Relationship Between Intraoperative Hypotension and Acute Kidney Injury After Living Donor Liver Transplantation: A Retrospective Analysis.

OBJECTIVE: Acute kidney injury (AKI) is common after liver transplantation (LT) and has a significant impact on outcomes. Although several risk factors for post-LT AKI have been identified, the effect of intraoperative hemodynamic status on post-LT AKI remains unknown. Therefore, the authors aimed to investigate the relationship between hemodynamic parameters during LT and postoperative AKI. DESIGN: A retrospective observational study. SETTING: University hospital. PARTICIPANTS: Patients who underwent living donor LT (n = 231). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Severe AKI (stages 2-3 according to recent guidelines) was the primary outcome. Multivariable logistic regression analysis was used to control for confounding variables to obtain the independent relationship between intraoperative hemodynamic parameters (mean arterial pressure [MAP] and cardiac index) and severe AKI. The prevalence of severe AKI was 30.7%. Nadir MAP during the surgery was independently predictive of severe AKI (adjusted odds ratio, 2.11 [95% confidence interval, 1.32-3.47] per 10-mmHg decrease; p = 0.002). Subgroup analyses based on various patient or operative variables and extensive sensitivity analyses showed substantially similar results. Severe hypotension (MAP<40 mmHg), even for fewer than 10 minutes, was related significantly to severe AKI (adjusted odds ratio, 3.80 [95% confidence interval, 1.17-12.30]; p = 0.026). In contrast, nadir cardiac index was not related significantly to severe AKI. CONCLUSIONS: The authors found an independent relationship between degree of intraoperative hypotension and risk of severe AKI in living donor LT recipients. Severe hypotension, even for a short duration, was related significantly to severe AKI.

Effect of arginine vasopressin on systemic and pulmonary arterial pressure in a patient with pulmonary hypertension secondary to pulmonary emphysema: a case report.

Although data from several studies support the use of arginine vasopressin (AVP) for the treatment of hypotension concomitant with pulmonary hypertension (PH) in the cardiac surgery setting, to our knowledge, no previous studies have reported the effect of AVP on the systemic and pulmonary circulation of patients with PH secondary to lung diseases. In this report, we present the hemodynamic responses to bolus administrations of AVP and noradrenaline in a patient with PH secondary to pulmonary emphysema. The patient showed low systemic vascular resistance hypotension during off-pump single-lung transplantation. The bolus administration of AVP (0.5 U) increased systemic arterial pressure by 35.2%, with a minimal change in pulmonary arterial pressure, resulting in a significant decrease in the pulmonary arterial pressure/systemic arterial pressure ratio. In contrast, the bolus administration of noradrenaline (10 or 20 µg) increased both systemic and pulmonary arterial pressures by 14.8 and 6.7%, respectively. In summary, the bolus administration of AVP effectively increased systemic arterial pressure with a minimal effect on pulmonary arterial pressure in a patient with PH secondary to pulmonary emphysema. This case highlights the potential utility of AVP to treat low systemic vascular resistance hypotension in patients with PH secondary to lung diseases.

[Difficult Ventilation Requiring Emergency Endotracheal Intubation during Awake Craniotomy Managed by Laryngeal Mask Airway].

We report a case of difficult ventilation requiring emergency endotracheal intubation during awake craniotomy managed by laryngeal mask airway (LMA). A 45-year-old woman was scheduled to receive awake craniotomy for brain tumor in the frontal lobe. After anesthetic induction, airway was secured using ProSeal LMA and patient was mechanically ventilated in pressure-control mode. Patient's head was fixed with head-pins at anteflex position, and the operation started. About one hour after the start of the operation, tidal volume suddenly decreased. We immediately started manual ventilation, but the airway resistance was extremely high and we could not adequately ventilate the patient. We administered muscle relaxant for suspected laryngospasm, but ventilatory status did not improve; so we decided to conduct emergency endotracheal intubation. We tried to intubate using Airwayscope or LMA-Fastrach, but they were not effective in our case. Finally trachea was intubated using transnasal fiberoptic bronchoscopy. We discuss airway management during awake craniotomy, focusing on emergency endotracheal intubation during surgery.

