Carvedilol Combined With Ivabradine Improves Left Ventricular Diastolic Dysfunction, Clinical Progression, and Survival in Cirrhosis.

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) refers to impaired cardiac diastolic relaxation and may be improved by targeted heart rate reduction (THR). The authors evaluated whether a combination of carvedilol and ivabradine, an If channel blocker that reduces heart rate without affecting blood pressure, could improve LVDD and outcomes in cirrhosis. PATIENTS AND METHODS: THR was defined as heart rate reduction to 55 to 65 beats per minute. Of 260 patients with cirrhosis, 189 (72%) with LVDD were randomized to THR [group (Gr.)A; n=94; carvedilol±ivabradine)] or standard care (Gr.B; n=95; no ß-blockers) and followed for 12 months. RESULTS: In Gr.A, THR was achieved at 4 weeks in 88 (93%) patients (responders, R): 48 (61.5%) with carvedilol alone and 40 (86.9%) of 46 patients with additional ivabradine. In Gr.A, LVDD reversed in 16 (20.5%) and improved from grade 2 to 1 in 34 (35.4%)], whereas in Gr.B, it progressed from grade 1 to 2 in 10 (10.5%) patients. At 12 months, 21 (11.1%) patients died, 6 (14%) in Gr.A and 15 (18%) in Gr.B (P=0.240), but no mortality was seen in those who had persistent THR at 1 year (n=78; P=0.000). In multivariate analysis, model for end-stage liver disease [hazard ratio (HR), 1.52; 95% confidence interval (CI), 1.22-2.75; P=0.034] and E-wave transmitral/early diastolic mitral annular velocity (HR, 1.28; 95% CI, 1.23-2.42; P=0.048) predicted 1-year mortality. Nonresponders had an increased mortality risk (HR, 1.3; 95% CI, 1.2-1.8; P=0.046) independent of age, gender, and baseline model for end-stage liver disease. Levels of norepinephrine, N terminal brain natriuretic peptide, plasma renin activity, and aldosterone were reduced (P<0.01) in responders. More patients in Gr.B developed acute kidney injury (odds ratio, 4.2; 95% CI, 2.8-10.5; P=0.027) and encephalopathy (odds ratio, 6.6; 95% CI, 1.9-9.7; P=0.040). CONCLUSIONS: Ivabradine combined with carvedilol improves LVDD, achieves THR more often and reduces risk of encephalopathy, acute kidney injury with improved survival in patients with cirrhosis.

Noninvasive estimation of intravascular volume status in cirrhosis by dynamic size and collapsibility indices of the inferior vena cava using bedside echocardiography.

BACKGROUND AND AIM: Echocardiographic assessment of the inferior vena cava diameter (IVCD) and collapsibility index (IVCCI) is a noninvasive estimate of intravascular volume status (IVS) but requires validation for cirrhosis. We evaluated IVC dynamics in cirrhosis and correlated it with conventional tools such as central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), and right atrial pressure (RAP). METHODS: A total of 673 consecutive cirrhotic patients were screened by echocardiography, and 125 patients underwent right heart catheterization with recording of hepatic venous pressure gradient (HVPG), RAP, pulmonary artery (PA) pressure, and PCWP. CVP data were available for 80 (64%) patients, and finally, 76 patients (84% male, 50% ethanol related, mean age 52.1 years, 57.8% with ascites) with complete data were enrolled. RESULTS: The mean CVP measured was 12.8 ± 4.8 mmHg, and IVCCI was 29.5 ± 10.9%. The IVCD ranged from 0.97 to 2.26 cm and from 0.76 to 1.84 cm during expiration and inspiration, respectively, with a mean of 1.8 ± 0.9 cm. The mean IVCD correlated with RAP (r = 0.633, P = 0.043) but not with HVPG (r = 0.344, P = 0.755), PCWP (r = 0.562, P = 0.072), or PA pressure (r = 0.563, P = 0.588). A negative linear correlation was observed between the CVP and the IVCCI (r = -0.827, P = 0.023) in all patients and substratified for those with (r = -0.748, P = 0.039) and without ascites (r = -0.761, P = 0.047). A positive correlation was observed between CVP and IVCDmax (r = 0.671, P = 0.037) and IVCDmin (r = 0.612, P = 0.040). CONCLUSIONS: IVCD and collapsibility index provides noninvasive IVS assessment, independent of HVPG or ascites, with the potential for calculating fluid requirements in cirrhosis.

