Effect of L-ornithine-L-aspartate on patients with and without TIPS undergoing glutamine challenge: a double blind, placebo controlled trial

BACKGROUND AND AIM: An oral glutamine load in cirrhotic patients awaiting liver transplantation was shown to cause a rise in blood ammonia and psychometric abnormalities which were reversed by hepatic transplantation. L-Ornithine-L-aspartate (LOLA) has been shown to reduce ammonia and improve psychometric function in patients with hepatic encephalopathy. The aim of the present study was to assess the effect of LOLA in healthy patients with cirrhosis and no evidence of clinical encephalopathy after challenging the central nervous system by administration of oral glutamine. PATIENTS AND METHODS: Eight cirrhotics (Child's B or C) without transjugular intrahepatic portosystemic shunts (TIPS) and seven with TIPS underwent two oral glutamine (20 g) challenges, receiving LOLA (5 g intravenously) on one occasion and placebo on the other in random order. Psychometric tests, including choice reaction time (CRT) and number connection test, were performed before and after glutamine, together with electroencephalography and blood ammonia. RESULTS: Mean basal ammonia was 27 (SEM 5) micromol/l in non-TIPS and 76 (10) micromol/l in TIPS patients (p<0.05). Basal CRT 2 was 0.643 (0.033) s in non-TIPS and 0.825 (0.076) s in TIPS patients (p<0.02). In non-TIPS patients, ammonia increased to 36 (10) micromol/l when LOLA was administered and to 62 (13) micromol/l with placebo (p<0.02). There was no alteration in psychometric function in non-TIPS patients after glutamine when LOLA was given but when placebo was given, glutamine caused prolongation of CRT (p=0.02). Glutamine did not affect psychometric function in TIPS patients with or without LOLA. CONCLUSION: This study showed that LOLA ameliorated the deleterious psychometric effects of glutamine in Child's grade B and C patients with cirrhosis without TIPS and supports its use in clinical practice in hepatic encephalopathy.     

Survival rate and prognostic factors in patients with intestinal failure

BACKGROUND: Intestinal failure impairs nutritional status and survival expectance. Though intestinal adaptation and enteral independence may be achieved, artificial nutrition is needed in about half of the patients. AIMS: This study is aimed at assessing the causes of death, survival rate, enteral independence in time, and factors affecting the clinical outcome in a group of patients with intestinal insufficiency. PATIENTS: Sixty-eight patients with intestinal insufficiency, due to major intestinal resection in 60 cases (short bowel syndrome) (remnant intestine length 101-150 cm in 31 cases, 50-100 cm in 23 cases, <50 cm in 6 cases), and due to chronic idiopathic pseudo-obstruction in 8 cases, were enrolled and followed-up for (median) 36 months (25th and 75th percentile in 12 and 60 months, respectively). In 60 short bowel syndrome patients, the main conditions that led to intestinal failure were ischemic bowel (28), major surgery complications or severe adhesions (17), radiation enteritis (10), Chron's disease, intestinal tuberculosis, small bowel lymphoma and trauma (others). METHODS: Seventeen variables age, underlying disorders, length of remnant bowel, type of surgery, hospital stay, type of nutrition (hospital and home) and its variations in time, causes of death, survival rate and time were considered. Statistical analysis was carried out by Mann-Whitney U-test, Pearson chi2, Spearman correlation test, Kaplan-Meyer method and Cox's proportion hazards regression model. RESULTS: At the time of admission to the hospital, none of the patients had nutritional independence, 54 (79.4%) were on parenteral nutrition and 14 (20.6%) were on enteral nutrition. At the time of discharge, 23 (33.8%) patients showed enteral independence, 39 were on home parenteral nutrition, 3 on enteral nutrition + i.v. feeding, 1 on enteral nutrition, and 2 needed oral supplementation with hydroelectrolyte solutions only. After a median value of 36 months, 30 and 2 patients were on home parenteral nutrition and enteral nutrition + i.v. feeding, respectively, 2 on enteral nutrition, 2 on oral supplementation with hydroelectrolyte solutions, and 26 cases reached enteral independence. A significant relationship was detected between the length of remnant bowel and types of nutrition at both admission (r = 0.38; P = 0.001) and discharge (r = 0.48; P = 0.001), parenteral nutrition being more frequent in patients with very short bowel. Twenty-two patients (32.4%) died (4 from newly occurring malignancies), 40 (58.8%) survived, and 6 (8.8%) were lost to the follow-up. Eleven of 22 patients died from conditions related to intestinal failure (8 cases) and/or home parenteral nutrition complications (3 cases). At 12, 24, 36, 48, 60 and 72 months, survival rates were 95.4, 93.3, 88.1, 78.6, 78.6 and 65.5%, respectively, but it was significantly lower for patients with <50 cm of remnant bowel than those with longer residual intestine (P < 0.05), and in patients who started home parenteral nutrition above the age of 45 years (P < 0.02). Survival rate was higher in patients with enteral independence than those with enteral dependence (P < 0.05). Better survival rates were registered in patients with chronic obstructive intestinal pseudo-obstruction and major surgery complications, whereas ischemic bowel and even more radiation enteritis were associated with a lower survival expectance. CONCLUSIONS: Actuarial survival rate of patients with intestinal failure quotes 88 and 78% at 3 and 5 years, respectively. It is influenced by the length of remnant intestine, age at the start of home parenteral nutrition, enteral independence and, to some extent at least, by the primary disorder. Enteral independence can be achieved in time by about 40% of the patients with intestinal insufficiency, but for home parenteral nutrition-dependent cases, intravenous feeding can be stopped in less than one out of five patients during a median 3-year period.     

