A guide to enteral nutrition in intensive care units: 10 expert tips for the daily practice

The preferential use of the oral/enteral route in critically ill patients over gut rest is uniformly recommended and applied. This article provides practical guidance on enteral nutrition in compliance with recent American and European guidelines. Low-dose enteral nutrition can be safely started within 48 h after admission, even during treatment with small or moderate doses of vasopressor agents. A percutaneous access should be used when enteral nutrition is anticipated for ≥ 4 weeks. Energy delivery should not be calculated to match energy expenditure before day 4–7, and the use of energy-dense formulas can be restricted to cases of inability to tolerate full-volume isocaloric enteral nutrition or to patients who require fluid restriction. Low-dose protein (max 0.8 g/kg/day) can be provided during the early phase of critical illness, while a protein target of > 1.2 g/kg/day could be considered during the rehabilitation phase. The occurrence of refeeding syndrome should be assessed by daily measurement of plasma phosphate, and a phosphate drop of 30% should be managed by reduction of enteral feeding rate and high-dose thiamine. Vomiting and increased gastric residual volume may indicate gastric intolerance, while sudden abdominal pain, distension, gastrointestinal paralysis, or rising abdominal pressure may indicate lower gastrointestinal intolerance.

Iron deficiency in Women of Childbearing Age with Self-reported Oral Iron Gastrointestinal Intolerance and Management with an oral Iron-Whey-Protein Formulation. PRospectivE study of women of Childbearing age with gastrointeStinal Intolerance to Oral Iron (PRECISION), a randomised, prospective, double-blind, double dummy clinical trial.

Background Intolerance to oral iron is thought to result in poor adherence and persistence of nutritional deficit amongst women of childbearing age, however few studies have evaluated oral iron intolerance, iron deficiency and anaemia in this setting. Iron-whey protein microspheres (IWP) could help. Methods We documented self-reported oral iron gastrointestinal intolerance, ferritin and haemoglobin levels in a screening study of women of childbearing age. Following a washout period of 16 days, we randomised 59 of these women with iron deficiency, stratified according to the presence of anaemia, to three doses of IWP: (14mg daily, 25mg daily and 50mg daily). We excluded those with established gastrointestinal disease, potential allergy to whey protein and severe anaemia. The primary endpoint was persistence and adherence (>80% based on pill-counts). Secondary endpoints included changes in self-reported oral iron gastrointestinal intolerance, gastro-intestinal symptom rating scale (GSRS), serum iron, serum ferritin, transferrin saturation and haemoglobin levels. Results A total of 128 (62.7%) of the participants had low iron stores (ferritin <30 μg/L), 65 (31.9%) had moderate to severe iron deficiency (ferritin <12 μg/L) and 33 (16.2%) had iron deficiency anaemia. Amongst 59 women who participated in the prospective study, 48 (81.4%) were classified as adherent/persistent with therapy using IWP compared to 12 (20.3%) taking the prior oral iron P<0.0001. These patients also showed significantly fewer reports of gastrointestinal intolerance with IWP (0.59 ± 0.91) and lower GSRS scores (6.2 ± 7.5) compared to the previous oral iron product (3.98 ± 2.22, and 15.6 ± 9.7 respectively, both P<0.0001). There were no differences in adherence, self-reported adverse GI effects and GSRS between the dose groups during the study. Serum iron levels increased across the whole cohort from 11.3 ± 7.4 μmol/L to 20.5 ± 11.0 μmol/L (P<0.0001), transferrin saturation levels increased from 18.4 ± 13.3 % to 33.6 ± 17.6 % (P<0.0001) and median ferritin levels overall increased from 8.00 [IQR 6.00;13.0] to 15.5 [IQR 9.00;24.2] μg/L at 12 weeks (P=0.0002). Haemoglobin levels increased from 11.36 g/dL (95%CI 10.95 to 11.77) to 12.40 g/dL (95%CI 12.03 to 12.76, P=0.0007) in patients with anaemia and were normalised in most patients taking 50mg IWP daily. Conclusions Low iron, iron deficiency and anaemia are common in women of childbearing age with a history of intolerance to oral iron. Patients with low iron (ferritin < 30 μg/L) and moderate to severe iron deficiency (ferritin <12 μg/L) have similar impairment of energy. IWP can improve self-reported oral iron adherence and tolerability as well as iron stores, haemoglobin and tiredness in these women.