Left Ventricular Diastolic Dysfunction is Associated with Renal Dysfunction, Poor Survival and Low Health Related Quality of Life in Cirrhosis.

BACKGROUND: The presence of left ventricular diastolic dysfunction (LVDD) in patients with cirrhosis leads to a restriction of activities and a poor health related quality of life (HRQoL), which should be taken into consideration when treating them for liver and cardiac complications. AIMS: The prevalence, complications, predictors of HRQoL and survival in cirrhotic patients with LVDD were studied. METHODS: We report a prospective cohort study of 145 consecutive cirrhotic patients with LVDD who were evaluated for cardiac functional status at enrollment and followed up for hepatic complications, cardiac events, outcome and HRQoL using the Minnesota Living With Heart Failure Questionnaire (MLHFQ) over a period of 2 years. RESULTS: In total, 145 (mean age 61 years, 59% male) patients were included. Seventeen patients died with 10.5%, 22.5% and 40% mortality rates in patients with Grades 1, 2 and 3 LVDD respectively over 24 months. The parameters that were significant for predicting mortality on bivariate analysis were MELD, MELDNa, hepatic venous pressure gradient, MLHFQ, and left ventricular (LV) diastolic function (e' and E/e' ratio), but only MELD, MELDNa and E/e' remained significant on multivariate analysis. The E/e' ratio (8.7 ± 3.3 in survivors vs. 9.1 ± 2.3 in non-survivors) predicted outcome. On univariate analysis, the predictors of poor HRQoL were the Child-Pugh score ≥9.8 (OR 2.6; 95% confidence intervals (CI) 2.3-9.1, P = 0.041), MELD score ≥ 15.7 (OR 2.48; 95% CI 1.4-3.9, P = 0.029), refractory ascites (OR 1.9; 95% CI 1.1-6.1, P = 0.050), and E/e' ratio ≥7.6 (OR 1.9; 95% CI 1.8-7.1, P = 0.036) The presence of Class II/III (P = 0.046) symptoms of heart failure and MLHFQ≥ 45 (P = 0.042) were predictors of mortality at 24 months. CONCLUSION: The grade of LVDD correlates with liver function, clinical events, risk of renal dysfunction and HRQoL. Evaluation of novel therapies which target symptomatic improvement in LVDD, should be done with suitable outcome measures, including HRQoL assessment.

Changes in cardiac output and incidence of volume overload in cirrhotics receiving 20% albumin infusion.

BACKGROUND & AIMS: Patients with cirrhosis are prone to develop volume over load, have increased capillary permeability and latent or overt cardiomyopathy. Whether albumin infusion causes volume overload in cirrhotics has not been adequately studied. METHODS: Ninety nine consecutive cirrhotic patients receiving 1gm per kg albumin infusion were evaluated for development of volume overload. Clinical, echocardiographic and haemodynamic changes were closely monitored during and after albumin infusion. RESULTS: Thirty (30.30%) patients developed volume overload. Patients with higher BMI (P=.003), lower CTP (P=.01) and MELD (P=.034) were more often associated with the development of volume overload. Though baseline diastolic dysfunction was present in 82.8% of the patients, it did not influence the development of volume overload or changes in the cardiac output. The cardiac output increased significantly after albumin infusion (4.9±1.554 L/min to 5.86±1.85 L/min, P<.001) irrespective of the development of volume overload, or the presence of diastolic dysfunction or the Child's status. CONCLUSION: Nearly, one-third of cirrhotics receiving standard albumin infusion develop volume overload, specially, those with higher BMI and lower severity of liver disease. Cardiac output increases after albumin infusion, and, baseline diastolic dysfunction has little effect on the development of volume overload or changes in cardiac output.

An unusual solution after bilateral lower extremity amputation.

The authors present a case of a 40-year-old male with devastating amputation trauma of both lower extremities. Reconstruction of the right lower extremity was solved by the unusual use of inserted vascularized bone-skin graft from the left crus with a simultaneous replantation of the right foot. The result after 3.5 years is preservation of one extremity with full knee mobility. The other lower extremity was fitted for thigh prosthesis.

[Primary adenocarcinoma of the appendix]. / Primární adenokarcinom apendixu.