早期空肠内营养联合中药肠内滴注对重症急性胰腺炎患者肠麻痹的改善作用

目的:评价早期空肠内营养联合中药加味大承气颗粒肠内滴注治疗对改善重症急性胰腺炎患者肠麻痹的作用,探索重症急性胰腺炎的中西医结合治疗的新途径.方法:39例重症急性胰腺炎患者在常规治疗基础上,随机分成3组分别进行全胃肠外营养(PN组)、早期肠内营养(EN组)、肠内营养+中药大承气颗粒(EN+中药组)肠内滴注,观察患者腹痛腹胀缓解时间、胃肠道功能恢复(肠鸣音出现、肛门排气及排便)时间,并动态监测血淀粉酶、高敏C反应蛋白(CRP)、血浆肿瘤坏死因子-α(TNF-α).结果:EN组、EN+中药组患者经治疗后腹痛腹胀症状均缓解或消失,胃肠道功能恢复正常.PN组12例中,有2例腹胀、肠麻痹持续加重,其中1例出现腹腔隔室综合征并发多脏器功能衰竭.EN组、EN+中药组在腹胀(d)、腹痛缓解时间(d)以及胃肠道功能恢复时间(d)均优于PN组(4.22±0.94,3.02±0.75vs5.72±1.55;4.66±1.14,3.14±0.62vs6.81±1.81;3.42±0.82,3.21±0.88vs6.04±1.67,均P<0.05),其中EN+中药组腹胀(d)、腹痛缓解时间(d)优于EN组(3.02±0.75vs4.22...     

Luminal fermentation and colonocyte metabolism in a rat model of enteral nutrition

Large intestinal fermentation and nutrient metabolism in colonocytes were investigated in a rat model of enteral feeding. Male Wistar rats (240–280 g) were submitted to 7 or 14 days of treatment: intragastric feeding (elemental formula) versus oral feeding (isocaloric and isonitrogenous diet, containing 5% purified cellulose) in the control group. Fermentation products and bacterial populations were analyzed in cecal contents. Colonic cells were isolated and tested for their capacities to metabolize [1-¹⁴C] butyrate and [U-¹⁴C]glutamine. After 7 days of enteral nutrition, short-chain fatty acid concentrations represented 52% of those measured in the control group, but colonocyte metabolism remained unchanged. After 14 days of enteral nutrition, short-chain fatty acid concentrations were still decreasing, although bacterial counts remained unchanged. In parallel, ammonia and lactate concentrations were significantly increased. The capacities to utilize butyrate and glutamine in colonocytes were only slightly affected. However, there was a dramatic increase in the ratio of -OH-butyrate to acetoacetate fluxes, suggesting a more reduced redox mitochondrial state associated with enteral feeding.     

