E. Mazza

Hepatocellular carcinoma: comparison between liver transplantation, resective surgery, ethanol injection, and chemoembolization

Abstract Between January 1989 and June 1997, 533 patients (423 male, 110 female, mean age 61 years, range 22–89 years) with hepatocellular carcinoma (HCC) were observed at our center. We report on 419 patients retrospectively compared for different treatments: liver transplantation (LT; 55 patients), resective surgery (RS; 41 patients), transarterial chemoembolization (TACE; 171 patients) and percutaneous ethanol injection (PEI; 152 patients). The 3‐ and 5‐year actuarial survival rates were, respectively, 72% and 68% for LT, 64 and 44% for RS, 54 and 36% for PEI, and 32 and 22% for TACE. Survival curves were compared for sex, age, tumor characteristics, alphafetoprotein level, Child class, and etiology of cirrhosis. All patient‐related characteristics examined (sex, age) are not significantly related to patient survival. Tumor‐related variables and associated liver disease variables significantly conditioned survival in relation to different treatments. LT seems to be the treatment of choice for monofocal HCC less then 5 cm in diameter and in selected cases of plurifocal HCC.

Lactate blood levels in the perioperative period of orthotopic liver transplantation

To investigate whether early postoperative changes in blood lactate concentration indicate the functional recovery of the newly grafted liver, changes in oxygen supply, oxygen consumption, acid-base equilibrium, and blood lactate concentrations were prospectively studied in a group of 53 postnecrotic cirrhotic patients during the various phases of orthotopic liver transplantation (preanhepatic, anhepatic, neohepatic) and for the first 48 h following reperfusion. The patients were divided into two groups according to the quality of the early graft function, as indicated by alanine aminotransferase, bile flow, and prothrombin activity: group A (49 patients), good immediate graft function and group B (4 patients), immediate graft non-function. Lactate levels rose in the same manner during the preanhepatic and anhepatic stages and peaked after revascularization of the graft. Following reperfusion, however, distinctly different blood lactate profiles were recorded in the two groups of patients. A fall in lactate concentration was recorded in group A patients, whereas a continuous rise occurred in group B patients: the difference becoming significant by the end of surgery (P<-0.05). During the first 48 h following revascularization of the graft, opposite trends in lactate concentration, bile flow, alanine aminotransferase, and prothrombin activity were evident in the two groups of patients: 24 h after reperfusion, lactate levels were below 2 mmol/1 in 47 of 49 patients from group A, while they plateaued above 4 mmol/1 in all patients from group B. Group A patients had lower alanine aminotransferase levels (P<-0.001), higher prothrombin activity, (P<-0.01), and greater bile flow (P<-0.02). If validated in larger series, the blood lactate profile, probably more than the absolute level, appears to be a useful indicator of the early recovery of liver metabolic capacities in the immediate postoperative period of orthotopic liver transplantation.

Indocyanine green kinetics to assess liver function: Ready for a clinical dynamic assessment in major liver surgery?

Indocyanine green (ICG) kinetics (PDR/R15) used to quantitatively assess hepatic function in the perioperative period of major resective surgery and liver transplantation have been the object of an extensive, updated and critical review. New, non invasive bedside monitors (pulse dye densitometry technology) make this opportunity widely available in clinical practice. After having reviewed basic concepts of hepatic clearance, we analysed the most common indications ICG kinetic parameters have nowadays in clinical practice, focusing in particular on the diagnostic and prognostic role of PDR and R15 in the perioperative period of major liver surgery and liver transplantation. As recently pointed out, even if of extreme interest, ICG clearance parameters have still some limitations, to be considered when using these tests.

Efficacy of Ceftazidime-avibactam Salvage Therapy in Patients with Infections Caused by KPC-producing Klebsiella pneumoniae