The authors published experience with the treatment of four patients with primary adenocarcinoma of the appendix and an analysis of 20 patients with primary adenocarcinoma of the appendix treated in the North Moravia region during a ten-year period (1980-1989). The incidence of the disease is rare. Usually it is manifested by symptoms imitating acute appendicitis. In exceptional instances there are other symptoms such as melaena, invagination, infiltration of neighbouring organs etc. Only rarely the disease is diagnosed during appendectomy. Most frequently an adenocarcinoma of the colonic type is involved with a tendency of rapid local spread. In that case right-sided hemicolectomy is the method of choice. In exceptional instances simple appendectomy is sufficient (mucinous type of adenocarcinoma, Dukes A). In advanced stages of the disease a palliative surgical operation may frequently suffice. Radiotherapy and chemotherapy should be always considered with regard to the stage of the disease and the general state of the patient. The prognosis is similar as in adenocarcinoma of the colon.

Investigation of protein metabolism with respect to amino acid administration.

A comparative study of the protein metabolism of two groups of patients having suffered major trauma (group I, n = 26, and group II, n = 16) and of two groups having undergone major surgery (group III, n = 10, and group IV, n = 9) was performed from the 2nd to the 11th day of treatment. All of the patients received approximately 35 kcal/kg body weight/day. In addition the patients in groups I and III received a 10% amino acid solution containing 0.24 g N/kg body weight/day whereas groups II and IV were administered a 5% solution containing only essential and semiessential amino acids amounting to 0, 12 g N/kg body weight/day. The 24-hr nitrogen output in urine, the serum free amino acid concentration as well as the serum protein fractions of transferrin and the C3c and C4 complements were contrasted. Significant differences between traumatised patients and those having had major surgery with respect to nitrogen balance and serum free amino acid concentrations were observed regardless of the pattern of nutrition. However, only slight differences in the concentrations of serum protein fractions of the two groups of patients were noted. Following amino acid solution the polytraumatized patients exhibited an average N balance of -11.9 g N/day, which is indicative of a severely catabolic metabolism. The average nitrogen loss observed in the postsurgical patients amounted to only half this amount. Following administration of the semiessential amino acid solution an appreciable difference in the nitrogen balance between comparable groups was not observed. However, the blood urea nitrogen was lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in essential fatty acids in plasma lipid fractions of traumatized patients.

Changes in the fatty acid pattern of plasma lipid in four different groups of polytraumatized patients were investigated. All of the patients received amino acid solutions containing 0.24 gN/day/kg body weight and 30 kal/day/kg body weight (BW). In group 1, all calories were administered as carbohydrates (glucose and fructose). In group 2, 30 to 40% of the calories were provided as a fat emulsion. When compared to the control group, a reduction in the essential fatty acid concentration in the phospholipid fraction was detected in both groups during the early post-traumatic period. In group 1, a continuous decline was observed during the remainder of the trial period. In group 2, however, the concentration of essential fatty acids remained constant after the initial decline and increased slightly from the 7th day on. In the second part of the investigation, the effect of human growth hormone (HGH) administration on the fatty acid pattern was evaluated. Group 3 and 4 received intravenous feedings identical to the patients in group 2; in group 4, however, 10 mg of HGH per day were added to the infusion. The results of this study confirm the hypothesis that supplemental infusion of a fat emulsion prevents a continuous reduction of essential fatty acids in plasma lipids. An effect of 10 mg/day of HGH on essential fatty acid concentration or composition, however, could not be observed. There were no detectable differences in the percentage of essential fatty acids between those patients receiving and those not receiving HGH.

[A retrospective study of the impressions and psychic reactions experienced by patients in a traumatological intensive care unit (author's transl)]. / Katamnestische Erhebungen über seelisch-geistige Erfahrungen während der Behandlung auf einer operativtraumatologischen Intensivstation.

30 persons who had been treated for an average of 22 days on a traumatological intensive care unit were asked to comment on their impressions and experiences. 80% of the patients had been in need of artificial respiration; but this had not unduly distressed them and they remembered it only vaguely. The major worry in 30% of the cases was awareness of their condition and the fear of permanent physical and mental disablement. 25% had greatly suffered from thirst. There was no mention that finding themselves in an intensive care ward, being dependent on a respirator or monitoring equipment or being disorientated had caused distress. None of them had seriously contemplated the possibility of his own death. The frequent visits by relatives were regarded as great comfort and help towards achieving mental equilibrium. All these critically ill persons were highly impressed by the constant and dedicated medical and nursing care they had received.