Hepatic intestinal uptake and release of catecholamines in alcoholic cirrhosis. Evidence of enhanced hepatic intestinal sympathetic nervous activity.

Hepatic intestinal and whole body plasma clearance and appearance of noradrenaline (NA) was quantified in patients with alcoholic cirrhosis (n = 12) and in controls (n = 6). As NA may be released as well as removed in the same vascular bed, infusion of tritium labelled NA (3H-NA) was carried out during hepatic vein catheterisation in order to determine both flux rates. In alcoholic cirrhosis plasma concentrations of endogenous NA and adrenaline (A) were significantly above control values (NA: median 2.4 v 1.7 nmol/l, p less than 0.02; A: 0.38 v 0.19 nmol/l, p less than 0.01). Whole body clearance of 3H-NA equal in the two groups (1.6 v 1.7 l/min, ns), while as the overall appearance rate of NA was significantly higher in alcoholic cirrhosis (4.2 v 2.6 nmol/min, p less than 0.02) indicating an enhanced sympathoadrenal activity in this group. The hepatic intestinal clearances of A, NA, and 3H-NA were not significantly different in patients and controls, but the estimated hepatic intestinal spillover rate of NA was 0.24 nmol/min in patients as compared with 0.0 nmol/min in controls (p less than 0.02). As a result of portosystemic shunting in cirrhosis the present estimation of NA spillover represents a minimum value. Our results indicate that the augmented circulating catecholamines in cirrhosis do not result from diminished removal but are contributed to from increased sympathetic nervous activity in the hepatic intestinal area (enhanced mesenteric sympathetic nervous activity).     

Interorgan ammonia and amino acid metabolism in metabolically stable patients with cirrhosis and a TIPSS

Ammonia is central to the pathogenesis of hepatic encephalopathy. This study was designed to determine the quantitative dynamics of ammonia metabolism in patients with cirrhosis and previous treatment with a transjugular intrahepatic portosystemic stent shunt (TIPSS). We studied 24 patients with cirrhosis who underwent TIPSS portography. Blood was sampled and blood flows were measured across portal drained viscera, leg, kidney, and liver, and arteriovenous differences across the spleen and the inferior and superior mesenteric veins. The highest amount of ammonia was produced by the portal drained viscera. The kidneys also produced ammonia in amounts that equaled total hepatosplanchnic area production. Skeletal muscle removed more ammonia than the cirrhotic liver. The amount of nitrogen that was taken up by muscle in the form of ammonia was less than the glutamine that was released. The portal drained viscera consumed glutamine and produced ammonia, alanine, and citrulline. Urea was released in the splenic and superior mesenteric vein, contributing to whole-body ureagenesis in these cirrhotic patients. In conclusion, hyperammonemia in metabolically stable, overnight-fasted patients with cirrhosis of the liver and a TIPSS results from portosystemic shunting and renal ammonia production. Skeletal muscle removes more ammonia from the circulation than the cirrhotic liver. Muscle releases excessive amounts of the nontoxic nitrogen carrier glutamine, which can lead to ammonia production in the portal drained viscera (PDV) and kidneys. Urinary ammonia excretion and urea synthesis appear to be the only way to remove ammonia from the body.     

Does enteral glutamine modulate whole-body leucine kinetics in hypercatabolic dogs in a fed state?