Living-donor liver transplantation for congenital biliary atresia with porto-pulmonary hypertension and moderate or severe pulmonary arterial hypertension: Kyoto University experience.

Porto-pulmonary hypertension with moderate or severe pulmonary arterial hypertension (PAH) is viewed as a contraindication to liver transplantation (LT) because of associated poor outcomes; however, patients with biliary atresia (BA) are generally good candidates for LT. Ten patients with moderate/severe PAH underwent living-donor liver transplantation (LDLT) at our institution; eight of these patients had BA and were the focus of this study. Preoperative therapies, including prostaglandin (PG)I2 , were introduced. When mean pulmonary arterial pressure (mPAP) after treatment was <40 mmHg or initial mPAP without therapy was <35 mmHg, we performed an acute volume challenge test to evaluate right ventricular function. LDLT was performed when mPAP after anesthetic induction was confirmed at ≤35 mmHg. Six patients had favorable responses to preoperative treatment and catheter testing, but two patients showed poor responses. The two patients with poor responses had poor clinical courses with unstable mPAP after LDLT. The other six patients had successful courses with well-controlled mPAP, and PGI2 was withdrawn or weaned following LDLT. Survival did not significantly differ between the eight BA recipients with moderate/severe PAH and 77 age-matched BA recipients without PAH from the same time period. LDLT has major benefits for BA patients with well-controlled PAH.

How do transplant surgeons accomplish optimal portal venous flow during living-donor liver transplantation? Noninvasive measurement of indocyanine green elimination rate.

BACKGROUND: Balancing donor safety and graft volume is difficult. We previously reported that intentional modulation of portal venous pressure (PVP) during living-donor liver transplantation (LDLT) is crucial to overcoming problems with small-for-size grafts; however, detailed studies of portal venous flow (PVF) and a reliable parameter are still required. PATIENTS AND METHODS: The elimination rate (k) of indocyanine green (ICG) was measured in 49 adult LDLT recipients. PVP was controlled during LDLT, with a target of <20 mm Hg. ICG reflects hepatocyte volume and effective PVF. The kICG value is divided by the graft weight to calculate PVF. Recipients were divided into 2 groups: those with severe and/or fatal complications within 1 month after LDLT and those without. RESULTS: Survival rates and postoperative profiles were significantly different between the 2 groups. Univariate analysis showed significant differences in ABO blood group, final PVP, final kICG, and the final kICG/graft weight value; however, multivariate analysis showed that only the kICG/graft weight value was significant. The cutoff level for the final kICG/graft weight value for predicting successful LDLT was 3.1175 × 10(-4)/g. CONCLUSION: Accurate evaluation and monitoring of optimal PVF during LDLT should overcome the use of small-for-size grafts and improve donor safety and recipient outcomes.

A malignant hyperthermialike episode in a liver transplant recipient.

We report a case of malignant hyperthermialike syndrome in a living-donor liver transplant recipient with no familial history of malignant hyperthermia or exposure to known triggering drugs. The patient showed many features of a typical malignant hyperthermia episode, and The Clinical Grading Scale defined this case as almost certain to be an episode of malignant hyperthermia (rank 5). However, the diagnosis was questionable. The intraoperative and perioperative periods during liver transplant can involve drastic alterations of physiological parameters, which can make malignant hyperthermia difficult to diagnosis. The data we obtained using a pulmonary artery catheter suggest an intraoperative increase in systemic oxygen consumption.

How transplant surgeons can overcome the inevitable insufficiency of allograft size during adult living-donor liver transplantation: strategy for donor safety with a smaller-size graft and excellent recipient results.