Pharmacogenetic-Guided Antidepressant Selection as an Opportunity for Interprofessional Collaboration: A Case Report

In the herein reported case of a 42-year-old woman diagnosed with anxiety and depression, a long history of antidepressant ineffectiveness and adverse drug reactions was decisive for an in-depth medication review including pharmacogenetic panel testing. In detail, treatment attempts with paroxetine and escitalopram were ineffective and discontinued due to subjective gastrointestinal intolerance. Due to the worsening of the depression after the failed treatment attempts, admission to our clinic became necessary. Herein, owing to the collaboration of psychiatrists with clinical pharmacists, individualized incorporation of pharmacogenetic data into the process of antidepressant selection was enabled. We identified vortioxetine as a suitable therapeutic, namely for being most likely pharmacokinetically unaffected as predicted by pharmacogenetic panel testing and taking into account the current comedication, as well as for its favorable action profile. Herein, our collaborative effort proved to be successful and resulted in the patient’s depression remission and clinic discharge with the interprofessionally selected pharmacotherapy. This exemplary case not only highlights the potential benefits and challenges of pre-emptive pharmacogenetic testing in antidepressant prescription, but also proposes an approach on how to put pharmacogenetics into practice.

Occupational infection to Brucella abortus B19 vaccine despite antimicrobial prophylaxis

The authors report the case of a veterinarian who acquired brucellosis infection by accidental exposure to Brucella abortus vaccine (BRUCEL-VET B19) while performing animal vaccination. Antibiotic prophylaxis with doxycycline and rifampin for six weeks was indicated, but rifampin was discontinued after 10 days due to gastrointestinal intolerance. Despite prophylaxis, the patient seroconverted after 30 days, but was asymptomatic and did not require additional antibiotic therapy. Post-exposure prophylaxis of Brucella is not free from side effects and asymptomatic seroconversion can occur despite prophylaxis.

CLINICO-DEMOGRAPHIC PROFILE OF SCRUB TYPHUS IN UTTARAKHAND

BACKGROUND: Scrub typhus(ST) a rickettsial infection caused by Orientia tsutsugamushi and transmitted by trombiculid mites“chiggers” particularly Leptotrombidium deliense. It is one of the differential diagnoses of haemorrhagic fevers, especially if associated with acute respiratory distress syndrome and/or jaundice. A necrotic eschar at the inoculating site of the mite is pathognomic of ST.The western Himalayan regions of India, has been witnessing increased incidence of acute febrile illnesses over the years. AIM & OBJECTIVES : 1) To determine the frequency of ST in a tertiary health care hospital in Uttarakhand. 2) To understand the clinical spectrum and associated complications. 3) To analyze the demographic prole of ST cases. MATERIAL & METHODS: The retrospective study was carried out, over a period of 24 months (August 2015 to July 2017), which included cases of AFI, clinically suspected of ST. Serological testing was carried out by using commercial ELISA for specic IgM antibodies against O.tsutsugamushi. RESULTS: Out of the total 3854 cases of AFI attending the tertiary care hospital, the microbiology laboratory received a total of 760 clinically suspected cases of ST for serological testing, 494 cases (12.81%) were found positive for IgM antibodies against O.tsutsugamushi.The common symptoms noted were fever with headache, myalgias, gastrointestinal intolerance, followed by breathlessness, rash and jaundice. Eschar was seen only in 69 patients. The most common complication noticed was ARDS (8.29%) followed by hepatitis (6.88%), petechial heamorrhagic spots (38.3%) and sepsis (6.07%). Mortality rate was found to be 1.8%. The cases were mainly seen in the months between August to October which correlates the infection with the rainy season. CONCLUSION: ST should be considered as one of the differential diagnosis of AFI. Timely diagnosis and management becomes crucial to decrease/limit the diease burden, thus thwarting the onset of complications and mortality