To determine whether enteral glutamine alters whole-body leucine metabolism in a state of hypercatabolism, 6 dogs adapted to a normocaloric, low-protein diet received intramuscular dexamethasone (0.44 mg. kg(-1). d(-1)) for 1 week, during 2 separate study periods. On the last day of each period, intravenous infusions of L-[1-(13)C]leucine and L-[2-(15)N]glutamine were performed to assess whole-body leucine and glutamine metabolism, and duodenal biopsies were obtained to determine gut protein fractional synthesis rate (FSR), while dogs were receiving enteral nutrition. The nutrient mixture supplied 6.2 kcal. h(-1) nonprotein energy per kg(0.75) of body weight (84% glucose, 16% fat) and 0.2 g amino acid per kg(-0.75). h(-1); the nutrient mixture was glutamine-free on the "control day," and supplemented with 1,150 micromol. kg(-1). h(-1) natural L-glutamine on the "glutamine day." Glutamine supplementation induced an approximately 56% rise in plasma glutamine appearance rate (P <.05), and was associated with an approximately 26% reduction in leucine oxidation (P <.05) with no change in leucine release from protein breakdown or nonoxidative leucine disposal, an index of whole-body protein synthesis. Glutamine supplementation improved net leucine balance (protein synthesis-protein breakdown) (-26 +/- 4 v -48 +/- 11 micromol. kg(-1). h(-1); P <.05). In addition, glutamine enhanced intestinal protein FSR by approximately 22% in the 4 dogs where it was assessed. We conclude that, in hypercatabolic adult dogs in the fed state, enteral glutamine supplementation acutely decreases leucine oxidation and improves net leucine balance, and may thus preserve body protein.     

Nutrition and survival in intensive care

Summary The potential role of nutrition to influence survival in the critically-ill is discussed. Increasing benefits are described to enteral nutrition but there remain some patients who have high mortality in whom only parenteral nutrition is possible. The clinical relevance of glutamine in parenteral nutrition is reviewed in the context of how it might influence survival from severe illness. Received: 7 May 1997 Accepted: 12 August 1997     

Helicobacter pylori, hyperammonemia and subclinical portosystemic encephalopathy: effects of eradication

BACKGROUND/AIMS: An involvement of Helicobacter pylori in the development of hepatic encephalopathy in cirrhotic patients has been proposed, but data confirming such an association are lacking. This prospective study aimed to assess whether ammonia levels and indicators of subclinical portosystemic encephalopathy were influenced by H. pylori status in a series of 62 cirrhotic patients. The effects of H. pylori eradication on such parameters were also investigated. METHODS: Fasting blood ammonia levels, mental state, number connection test, flapping tremor, and EEG tracings were recorded at baseline, and in H. pylori-positive patients (as diagnosed by rapid urease test and 14C-urea breath test) these parameters were reassessed 2 months following eradication therapy. RESULTS: In this series of non-advanced cirrhotic patients, the prevalence of H. pylori infection was 52%. No significant differences were observed between H. pylori+ and H. pylori- cases with respect to fasting venous blood ammonia concentration (47+/-24 vs. 43+/-22 micromol/l) or to the remaining parameters assessing portosystemic encephalopathy. In addition, H. pylori eradication failed to induce any significant variation in either fasting blood ammonia levels (from 45+/-23 to 48+/-26 micromol/l) or neurologic disturbances. CONCLUSION: These results indicate that H. pylori infection is not a major contributing factor to either fasting blood ammonia levels or parameters assessing subclinical portosystemic encephalopathy in patients with non-advanced liver cirrhosis.     

Oral glutamine challenge and magnetic resonance spectroscopy in three patients with congenital portosystemic shunts

BACKGROUND/AIMS: Congenital portosystemic shunts are rare abnormalities of liver vasculature that can cause neurological symptoms, probably secondarily to the effects of the metabolism of ammonia in the brain. Our aim was to investigate the relationship between capillary blood ammonia after oral glutamine challenge and magnetic resonance spectroscopy in three patients with congenital portosystemic shunts. METHODS: Neuropsychological tests, oral glutamine challenge and magnetic resonance spectroscopy were performed at baseline and after 6 months of follow-up in three patients with congenital portosystemic shunts. The results were compared to those obtained in a group of six cirrhotic patients with prior episodes of hepatic encephalopathy and healthy controls. RESULTS: Patients with congenital portosystemic shunts exhibited abnormalities of neuropsychological tests, magnetic resonance spectroscopy and a response to the oral glutamine challenge similar to those observed in patients with cirrhosis. The intensity of the rise of brain glutamine was correlated to the area under the curve of ammonia after the oral glutamine challenge (R=0.72). CONCLUSIONS: Neurological manifestations of patients with congenital portosystemic shunts are mediated through similar mechanisms that are involved in the pathogenesis of hepatic encephalopathy. The area under the curve appears to be the better parameter that defines the response to the oral glutamine challenge.     