Small-for-size grafts are an issue in liver transplantation. Portal venous pressure (PVP) was monitored and intentionally controlled during living-donor liver transplantation (LDLT) in 155 adult recipients. The indocyanine green elimination rate (kICG) was simultaneously measured in 16 recipients and divided by the graft weight (g) to reflect portal venous flow (PVF). The target PVP was <20 mmHg. Patients were divided by the final PVP (mmHg): Group A, PVP < 12; Group B, 12 ≤ PVP < 15; Group C, 15 ≤ PVP < 20; and Group D, PVP ≥ 20. With intentional PVP control, we performed splenectomy and collateral ligation in 80 cases, splenectomy in 39 cases, and splenectomy, collateral ligation, and additional creation in five cases. Thirty-one cases received no modulation. Groups A and B showed good LDLT results, while Groups C and D did not. Final PVP was the most important factor for the LDLT results, and the PVP cutoffs for good outcomes and clinical courses were both 15.5 mmHg. The respective kICG/graft weight cutoffs were 3.5580 × 10(-4) /g and 4.0015 × 10(-4) /g. Intentional PVP modulation at <15 mmHg is a sure surgical strategy for small-for-size grafts, to establish greater donor safety with good LDLT results. The kICG/graft weight value may have potential as a parameter for optimal PVF and a predictor for LDLT results.

Use of noninvasive ventilation for pediatric patients after liver transplantation: decrease in the need for reintubation.

Noninvasive ventilation (NIV) refers to ventilation delivered through a noninvasive interface (a nasal or face mask) rather than an invasive interface (an endotracheal tube or tracheostomy). The role of NIV in preventing reintubation after abdominal surgery in pediatric patients is uncertain. Therefore, we evaluated the role of NIV for this purpose in pediatric patients after liver transplantation. We successfully started using NIV for respiratory complications (RCs) in pediatric patients undergoing liver transplantation in 1999. For this report, we screened all medical records of patients under the age of 12 years who underwent liver transplantation between 2001 and 2009, and we retrieved data for cases at high risk of extubation failure. We retrospectively compared the clinical outcomes of patients who received NIV during their intensive care unit (ICU) stay and patients who did not. Data for 94 cases (92 patients) were included in this analysis. NIV was used in 47 patients during their ICU stay. The rate of reintubation for RCs was significantly lower in NIV patients versus non-NIV patients [3/47 (6.4%) versus 11/47 (23.4%), P = 0.02]. Furthermore, the discharge rate from the ICU was significantly better for NIV patients versus non-NIV patients. The use of NIV after extubation prevented the worsening of atelectasis and stabilized respiratory conditions in this cohort. No major changes in operative procedures or other treatments during the examined period were found. In conclusion, NIV is acceptable and promising for the respiratory management of pediatric patients undergoing liver transplantation. Its use may stabilize respiratory conditions and decrease the need for reintubation in pediatric liver transplant patients, and it may also facilitate an early ICU discharge.

Living-donor liver transplantation for moderate or severe porto-pulmonary hypertension accompanied by pulmonary arterial hypertension: a single-centre experience over 2 decades in Japan.

BACKGROUND: Candidates for orthotopic liver transplantation (OLT) often have porto-pulmonary hypertension (PPHTN) with pulmonary arterial hypertension (PAH). Poor outcomes of PPHTN contraindicate OLT. There are no guidelines for living-donor liver transplantation (LDLT) in PPHTN patients. METHODS: We present our experiences of LDLT in six patients with moderate or severe PPHTN, along with our institutional guidelines. Three had liver cirrhosis and three were non-cirrhotic. Catheterization studies were undertaken before, during and after LDLT, and the mean pulmonary arterial pressure (mPAP), cardiac output (CO), pulmonary vascular resistance and total peripheral resistance (TPR) were monitored. RESULTS: The results showed significant differences in CO and TPR between cirrhotic and non-cirrhotic patients before, during and after LDLT. Cirrhotic patients showed systemic hyperdynamic state. Two cirrhotic patients showed poor responses to pre-transplant treatment, and continued to have increased PAH and poor clinical courses after LDLT. LDLT has an advantage of flexible timing of LT. Currently in our institution, PPHTN patients with mPAP <40 mmHg are registered for LDLT after treatment and catheterization. However, LDLT is performed when mPAP is ≤35 mmHg, leading to improved outcomes. CONCLUSION: PPHTN patients with well-controlled PAH, or secondary PAH resulting from porto-systemic shunts, may be appropriate candidates for LDLT after careful considerations.