Thiopurines’ Metabolites and Drug Toxicity: A Meta-Analysis

Many questions remain unanswered regarding therapeutic drug monitoring (TDM) utility with thiopurines. This study aims to establish a relationship between thiopurines’ metabolites and drug toxicity. We performed a systematic review with inclusion of studies evaluating the relationship between thiopurines’ metabolites and drug toxicity. Meta-analysis of mean difference (MD), correlations and odds ratio (OR) was performed. We identified 21,240 records, 72 of which were eligible for meta-analysis. Levels of 6-thioguanine nucleotides (6-TGN) were higher in patients with leukopenia (MD 127.06 pmol/8 × 108 RBC) and gastrointestinal intolerance (MD 201.46 pmol/8 × 108 RBC), and lower in patients with hepatotoxicity (MD −40.6 pmol × 108 RBC). We established a significant correlation between 6-TGN and leukocytes (r = −0.21), neutrophils (r = −0.24) and alanine aminotransferase levels (r = −0.24). OR for leukopenia in patients with elevated 6-TGN was 4.63 (95% CI 2.24; 9.57). An optimal cut-off of 135 pmol/8 × 108 RBC for leukopenia was calculated (sensitivity 75.4%; specificity 46.4%). 6-methylmercaptopurine ribonucleotides (6-MMPR) were significantly associated with hepatotoxicity (MD 3241.2 pmol/8 × 108 RBC; OR 4.28; 95% CI 3.20; 5.71). Levels of 6-MMPR measured in the first 8 weeks of treatment were associated with leukopenia. We conclude that TDM could be used to prevent thiopurines’ toxicity. As optimal metabolites level may vary according to indication, physicians may adapt posology to decrease toxicity without compromising efficacy.

AB0621 TOLERABILITY AND SAFETY OF ACETYLSALICYLIC ACID IN PATIENTS WITH SYSTEMIC SCLEROSIS

Background:Systemic Sclerosis (SSc) is characterized by an increased incidence of macro- and microvascular complications. Current evidences on efficacy, safety and tolerability of acetylsalicylic acid (ASA) in SSc patients are limited, and the indication to this treatment is based on the experience of each single centre or physician. Esophagus and stomach are the portions of the digestive tract that are more frequently affected by adverse events due to ASA exposure.Objectives:We evaluated the incidence of adverse events associated with low-dose ASA treatment in a cohort of patients affected by SSc.Methods:Demographic data and disease features of 302 patients affected by SSc treated with low-dose ASA were collected and patients were followed-up for a median period of 6.9 years (range: 0-20 years). The proportion of patients taking ASA for secondary prevention for cardiovascular disease was also noted. The incidence of discontinuation of the drug, gastrointestinal intolerance, bleeding and death in the observation period was recorded.Results:Patients had a median age of 54.0 years (19.6-89.4); 91.9% were female, 13.2% were smokers and 44.0% had a BMI≥30Kg/m2. The prevalence of ischemic heart disease, peripheral vascular disease and stroke was of 8.6%, 5.3% and 3.3%, respectively; 48.7% of the patient took ASA in primary cardiovascular prevention. Therapy started after a median disease duration of 4.8 years (range: 0.0- 30.1 years) since the first non-Raynaud symptom and 56.6% of patients had an early disease (less than three years of disease duration). During the observation period, 30 patients (14.3 per 1000 person-years) discontinued ASA after an average period of assumption of 4.6 years (range: 0.3-18.0 years). The main adverse events were heartburn, dyspepsia and hematochezia, recorded in 18 patients (8.6 per 1000 person-years). Eight of them (3.8 per 1000 person-years) had evidence of digestive tract bleeding. Five patients (2.4 per 1000 person-years) discontinued ASA due to recurrent epistaxis. Twenty-eight patients (13.4 per 1000 person-years) died in the follow-up period, 16 of these (7.6 per 1000 person-years) because of SSc-related causes. None of them had evidence of major bleeding. We used Kaplan-Meier analysis to evaluate the incidence of ASA discontinuation. The history of digital ulcers (Log rank test X24.7, p=0.037) and male sex (Log rank test X24.3, p=0.03) were associated with a higher cumulative ASA discontinuation rate due to gastrointestinal intolerance.Conclusion:In our cohort of SSc patients, ASA resulted safe and well tolerated in most cases, despite the risk of gastroesophageal abnormalities due to disease. Although this comforting results, taking in account the lack of controlled-randomized trials about efficacy and safety, the choice to start antiplatelet therapy with ASA should be mandatorily preceded by a careful evaluation of risks and benefits. Furthermore, an attentive monitoring for possible adverse effects is needed during ASA treatment. Patients with digital ulcers and male sex could present less drug tolerability.References:[1]Valentini G et al. Ann Rheum Dis 2019. Beckett VL et al. Arthritis Rheum 1984. Kavian N et al. Vascul Pharmacol 2015. Lavie CJ et al. Curr Probl Cardiol 2017.Disclosure of Interests:Lucrezia Verardi: None declared, Enrico De Lorenzis: None declared, Gerlando Natalello: None declared, Laura Gigante: None declared, Umberto La Porta: None declared, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Silvia Laura Bosello Speakers bureau: Abbvie, Pfizer, Boehringer