Background Ceftazidime-avibactam (CAZ-AVI) has been approved in Europe for the treatment of complicated intra-abdominal and urinary tract infections, as well as hospital-acquired pneumonia, and for gram-negative infections with limited treatment options. CAZ-AVI displays in vitro activity against Klebsiella pneumoniae carbapenemase (KPC) enzyme producers, but clinical trial data on its efficacy in this setting are lacking. Methods We retrospectively reviewed 138 cases of infections caused by KPC-producing K. pneumoniae (KPC-Kp) in adults who received CAZ-AVI in compassionate-use programs in Italy. Case features and outcomes were analyzed, and survival was then specifically explored in the large subcohort whose infections were bacteremic. Results The 138 patients started CAZ-AVI salvage therapy after a first-line treatment (median, 7 days) with other antimicrobials. CAZ-AVI was administered with at least 1 other active antibiotic in 109 (78.9%) cases. Thirty days after infection onset, 47 (34.1%) of the 138 patients had died. Thirty-day mortality among the 104 patients with bacteremic KPC-Kp infections was significantly lower than that of a matched cohort whose KPC-Kp bacteremia had been treated with drugs other than CAZ-AVI (36.5% vs 55.8%, P = .005). Multivariate analysis of the 208 cases of KPC-Kp bacteremia identified septic shock, neutropenia, Charlson comorbidity index ≥3, and recent mechanical ventilation as independent predictors of mortality, whereas receipt of CAZ-AVI was the sole independent predictor of survival. Conclusions CAZ-AVI appears to be a promising drug for treatment of severe KPC-Kp infections, especially those involving bacteremia.

Prospective monocentric study of non-tunnelled central venous catheter-related complications in hematological patients

Indwelling central venous catheters (CVCs) are used in the management of hematologic patients. However, insertion and maintenance of CVCs are susceptible to complications. Study design and methods data concerning 388 consecutive catheterisations, performed in oncohematologic patients between April 2003 and December 2004, were prospectively collected. At insertion thrombocytopenia was present in 109 cases (28.1%) and neutropenia in 67 (17.3%). Hemorrhage after CVC insertion occurred in five thrombocytopenic patients (1.3%). The median duration of catheterisation was 18.8 days (range 1–89), longer in the 7-French CVCs utilised in leukemic patients (24.3 days) and shorter in 12-French CVCs (11 days), used for PBSC harvesting. Deep venous thrombosis was diagnosed in 13 cases (3.3%). Ninety-two catheterisations (12.6/1000 days-catheter) were complicated by infections: 19 local infections (4.8%) and 73 (18.8%) bacteraemias of which 45 (11.6%) were catheter-related, mainly due to Gram positive germs (32/45, 71.1%). The frequency of catheter-related bacteraemia was 7.2 events/1000 days-catheter. Thirteen CVCs were removed due to thrombosis, 15 due to infections, 20 due to malfunction, the remaining 333 at patients discharge. At univariate analysis high-dose chemotherapy (p = 0.013), 7-Fr lumen (p = 0.023), acute myeloid leukemia (AML) (p = 0.001), duration of neutropenia >10 days and length of catheterisation were significantly correlated to infection. Multivariate analysis confirmed the duration of catheterisation, AML and high-dose chemotherapy as risk factors. Even though hematological in-patients are at increased risk for bleeding and infections, non-tunnelled CVCs offer a safe venous access also in patients affected by severe thrombocytopenia and prolonged neutropenia.

Changes in circulating levels of atrial natriuretic factor (ANF) during orthotopic liver transplantation in humans.

Abstract Atrial natriuretic factor (ANF) is a 28 amino acid peptide secreted by the atrial cardiocytes. Clearance is via the lung (50%) and the liver (25%). The main stimulus to ANF secretion is atrial distension but vasoconstrictors, sympathetic stimulation, catecolamines and tachycardia are able to enhance its circulating blood levels. ANF blood concentrations were measured during orthotopic liver transplantation in six postnecrotic cirrhotic patients. Significant increases in ANF blood levels occurred at the end of the anhepatic phase (P≤ 0.02 vs baseline) associated with low cardiac filling pressures (P≤ 0.02 vs baseline) and increased systemic vascular resistances (P≤ 0.02 vs preanhepatic phase). Aldosterone blood levels showed a similar behaviour, increasing significantly (P≥ 0.001 vs baseline) at the end of the anhepatic phase. ANF fell after reperfusion of the graft and returned towards baseline values at the end of the procedure. Since most of the total body clearance of ANF is performed by the lungs, its sharp increase at the end of the anhepatic phase could be considered a counterregulatory response to vasoconstricting stimulation and to fluid‐paring mechanisms in the presence of relative hypovolaemia. Its decrease after reperfusion could be related to volume normalization and partly to the enhanced clearance performed by the newly grafted liver.