Rat CCl4‐induced cirrhosis plus total portal vein ligation: a new model for the study of hyperammonaemia and brain oedema

Introduction: Animal models used to study hyperammonaemic disorders related to chronic liver disease are unsatisfactory. These animals only develop hyperammonaemia and brain oedema when fed with diets supplemented with amonium acetate. Aim: To develop a novel experimental model of hyperammonaemia and brain oedema in CCl₄‐induced cirrhosis in rats. Methods: Four groups were studied: rats with sham intervention (S), rats with total portal vein ligation (TPVL), cirrhotic rats (LC), and cirrhotic rats with TPVL (LC+TPVL). When ascites was diagnosed, oral glutamine challenge (OGC) test was performed. Blood, liver, lungs and brain samples were collected to quantify liver function parameters, plasmatic and cerebral ammonia, endotoxaemia, liver and brain histology, brain oedema and portosystemic shunting degree. Results: LC+TPVL rats showed a significant increase in portosystemic shunting when compared with LC group and a significant derangement in liver function when compared with TPVL group. These alterations resulted in a significant increase in plasmatic and brain ammonia concentrations and a higher plasmatic endotoxaemia as compared with others. Similarly, the area under OGC curve was significantly increased in LC+TPVL group as compared with the others, and correlates with portal shunting. Low‐grade brain oedema was only observed in LC+TPVL group. All cirrhotic groups showed liver regeneration nodules and type‐II Alzheimer astrocytes Conclusion: LC+TPVL reproduce the main alterations – portosystemic shunting, plasmatic and cerebral hyperammonaemia and low‐grade brain oedema – observed in cirrhotic patients with hepatic encephalopathy.     

Clinical nutrition practice in Italian Gastroenterology Units

BACKGROUND: Nutritional status affects the course, ensuing complications and prognosis of virtually all diseases. AIMS: To define the role of nutrition in Gastroenterology Units by means of two investigations that analyse: a) availability of devices for assessing nutritional status; b) nutritional treatment in clinical practice: incidence and frequency of indications for its use, together with type of treatment adopted. PATIENTS AND METHODS: Two questionnaires were sent to Italian Academic and Hospital Gastroenterology Units, all with clinical wards. RESULTS: Results refer to 27 Units, 22 of which took part in both parts of the analysis, enrolling 547 patients during the two-week study The first analysis shows that scales and the altimeter are not available everywhere, while more specific tools, such as skinfold calipers are available in 54% of the Units, and caloric intake can be assessed in 22-41%. The second analysis reveals that nutritional treatment was necessary in 50% of patients in the series examined, and that this was taken into account and prescribed in almost all cases (91%). Of the patients treated, 69% received dietetic supplementation and 31% artificial nutrition [12% enteral, 88% parenteral), although supportive parenteral nutrition is often contraindicated in conditions where good bowel function provides the conditions for enteral nutrition. CONCLUSION: Data emerging from the investigation showed that i) artificial nutrition is commonly used in gastroenterology Units in Italy although 23% of them never consider either enteral or parenteral nutrition as medical treatment of gastrointestinal disease; ii) malnutrition is a very frequent complication (mean 27%; range 4-55%0) in Gastroenterology Unit patients albeit only 42% of malnourished patients received artificial nutrition; iii) indications for enteral and parenteral nutrition are not always respected, as there is an excessive use of parenteral nutrition and an unjustified resistance to the use of enteral nutrition; iv] nutritional treatment is often administered without adequate nutritional assessment and without a complete adherence to the standards recommended for preparation of parenteral bags, supported by suitable technology; v) only two Gastroenterology Units report admitting and following patients in a home parenteral nutrition programme; vi) this investigation probably reflects the response of those Gastroenterology Units most aware of the importance of nutritional problems. Better awareness of correct practices for nutritional support should be promoted, encouraging greater use of diagnostic and monitoring techniques and a more discerning choice of the most suitable type of artificial nutrition to be administered in gastroenterology     

Influence of glutamine and branched chain amino acids on the jejunal atrophy associated with parenteral nutrition

Infusions of conventional parenteral nutrients (CPN) are associated with gut atrophy. This may be due to the absence of glutamine in such solutions. Although glutamine is a preferred gut nutrient, it is excluded from CPN because it is unstable at room temperature. This problem may be circumvented either directly by the infusion of fresh solutions of glutamine, or indirectly by the infusion of branched chain amino acids (BCAA). We evaluated the effect of infusing either glutamine, BCAA, or glutamine plus BCAA-enriched CPN on the rat jejunum. Sixty male Wistar rats were randomized to receive 6 days of either conventional parenteral nutrition (CPN), CPN plus 1.5% glutamine (GLN), CPN plus 2% BCAA (BCAA), CPN plus 0.8% BCAA and 1.0% glutamine (GLN/BCAA), or a normal oral diet (Chow). Standardized segments of jejunum were then removed for assessment. Compared with the CPN group, both the GLN/BCAA and the BCAA groups had greater mucosal weights (P less than 0.05) and mucosal protein concentrations (P less than 0.05), the GLN/BCAA group had greater jejunal weights (P less than 0.05), and the GLN group had an increased jejunal weight (P less than 0.05) and a higher crypt cell production rate (P less than 0.05). We conclude that the infusion of glutamine or BCAA-enriched parenteral nutrition improves jejunal morphology compared with conventional parenteral nutrition.     

Clinical outcomes of transcatheter selective superior mesenteric artery urokinase infusion therapy vs transjugular intrahepatic portosystemic shunt in patients with cirrhosis and acute portal vein thrombosis

AIM To compare the outcomes of transcatheter superior mesenteric artery(SMA) urokinase infusion and transjugular intrahepatic portosystemic shunt(TIPS) for acute portal vein thrombosis(PVT) in cirrhosis.METHODS From January 2013 to December 2014, patients with liver cirrhosis and acute symptomatic PVT who met the inclusion criteria were randomly assigned to either an SMA group or a TIPS group. The two groups accepted transcatheter selective SMA urokinase infusion therapyand TIPS, respectively. The total follow-up time was24 mo. The primary outcome measure was the change in portal vein patency status which was evaluated by angio-computed tomography or Doppler ultrasound.Secondary outcomes were rebleeding and hepatic encephalopathy.RESULTS A total of 40 patients were enrolled, with 20 assigned to the SMA group and 20 to the TIPS group. The symptoms of all patients in the two groups improved within 48 h. PVT was improved in 17(85%) patients in the SMA group and 14(70%) patients in the TIPS group. The main portal vein(MPV) thrombosis was significantly reduced in both groups(P 0.001), and there was no significant difference between them(P= 0.304). In the SMA group, superior mesenteric vein(SMV) thrombosis and splenic vein(SV) thrombosis were significantly reduced(P = 0.048 and P = 0.02),which did not occur in the TIPS group. At 6-, 12-,and 24-mo follow-up, in the SMA group and the TIPS group, the cumulative rates free of the first episode of rebleeding were 80%, 65%, and 45% vs 90%, 80%,and 60%, respectively(P = 0.320); the cumulative rates free of the first episode of hepatic encephalopathy were 85%, 80%, and 65% vs 50%, 40%, and 35%,respectively(P = 0.022).CONCLUSION Transcatheter selective SMA urokinase infusion and TIPS are safe and effective for acute symptomatic PVT in cirrhosis.     

Hepatic and intestinal cytochrome P450 3A activity in cirrhosis: effects of transjugular intrahepatic portosystemic shunts.

Transjugular intrahepatic portosystemic shunt (TIPS) is performed to treat some complications of cirrhosis. This study investigated the effects of cirrhosis and TIPS on intestinal and hepatic cytochrome P450 3A (CYP3A) activity. Nine volunteers were cirrhotic patients with TIPS, 9 were cirrhotic controls (matched for sex, age, etiology, and Child-Pugh class), and 9 were sex- and age-matched healthy volunteers. Simultaneous doses of midazolam were given intravenously (0.05 mg/kg) and orally (3 mg of [15N3]midazolam). Peripheral and portal venous blood samples were assayed for midazolam and [15N3]midazolam. The systemic clearance of midazolam was significantly greater (P <.05) in healthy volunteers (0.42 +/- 0.10 L x h(-1) x kg(-1)) compared with cirrhotic controls (0.20 +/- 0.05) and with cirrhotic patients with TIPS (0.21 +/- 0.09). Hepatic availability followed the same trend. The bioavailability of midazolam was significantly higher (P <.05) in cirrhotic patients with TIPS (0.76 +/- 0.20) compared with cirrhotic controls (0.27 +/- 0.14) and with healthy volunteers (0.30 +/- 0.10). The intestinal availability was significantly greater (P <.05) in cirrhotic patients with TIPS (0.83 +/- 0.17) compared with cirrhotic controls (0.32 +/- 0.16) and with healthy volunteers (0.42+/-0.15). As expected, hepatic CYP3A activity was reduced in cirrhosis. However, in cirrhotic patients with TIPS, there was a marked loss in first-pass metabolism of midazolam as a result of diminished intestinal CYP3A activity.     

Cerebral metabolism of ammonia and amino acids in patients with fulminant hepatic failure.

BACKGROUND & AIMS: High circulating levels of ammonia have been suggested to be involved in the development of cerebral edema and herniation in fulminant hepatic failure (FHF). The aim of this study was to measure cerebral metabolism of ammonia and amino acids, with special emphasis on glutamine metabolism. METHODS: The study consisted of patients with FHF (n = 16) or cirrhosis (n = 5), and healthy subjects (n = 8). Cerebral blood flow was measured by the 133Xe washout technique. Blood samples for determination of ammonia and amino acids were drawn simultaneously from the radial artery and the internal jugular bulb. RESULTS: A net cerebral ammonia uptake was only found in patients with FHF (1.62 +/- 0.79 micromol x 100 g(-1) x min(-1)). The cerebral glutamine efflux was higher in patients with FHF than in the healthy subjects and cirrhotics, -6.11 +/- 5.19 vs. -1.93 +/- 1.17 and -1.50 +/- 0.29 micromol x 100 g(-1) x min(-1), respectively (P < 0.05). Patients with FHF who subsequently died of cerebral herniation (n = 6) had higher arterial ammonia concentrations, higher cerebral ammonia uptake, and higher cerebral glutamine efflux than survivors. Intervention with short-term mechanical hyperventilation in FHF reduced the net cerebral glutamine efflux, despite an unchanged net cerebral ammonia uptake. CONCLUSIONS: Patients with FHF have an increased cerebral glutamine efflux, and short-term hyperventilation reduces this efflux. A high cerebral ammonia uptake and cerebral glutamine efflux in patients with FHF were associated with an increased risk of subsequent fatal intracranial hypertension.     

Effects of high-volume plasmapheresis on ammonia, urea, and amino acids in patients with acute liver failure