P1009RENAL OUTCOMES IN DIABETIC KIDNEY PATIENTS TREATED WITH GLP1 AGONIST RECEPTORS VS SGLT2 INHIBITORS

Background and Aims End stage renal disease of diabetic cause is an increasing issue worldwide. Both GLP1 antagonist receptors (GLP1ar) and the sodium-glucose co-transporter 2 inhibitors (SGLT2i) have shown promising results in preventing or ameliorating the progression of renal disease, however there is no data comparing the effect of both drugs on renal outcomes. Method Here we present the result of a retrospective study analyzing the main renal outcomes of 98 T2DM patients treated with GLP1ar (25% dulaglutide, 25% liraglutide, 50% semaglutide) or SLGT2 (46.9% dapagliflozin, 21% empagliflozin, 32.1% canagliflozin). All participants were on ACEi/ARB on maximally tolerated dose and patients that have been on both treatments at any time during observation period were excluded. Mean follow-up was 1,9 years, (SD 1,1). Results Main descriptive data are shown on the table: in summary, patients on SGLT2i had higher eGFR (64,7 SD 22,7 vs 43,7 SD 13,5) ml/min/1,73m2 (p&lt;0.001), lower BMI (30,2 SD 4,8 vs 35,0 SD 4,0 p&lt;0,001) and were more frequently free from previous cardiovascular events (60% vs 29,4%, p 0,02)Incident kidney disease defined as drop of eGFR below 60 ml/min/1,73m2 and/or new onset albuminuria occurred on 18 (39,1%) and 7 (87,5%) of patients on SGLT2i and GLP1ar respectively (p 0,01), however, nor SGLT2i or GLP1ar treated patients suffered significant decrease on eGFR along the study period (2.5% change in eGFR-SGLT2i and 5% in GLP1ar). We found no significant differences on arterial blood pressure or glycemic control along the study period and BMI decrease was only significative on GLP1ar patients (-7,7%, p&lt;0.001)6,7% and 15,8% of patients treated with GLP1ar and SGLT2i respectively suffered one CV event along the follow-up period (p ns) with 6,7% deaths on both groups (0.03 death/patient-year). Adverse events were similar on both groups though discontinuation rate was higher on SGLT2i (16,7% gastrointestinal intolerance, 58% “others”) Conclusion We conclude that both GLP1ar and SGLT2i prevent progression of kidney disease in T2DM patients. Though GLP1ar patients showed higher rates of incident kidney disease, when initiated on already decreased GFR this treatment achieved similar results to SGLT2i in preventing progression of kidney disease even in high cardiovascular risk patients.