Thrombotic microangiopathy-like disorder after living-donor liver transplantation: a single-center experience in Japan.

AIM: To investigate thrombotic microangiopathy (TMA) in liver transplantion, because TMA is an infrequent but life-threatening complication in the transplantation field. METHODS: A total of 206 patients who underwent living-donor liver transplantation (LDLT) were evaluated, and the TMA-like disorder (TMALD) occurred in seven recipients. RESULTS: These TMALD recipients showed poor outcomes in comparison with other 199 recipients. Although two TMALD recipients successfully recovered, the other five recipients finally died despite intensive treatments including repeated plasma exchange (PE) and re-transplantation. Histopathological analysis of liver biopsies after LDLT revealed obvious differences according to the outcomes. Qualitative analysis of antibodies against a disintegrin-like domain and metalloproteinase with thrombospondin type 1 motifs (ADAMTS-13) were negative in all patients. The fragmentation of red cells, the microhemorrhagic macules and the platelet counts were early markers for the suspicion of TMALD after LDLT. Although the absolute values of von Willebrand factor (vWF) and ADAMTS-13 did not necessarily reflect TMALD, the vWF/ADAMTS-13 ratio had a clear diagnostic value in all cases. The establishment of adequate treatments for TMALD, such as PE for ADAMTS-13 replenishment or treatments against inhibitory antibodies, must be decided according to each case. CONCLUSION: The optimal induction of adequate therapies based on early recognition of TMALD by the reliable markers may confer a large advantage for TMALD after LDLT.

Ectopic ACTH syndrome revealed as severe hypokalemia and persistent hypertension during the perioperative period: a case report.

Both severe hypokalemia and persistent hypertension are clinical symptoms of hyperaldosteronism. Hyperaldosteronism may occur as a primary or secondary syndrome. Excess ACTH produced ectopically by tumors may induce hyperaldosteronism through the mineralocorticoid activity of glucocorticoids that are upregulated by ACTH. Licorice, with the active ingredient glycyrrhiza, is also a well-known inducer of hyperaldosteronism under specific conditions. In this report, we describe a case of severe hypokalemia caused by ectopic ACTH syndrome (EAS) elicited by an intrathoracic carcinoid tumor, which had transformed to produce ACTH during the 6-year clinical course, and was modulated by licorice ingestion. Hypokalemia was not clearly recognized preoperatively but became obvious within 3 h of general anesthesia with epidural blockade. At the end of anesthesia, arterial blood gas analysis indicated severe hypokalemia ([K(+)] = 1.7 mEq/l) and metabolic alkalosis (pH 7.56, PaCO(2) = 54.9 mmHg, HCO(3)(-) = 44.5 mmol/l, BE = 21.8 mmol/l), without any typical symptoms such as muscle weakness or ECG abnormalities. The hypokalemia was resistant to potassium supplementation and persisted for 4 days. Perioperative imbalance between the administration and elimination of potassium and surgical stress might contribute to the rapid exacerbation and induce the clinical manifestation of EAS.

Necrotizing fasciitis caused by Haemophilus influenzae type b in an elderly patient.

Necrotizing fasciitis caused by Haemophilus influenzae type b is a rare infection of the skin and soft tissues. The only previously reported case involved a healthy infant. We report herein the case of an 81-year-old Japanese woman with diabetes mellitus who developed necrotizing fasciitis caused by H. influenzae type b.

Effects of injectable propofol emulsion on singlet oxygen released from activated human neutrophils and that chemically generated.