Hypotension After Pancreatic Reperfusion During Combined Kidney- Pancreas Transplantation

OMBINED kidney‐pancreas transplantation (KPTx) is an accepted and ever-increasing therapeutic option for patients suffering for diabetes mellitus (DM) type I who had developed end-stage renal failure (ESRF). Two of the main goals of this surgical procedure are capable of improving significantly the quality of life of these subjects: (1) recovery of renal function; (2) euglicemic state without insulin supplementation. 1 Correction of the metabolic abnormalities could prevent (or delay) the onset of severe secondary complications. Patients considered for combined KPTx manifest most of the multisystem dysfunctions associated with both diseases; generally, they are in poor medical condition and more prone to develop perioperative complications. Arterial hypertension and preoperative cardiac dysfunction secondary to autonomic neuropathy and microvascular changes are frequent findings in these patients and could be responsible for the cardiovascular complications occurring during surgery or in the immediate postoperative period: silent coronary artery disease has been reported in 20% to 40% of the candidates and hypertensive cardiomyopathy is a frequent echocardiographic finding in individuals affected by ESRF. 2 Because preoperative cardiovascular impairment has been associated with high morbidity and mortality and decreased graft survival, perioperative hemodynamic stability has been considered essential for the early functional recovery of the grafts and for the containment of postoperative complications. 3 Recent advances in invasive hemodynamic monitoring and anesthetic techniques made it possible to preserve or improve cardiovascular homeostasis. However, studies dealing with the hemodynamic profile during KPTx are scarce. In this paper we will describe the cardiovascular changes occurring during the various phases of surgery, specifically addressing the problem of hypotension following pancreatic reperfusion. 3 PATIENTS AND METHODS Our series includes 17 patients (mean age, 32 6 17 years) admitted to combined KPTx for ESRF and severe DM type 1. Eighty percent of the patients were affected by severe hypertension; one had ejection fraction lower than 40%. Heart rate and rhythm, pulse oxymetry, right atrial (RAP), and radial artery pressures were continuously monitored in all the cases. Right heart catheterization with a modified Swan‐Ganz catheter (SG cath Intellicath, Baxter) for complete invasive hemodynamic monitoring (pulmonary capillary wedge pressure [PWP] and cardiac output [CO] for continuous monitoring) was used in eight patients. Systemic vascular resistance (SVR, dynes sec 21 /cm 25 ) was calculated according to standard formulae. Hemodynamic data reported in this paper were recorded after the induction of the anesthesia (baseline, A), 5 minutes before (pre-pancreas reperfusion, B) and 2 minutes after pancreas reperfusion (post-pancreas reperfusion, C), 2 minutes after renal reperfusion (post-kidney reperfusion, D), and at the end of surgery (end of surgery, E). Severe arterial hypotension following pancreas reperfusion was considered mean arterial pressure (MAP) less than 70 mm Hg or less than 70% of the baseline values. General anesthesia and mechanical ventilation were used in all the patients: anesthesia was induced with thiopental and maintained with fentanyl and isoflurane (0.8 to 1.2% in air/O2 mixture 50%); atracurium besylate was used for muscle relaxation. Data are presented as mean 6 SD. Statistical analysis was performed using ANOVA. A P value # .05 was considered statistically significant.

