIONS: We found that there is an interactive effect between MELD score and size-mismatch. Also high MELD recipient has a narrower safety margin for size-mismatched graft. The risk calculated from our nonparametric model with MELD and BSAi well predicts outcome in liver transplantation.