SAT0405 CLINICAL AND PSYCHOLOGICAL PREDICTORS OF GASTROINTESTINAL INTOLERANCE TO METHOTREXATE IN PATIENTS WITH PSORIATIC ARTHRITIS

Background:Methotrexate (MTX) is a first-line treatment for psoriatic arthritis (PsA). Gastrointestinal intolerance (GI) to the drug is a common adverse event that limits its use and can be mediated by autonomic dysfunction or classical conditioning phenomena to repeated drug exposure. Anxiety and depression could promote these processes.Objectives:To assess the prevalence of GI to MTX and its association with anxiety and depression in PsA patients.Methods:One hundred unselected PsA patients in stable MTX treatment were characterized by disease characteristics, adherence to treatment by Morisky Medication Adherence Scale (MMAS-8) and comorbidity by Rheumatic Disease Comorbidity Index (RDCI). Depressive and anxious symptoms were assessed by Hospital Anxiety and Depression Scale (HADS). The presence and the severity of nausea, vomiting, abdominal pain and diarrhoea after administration (associative symptoms) and just before or even at the thought of taking MTX (anticipatory symptoms) were recorded.Results:Patients had a mean age of 56.9±12.0 years and a disease duration of 9.5 years (0.1-58.0 years). They were male, smokers and overweight in 40.0%, 20.0% and 65.0% of cases, respectively. The prevalence of both significant anxious and depressive symptoms was 42.0%. DAPSA showed remission, low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA) in 24.0%, 41.0%, 32.0% and 3.0% of patients, respectively. MTX was taken orally by 15.0% of patients and associated with another conventional or biological DMARD in 14.0% and 35.0% of cases, respectively. Symptoms of GI to MTX were complained by 69.3% of patients. Specifically, the prevalence of nausea, diarrhea, vomiting and abdominal pain was 59.0%, 23.0%, 21.0% and 30.0% with associative pattern and 43.0%, 12.0%, 10.0% and 16.0% with anticipatory pattern, respectively. Patients with anxious symptoms experienced more frequently moderate to severe associative nausea (71.4% vs 50.0%, p=0.032) and abdominal pain (42.9% vs 20.7%, p=0.017), and anticipatory nausea (42.9% vs 19.0%, p=0.009), vomiting (14.3% vs 6.9%,p=0.046), and abdominal pain (26.2% vs 8.6%, p=0.018) than non-anxious patients. Patients with depressive symptoms more commonly had associative diarrhea (33.0% vs 15.5%, p=0.037), with no difference in the prevalence of anticipatory symptoms. The presence of associative and anticipatory nausea was associated with higher anxiety scores (p=0.006 and p=0.02 respectively) without differences in the depression score. Associative nausea characterized younger patients (p=0.001), female (p=0.02), with lower BMI (p=0.02) and treated with higher MTX doses (p=0.05). Anticipatory nausea was associated with a lower age (p=0.02), a lower BMI (p=0.005), a longer disease duration (p=0.028), a lower DAPSA (p=0.02), an higher MTX doses (p=0.02) and a lower comorbidity burden (p=0.03). The anticipatory and associative nausea determined lower compliance according to MMAS-8 (p=0.007 and p=0.001, respectively). An anxious profile characterized patients with moderate to severe associative nausea also in the logistic regression model corrected for age (≥65 years), gender, BMI (≥25 kg/m2) and MTX dose (≥0.2mg/kg/week) (OR 3.0, IC 1.1-8.4, p=0.036), and patients with anticipatory nausea also in the model corrected for age (≥65 years), gender, BMI (≥25 kg/m2) and MTX dose (≥0.2mg/kg/week) and disease duration (≥6 years) (OR 3.0, IC 1.1-8.0,p=0.027).Conclusion:Up to two-thirds of patients with PsA who have been treated with MTX experienced symptoms of GI, leading to reduced therapeutic adherence. Associative and anticipatory symptoms characterize patients with a specific clinical and psychological profile.Disclosure of Interests:Gerlando Natalello: None declared, Enrico De Lorenzis: None declared, Giacomo Tanti: None declared, Pietro Rubortone: None declared, Maria Rosaria Magurano: None declared, Giusy Peluso: None declared, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer