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Continuous terlipressin infusion is associated with improved diet intake and muscle strength in patients awaiting liver transplant.

ABSTRACT: Background & Aims:Portal hypertension contributes to the pathogenesis of malnutrition and sarcopenia in cirrhosis via multiple mechanisms. Terlipressin is a vasopressin analogue that we administer via continuous outpatient infusion, as a bridge to transplantation in patients with hepatorenal syndrome or refractory ascites. We describe, for the first time, the impact of outpatient terlipressin on nutritional and muscle parameters. Methods:Nutrition (subjective global assessment), handgrip strength, dietary intake (energy, protein), frequency of paracentesis and severity of liver disease (model for end-stage liver disease score) were prospectively recorded at terlipressin commencement and follow-up (transplantation, cessation or census date). Results:Nineteen patients were included (89% male, median age 59.6 years, median model for end-stage liver disease score 24), of whom 12 had hepatorenal syndrome and 7 had refractory ascites. All patients were malnourished at baseline, 63% (n = 12) had sarcopenic-range grip strength, and mean paracentesis frequency was 2.86 ± 1.62/month. Median duration of terlipressin was 51 days (interquartile range 29-222). Fourteen patients (74%) were transplanted, 2 delisted (10%) and 3 (16%) continued terlipressin. Energy and protein intake improved significantly following terlipressin, from 17.94 ± 5.43 kcal/kg to 27.70 ± 7.48 kcal/kg, and 0.74 ± 0.28 g/kg to 1.16 ± 0.31 g/kg, respectively (both p < 0.001). Handgrip strength increased from 25.36 ± 8.13 kg to 28.49 ± 7.63 kg (p = 0.001). Linear regression analysis demonstrated hand grip strength increased 0.075% for every 1-day of terlipressin (p = 0.005). The frequency of large-volume paracentesis reduced by 46%, to 1.57 ± 1.51/month (p = 0.001). Conclusion:Continuous terlipressin infusion reduces the complications of portal hypertension and is associated with an improvement in nutritional and muscle parameters in patients on the liver transplant waiting list, in whom such characteristics usually demonstrate progressive decline. This validates both the aetiological role of portal hypertension in malnutrition and represents a promising new anabolic therapy. Lay summary:Malnutrition and poor muscle strength are common in liver disease and often get worse while patients await liver transplant. Terlipressin is a medication used to treat portal hypertension in patients with hepatorenal syndrome. It is usually given for a few days or weeks in patients confined to hospital. Our centre provides outpatient terlipressin for weeks to months as a bridge to liver transplant. In patients treated with terlipressin at our hospital, we observed a substantial increase in their dietary intake and muscle strength, which may improve their quality of life and outcomes after liver transplant.

SUBMITTER: Chapman B

PROVIDER: S-EPMC7001556 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Continuous terlipressin infusion is associated with improved diet intake and muscle strength in patients awaiting liver transplant.

Chapman Brooke B Gow Paul P Sinclair Marie M Hanrahan Timothy T Angus Peter P McClure Tess T Mills Chris C Terbah Ryma R Testro Adam A

JHEP reports : innovation in hepatology 20190517 2

<h4>Background & aims</h4>Portal hypertension contributes to the pathogenesis of malnutrition and sarcopenia in cirrhosis via multiple mechanisms. Terlipressin is a vasopressin analogue that we administer via continuous outpatient infusion, as a bridge to transplantation in patients with hepatorenal syndrome or refractory ascites. We describe, for the first time, the impact of outpatient terlipressin on nutritional and muscle parameters.<h4>Methods</h4>Nutrition (subjective global assessment), h ...[more]

PMID: 32039358

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Project description:IntroductionRecent clinical data suggest that early administration of vasopressin analogues may be advantageous compared to a last resort therapy. However, it is still unknown whether vasopressin and terlipressin are equally effective for hemodynamic support in septic shock. The aim of the present prospective, randomized, controlled pilot trial study was, therefore, to compare the impact of continuous infusions of either vasopressin or terlipressin, when given as first-line therapy in septic shock patients, on open-label norepinephrine requirements.MethodsWe enrolled septic shock patients (n = 45) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation. Patients were randomized to receive continuous infusions of either terlipressin (1.3 microg.kg-1.h-1), vasopressin (.03 U.min-1) or norepinephrine (15 microg.min-1; n = 15 per group). In all groups, open-label norepinephrine was added to achieve a mean arterial pressure between 65 and 75 mmHg, if necessary. Data from right heart and thermo-dye dilution catheterization, gastric tonometry, as well as laboratory variables of organ function were obtained at baseline, 12, 24, 36 and 48 hours after randomization. Differences within and between groups were analyzed using a two-way ANOVA for repeated measurements with group and time as factors. Time-independent variables were compared with one-way ANOVA.ResultsThere were no differences among groups in terms of systemic and regional hemodynamics. Compared with infusion of .03 U of vasopressin or 15 microg.min-1 of norepinephrine, 1.3 microg.kg-1.h-1 of terlipressin allowed a marked reduction in catecholamine requirements (0.8 +/- 1.3 and 1.2 +/- 1.4 vs. 0.2 +/- 0.4 microg.kg-1.min-1 at 48 hours; each P < 0.05) and was associated with less rebound hypotension (P < 0.05). At the end of the 48-hour intervention period, bilirubin concentrations were higher in the vasopressin and norepinephrine groups as compared with the terlipressin group (2.3 +/- 2.8 and 2.8 +/- 2.5 vs. 0.9 +/- 0.3 mg.dL-1; each P < 0.05). A time-dependent decrease in platelet count was only observed in the terlipressin group (P < 0.001 48 hours vs. BL).ConclusionsThe present study provides evidence that continuous infusion of low-dose terlipressin--when given as first-line vasopressor agent in septic shock--is effective in reversing sepsis-induced arterial hypotension and in reducing norepinephrine requirements.

Project description:BackgroundSurvival of kidney transplant recipients (KTR) is low compared with the general population. Low muscle mass and muscle strength may contribute to lower survival, but practical measures of muscle status suitable for routine care have not been evaluated for their association with long-term survival and their relation with each other in a large cohort of KTR.MethodsData of outpatient KTR ≥ 1 year post-transplantation, included in the TransplantLines Biobank and Cohort Study (ClinicalTrials.gov Identifier: NCT03272841), were used. Muscle mass was determined as appendicular skeletal muscle mass indexed for height2 (ASMI) through bio-electrical impedance analysis (BIA), and by 24-h urinary creatinine excretion rate indexed for height2 (CERI). Muscle strength was determined by hand grip strength indexed for height2 (HGSI). Secondary analyses were performed using parameters not indexed for height2. Cox proportional hazards models were used to investigate the associations between muscle mass and muscle strength and all-cause mortality, both in univariable and multivariable models with adjustment for potential confounders, including age, sex, body mass index (BMI), estimated glomerular filtration rate (eGFR) and proteinuria.ResultsWe included 741 KTR (62% male, age 55 ± 13 years, BMI 27.3 ± 4.6 kg/m2), of which 62 (8%) died during a median [interquartile range] follow-up of 3.0 [2.3-5.7] years. Compared with patients who survived, patients who died had similar ASMI (7.0 ± 1.0 vs. 7.0 ± 1.0 kg/m2; P = 0.57), lower CERI (4.2 ± 1.1 vs. 3.5 ± 0.9 mmol/24 h/m2; P < 0.001) and lower HGSI (12.6 ± 3.3 vs. 10.4 ± 2.8 kg/m2; P < 0.001). We observed no association between ASMI and all-cause mortality (HR 0.93 per SD increase; 95% confidence interval [CI] [0.72, 1.19]; P = 0.54), whereas CERI and HGSI were significantly associated with mortality, independent of potential confounders (HR 0.57 per SD increase; 95% CI [0.44, 0.81]; P = 0.002 and HR 0.47 per SD increase; 95% CI [0.33, 0.68]; P < 0.001, respectively), and associations of CERI and HGSI with mortality remained independent of each other (HR 0.68 per SD increase; 95% CI [0.47, 0.98]; P = 0.04 and HR 0.53 per SD increase; 95% CI [0.36, 0.76]; P = 0.001, respectively). Similar associations were found for unindexed parameters.ConclusionsHigher muscle mass assessed by creatinine excretion rate and higher muscle strength assessed by hand grip strength are complementary in their association with lower risk of all-cause mortality in KTR. Muscle mass assessed by BIA is not associated with mortality. Routine assessment using both 24-h urine samples and hand grip strength is recommended, to potentially target interdisciplinary interventions for KTR at risk for poor survival to improve muscle status.

Project description:BackgroundMeasures of skeletal muscle function decline at a faster rate with ageing than do indices of skeletal muscle mass. These observations have been attributed to age-related changes in muscle quality, another functional determinant separate from skeletal muscle mass. This study tested the hypothesis that improved predictions of skeletal muscle strength can be accomplished by combining clinically available measures of skeletal muscle mass and quality.MethodsThe participants included 146 healthy adult (age ≥ 18 years, range 18-77 years; X ± SD 47 ± 17 years and body mass index 16.5-51.8 kg/m2 ; 27.7 ± 6.2 kg/m2 ) men (n = 60) and women (n = 86) in whom skeletal muscle mass was estimated as appendicular lean soft tissue (LST) measured by dual-energy X-ray absorptiometry and skeletal muscle quality as bioimpedance analysis-derived phase angle and B-mode-evaluated echogenicity of mid-thigh skeletal muscle. Strength of the right leg and both arms was quantified as knee isokinetic extension and handgrip strength using dynamometers. The statistical significance of adding phase angle or echogenicity to strength prediction multiple regression models that included extremity-specific LST and other covariates (e.g. age and sex) was evaluated to test the study hypothesis.ResultsRight leg LST mass alone was significantly (P < 0.0001) correlated with isokinetic right leg strength (R2 = 0.57). The addition of segmental phase angle measured in the right leg at 50 kHz increased the R2 of this model to 0.66 (P < 0.0001); other phase angle frequencies (5 and 250 kHz) did not contribute significantly to these models. Results were similar for both right and left arm handgrip strength prediction models. Adding age and sex as model covariates increased the R2 values of these models further (e.g. right leg strength model R2 increased to 0.71), but phase angle continued to remain a significant (all P < 0.01) predictor of extremity strength. Similarly, when predicting isokinetic right leg strength, mid-thigh skeletal muscle echogenicity added significantly (P < 0.0001) to right leg LST, increasing R2 from 0.57 to 0.64; age was a significant (P < 0.0001) covariate in this model, increasing R2 further to 0.68.ConclusionsThe hypothesis of the current study was confirmed, strongly supporting and extending earlier reports by quantifying the combined independent effects of skeletal muscle mass and quality on lower-body and upper-body measures of strength. These observations provide a clinically available method for future research aimed at optimizing sarcopenia and frailty risk prediction models.

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Continuous terlipressin infusion is associated with improved diet intake and muscle strength in patients awaiting liver transplant.

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Continuous terlipressin infusion is associated with improved diet intake and muscle strength in patients awaiting liver transplant.

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