OBJECTIVE: In acute liver failure (ALF), urea production is severely impaired, and detoxification of ammonia by glutamine synthesis plays an important protective role. The aim of this study was to examine the effects of therapeutic high-volume plasmapheresis (HVP) on arterial concentrations and splanchnic exchange rates of ammonia, urea, and amino acids-in particular, glutamine. METHODS: A quantity of 8 L of plasma was exchanged over the course of 7 h in 11 patients with ALF after development of hepatic encephalopathy grade III-IV. Splanchnic exchange rates of ammonia, urea, and amino acids were measured by use of liver vein catheterization. RESULTS: HVP removed ammonia and glutamine at a rate of 1 micromol/min and 27 micromol/min, respectively. Arterial ammonia decreased from 160 +/- 65 to 114 +/- 50 micromol/L (p < 0.001). In contrast, arterial glutamine was only minimally changed from 1791 +/- 1655 to 1764 +/- 1875 micromol/L (NS). This implied that the rate of systemic glutamine synthesis was increased by 27 micromol/min. Splanchnic exchange rates (before vs after HVP) were as follows: for ammonia, -93 +/- 101 versus -70 +/- 80 micromol/min (NS); urea-nitrogen, 0.08 +/- 1.64 versus -0.31 +/- 0.45 mmol/min (NS); alanine, -73 +/- 151 versus 12 +/- 83 micromol/min (p < 0.05); and glutamine: 132 +/- 246 versus 186 +/- 285 micromol/min (NS), with negative values denoting release. CONCLUSIONS: Arterial ammonia decreased during HVP in patients with ALF. The data suggest that this effect of HVP could be explained by increased hepatic urea synthesis and possibly by increased glutamine synthesis in muscle tissue.     

The effect of minimum luminal nutrition on mucosal cellularity and immunity of the gut

Many catabolic patients can only consume small volumes of enteral nutrients. The aim of this study was to evaluate markers of cellularity and immunity in the small intestine of rats randomized to receive 6 days of parenteral nutrition, 25% enteral and 75% parenteral nutrition (i.e. minimum luminal nutrition) or enteral nutrition. The same glutamine-enriched solution was used for both parenteral and enteral nutrition. Enteral nutrition was associated with the least amount of jejunal atrophy ( P < 0.01), with the results from the minimum luminal nutrition group approximating those of the parenteral nutrition group. Parenteral nutrition was associated with the greatest number of CD2+ cells ( P < 0.05) and the lowest CD4/CD8 cell ratio ( P < 0.01) in the jejunal mucosa. In essence, we failed to demonstrate that there are any appreciable benefits associated with the enteral consumption of 25% of a nutrient load.     

Immunonutrition and enteral hyperalimentation of critically ill patients

Physicians need to be maximally aggressive in their use of total enteral nutrition (TEN) in the critically ill patient, due to its lower cost, better physiology, and lower complication rate when compared to parenteral therapy. Various components in TEN such as glutamine, arginine, RNA nucleotides, omega-3 fish oils, and fiber, may have important roles in immunonutrition by maintaining gut integrity, stimulating the immune system, and preventing bacterial translocation from the gut. For each patient, the physician must choose the optimal enteral formula for that particular disease or organ failure state to maximize nutrient substrate assimilation and tolerance. Total parenteral nutrition (TPN) should be used only when a true contraindication to enteral feedings exists or as adjunctive therapy when full nutritional requirements cannot be met by TEN alone.     

京津三级甲等医院普外科术后患者液体治疗现状初步调查

目的 调查京津三家三级甲等医院普外科术后患者液体治疗现状. 方法 回顾性调查接受普外科手术的住院且术后禁食3 d以上的患者600例,不限年龄和性别、所患疾病种类和接受的手术类型.统计指标包括患者的一般资料、手术前后实验室检查、术后3 d液体治疗内容和部分临床指标(术后并发症、输液反应等). 结果 588例有效病例术后每天平均补液总量为(3030±638)ml;平均每天给予葡萄糖(142±67)g、氯化钾(59.9±23.9)mmol、氯化钠(179.5±66.7)mmol;85.2%的患者接受营养支持,肠外营养与肠内营养比为28:1;术前体质指数(BMI)≥18.5 kg/m2的患者有549例,其中接受肠外营养和肠内营养支持共有470例(85.6%);BMI<18.5 kg/m2共39例,给予规范的肠外营养支持27例(69.2%).均未给予肠内营养.术后3 d液体治疗中未给予氯化钾36例次. 结论 京津三级甲等医院普外科术后患者接受营养支持和肠外营养的比例均过高;即用型复合糖电解质制剂可减少差错和有益于大多数术后患者.