Effects of an injectable emulsion of propofol and its emulsifier on singlet oxygen (1O2) were examined. 1O2 released from activated human neutrophils was detected by chemiluminescence, and chemically generated 1O2 was detected by electron paramagnetic resonance (EPR). Both the propofol emulsion and the emulsifier suppressed 1O2 release from neutrophils. However, the emulsifier did not quench chemically generated 1O2, while the propofol emulsion quenched it. These results indicated that the emulsifier did not scavenge 1O2 released from neutrophils but inhibited 1O2 generation. The suppressive effects of propofol emulsion on 1O2 release from neutrophils consist of 1O2 scavenging and inhibition of 1O2 generation.

Omission of fentanyl during sevoflurane anesthesia decreases the incidences of postoperative nausea and vomiting and accelerates postanesthesia recovery in major breast cancer surgery.

PURPOSE: Our purpose was to investigate the effect of omission of fentanyl during sevoflurane anesthesia on the incidences of postoperative nausea and vomiting and on postanesthesia recovery in female patients undergoing major breast cancer surgery. METHODS: Female patients (American Society of Anesthesiologists [ASA] physical status [PS] class I-II; age, 28-84 years) undergoing major breast cancer surgery were randomized to one of two anesthesia maintenance groups: sevoflurane-fentanyl anesthesia (SF; n = 25) or fentanyl-free sevoflurane anesthesia (S; n = 26). All patients were administered with propofol 2 mg x kg(-1) intravenously for anesthesia induction, a laryngeal mask airway was placed, and they received rectal diclofenac and local infiltration anesthesia. Anesthesia was maintained with sevoflurane in oxygen-air and they breathed spontaneously. The patients in group SF received fentanyl 0.1 mg intravenously and those in group S received normal saline during anesthesia. RESULTS: Group SF revealed higher incidences of postoperative nausea (68% vs 27%) and vomiting (32% vs 8%) in the first 24 postoperative hours than group S. The median (25th-75th percentile) length of time from postanesthesia care unit (PACU) admission to ambulation was significantly longer in group SF (n = 23) at 195 min (158-219 min), than in group S, at 141 min (101-175 min). Two patients in group SF could not walk during the PACU stay. CONCLUSION: Omission of fentanyl during sevoflurane anesthesia, combined with diclofenac and local infiltration anesthesia, decreases the incidences of postoperative nausea and vomiting and accelerates postanesthesia recovery in patients undergoing major breast cancer surgery.

The role of CRF1 receptors for sympathetic nervous response to laparotomy in anesthetized rats.

Corticotropin-releasing factor (CRF) is released in response to various types of stressors and mediates endocrine, autonomic, immune, and behavioral responses to stress through interaction with CRF1 and CRF2 receptors. To investigate the role of CRF1 receptors in physiological responses to surgical stress, we analyzed the effects of two different non-peptide selective CRF1 receptor antagonists (JTC-017 and CP-154,526) and a peptide non-selective CRF receptor antagonist (astressin) on laparotomy-induced sympathetic nervous responses in isoflurane-anesthetized rats. JTC-017, CP-154,526, and astressin similarly suppressed plasma ACTH elevation induced by laparotomy. JTC-017 and CP-154,526 significantly augmented plasma noradrenaline and adrenaline responses to laparotomy, while astressin showed no effect on these responses. Laparotomy-induced maximum increases in mean blood pressure and heart rate were augmented by JTC-017, but were not affected by astressin. The results suggested for the first time that there was a pathway to attenuate sympathetic nervous response to surgical stress through CRF1 receptors in the central nervous system.

[Perioperative management of living-donor liver transplantation in two patients with severe portopulmonary hypertension].