[A case of severe multiple trauma (author's transl)]. / Krankheitsverlauf eines polytraumatisierten Patienten.

A case of severe multiple trauma sustained in a road accident is reported. The aim of the report is to show the determing role played by diagnostic and surgical methods and therapeutic possibilities available in the intensive care unit (shock treatment, controlled respiration, parenteral feeding, haemodialysis) in winning the five-months' battle for the life of the patient. Early haemodyalisis as supporting therapy in respiratory failure and conservation treatment of intestinal fistulae are important. Post-traumatic pancreatitis which is a not infrequent complicating feature of severe multiple trauma may present diagnostic difficulties.

[Changes of the essential fatty acids in plasmalipid fractions of polytraumatized patients with different parenteral nutrition (author's transl)]. / Veränderungen der essentiellen Fettsäuren in Plasmalipidfraktionen polytraumatisierter Patienten bei unterschiedlicher parenteraler Ernährung.

In two groups of polytraumatized patients we investigated changes in the fatty acid pattern of plasma-lipids during the phase of total parenteral nutrition. For parenteral nutrition we gave L-amino acid solutions in a dose of 0.24 g N/kg body weight/day. In addition, we administered in the first group glucose and fructose and in the second group glucose, fructose and fat emulsions in a total dose of 30 kcal/kg body weight/day. In the latter group, the proportion of the fat emulsions was 30-40% of the administered calories. We compared the achieved results with the values of a group of control persons. The most essential findings of these studies were the striking decrease of the essential fatty acids with regard to the phospholipid fraction in the early post-traumatic phase. In the first group we observed a further reduction of essential fatty acids during the period of observation. This could be avoided by administering fat emulsions of the same type as we gave in the case of the second group of patients. The functions of essential fatty acids in membranes and in intermediary metabolism are discussed.

Transthoracic electrical impendance in anaesthesia and intensive care.

Pulmonary fluid accumulation plays an important role in the development of post-traumatic pulmonary insufficiency. Yet initially diagnosis may be difficult. The measurement of transthoracic electrical impedance was used to detect early pulmonary fluid overload. In healthy test persons infusions of isotonic electrolyte solutions and diuresis were accompanied by changes of impedance dependent on the amount of infused or withdrawn fluid. In patients with pulmonary insufficiency a relatively low mean body impedance was recorded. Enforced diuresis resulted in a rise and in diminution of the alveolar-arterial oxygen difference.

Changes in essential fatty acids in plasma lipid fractions of polytraumatized patients with different parenteral nutrition.

We investigated changes in the fatty acid pattern of plasma lipids during the phase of total parenteral nutrition in two groups of polytraumatized patients. For parenteral nutrition we gave L-amino acid solutions in a dose of 0.24 g N day-1kg-1 body weight. In addition, we administered in the first group glucose and fructose, and in the second group glucose, fructose and fat emulsions in a total dose of 30 kcal day-1kg-1 body weight. In the latter group, the proportion of the fat emulsions was 30-40% of the calories administered. The most striking findings were the decrease of the essential fatty acids with regard to the phospholipid fraction from about 60% to 30% in the early post-traumatic phase. In the first group of patients we observed a further reduction of the essential fatty acids in the period of observation. This could be avoided by administering fat emulsions of the same type as we gave in the second group of patients. The functions of essential fatty acids in membranes and in the intermediary metabolism are discussed.

[Acute respiratory distress syndrome after near-drowning (author's transl)]. / Entstehung und Verlauf einer schweren respiratorischen Insuffizienz nach Ertrinkungsunfall.

After successful rescue from drowning there may develop a situation which is called secondary drowning, resulting in acute respiratory distress characterized by interstitial pulmonary oedema, hypoxaemia, hypercapnia and acidosis during drowning, direct alteration of the alveolar membrane by aspirated water and particulate matters and a volume overloading by adsorption and--not seldom--inept therapy. This situation requires mechanical ventilation and forced diuresis, combined with high doses of steroids, antibiotics and digitalis. We present the case of an eleven year old patient whose clinical course demonstrate the necessity of exact clinical observation after rescue from drowning. After development of acute respiratory distress only the immediate utilization of the therapeutic modalities of an intensive care may result in a satisfactory outcome. Four months later our patient had normal pulmonary function except for a moderate reduction of compliance.