Video Laryngoscope: A Review of the Literature

Orotracheal intubation is the gold standard technique to secure the airways during general anesthesia, in the intensive care unit and in the often hostile prehospital setting. Major complications during airway management are mainly due to inability to secure or maintain the airways, because of an unexpected difficult tracheal intubation, an esophageal intubation, gastric aspiration, and/or iatrogenic trauma of the upper airways [1]. According to one of the most recent observational studies, difficult endotracheal intubation or problematic airway management may be not infrequent. Severe complications are reported to be close to 1/22,000, while death or brain damage occurs in 1:150,000 [2]; these complications are the main cause of anesthesia-related injury, possibly leading to major morbidity and mortality [3]. Large part of the perioperative adverse events associated with a problematic airway management occur to healthy individuals undergoing elective surgery under general anesthesia. Obesity and upper airway obstruction are since long-recognized risk factors for difficult airways, accounting by themselves for approximately 80 % of major complications. In “cannot ventilate and cannot intubate” situations, reiterations of attempts before changing strategy or considering alternative devices are associated with poor outcomes such as death and brain damage [2, 3]. Prediction of a difficult airway management is sometimes unreliable, being at best an inexact science, with poor sensitivity and specificity. Bedside predictors of difficulty are thyromental distance, sternomental distance, mouth opening, or a combination of tests and the laryngeal view obtained. Mallampati and more recently and perhaps more precisely El Ganzouri classifications can be used to predict difficult intubation [4]. Difficult glottic vision during intubation attempts is more frequent in emergency situations and in the critical care setting than during general anesthesia (grade III Cormack & Lehane: 13 % in emergency vs 5 % in general anesthesia; grade IV Cormack–Lehane 7 % vs 1 %, respectively) [2]. After the introduction in the early 1940s of Miller (1941) and Macintosh (1943), straight and curved laryngoscope blades to ease direct laryngoscopy, laryngoscopes (LA) remained largely unchanged for more than 50 years. With the development of rigid fiber-optic laryngoscopes – the first generation of video laryngoscopes – clinicians benefited from advances such as eyepieces that could be attached to optional video cameras. Rigid fiber-optic laryngoscopes placed the observer’s eye close to but above the glottis, allowing a controlled insertion and advancement of an endotracheal tube between the vocal cords. Flexible bronchoscopic intubation in case of intrahospital difficult airway management is today the standard method; this technique, however, requires adequate training and a routine use to be effective. In recent years the development of digital photographic and video techniques has led to video laryngoscopes (VDLs). These devices offer an improved (and shared) indirect view of the glottis on a remote or built-in video screen. A handle and a blade are the components of both LA and VDL, the latter having a fiber-optic or microvideo camera encased close to the end of the blade. The particular shape of the curve blade allows a wider viewing angle, making oral pharyngeal and tracheal axes alignment unnecessary, optical alignment being achieved by the video camera. According to Donati et al., VDLs are generally classified in three groups: (1) standard or Macintosh blade type, (2) angulated blade type, and (3) anatomically shaped with a guide channel [5]. The majority of these devices use a digital camera on the tip of a standard Macintosh or Miller laryngoscope blade providing the indirect visualization of the glottis on a video display (C-MAC, Glidescope, McGrath, Pentax Airway Scope). Less frequent is the use of fiber-optic cables connected to a display (Airtraq). Video laryngoscopes lack the versatility of flexible bronchoscopic intubation (FBI), but are more easy to use, less fragile, and provide a supraglottic vantage point. Learning curve, however, is not as short as proposed by someone.

Clinical Use of Indocyanine Green (ICG) Kinetics in Liver Anaesthesia and ICU

This chapter provides an updated and critical review of the use of indocyanine green (ICG) kinetics as a dynamic assessment of liver function using the new noninvasive bedside monitors now available in clinical practice. The analysis encompasses the most common indications ICG has today in clinical practice [1]: the diagnostic and prognostic role in the perioperative period of major liver surgery and liver transplantation [2] and the role in the critically ill patients in ICU to predict mortality and to assess the impact of intraabdominal hypertension on splanchnic perfusion.

Acute Liver Failure in Intensive Care

Acute liver failure (ALF) is a rare syndrome characterized by sudden and acute hepatic injury which can be attributed to a number of different causes although not all of them are always clearly identifiable [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13]. A severe compromise of parenchymal function is followed, at different intervals, by the onset of hepatic encephalopathy, serious haemostasis alteration and, in many cases, multiple organ failure. In the 70s the term FHF (fulminant hepatic failure) had been introduced to describe serious hepatic damage, in absence of known pre-existing hepatic disease, with subsequent onset of encephalopathy within 8 weeks. The syndrome was described as “potentially reversible” [1, 2, 12]. The definition proposed by O’Grady in 1993 and still used today recognizes that the onset of encephalopathy and of altered awareness at different degree is fundamental from a prognostic point of view [2, 12]. Elevated transaminase, hyperbilrubinemia, encephalopathy and serious coagulopathy are the main characteristics of ALF [1, 2, 3, 4, 5, 6, 7, 10]. All the identifying factors that have been proposed include the onset of encephalopathy in the course of ALF, the lack of pre-existing hepatic disease and the high incidence of spontaneous mortality (>85%). This pathology presents itself in a variety of ways and it may be a combination of different aetiologies, each producing a very different outcome. ALF is identifiable by a progressive bilirubin increase [1, 2, 3, 4, 5, 6, 7] within a time span of 7 days to 26 weeks after acute liver damage. Depending on the interval between the onset of jaundice and the clinical signs of encephalopathy, the syndrome is classified as hyper-acute (jaundice-encephalopathy interval: <7 days); acute (jaundice-encephalopathy interval: 8–28 days); sub-acute (jaundice-encephalopathy interval: 28 days–26 weeks). Bernal et al. [1] agree with this classification in the most recent review published on the subject.