Liver transplantation for patients with severe portopulmonary hypertension (PPHTN) has been associated with high mortality. We conducted perioperative management of two patients with severe PPHTN for living-donor liver transplantation. The first case was a 17-year-old male with biliary atresia. He developed dyspnea at the age of 14, for which he was treated with intravenous epoprostenol for 8 months. As a result, the mean pulmonary artery pressure (MPAP) was reduced from 61 to 40 mmHg. Intraoperatively, he was treated with intravenous epoprostenol and nitric oxide (NO) inhalation. His intraoperative course was uneventful but he died from right heart failure on postoperative day (POD) 11. The second case was a 6-year-old girl with biliary atresia. When she was 5 years old, examination for a persistent cough revealed MPAP of 49 mmHg. Neither intravenous epoprostenol nor NO inhalation was effective, and she twice showed transient pulmonary hypertension during the operation. She was extubated 14 hours after the surgery, transferred out of ICU on POD 3 and discharged from the hospital on POD 99. When we compare the two cases, the factors responsible for the success of the management of the second case appear to be early extubation and the short duration of PPHTN.

Potentiation of proopiomelanocortin gene expression in cultured pituitary cells by benzodiazepines.

BACKGROUND: Benzodiazepines are frequently used not only as a part of general anesthesia but also for the purpose of sedation during regional anesthesia. Effects of these drugs on the hypothalamic-pituitary-adrenal axis activity have been studied, but are still controversial. It is not known whether benzodiazepines affect expression of proopiomelanocortin, precursor protein of adrenocorticotropic hormone and related peptides. METHODS: AtT20PL cell line, a clone of AtT20/D16v mouse corticotroph tumor cells stably transfected with approximately 0.7 kilobases (kb) of the rat proopiomelanocortin 5' promoter-luciferase fusion gene, was used. In the presence or absence of diazepam or midazolam, cells were stimulated by corticotropin-releasing hormone (CRH) or forskolin. Proopiomelanocortin gene expression was estimated by measurement of luciferase activity. Furthermore, to study the mechanism of benzodiazepine effects, cyclic adenosine 3',5'-monophosphate (cyclic AMP) efflux was measured by enzyme immunoassay. RESULTS: Diazepam and midazolam dose-dependently increased the proopiomelanocortin gene expression induced by CRH or forskolin. The potentiating effect was not affected by benzodiazepine receptor antagonists flumazenil and PK11195, but was abolished by a cyclic AMP-dependent protein kinase inhibitor H89. Cyclic AMP efflux induced by CRH or forskolin was also enhanced by diazepam and midazolam. In the presence of isobutylmethylxanthine, a nonspecific phosphodiesterase inhibitor, potentiation of proopiomelanocortin gene expression and enhancement of cyclic AMP efflux by benzodiazepines were not observed. CONCLUSIONS: Benzodiazepines potentiate the effect of CRH or forskolin on proopiomelanocortin gene expression. The potentiating effect is not mediated by the benzodiazepine receptors, but its mechanism probably involves inhibition of phosphodiesterase.

[Anesthesia for living-donor liver transplantation in a patient with adult polycystic liver disease].

Anesthesia for living-donor liver transplantation (LDLT) was performed for two patients with adult polycystic liver disease (APLD). APLD is characterized by gradual cystic transformation of both lobes of the liver. Abdominal enlargement, poor appetite, abdominal pain, infection of liver cysts and portal hypertension are symptoms of this disease. Liver transplantation is indicated as the final therapy. Our two patients had very large livers (7400 g and 9500 g). The second patient had suffered renal failure due to a polycystic kidney so that continuous hemodiafiltration had to be performed after surgery. In both cases, sudden hypotension frequently occurred during manipulation of the enlarged liver. In the first case, sudden massive bleeding occurred as a result of laceration of the middle and left hepatic vein when the liver was dropped from the surgeon's hand. In both cases, the position of endotracheal tube became 2 cm shallower after surgery probably because of the shift in the position of the mediastinum after elimination of abdominal compression caused by the enlarged liver. One patient was discharged 39 days and the other 115 days after surgery. Anesthesiologists should pay special attention to the features reported here during LDLT for patients with APLD.